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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.
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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.
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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) 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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