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CONGESTIVE HEART FAILURE AND CARDIOMYOPATHY


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Table of Contents

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book Coenzyme Q10: a vital therapeutic nutrient for the heart with special application in congestive heart failure.
book Refractory congestive heart failure successfully managed with high dose coenzyme Q10 administration.
book Treatment of congestive heart failure with coenzyme Q10 illuminated by meta-analyses of clinical trials.
book Magnesium supplementation in patients with congestive heart failure
book Carvedilol update iv: Prevention of oxidative stress, cardiac remodeling and progression of congestive heart failure
book Focus on carvedilol: A novel beta-adrenergic blocking agent for the treatment of congestive heart failure
book The use of oral magnesium in mild-to-moderate congestive heart failure
book Sympathetic deactivation by growth hormone treatment in patients with dilated cardiomyopathy.
book L-carnitine in children with idiopathic dilated cardiomyopathy.
book The prevention and management of iodine-induced hyperthyroidism and its cardiac features.
book Thyroid hormone and cardiovascular disease.
book Comparison of effects of ascorbic acid on endothelium-dependent vasodilation in patients with chronic congestive heart failure secondary to idiopathic dilated cardiomyopathy versus patients with effort angina pectoris secondary to coronary artery disease.
book A study of fatty acid content in the myocardium of dilated cardiomyopathy
book Serum concentration of lipoprotein(a) decreases on treatment with hydrosoluble coenzyme Q10 in patients with coronary artery disease: discovery of a new role.
book Coenzyme Q10 administration increases brain mitochondrial concentrations and exerts neuroprotective effects.
book The clinical and hemodynamic effects of Coenzyme Q10 in congestive cardiomyopathy
book Fish oil and other nutritional adjuvants for treatment of congestive heart failure
book The use of oral magnesium in mild-to-moderate congestive heart failure
book Guidelines on treatment of hypertension in the elderly, 1995 -A tentative plan for comprehensive research projects on aging and health-
book Predictors of sudden death and death from pump failure in congestive heart failure are different. Analysis of 24 h Holter monitoring, clinical variables, blood chemistry, exericise test and radionuclide angiography
book Magnesium supplementation in patients with congestive heart failure
book How best to determine magnesium requirement: Need to consider cardiotherapeutic drugs that affect its retention
book Magnesium: A critical appreciation
book Sarcoplasmic reticular Ca2+ pump ATPase activity in congestive myocardial infarction
book Significance of magnesium in congestive heart failure
book The rationale of magnesium as alternative therapy for patients with acute myocardial infarction without thrombolytic therapy
book Mortality risk and patterns of practice in 4606 acute care patients with congestive heart failure: The relative importance of age, sex, and medical therapy
book The study of renal magnesium handling in chronic congestive heart failure
book Management of acute myocardial infarction in the elderly
book Supraventricular tachycardia after coronary artery bypass grafting surgery and fluid and electrolyte variables
book Growth hormone in end-stage heart failure (multiple letters) (6)
book Haemodynamic effects of intravenous growth hormone in congestive heart failure (1)
book Skeletal muscle metabolism in experimental heart failure
book Hydralazine prevents nitroglycerin tolerance by inhibiting activation of a membrane-bound NADH oxidase: A new action for an old drug
book Edema and principles of diuretic use
book Alterations in ATP-sensitive potassium channel sensitivity to ATP in failing human hearts
book Effective water clearance and tonicity balance: The excretion of water revisited
book Hypertension update


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Coenzyme Q10: a vital therapeutic nutrient for the heart with special application in congestive heart failure.

Sinatra ST
Manchester Hospital.
Conn Med (United States) Nov 1997, 61 (11) p707-11

Vitamin coenzyme Q10 is a critical adjuvant complementary therapy for patients with congestive heart failure, especially when traditional medical therapy is unsuccessful. The following case studies, with systolic and/or diastolic dysfunction, demonstrate the effectiveness of coenzyme Q10 in improving quality of life, as well as survival.



Refractory congestive heart failure successfully managed with high dose coenzyme Q10 administration.

Sinatra ST
Manchester Hospital, CT, USA.
Mol Aspects Med (England) 1997, 18 Suppl pS299-305

Coenzyme Q10 (CoQ10) is a critical adjuvant therapy for patients with congestive heart failure (CHF), even when traditional medical therapy is successful. Adjunctive therapy with Q10 may allow for a reduction of other pharmacological therapies, improvement in quality of life, and a decrease in the incidence of cardiac complications in congestive heart failure. However, dosing, clinical application, bioavailability and dissolution of CoQ10 deserve careful scrutiny whenever employing the nutrient. The assessment of blood levels in 'therapeutic failures' appears warranted.



Treatment of congestive heart failure with coenzyme Q10 illuminated by meta-analyses of clinical trials.

Soja AM; Mortensen SA
Department of Medicine, County Hospital Sct. Elisabeth, Copenhagen, Denmark.
Mol Aspects Med (England) 1997, 18 Suppl pS159-68

The purpose of this was to investigate the effect of coenzyme Q10 (CoQ10) in patients with congestive heart failure (CHF) by measuring the possible improvement of certain relevant hemodynamic heart parameters. A statistic aggregation method know as a meta-analysis was used to measure the changes in the cardiac parameters. To begin with we collected the total number of randomized controlled trials and from a total of 14 studies published in the period of 1984-1994, eight studies met our inclusion criteria. The rest were excluded because of a lack of data which made a meta-analysis impossible. The relevant effect parameters investigated were stroke volume (SV), cardiac output (CO), ejection fraction (EF), cardiac index (CI), end diastolic volume index (EDVI), systolic time intervals (PEP/LVET) and total work capacity (Wmax). Seven meta-analyses were performed, one for each of the parameters, and the calculated effect sizes were all positive. Statistical significance could be demonstrated for all of the parameters except the PEP/LVET and Wmax thereby indicating an improvement of greater or lesser magnitude in the CoQ10 group as opposed to the placebo group. Accordingly, the average patient in the CoQ10 group had a better score with regard to SV and CO than 76 and 73% respectively of the patients in the placebo group. In conclusion, supplemental treatment of CHF with CoQ10 is consistent with an improvement of SV, EF, CO, CI and EDVI. Homogeneity could be established for SV and CO. Additional clinical trials of the effect of CoQ10 on CHF are necessary, but, on the basis of the evidence currently available, the possibility remains that CoQ10 will receive a well-documented role as an adjunctive treatment of CHF.



Magnesium supplementation in patients with congestive heart failure

Costello RB; Moser-Veillon PB; DiBianco R
Department of Cardiology, Washington Adventist Hospital, Takoma Park, Maryland 20912, USA.
J Am Coll Nutr (United States) Feb 1997, 16 (1) p22-31

OBJECTIVE: To evaluate several potential clinical indicators of magnesium status (diet, blood, urine, 24-hour load retention) in patients with congestive heart failure before, during, and after oral magnesium supplementation.

METHODS: Twelve patients with New York Heart Association class II-III heart failure and 12 age and sex matched healthy control subjects were supplemented with 10.4 mmol oral magnesium lactate for 3 months. For the determination of magnesium status, samples of whole blood, serum, plasma, red blood cells, and urine (24-hour) were collected. Four-day dietary intake records were reviewed. A 4-hour IV magnesium load retention study was performed before and 3 months after magnesium supplementation. A non-supplemented control group was similarly studied.

RESULTS: At baseline, magnesium intakes for all groups were below the RDA. No significant differences were seen in serum, plasma, ultrafiltrates of serum or plasma or red cell magnesium concentrations among groups over time. At baseline 5/27 subjects (19%) compared to 11/27 subjects (41%) after supplementation demonstrated normal magnesium retentions (< 25%). Magnesium excretions among groups were significantly different during supplementation. Percent magnesium retentions among groups were not different.

CONCLUSIONS: Supplementation with 10.4 mmol oral magnesium daily for 3 months did not significantly alter blood levels or magnesium retention; however, patients demonstrated lower retention of magnesium after supplementation. Differences in magnesium retention was not related to basal magnesium intake, blood levels or excretion. Unfortunately, even an intensive effort at characterizing magnesium status did not identify a clinical indicator of utility for differentiating patients with congestive heart failure before, during, and after 3 months of magnesium supplementation.



Carvedilol update iv: Prevention of oxidative stress, cardiac remodeling and progression of congestive heart failure

Feuerstein G.Z.; Shusterman N.H.; Ruffolo R.R.
R.R. Ruffolo, Pharmacological Sciences, SmithKline Beecham Pharmaceuticals, UW2523, 709 Swedeland Road, King of Prussia, PA 1904-0939 United States
Drugs of Today (Spain) 1997, 33/7 (453-473)

Summary On May 29, 1997, the United States Food and Drug Administration granted final approval for the use of carvedilol in the treatment of mild to moderate congestive heart failure. In this action, the United States joined 20 countries worldwide that have approved carvedilol (Coreg(R)/Kredex(R)) for treatment of hypertension and congestive heart failure. Carvedilol is also approved for the treatment of angina in several countries. Carvedilol (Fig. 1) is a chemically distinct and pharmacologically unique agent that possesses multiple pharmacological actions, including: l)nonselective beta-adrenoceptor blockade, 2) alphainf 1-adrenoceptor blockade, 3) potent antioxidant activity, and 4) regulation of genes involved in cardiovascular organ remodeling and apoptosis. Based on this pharmacological profile, carvedilol is uniquely positioned to inhibit several of the major pathological processes that drive the progression of congestive heart failure, including: 1) hemodynamics: reduction of preload, afterload and heart rate; 2) neurohormonal: inhibition of the sympathetic nervous system, renin-angiotensin system and endothelin; 3) oxidative stress: scavenging potentially toxic oxygen radicals and restoring endogenous antioxidants; 4) genomic reformatting: suppression of several genes associated with pathological organ remodeling. Thus, carvedilol, through its multiple actions, has the capacity to provide broad cardiovascular organ protection. As a result of these multiple actions, carvedilol, when used in conjunction with standard therapy for heart failure (i.e., diuretics, digoxin, and angiotensin-converting enzyme inhibitors), significantly reduced morbidity, mortality and hospitalization in patients with congestive heart failure of either ischemic or nonischemic (i.e., idiopathic dilated cardiomyopathy) origin, independent of disease severity (mild to moderate) or left ventricular function (ejection fraction). The highly favorable clinical outcomes from the large multicenter clinical trials conducted with carvedilol in the United States and Australia/New Zealand merits a detailed update of the unique mechanisms of action of carvedilol, and a thorough review of the clinical trial results. Accordingly, we will highlight in this update our previous experimental findings with carvedilol as well as more recent data that shed light on the mechanisms by which this drug produces its effects in congestive heart failure. In addition, an update of the results from the large multicenter clinical trials, which formed the basis for the approval of the drug for the treatment of heart failure, will be presented.



Focus on carvedilol: A novel beta-adrenergic blocking agent for the treatment of congestive heart failure

Chen B.P.; Chow M.S.S.
Formulary (United States) 1997, 32/8 (795-805)

Carvedilol (Coreg) is a nonselective beta-adrenoreceptor blocker with vasodilating activity. In addition to its earlier approval for the treatment of essential hypertension, the drug has recently become the first beta-blocking agent cleared in the United States for the treatment of congestive heart failure (CHF). Clinical trials have shown that adding carvedilol to standard CHF therapy significantly reduces the risk of death and hospitalization in patients with mild to moderate CHF. To achieve these results, it is imperative that the dosage of carvedilol be titrated carefully. Because of its documented ability to improve survival and morbidity outcomes, carvedilol is a welcome addition to the formulary.



The use of oral magnesium in mild-to-moderate congestive heart failure

Forgosh L.B.; Zolotor W.
Dr. L.B. Forgosh, Arizona Heart Institute/Foundation, 2632 N. 20th Street, Phoenix, AZ 85006 United States
Congestive Heart Failure (United States) 1997, 3/2 (21-24)

Magnesium has been shown to increase cardiac output and low serum magnesium concentrations are associated with frequent arrhythmias and higher mortality in patients with HF. We investigated the use of oral magnesium oxide in decreasing the morbidity and mortality in patients with mild-to- moderate HF. Oral magnesium oxide or placebo was given to 10 patients with NYHA Class II and III HF in a double-blind manner. In monthly follow-up visits, we measured magnesium levels, Euroquol quality of life values, mean arterial pressures, heart rates, and feet walked in 6 minutes. The mean arterial pressure increased an average of 5.3 mm Hg in the magnesium oxide group and decreased an average of 0.67 mm Hg in the placebo group (p = 0.0174). In addition, the heart rate decreased in the patients receiving magnesium oxide, and increased in the patients receiving placebo (p=0.0994). In each group, the NYHA Class decreased, while the Euroquol scale values and feet walked in 6 minutes increased. Due to the small number of patients enrolled, studies with greater numbers of patients that analyze additional oral formulations of magnesium would be beneficial. In addition enrolling HF patients in outpatient programs would be helpful.



Sympathetic deactivation by growth hormone treatment in patients with dilated cardiomyopathy.

Capaldo B; Lembo G; Rendina V; Vigorito C; Guida R; Cuocolo A; Fazio S; Sacca L
Department of Internal Medicine, IRCCS, NEUROMED, Pozzilli Isernia, Italy
Eur Heart J (England) Apr 1998, 19 (4) p623-7

AIMS: We examined the effects of growth hormone administration on the sympathetic nervous system in patients with idiopathic dilated cardiomyopathy .

BACKGROUND: Growth factor therapy is emerging as a new potential option in the treatment of heart failure. Although growth hormone provides functional benefit in the short term, it is unknown whether it affects the sympathetic nervous system, which plays a role in the progression of heart failure.

METHODS: Seven patients with idiopathic cardiomyopathy received 3 months treatment with recombinant human growth hormone (0.15-0.20 IU.kg-1.week-1). Standard medical therapy was unchanged. Myocardial norepinephrine release, both at rest and during submaximal physical exercise, plasma aldosterone, and plasma volume were measured before and after growth hormone treatment. Myocardial norepinephrine release was assessed from arterial and coronary venous plasma concentrations of unlabelled and tritiated norepinephrine and coronary plasma flow (thermodilution).

RESULTS: Growth hormone induced a significant fall in myocardial norepinephrine release in response to physical exercise (from 180 +/- 64 to 99 +/- 34 ng.min-1; P < 0.05). Basally, plasma aldosterone was 189 +/- 28 and 311 +/- 48 pg.ml-1 in the supine and upright position, respectively, and fell to 106 +/- 16 (P < 0.01) and 182 +/- 29 pg.ml-1 (P < 0.05) after growth hormone therapy. Growth hormone increased plasma volume from 3115 +/- 493 ml to 3876 +/- 336 ml (P < 0.05), whereas serum sodium and potassium concentrations were unaffected.

CONCLUSIONS: The data demonstrate that growth hormone administration to patients with idiopathic cardiomyopathy reduces myocardial sympathetic drive and circulating aldosterone levels. This neurohormonal deactivation may be relevant to the potential, long-term use of growth hormone in the treatment of patients with heart failure.



L-carnitine in children with idiopathic dilated cardiomyopathy.

Kothari SS; Sharma M
Department of Cardiology, All India Institute of Medical Sciences, New Delhi.
Indian Heart J (India) Jan-Feb 1998, 50 (1) p59-61

L-carnitine has been used in dilated cardiomyopathy secondary to carnitine deficiency in children, with favourable results. There are no reports on the effects of L-carnitine in children with idiopathic dilated cardiomyopathy . We undertook a prospective study to evaluate the effects of L-carnitine in children with idiopathic dilated cardiomyopathy . Thirteen children, mean age 3.29 +/- 1.44 years, with idiopathic dilated cardiomyopathy underwent echocardiographic evaluation while on conventional treatment alone, and with additional L-carnitine (50 mg/kg/day). To obviate the effects of spontaneous improvement , eight patients (Group 1) were restudied three weeks after stopping the drug, and five (Group 2) were restudied three weeks after addition of carnitine. Conventional treatment was continued throughout. After repeat echocardiographic examination, the parameters were compared statistically. With addition of carnitine, besides symptomatic improvement , the mean left ventricular ejection fraction improved from 36.9 +/- 16.1 percent to 46.9 +/- 14.5 percent (p < 0.001) and the mean pre-ejection period/left ventricular ejection time ratio from 39.07 +/- 14.8 to 43.2 +/- 8.1 (p < 0.01) in the entire group. These changes were concordant in both the subgroups. It was concluded that L-carnitine therapy in children with idiopathic dilated cardiomyopathy led to modest improvement in left ventricular function.



The prevention and management of iodine-induced hyperthyroidism and its cardiac features.

Dunn JT; Semigran MJ; Delange F
Division of Endocrinology, Department of Medicine, University of Virginia Health Sciences Center, Charlottesville 22908, USA.
Thyroid (United States) Jan 1998, 8 (1) p101-6

Review of available literature and experience supports a recommended daily iodine intake of 150 microg for adults, 200 microg during pregnancy, 50 microg for the first year of life, 90 microg for ages 1 to 6, and 120 microg for ages 7 to 12. The amount of iodine added to salt in fortification programs should be adjusted to achieve these intakes. Iodine-induced hyperthyroidism (IIH) is an occasional consequence of the correction of iodine deficiency, occurring most frequently in older subjects with multinodular goiter. This complication is usually mild and self-limited, but may be serious and occasionally lethal. The most important clinical manifestations are cardiovascular. Thyrotoxicosis can aggravate pre-existing cardiac disease and can also lead to atrial fibrillation, congestive heart failure , worsening of angina, thromboembolism, and rarely, death. In the absence of pre-existing cardiac disease, treatment of thyrotoxicosis usually returns cardiac function to normal. Heightened awareness on the part of the health sector will promote early detection and prompt treatment of IIH. Monitoring should be an important part of a successful program of iodization, and in addition it offers the best opportunity for recognizing and treating IIH. Further research to improve the characterization and prevention of IIH is strongly encouraged. The most important conclusion is that IIH, while an issue that needs serious address, is not a reason to stop iodine supplementation in deficient regions. The benefits to the community from correcting iodine deficiency and avoiding its associated disorders far outweigh the damage from IIH. (36 Refs.)



Thyroid hormone and cardiovascular disease.

Gomberg-Maitland M; Frishman WH
Department of Medicine, New York Hospital-Cornell Medical Center, NY, USA.
Am Heart J (United States) Feb 1998, 135 (2 Pt 1) p187-96

Thyroid hormone directly affects the heart and peripheral vascular system. The hormone can increase myocardial inotropy and heart rate and dilate peripheral arteries to increase cardiac output. An excessive deficiency of thyroid hormone can cause cardiovascular disease and aggravate many preexisting conditions. In severe systemic illness and after major surgical procedures changes in thyroid function can occur, leading to the "euthyroid sick syndrome." Patients will have normal or decreased levels of T4, decreased free and total T3, and usually normal levels of thyroid stimulating hormone. This syndrome may be an adaptive response to systemic illness that usually will revert to normal without hormone supplementation as the illness subsides. Recently, however, many investigators have explored the benefits of thyroid hormone supplementation in those diseases associated with euthyroid sick syndrome. Thyroid hormone's effects on the cardiovascular system make it an attractive therapy for those patients with impaired hemodynamics and low T3. Thyroid hormone has also been considered a treatment for patients with congestive heart failure , for patients undergoing cardiopulmonary bypass and heart transplantation, and for patients with hyperlipidemia. At present there is no evidence suggesting a favorable treatment outcome using thyroid hormone supplementation for any systemic condition except in those patients with documented hypothyroidism. (112 Refs.)



Comparison of effects of ascorbic acid on endothelium-dependent vasodilation in patients with chronic congestive heart failure secondary to idiopathic dilated cardiomyopathy versus patients with effort angina pectoris secondary to coronary artery disease.

Ito K; Akita H; Kanazawa K; Yamada S; Terashima M; Matsuda Y; Yokoyama M
The First Department of Internal Medicine, Kobe University School of Medicine, Japan.
Am J Cardiol (United States) Sep 15 1998, 82 (6) p762-7

Impaired endothelium-dependent vasodilation has been reported to play an important role in the pathogenesis of cardiovascular diseases such as coronary artery disease (CAD) and congestive heart failure (CHF). However, the precise mechanism of endothelial dysfunction has not been elucidated in these conditions. To evaluate the role of oxidative stress in endothelial dysfunction, the effect of antioxidant ascorbic acid on brachial flow-mediated, endothelium-dependent vasodilation during reactive hyperemia and nitroglycerin-induced endothelium-independent vasodilation was examined with high resolution ultrasound in 12 patients with CHF caused by idiopathic dilated cardiomyopathy without established coronary atherosclerosis and in 10 patients with CAD. Flow-mediated vasodilation in CHF (4.4+/-0.5%) and CAD (4.0 - 0.8%) was significantly (p <0.05) attenuated compared with that in 10 control subjects (9.6+/-0.9%). However, nitroglycerin-induced vasodilation was similar in 3 groups (13.7+/-1.3% in control, 13.9+/-1.1% in CHF, 12.7+/-1.4% in CAD). Ascorbic acid could significantly improve flow-mediated vasodilation only in patients with CAD (9.1+/-0.9%) but not with CHF (5.6+/-0.6%), and had no influence on nitroglycerin-induced vasodilation (13.6+/-1.1% in CHF, 14.0+/-1.3% in CAD). These results suggest that, in brachial circulation, augmented oxidative stress mainly leads to endothelial dysfunction in CAD but not in CHF caused by idiopathic dilated cardiomyopathy .



A study of fatty acid content in the myocardium of dilated cardiomyopathy

Ning Z.; Connor W.E.; Ott G.Y.
Z. Ning, Department of Cardiovascular Disease, Second Affiliated Hospital, Dalian Medical University, Dalian 116027 China
Chinese Journal of Cardiology (China), 1998, 26/1 (12-14)

Objective: To study the biochemical changes of the myocardium in dilated cardiomyopathy (DCM), the myocardial fatty acid composition was determined.

Methods: From samples of the left ventricular myocardium, removed either, from patients at the time of surgery for cardiac transplantation in OHSU. U.S.A. or from accidental death of normal person, the fatty acid compositions of 10 DCM hearts, 10 coronary disease hearts and 10 control hearts were analyzed. Myocardial phospholipid and triglyceride from the lipid extracts were subjected to thin layer chromatography. Then the fatty acids were analysed by gas-liquid chromatography.

Results: Phospholipids of the DCM had a lower content of essential fatty acid, linoleic acid (18: 2n-6), in comparing with the control hearts. Linoleic acid was lowered to 18.3plus or minus0.9% of the total phospholipid fatty acids in DCM versus 25.3plus or minus3.0% in control hearts (P<0.05). The content of linoleic acid in the myocardial phospholipid of coronary heart disease patients was also lower than that of controls (P<0.05) but higher than DCM. The myocardial triglyceride fatty acids were similar among the three groups.

Conclusion: Our data demonstrated that the phospholipid of the myocardium from patients with DCM had a lower content of linoleic acid. Arachidonic acid is synthesized from linoleic acid. Since arachidonic acid is the precursor of prostaglandin, a lower linoleic acid content might affect prostaglandin production and membrane composition and, in turn, affect myocardial function. Its correction by dietary linoleic acid supplementation may be beneficial to DCM patients.



Serum concentration of lipoprotein(a) decreases on treatment with hydrosoluble coenzyme Q10 in patients with coronary artery disease: discovery of a new role.

Singh RB, Niaz MA
Centre of Nutrition, Medical Hospital and Research Centre, Moradabad, India.
Int J Cardiol 1999 Jan;68(1):23-9

OBJECTIVE: To examine the effect of coenzyme Q10 supplementation on serum lipoprotein(a) in patients with acute coronary disease.

STUDY DESIGN: Randomized double blind placebo controlled trial.

SUBJECTS AND METHODS: Subjects with clinical diagnosis of acute myocardial infarction, unstable angina, angina pectoris (based on WHO criteria) with moderately raised lipoprotein(a) were randomized to either coenzyme Q10 as Q-Gel (60 mg twice daily) (coenzyme Q10 group, n=25) or placebo (placebo group, n=22) for a period of 28 days.

RESULTS: Serum lipoprotein(a) showed significant reduction in the coenzyme Q10 group compared with the placebo group (31.0% vs 8.2% P<0.001) with a net reduction of 22.6% attributed to coenzyme Q10. HDL cholesterol showed a significant increase in the intervention group without affecting total cholesterol, LDL cholesterol, and blood glucose showed a significant reduction in the coenzyme Q10 group. Coenzyme Q10 supplementation was also associated with significant reductions in thiobarbituric acid reactive substances, malon/dialdehyde and diene conjugates, indicating an overall decrease in oxidative stress.

CONCLUSION: Supplementation with hydrosoluble coenzyme Q10 (Q-Gel) decreases lipoprotein(a) concentration in patients with acute coronary disease.



Coenzyme Q10 administration increases brain mitochondrial concentrations and exerts neuroprotective effects.

Matthews RT, Yang L, Browne S, Baik M, Beal MF
Neurochemistry Laboratory, Neurology Service, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Proc Natl Acad Sci U S A 1998 Jul 21;95(15):8892-7

Coenzyme Q10 is an essential cofactor of the electron transport chain as well as a potent free radical scavenger in lipid and mitochondrial membranes. Feeding with coenzyme Q10 increased cerebral cortex concentrations in 12- and 24-month-old rats. In 12-month-old rats administration of coenzyme Q10 resulted in significant increases in cerebral cortex mitochondrial concentrations of coenzyme Q10. Oral administration of coenzyme Q10 markedly attenuated striatal lesions produced by systemic administration of 3-nitropropionic acid and significantly increased life span in a transgenic mouse model of familial amyotrophic lateral sclerosis. These results show that oral administration of coenzyme Q10 increases both brain and brain mitochondrial concentrations. They provide further evidence that coenzyme Q10 can exert neuroprotective effects that might be useful in the treatment of neurodegenerative diseases.



The clinical and hemodynamic effects of Coenzyme Q10 in congestive cardiomyopathy

Sacher H.L.; Sacher M.L.; Landau S.W.; Kersten R.; Dooley F.; Sacher A.; Sacher M.; Dietrick K.; Ichkhan K.
H.L. Sacher, 510 Hicksville Road, Massapequa, NY 11758 USA
American Journal of Therapeutics (USA), 1997, 4/2-3 (66-72)

Despite major advances in treatment congestive heart failure (CHF) is still one of the major causes of morbidity and mortality. Coenzyme Q10 is a naturally occurring substance that has antioxidant and membrane stabilizing properties. Administration of coenzyme Q10 in conjunction with standard medical therapy has been reported to augment myocardial kinetics, increase cardiac output, elevate the ischemic threshold, and enhance functional capacity in patients with congestive heart failure. The aim of this study was to investigate some of these claims. Seventeen patients (mean New York Heart Association functional class 3.0 plus or minus 0.4) were enrolled in an open-label study. After 4 months of coenzyme Q10 therapy, functional class improved 20% (3.0 plus or minus 0.4 to 2.4 plus or minus 0.6, p < 0.001) and there was a 27% improvement in mean CHF score (2.8 plus or minus 0.4 to 2.2 plus or minus 0.4, p < 0.001). Percent change in the resting variables included the following: left ventricular ejection fraction (LVEF), +34.8%; cardiac output, +15.7%; stroke volume index, +18.9%; end- diastolic volume area, -8.4%; systolic blood pressure (SBP), -4.4%; and E(max), (SBP + end-systolic volume index (ESVI)) +11.7%. MV(O2) decreased by 5.3% (31.9 plus or minus 2.6 to 30.2 plus or minus 2.4, p = NS). Therapy with coenzyme Q10 was associated with a mean 25.4% increase in exercise duration and a 14.3% increase in workload. Percent changes after therapy include the following: exercise LVEF, +24.6%; cardiac output, +19.1%; stroke volume index, +13.2%; heart rate, +6.5%; SBP, -4.3%; SBP + ESVI, +18.6%; end-diastolic volume (EDV) area, -6.0%; MV(O2), -7.0%; and ventricular compliance (%Delta SV + EDV) improved >100%. In summary, coenzyme Q10 therapy is associated with significant functional, clinical, and hemodynamic improvements within the context of an extremely favorable benefit-to-risk ratio. Coenzyme Q10 enhances cardiac output by exerting a positive inotropic effect upon the myocardium as well as mild vasodilatation.



Fish oil and other nutritional adjuvants for treatment of congestive heart failure

McCarty M.F.
Nutrition 21, 1010 Turquoise Street, San Diego, CA 92109 USA
Medical Hypotheses (United Kingdom), 1996, 46/4 (400-406)

Published clinical research, as well as various theoretical considerations, suggest that supplemental intakes of the 'metavitamins' taurine, coenzyme Q10, and L-carnitine, as well as of the minerals magnesium, potassium, and chromium, may be of therapeutic benefit in congestive heart failure. High intakes of fish oil may likewise be beneficial in this syndrome. Fish oil may decrease cardiac afterload by an antivasopressor action and by reducing blood viscosity, may reduce arrhythmic risk despite supporting the heart's beta-adrenergic responsiveness, may decrease fibrotic cardiac remodeling by impeding the action of angiotensin II and, in patients with coronary disease, may reduce the risk of atherothrombotic ischemic complications. Since the measures recommended here are nutritional and carry little if any toxic risk, there is no reason why their joint application should not be studied as a comprehensive nutritional therapy for congestive heart failure.



The use of oral magnesium in mild-to-moderate congestive heart failure

Forgosh L.B.; Zolotor W.
Dr. L.B. Forgosh, Arizona Heart Institute/Foundation, 2632 N. 20th Street, Phoenix, AZ 85006 USA
Congestive Heart Failure (USA), 1997, 3/2 (21-24)

Magnesium has been shown to increase cardiac output and low serum magnesium concentrations are associated with frequent arrhythmias and higher mortality in patients with HF. We investigated the use of oral magnesium oxide in decreasing the morbidity and mortality in patients with mild-to- moderate HF. Oral magnesium oxide or placebo was given to 10 patients with NYHA Class II and III HF in a double-blind manner. In monthly follow-up visits, we measured magnesium levels, Euroquol quality of life values, mean arterial pressures, heart rates, and feet walked in 6 minutes. The mean arterial pressure increased an average of 5.3 mm Hg in the magnesium oxide group and decreased an average of 0.67 mm Hg in the placebo group (p = 0.0174). In addition, the heart rate decreased in the patients receiving magnesium oxide, and increased in the patients receiving placebo (p=0.0994). In each group, the NYHA Class decreased, while the Euroquol scale values and feet walked in 6 minutes increased. Due to the small number of patients enrolled, studies with greater numbers of patients that analyze additional oral formulations of magnesium would be beneficial. In addition enrolling HF patients in outpatient programs would be helpful.



Guidelines on treatment of hypertension in the elderly, 1995 -A tentative plan for comprehensive research projects on aging and health-

Ogihara T.; Hiwada K.; Matsuoka H.; Matsumoto M.; Shimamoto K.; Ouchi Y.; Abe I.; Fujishima M.; Morimoto S.; Nakahashi T.; Mikami H.; Kohara K.; Takasaki M.; Takizawa S.; Kiyohara Y.; Ibayashi S.; Eto M.; Ishimitsu T.; Nakamura T.; Masusa A.; Takagawa Y.
Japanese Journal of Geriatrics (Japan), 1996, 33/12 (945-974)

We propose the following guidelines for treatment of hypertension in the elderly.

1. Indications for Treatment.

1) Age: Lifestyle modification is recommended for patients aged 85 years and older. Antihypertensive therapy should be limited to patients in whom the merit of the treatment is obvious.

2) Blood pressure: Systolic BP > 160 mmHg, diastolic BP>90similar100 mmHg. Systolic BP<age . 100 mmHg for those aged 70 years and older. Patients with mild hypertension (140 160/90 95 mmHg) associated with cardiovascular disease should be considered for antihypertensive drug therapy.

2. Goal of Therapy for BP: The goal BP in elderly patients is higher than that in younger patients (BP reduction of 10-20 mmHg for systolic BP and 5-10 mmHg for diastolic BP). In general, 140 160/<90 mmHg is recommended as the goal. However, lowering the BP below 150/85 should be done with caution.

3. Rate of Lowering BP: Start with half the usual dose, observe at the same dose for at least four weeks, and reach the target BP over two months. Increasing the dose of antihypertensive drugs should be done very slowly.

4. Lifestyle Modification:

1) Dietary modification:

(1) Reduction of sodium intake is highly effective in elderly patients due to their high salt-sensitivity. NaCl intake of less than 10 g/day is recommended. Serum Na+ should be occasionally measured.
(2) Potassium supplementation is recommended, but with caution in patients with renal insufficiency,
(3) Sufficient intake of calcium and magnesium is recommended.
(4) Reduce saturated fatty acids. Intake of fish is recommended.

2) Regular physical activity: Recommended exercise for patients aged 60 years and older: peak heart rate 110/minute, for 30-40 minutes a day, 3-5 days a week.

3) Weight reduction.

4) Moderation of alcohol intake, smoking cessation.

5. Pharmacologic Treatment:

1) Initial drug therapy. First choice: Long-acting (once or twice a day) Ca antagonists or ACE inhibitors. Second choice: Thiazide diuretics (combined with potassium-sparing diuretic).

2) Combination therapy.


(1) For patients without complications, either of the following is recommended.

i) Ca antagonist + ACE inhibitor,
ii) ACE inhibitor + Ca antagonist (or low-dose diuretic),
iii) diuretic + Ca antagonist (or ACE inhibitor),
iv) beta- blockers, alpha1-blockers, alpha + beta blockers can be used according to the pathophysiological state of the patient.

(2) For patients with complications. Drug(s) should be selected according to each complication.

3) Relatively contraindicated drugs. beta-Blockers and alpha1-blockers are relatively contraindicated in elderly patients with hypertension in Japan. Centrally acting agents such as reserpine, methyldopa and clonidine are also relatively contraindicated. beta-Blockers are contraindicated in patients with congestive heart failure, arteriosclerosis obliterans, chronic obstructive pulmonary disease, diabetes mellitus (or glucose intolerance), or bradycardia. These conditions are often present in elderly subjects. Elderly subjects are susceptible to alpha1-blocker-induced orthostatic hypotension, since their baroreceptor reflex is diminished. Orthostatic hypotension may cause falls and bone fractures in the elderly.



Predictors of sudden death and death from pump failure in congestive heart failure are different. Analysis of 24 h Holter monitoring, clinical variables, blood chemistry, exericise test and radionuclide angiography

Madsen B.K.; Rasmussen V.; Hansen J.F.
Denmark
International Journal of Cardiology (Ireland), 1997, 58/2 (151-162)

One hundred and ninety consecutive patients discharged with congestive heart failure were examined with clinical evaluation, blood chemistry, 24 h Holter monitoring, exercise test and radionuclide angiography. Median left ventricular ejection fraction was 0.30, 46% were in New York Heart Association class II and 44% in III. Total mortality after 1 year was 21%, after 2 years 32%. Of 60 deaths, 33% were sudden and 49% due to pump failure. Multivariate analyses identified totally different risk factors for sudden death: ventricular tachycardia, s-sodium less than or equal to 137 mmol/l, s-magnesium less than or equal to 0.80 mmol/l, s-creatinine > 121 micromol/l, and maximal change in heart rate during exercise less than or equal to 35 min-1, and for death from progressive pump failure: New York Heart Association class III + IV, Deltaheart rate over 24 h less than or equal to 50 min-1, low ejection fraction, high resting p-noradrenaline, s-urea > 7.6 mmol/l, s-potassium < 3,5 mmol/l, and maximal exercise duration less than or equal to 4 min. In conclusion, this study demonstrated different risk factors for sudden death and for death from progressive pump failure.



Magnesium supplementation in patients with congestive heart failure

Costello R.B.; Moser-Veillon P.B.; DiBianco R.
USA
Journal of the American College of Nutrition (USA), 1997, 16/1 (22-31)

Objective: To evaluate several potential clinical indicators of magnesium status (diet, blood, urine, 24-hour load retention) in patients with congestive heart failure before, during, and after oral magnesium supplementation.

Methods: Twelve patients with New York Heart Association class II-III heart failure and 12 age and sex matched healthy control subjects were supplemented with 10.4 mmol oral magnesium lactate for 3 months. For the determination of magnesium status, samples of whole blood, serum, plasma, red blood cells, and urine (24-hour) were collected. Four-day dietary intake records were reviewed. A 4-hour IV magnesium load retention study was performed before and 3 months after magnesium supplementation. A non-supplemented control group was similarly studied.

Results: At baseline, magnesium intakes for all groups were below the RDA. No significant differences were seen in serum, plasma, ultrafiltrates of serum or plasma or red cell magnesium concentrations among groups over time. At baseline 5/27 subjects (19%) compared to 11/27 subjects (41%) after supplementation demonstrated normal magnesium retentions (<25%). Magnesium excretions among groups were significantly different during supplementation. Percent magnesium retentions among groups were not different.

Conclusions: Supplementation with 10.4 mmol oral magnesium daily for 3 months did not significantly alter blood levels or magnesium retention; however, patients demonstrated lower retention of magnesium after supplementation. Differences in magnesium retention was not related to basal magnesium intake, blood levels or excretion. Unfortunately, even an intensive effort at characterizing magnesium status did not identify a clinical indicator of utility for differentiating patients with congestive heart failure before, during, and after 3 months of magnesium supplementation.



How best to determine magnesium requirement: Need to consider cardiotherapeutic drugs that affect its retention

Seelig M.; Altura B.M.
USA
Journal of the American College of Nutrition (USA), 1997, 16/1 (4-6)

No abstract.



Magnesium: A critical appreciation

Meinertz T.
Prof. Dr. T. Meinertz, Abteilung fur Kardiologie, Medizinische Klinik, Universitatskrankenhaus Eppendorf, Martinistr. 52, 20246 Hamburg Germany
Zeitschrift fur Kardiologie (Germany), 1996, 85/Suppl. 6 (147-151)

The therapeutic efficacy of magnesium has been studied during recent years in a number of cardiovascular diseases: supraventricular and ventricular arrhythmias (multifocal atrial tachycardia, Torsade de pointes-tachycardia, glycoside-associated arrhythmias, sustained ventricular tachycardia), acute myocardial infarction, heart failure and arterial hypertension. Although only a few of these arrhythmias were studied under controlled conditions, the therapeutic efficacy of intravenous magnesium given in a high dose in these arrhythmias seems to be established. By contrary, the efficacy of magnesium in acute myocardial infarction, congestive heart failure and arterial hypertension remains controversial up to now. Magnesium cannot be regarded as standard therapy for example for patients with acute myocardial infarction.



Sarcoplasmic reticular Ca2+ pump ATPase activity in congestive myocardial infarction

Azfal N.; Dhalla N.S.
Institute of Cardiovascular Sciences, St Boniface General Hosp. Res. Ctr., 351 Tache Avenue, Winnipeg, Man. R2H 2A6 Canada
Canadian Journal of Cardiology (Canada), 1996, 12/10 (1065-1073)

Objective: Earlier studies have shown a depression in the sarcoplasmic reticular (SR) Ca2+ uptake and gene expression in Ca2+ pump ATPase protein in congestive heart failure subsequent to myocardial infarction. It is the objective of this study to understand further the mechanisms of depressed SR Ca2+ pump activity in the failing heart.

Methods: Heart failure in rats was induced by occluding the left coronary artery for 16 weeks and the viable left ventricle was processed for the isolation of SR membranes. Sham-operated animals were used as control. The characteristics of SR Ca(2+) pump ATPase in the presence of different concentrations of K+, Ca2+ and ATP were examined and that the purity of these membranes was monitored by determining the marker enzyme activities. In addition to measuring changes in cyclic adenosine monophosphate (cAMP) protein kinase and C2+ calmodulin induced phosphorylation, alterations in SR phospholipid composition as well as sulfhydryl (SH) group content were investigated.

Results: Ca2+stimulated ATPase activity, unlike Mg2+-ATPase activity, was depressed in the left ventricular SR from failing hearts as compared to control. The decreased in Ca2+stimulated ATPase activity was seen at different concentrations of Ca2+, K+ and ATP but no change in the affinities of the enzyme for Ca2+ and ATP were evident. The SR Ca2+stimulated ATPase activities in the presence of both cAMP-dependent protein kinase and Ca2+-calmodulin were markedly decreased in the failing hearts when compared to control preparations. Furthermore, the 32P incorporation in the presence of cAMP-dependent protein kinase or Ca2+-calmodulin was also reduced in the experimental heart SR membranes. The phospholipid composition of the SR membranes from the failing heart was markedly altered. No changes in SH-group of the degree of cross contaminaton with other membranes were apparent in the failing heart SR.

Conclusions: The results suggest the abnormalities in membrane phospholipid composition and phosphorylation of the enzyme may partly explain the observed depression in SR Ca(2+) pump ATPase activity in heart following myocardial infarction.



Significance of magnesium in congestive heart failure

Douban S.; Brodsky M.A.; Whang D.D.; Whang R.
Division of Cardiology, Irvine Medical Center, University of California, 101 The City Dr., Orange, CA 92668-3298 USA
American Heart Journal (USA), 1996, 132/3 (664-671)

Electrolyte balance has been regarded as a factor important to cardiovascular stability, particularly in congestive heart failure. Among the common electrolytes, the significance of magnesium has been debated because of difficulty in accurate measurement and other associated factors, including other electrolyte abnormalities. The serum magnesium level represents <1% of total body stores and does not reflect total-body magnesium concentration, a clinical situation very similar to that of serum potassium. Magnesium is important as a cofactor in several enzymatic reactions contributing to stable cardiovascular hemodynamics and electrophysiologic functioning. Its deficiency is common and can be associated with risk factors and complications of heart failure. Typical therapy for heart failure (digoxin, diuretic agents, and ACE inhibitors) are influenced by or associated with significant alteration in magnesium balance. Magnesium therapy, both for deficiency replacement and in higher pharmacologic doses, has been beneficial in improving hemodynamics and in treating arrhythmias. Magnesium toxicity rarely occurs except in patients with renal dysfunction. In conclusion, the intricate role of magnesium on a biochemical and cellular level in cardiac cells is crucial in maintaining stable cardiovascular hemodynamics and electrophysiologic function. In patients with congestive heart failure, the presence of adequate total-body magnesium stores serve as an important prognostic indicator because of an amelioration of arrhythmias, digitalis toxicity, and hemodynamic abnormalities.



The rationale of magnesium as alternative therapy for patients with acute myocardial infarction without thrombolytic therapy

Shechter M.; Hod H.; Kaplinsky E.; Rabinowitz B.
Prev./Rehabilitative Cardiac Center, Cedars-Sinai Medical Center, 444 South San Vicente Blvd., Los Angeles, CA 90048 USA
American Heart Journal (USA), 1996, 132/2 II (483-486)

Only one third of hospitalized patients with acute myocardial infarction receive thrombolytic therapy despite its proven benefits on outcomes. Elderly patients, for example, have a greater risk cf death after myocardial infarction, but studies demonstrate that thrombolytic therapy is less likely to be used in older patients. Intravenous magnesium supplementation, both theoretically and experimentally, has been demonstrated to decrease myocardial damage and reduce the mortality rate in subsets of patients, including the elderly and/or patients not suitable for thrombolysis, if it is administered before reperfusion occurs. The aim of this study is to review the rationale of magnesium supplementation as alternative therapy for patients with acute myocardial infarction without thrombolytic therapy.



Mortality risk and patterns of practice in 4606 acute care patients with congestive heart failure: The relative importance of age, sex, and medical therapy

Teo K.K.; Montague T.; Ackman M.; Barnes M.; Taylor C.; Mansell G.; Greenwood P.; Prosser A.; Tsuyuki R.; Nilsson C.; Kornder J.; Ashton T.; McLeod D.; Morris A.; Robinson K.; Johnstone D.; Barnhill S.; Chatterton P. ; Montague P.; et al.
Division of Cardiology, 2C2 Mackenzie Centre, University of Alberta Hospitals, Edmonton, Alta. T6G 2B7 Canada
Archives of Internal Medicine (USA), 1996, 156/15 (1669-1673)

Objective: To define contemporary patterns of risk and management among patients with congestive heart failure (CHF).

Methods: Cross-sectional records audit of 4606 hospitalized patients with CHF in 1992 and 1993.

Results: Overall medication use was diuretics, 82%; angiotensin-converting enzyme inhibitors, 53%; nitrates, 49%; digoxin, 46%; potassium, 40%; acetylsalicylic acid, 36%; calcium antagonists, 20%; warfarin, 17%; beta- blockers, 15%; and magnesium, 10%. Angiotensin-converting enzyme inhibitors were used less frequently in women and patients 70 years or older (P<.01). Total in-hospital mortality was 19%. The most common single cause of death was CHF progression, but noncardiac causes accounted for 30% of all deaths. Logistic regression analysis revealed age 70 years or older and the use of magnesium and nitrates to be associated with increased relative risk of in- hospital mortality; angiotensin-converting enzyme inhibitors, acetylsalicylic acid, calcium antagonists, beta-blockers, and warfarin were associated with decreased risk.

Conclusions: Hospitalized patients with CHF have high all-cause mortality risk and less than optimal use of proven efficacious therapy, particularly among women and the elderly. Increased use of proven CHF therapy would likely decrease the risk of cardiac events, but the competing noncardiac risks in this patient population are high and may not be affected by improved use of efficacious cardiac therapies.



The study of renal magnesium handling in chronic congestive heart failure

Marusaki S.; Shimamoto K.
Second Dept. of Internal Medicine, Sapporo Medical Univ. School of Med., S.1, W.17, Chuo-ku, Sapporo 060 Japan
Sapporo Medical Journal (Japan), 1996, 65/1 (23-32)

It is now known that the serum magnesium level is low in patients with chronic congestive heart failure (CHF). In this study, to clarify the role of renal magnesium handling in CHF, the following parameters were examined in normal subjects (control: n = 28) and patients with CHF (n = 37): serum magnesium (s-Mg), plasma aldosterone concentration (PAC), endogenous creatinine clearance (C(Cr)), urinary excretions of magnesium (U(Mg)V) and sodium (U(Na)V), and fractional excretions of magnesium (FE(Mg)), sodium (FE(Na)) and potassium (FE(K)). The relationship between s-Mg and the severity of cardiac dysfunction (NYHA subclass in CHF) was also investigated in CHF. All subjects were admitted to our hospital and given a standard diet including 120 mEq of Na and 75 mEq of K/day, and all the parameters were measured in the early morning after an overnight fast. Compared with the controls, the patients with CHF showed lower levels of s-Mg, C(Cr), U(Na)V and FE(Na), and higher levels of FE(Mg) and PAC. On the other hand, there was no significant difference in U(Mg)V between the controls and CHF patients. In both groups, significant positive correlations were observed between U(Mg)V and FE(Mg), and between U(Mg)V and C(Cr). FE(Mg) correlated positively with FE(K) and PAC in patients with CHF, suggesting an important role of mineralocorticoids in magnesium handling in the distal renal tubules. In the severe CHF (NYHA II or III) subgroup, levels of s-Mg and FE(Mg) were quite similar to those in the mild CHF (NYHA I) subgroup, but the severe CHF subgroup used potassium-magnesium sparing drugs (spironolactone, triamterene and angiotensin converting enzyme inhibitor) more frequently. In CHF patients, combined use of loop diuretics and potassium-magnesium sparing drugs did not show any significant influence on the levels of s-Mg and FE(Mg). These results suggest that the low level of s-Mg in CHF patients is attributable to enhancement of renal magnesium excretion by secondary aldosteronism, and that use of potassium-magnesium sparing drugs may be beneficial for prevention of magnesium deficiency in CHF.



Management of acute myocardial infarction in the elderly

Forman D.E.; Rich M.W.
Division of Geriatrics, Miriam Hospital, Brown University, Providence, RI 02906 USA
Drugs and Aging (New Zealand), 1996, 8/5 (358-377)

The prevalence of myocardial infarction (MI) is high among the elderly population. Many of the physiological and morphological changes attributable to 'normal' aging predispose older adults to cardiovascular instability. The incidence of both MIs and their associated morbidity and mortality increase with aging. Older MI patients may therefore derive substantial benefit from appropriately selected therapeutic intervention. In fact, given the high morbidity and mortality associated with MI in the elderly, aggressive therapeutic strategies may be particularly warranted. There are a number of age-related cardiovascular changes that contribute to the increasing incidence of MI as adults age. However, age itself is not a contraindication to aggressive therapy. Common MI management options include invasive and pharmaceutical strategies. The relative advantages of angioplasty and thrombolytics must be considered. Other drugs used in the treatment of MI include beta-blockers, ACE inhibitors, nitrates, aspirin, anticoagulants, magnesium, antiarrhythmics and calcium antagonists. Significant peri-infarction complications, including heart failure, hypotension, arrhythmias, myocardial rupture and cardiogenic shock, often occur in older adults. Age-specific management strategies for these complications are reviewed.



Supraventricular tachycardia after coronary artery bypass grafting surgery and fluid and electrolyte variables

Nally B.R.; Dunbar S.B.; Zellinger M.; Davis A.
PO Box 1253, Cartersville, GA 30120 USA
Heart and Lung: Journal of Acute and Critical Care (USA), 1996, 25/1 (31-36)

Objective: To explore the relationship between fluid and electrolyte variables and the development of supraventricular tachycardia (SVT) after coronary artery bypass grafting (CABG) surgery.

Design: Retrospective chart review. Random selection from a list obtained from the medical records department and with use of the International Classification of Diseases code to identify patients undergoing their initial CABG.

Setting: Medical records department of a southeastern 600-bed urban referral hospital with a large cardiovascular surgical program.

Patients: Forty patients experiencing SVT and 40 patients not experiencing SVT during their stay in an intensive care unit after CABG.

Outcome Measures: Fluid and electrolyte variables and the development of SVT in the intensive care unit after CABG. Variables: Data collected included preoperative demographic variables such as age and gender; previous history of SVT, congestive heart failure, cardiac arrest, previous surgery, diabetes, hypertension, valve disease, tobacco use, obesity; preoperative and postoperative medications; postoperative laboratory values of potassium, calcium, and magnesium; intravenous intake; hourly urine output; and chest tube drainage.

Results: Demographic variables revealed that patients with SVT were older (p = 0.001) and had a higher incidence of preoperative SVT (p = 0.04). Although groups did not differ by numbers of patients with high or low potassium, calcium, or magnesium, patients receiving additional intravenous potassium by bolus after surgery had a higher incidence of SVT (p = 0.02). Patients who lost blood via the chest tube at a rate greater than 100 ml per hour for at least 1 hour after surgery had a higher incidence of SVT (p = 0.02). Patients with a urine output greater than 300 ml per hour for longer than 9 hours had an increased incidence of SVT (p = 0.02). In the patients experiencing SVT, 62% had it occur 24 to 48 hours after surgery.

Conclusions: These data suggest that shifts in fluid and electrolytes may be important characteristics of patients in whom SVT will develop, which could lead to better identification and nursing management of SVT and improve hemodynamic status, patient recovery, and cost after CABG.



Growth hormone in end-stage heart failure

Dreifuss P.M.; Khardori R.; Taraben A.; Taylor G.J.; Falcone H.; Wilmshurst P.; Giustina A.; Volterrani M.; Desenzani P.
P.M. Dreifuss, Division of Cardiology, University Hospital of Basel, 4055 Basel Switzerland
Lancet (United Kingdom), 1997, 349/9068 (1841-1843)

No abstract.



Haemodynamic effects of intravenous growth hormone in congestive heart failure

Volterrani M.; Desenzani P.; Lorusso R.; D'Aloia A.; Manelli F.; Giustina A.
Italy
Lancet (United Kingdom), 1997, 349/9058 (1067-1068)

No abstract.



Skeletal muscle metabolism in experimental heart failure

Bernocchi P.; Ceconi C.; Pedersini P.; Pasini E.; Curello S.; Ferrari R.
Fondazione Salvatore Maugeri, Clinica Lavoro delia Riabilitazione, Lab Ricerca Fisiopatol Cardiovascol, Via Pinidolo 23, 25064 Gussago (Brescia) Italy
Journal of Molecular and Cellular Cardiology (United Kingdom), 1996, 28/11 (2263-2273)

We studied peripheral skeletal muscle metabolism in monocrotaline-treated rats. Two distinct groups emerged: a percentage of the animals developed ventricular hypertrophy, with no signs of heart failure (compensated group), whilst others, besides ventricular hypertrophy, developed the syndrome of congestive heart failure (CFH group). Oxidative metabolism and redox cellular state were expressed in terms of creatine phosphate, purine (ATP, ADP and AMP) and pyridine (NAD and NADH) nucleotides tissue content. Skeletal muscles with different metabolism were studied: (a) Soleus (oxidative), (b) extensor digitorum longus (glycolytic) and tibialis anterior (oxidative and glycolytic). The results showed that in CFH animals a decreased high-energy phosphates content occurs in the soleus and extensor digitorum longus, but not in the tibialis anterior. In the soleus, ATP declined from 20.31 plus or minus 2.5 of control group to 9.55 plus or minus 0.61 micromol/g dry wt, while in the extensor digitorum longus ATP declined from 30.92 plus or minus 2.68 to 22.7 plus or minus 1.54 micromol/g dry wt. In both these muscles, a shift of NAD/NADH couple towards oxidation was also observed (from 26.58 plus or minus 3.34 to 6.95 plus or minus 0.97 and from 18.88 plus or minus 3.43 to 10.57 plus or minus 1.61, respectively). These alterations were more evident in the aerobic soleus muscle. On the contrary, no major changes occurred in skeletal muscle metabolism of compensated animals. The results show that: (1) a decrease in muscle high-energy phosphates occurs in CFH; (2) this is accompanied by a decrease of NAD/NADH couple suggesting an impairment in oxygen utilization or availability.



Hydralazine prevents nitroglycerin tolerance by inhibiting activation of a membrane-bound NADH oxidase: A new action for an old drug

Munzel T.; Kurz S.; Rajagopalan S.; Thoenes M.; Berrington W.R.; Thompson J.A.; Freeman B.A.; Harrison D.G.
Cardiology Division, Emory University School of Medicine, Atlanta, GA 30322 USA
Journal of Clinical Investigation (USA), 1996, 98/6 (1465-1470)

Hydralazine has been shown to reduce mortality in patients with congestive heart failure when given concomitantly with isosorbide dinitrate. Recently, we demonstrated that nitrate tolerance is in part due to enhanced vascular superoxide .O2/- production. We sought to determine mechanisms whereby hydralazine may prevent tolerance. Rabbits either received no treatment, nitroglycerin patches (1.5 microg/kg/min x 3 d), hydralazine alone (10 mg/kg/d in drinking water), or hydralazine and nitroglycerin. Aortic segments were studied in organ chambers and relative rates of vascular .O2 production were determined using lucigenin-enhanced chemiluminescence. Nitroglycerin treatment markedly inhibited relaxations to nitroglycerin (maximum relaxations in untreated: 92 plus or minus 1 vs. 64 plus or minus 3% in nitroglycerin- treated patients and increased vascular .O2 production by over twofold (P < 0.05). Treatment with hydralazine in rabbits not receiving nitroglycerin significantly decreased .O2 production in intact rabbit aorta and increased sensitivity to nitroglycerin. When given concomitantly with nitroglycerin, hydralazine completely prevented the development of nitrate tolerance and normalized endogenous rates of vascular .O2 production. Studies of vessel homogenates demonstrated that the major source of .O2 was an NADH-dependent membrane-associated oxidase displaying activities of 67 plus or minus 12 vs. 28 plus or minus 2 nmol .O2 .min-1.mg protein-1 in nitroglycerin-treated vs. untreated aortic homogenates. In additional studies, we found that acute addition of hydralazine (10 microM) to nitroglycerin-tolerant vessels immediately inhibited .O2 production and NADH oxidase activity in vascular homogenates. The chemiluminescence signal was inhibited by a recombinant heparin-binding superoxide dismutase (HB-SOD) demonstrating the specificity of this assay for .O2. These observations suggest that a specific membrane-associated oxidase is activated by chronic nitroglycerin treatment, and the activity of this oxidase is inhibited by hydralazine, providing a mechanism whereby hydralazine may prevent tolerance. The ability of hydralazine to inhibit vascular .O2 anion production represents a novel mechanism of action for this drug.



Edema and principles of diuretic use

Morrison R.T.
Dr. R.T. Morrison, 386 North Detroit Street, Xenia, OH 45385 USA
Medical Clinics of North America (USA), 1997, 81/3 (689-704)

Diuretics have changed the approach to many diseases and have turned once fatal conditions into tolerable ones. Treatment of salt and water overload and edema can be quite satisfying for the clinician as long as the patient is closely watched for side effects. Thiazide diuretics have their greatest use in hypertension, loop diuretics in edema and congestive heart failure, CA inhibitors in glaucoma and altitude sickness, potassium-sparing diuretics in hypokalemia induced by other diuretics and ascites, and osmotic diuretics in acute renal failure and dialysis. They are among the most widely prescribed medications in the world today and rightly have a prominent place in the armamentarium against disease.



Alterations in ATP-sensitive potassium channel sensitivity to ATP in failing human hearts

Koumi S.-I.; Martin R.L.; Sato R.
Japan
American Journal of Physiology - Heart and Circulatory Physiology (USA), 1997, 272/4 41-4 (H1656-H1665)

Little is known about the involvement of preexisting heart disease on characteristics of ATP-sensitive K channels (I(K(ATP))) in human heart. We have characterized I(K(ATP)) in isolated cardiac myocytes from patients with congestive heart failure (HF) and compared these channel characteristics with those from donor hearts (healthy control) using the patch-clamp technique. During metabolic inhibition induced by treatment with cyanide (1 mM) and 2- deoxyglucose (10 mM), action potential shortening occurred in atrial myocytes isolated from both HF and donors, but this response was significantly greater and sooner in HF than in donors. The action potential duration at 90% repolarization was 24.7 plus or minus 4.1% (n = 15) of control in HF, whereas it was 58.7 plus or minus 5.9% (n = 10, P < 0.001) of control in donors measured at 30-min metabolic inhibition. The shortening of the action potential was partially reversed by glibenclamide (0.5 microM) in both groups. Consistent with the action potential measurements, the whole cell membrane current response to metabolic inhibition, evaluated by the differential current measurement, was sooner and greater in HF than in donors. Single channel atrial I(K(ATP)) from both HF and donors, recorded in the excised inside-out patch configuration, exhibited bursting opening, conductance, and gating behaviors that did not differ between the two groups. However, the concentration of ATP at half- maximal inhibition of the channel in HF was greater (131.0 microM) than in donors (26.1 microM). We conclude that I(K(ATP)) in cardiac myocytes from patients with HF has channel characteristics substantially similar to those in donors, but that the channel is less sensitive to ATP inhibition in HF than in donors.



Effective water clearance and tonicity balance: The excretion of water revisited

Mallie J.P.; Bichet D.G.; Halperin M.L.
Dr. J.P. Mallie, Explorations Fonctionnelles Renales, Centre Hospitalier, Universitaire de Nancy, 54511 Vandoeuvre Cedex France
Clinical and Investigative Medicine (Canada), 1997, 20/1 (16-24)

Objective: To demonstrate

(1) that hyponatremia is usually due to an inappropriately low rate of excretion of electrolyte-free water and

(2) that the measure 'effective water clearance' (EWC) provides better information about renal defence of the body tonicity than does the classic measure free-water clearance, and to provide the rationale for calculating a 'tonicity balance,' which involves using water and sodium plus potassium intakes and their renal excretion to reveal the basis for changes in body tonicity.

Design: Prospective study.

Participants: Four normal subjects with no conditions affecting excretion, 10 patients with advanced congestive heart failure (CHF) and 5 patients with the syndrome of inappropriate antidiuretic hormone secretion (SIADH).

Intervention: Normals and patients were administered a standard water load (20 mL per kg of body weight) during 45 minutes, and blood and urine samples were taken before, during and after the load was given.

Main outcome measures: Urine and blood sodium and potassium concentrations, osmolar clearance, free-water clearance, electrolyte clearance and EWC.

Results: The water load was excreted rapidly by normals, more slowly by patients with CHF, and not at all by patients with SIADH. The EWC was positive in normals and those with CHF, but negative in those with SIADH. In patients with CHF, the EWC, but not the free-water clearance, helped explain why hyponatremia was corrected after the water load was given.

Conclusions: In subjects with abnormal water excretion, the EWC provides the physiologic explanation for the renal role in variations in natremia. The authors propose a bedside evaluation of renal water and electrolyte handling that takes into consideration the role of urinary potassium in body tonicity. Changes in body tonicity can be explained by a 'tonicity balance,' a calculation in which the source and the net balance of sodium, potassium and water are considered.



Hypertension update

Hyman B.N.; Moser M.
7707 Fannin, Houston, TX 77054 USA
Survey of Ophthalmology (USA), 1996, 41/1 (79-89)

Hypertension affects approximately fifty million Americans. About 80% of hypertensive patients are aware that their blood pressure is elevated. While more than 50% are on medication, only about 20% of all hypertensive adults are controlled at normotensive levels. Ophthalmologists should be aware of the seriousness of' hypertension because it affects many of' their patients and is a risk factor for myocardial infarction, stroke, congestive heart failure, end-stage renal disease and peripheral vascular disease. As medically trained eye specialists, ophthalmologists should be knowledgeable about and take all interest in their patients medical problems, thus playing an integral role on the health care team. As a primary health care provider, ophthalmologists should perform in office blood pressure monitoring.


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