Magnesium in supraventricular and ventricular arrhythmias
Zeitschrift fur Kardiologie (Germany), 1996, 85/Suppl. 6 (135-145)
The use of magnesium as an antiarrhythmic agent in ventricular and supraventricular arrhythmias is a matter of an increasing but still controversial discussion during recent years. With regard to the well established importance of magnesium in experimental studies for preserving electrical stability and function of myocardial cells and tissue, the use of magnesium for treating one or the other arrhythmia seems to be a valid concept. In addition, magnesium application represents a physiologic approach, and by this, is simple, cost-effective and safe for the patient. However, when one reviews the available data from controlled studies on the antiarrhythmic effects of magnesium, there are only a few types of diac arrhythmias, such as torsade de pointes, digitalis-induced ventricular arrhythmias and ventricular arrhythmias occurring in the presence of heart failure or during the perioperative state, in which the antiarrhythmic benefit of magnesium has been shown and/or established. Particularly in patients with one of these types of cardiac arrhythmias, however, it should be realized that preventing the patient from a magnesium deficit is the first, and the application of magnesium the second best strategy to keep the patient free from cardiac arrhythmias.
Effect of intravenous magnesium sulfate on cardiac arrhythmias in critically III patients with low serum ionized magnesium
Kasaoka S.; Tsuruta R.; Nakashima K.; Soejiina Y.; Miura T.; Sadamitsu D. ; Tateishi A.; Maekawa T.
Critical Care Medical Center, Yamaguchi University Hospital, 1144 Kogushi, Ube, Yamaguchi 755 Japan
Japanese Circulation Journal (Japan), 1996, 60/11 (871-875)
Magnesium affects cardiac function, although until the recent development of a new ion selective electrode no method existed for measuring the physiologically active form of magnesium, free ions (iMg2+), in the blood. We investigated the antiarrhythmic effect of magnesium sulfate administered to critically ill patients with cardiac arrhythmias and reduced iMg2+ as determined using the ion-selective electrode. Eight patients with a low iMg2+ level (less than 0.40 mmol/L) were given intravenous magnesium sulfate (group L). Magnesium sulfate was also administered to patients with a normal iMg2+ level (more than 0.40 mmol/L) but who did not respond to conventional antiarrhythmic drugs (group N). Intravenous magnesium sulfate significantly increased the iMg2+ level in patients in group L from 0.35plus or minus0.06 mmol/L (mean plus or minus SD) to 0.54 plus or minus 0.09 mmol/L (p<0.01), and had an antiarrhythmic effect in 7 of the 8 patients (88%). However, in group N patients, intravenous magnesium sulfate had an antiarrhythmic effect in only 1 of the 6 patients (17%) (p<0.05 vs group L). These results suggest that intravenous magnesium sulfate may be effective in the acute management of cardiac arrhythmias in patients with a low serum iMg2+ level.
Ionic mechanisms of ischemia-related ventricular arrhythmias
Ducceschi V.; Di Micco G.; Sarubbi B.; Russo B.; Santangelo L.; Iacono A.
Facolta di Medicina e Chirurgia, Isto. Medico-Chirurgico Cardiologia, Seconda Universita di Napoli, Piazza L. Miraglia, 80138 Naples Italy
Clinical Cardiology (USA), 1996, 19/4 (325-331)
The aim of this review is the utmost simplification of the cellular electrophysiologic background of ischemia-related arrhythmias. In the acute and subacute phase of myocardial infarction, arrhythmias can be caused by an abnormal impulse generation, abnormal automaticity or triggered activity caused by early or delayed afterdepolarizations (EAD and DAD), or by abnormalities of impulse conduction (i.e., reentry). This paper addresses therapeutic intervention aimed at preventing the depolarization of 'pathologic' slow fibers, counteracting the inward calcium (Ca) influx that takes place through the L-type channels (Ca antagonists), or hyperpolarizing the diastolic membrane action potential increasing potassium (K) efflux (K- channel openers) in arrhythmias generated by an abnormal automaticity (ectopic tachycardias or accelerated idioventricular rhythms). If the cause of enhanced impulse generation is related to triggered activity, and since both EAD and DAD are dependent on calcium currents that can appear during a delayed repolarization, the therapeutic options are to shorten the repolarization phase through K-channel openers or Ca antagonists, or to suppress the inward currents directly responsible for the afterdepolarization with Ca blockers. Magnesium seems to represent a reasonable choice, as it is able to shorten the action potential duration and to function as a Ca antagonist. Abnormalities of impulse conduction (reentry) account for the remainder of arryhythmias that occur in the acute and subacute phase of ischemia and for most dysrhythmias that develop during the chronic phase. Reentrant circuits due to ischemia are usually Na channel-dependent. During choice will depend on the length of the excitable gap: in case of a short gap (ventricular fibrillation, polymorphic ventricular tachycardia, etc.), the refractory period has been identified as the most vulnerable parameter, and therefore a correct therapeutic approach will be based on drugs able to prolong the effective refractory period (K-channel blockers, such as class III antiarrhythmic drugs); on the other hand, for those arrhythmias characterized by a long excitable gap (most of the monomorphic ventricular tachycardias), the most appropriate therapeutic intervention consists of depressing ventricular excitability and conduction by use of sodium-channel blockers such as mexiletine and lidocaine. Compared with other class I antiarrhythmic agents, these drugs minimally affect refractoriness and exhibit a use-dependent effect and a voltage dependent action (i.e., more pronounced on the ischemic tissue because of its partial depolarization).
Myocardial infarction: The first 24 hours
Gavagan T.; Reddy M.J.
Dept. of Family Practice, 1900 W. Polk St., Chicago, IL 60612 USA
American Family Physician (USA), 1996, 54/3 (921-938)
Myocardial infarction is the most common cause of death in the United States. Rapid postinfarction intervention in the first 24 hours decreases mortality. Treatment modalities are rapidly evolving as new data from basic science research and clinical trials become available. Rapid thrombolysis, accurate criteria for diagnosis and administration of effective adjunctive therapy are crucial in preventing complications of myocardial infarction. Initial measures in the emergency department include intravenous access, accurate history and physical assessment, placement of oxygen, electrocardiography, use of aspirin and nitrates, and consideration of thrombolysis or angioplasty in appropriate candidates, optimally within one to two hours of myocardial infarction. After hospital admission, additional adjunctive treatment, including beta blockers, angiotensin-converting enzyme inhibitors and anticoagulation, can be instituted.
Proarrhythmic and antiarrhythmic actions of ion channel blockers on arrhythmias in the heart: Model study
Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA 15260 USA
American Journal of Physiology - Heart and Circulatory Physiology (USA), 1996, 271/1 40-1 (H329-H356)
We explain why 1) some class I and IV antiarrhythmia drugs could exert proarrhythmic action, 2) some class III drugs are effective in controlling reentrant arrhythmias, and 3) cycle length (CL) oscillation is involved in the termination or initiation of reentry. To explain these phenomena, we employ the following three means: bifurcation analysis, simulation, and model construction. Antiarrhythmia drugs are modeled by varying maximal conductances of Na+, Ca2+, and time-dependent delayed rectifying and time- independent inward rectifying K channels in the Beeler-Reuter model, where the model cells are arranged in a ring. Bifurcation analysis predicts that there is a critical ring size (CRS) at which infinite ring behavior suddenly breaks down. Channel blockers can affect CRS in different manners: Na+ and Ca2+ blockers shorten CRS, whereas delayed rectifying K+ channel blockers and the inward K+ channel blockers lengthen CRS. This differential explains why some antiarrhythmia drugs are proarrhythmic (i.e., shorten CRS) whereas others are antiarrhythmic (i.e., lengthen CRS). Simulation is then used to investigate how the drugs affect reentrant rhythms in the neighborhood of the CRS. We find that, in this region, CL, conduction velocity, and action potential duration become oscillatory. As ring size shrinks, the pattern of the oscillation becomes more complex. When the ring shrinks to a certain size, reentry can no longer be sustained, and it terminates after a few oscillatory cycles. To explain the basic mechanism involved in CL oscillation, we then construct a minimal model that contains a low-threshold fast inward current and a high-threshold slow inward current. With this model, we show that the two inward currents, with vastly different activation and inactivation kinetics, cause CL oscillations. Our results thus give theoretical explanations for the experimental finding of Frame's group in canine atrial tricuspid ring in vitro that class IC drugs can bring about stable reentry from nonsustained transient reentry, whereas class III drugs transform stable reentry to complex oscillations in CL. Our results also support the result of Frame's group, in that, in 'adjustable' tricuspid rings, CL oscillation becomes more complex and its period becomes shorter as an excitable gap is shortened.
Prophylactic effects of taurine and diltiazem, alone or combined, on reperfusion arrhythmias in rats
Li P.; Kang Y.; Wang G.-X.
Department of Pharmacology, Tianjin Medical University, Tianjin 300070 China
Acta Pharmacologica Sinica (China), 1996, 17/2 (122-124)
Aim: To study the effects of taurine (Tau) and diltiazem (Dil), alone or in combination, on reperfusion arrhythmias in anesthetized rats.
Methods: The arrhythmias were produced by coronary artery ligation for 15 min followed by reperfusion. Malondialdehyde (MDA) content and superoxide dismutase (SOD) activity were measured by thiobarbituric acid fluorescence assay and colorimetric determination.
Results: Taurine 70 mg . kg-1 in combination with Dil 1 mg . kg-1 were more effective on prevention of the reperfusion arrhythmias than each drug alone. The combination of both drugs not only decreased the content of MDA, but also increased the activity of SOD in reperfusion myocardium.
Conclusion: The inhibition of lipoperoxides formation as well as the inhibition of the calcium influx was involved in the anti-arrhythmic effect of both taurine and diltiazem.
The cardiovascular protective role of docosahexaenoic acid
McLennan P.; Howe P.; Abeywardena M.; Muggli R.; Raederstorff D.; Mano M. ; Rayner T.; Head R.
CSIRO, Division of Human Nutrition, Gouger Street, Adelaide, SA 5000 Australia
European Journal of Pharmacology (Netherlands), 1996, 300/1-2 (83-89)
Dietary fish oils rich in n-3 polyunsaturated fatty acids can modulate a diverse range of factors contributing to cardiovascular disease. This study examined the relative roles of eicosapentaenoic acid (20:5 n-3; EPA) and docosahexaenoic acid (22:6 n-3; DHA) which are the principal n-3 polyunsaturated fatty acids regarded as candidates for cardioprotective actions. At low dietary intakes (0.4-1.1% of energy (%en)), docosahexaenoic acid but not eicosapentaenoic acid inhibited ischaemia-induced cardiac a rrhythmias. At intakes of 3.9-10.0%en, docosahexaenoic acid was more effective than eicosapentaenoic acid at retarding hypertension development in spontaneously hypertensive rats (SHR) and inhibiting thromboxane-like vasoconstrictor responses in aortas from SHR. In stroke-prone SHR with established hypertension, docosahexaenoic acid (3.9-10.0%en) retarded the development of salt-loading induced proteinuria but eicosapentaenoic acid alone was ineffective. The results demonstrate that purified n-3 polyunsaturated fatty acids mimic the cardiovascular actions of fish oils and imply that docosahexaenoic acid may be the principal active component conferring cardiovascular protection.
Trace elements in prognosis of myocardial infarction and sudden coronary death
Kusleikaite M.; Masironi R.
Trace Element Institute for UNESCO, Lyon France
Journal of Trace Elements in Experimental Medicine (USA), 1996, 9/2 (57-62)
Ca, Cu, Mg, Mn, and Zn concentrates were measured in plasma, RBC, and hair of 350 men aged 40-59 years with myocardial infarction (MI) and/or who died from sudden cardiac death (SCD), as compared with normal controls. Analyses were done by flame atomic absorption spectrophotometry. Cu in plasma of MI patients was significantly higher than the controls'. Plasma Mn was significantly lower in SCD than in MI subjects. No other consistent and significant changes were observed. Past and present evidence indicates that high plasma Cu levels may be associated with heart failure and rhythm disorders. The low plasma Mn levels may be an indicator of decreased parasympathetic tonus thus favouring myocardial desynchronization and A-V block. Cu inhibits phosphodiesterase activity and Mn inhibits andenylate cyclase activity thus exerting an influence on the contractility of cardiomyocites and of smooth muscle cells in coronary arteries. Cu and Mn analyses may thus have a prognostic significance for MI and SCD.
Prevention of cardiac arrhythmia by dietary (n-3) polyunsaturated fatty acids and their mechanism of action
Nair S.S.D.; Leitch J.W.; Falconer J.; Garg M.L.
Journal of Nutrition (USA), 1997, 127/3 (383-393)
The role of marine fish oil (n-3) polyunsaturated fatty acids in the prevention of fatal ventricular arrhythmia has been established in experimental animals. Prevention of arrhythmias arising at the onset of ischemia and reperfusion is important because if untreated, they result in sudden cardiac death. Animals supplemented with fish oils in their diet developed little or no ventricular fibrillation after ischemia was induced. Similar effects have also been observed in cultured neonatal cardiomyocytes. Several mechanisms have been proposed and studied to explain the antiarrhythmic effects of fish oil polyunsaturated fatty acids, but to date, no definite mechanism has been validated. The sequence of action of these mechanisms and whether more than one mechanism is involved is also not clear. Some of the mechanisms suggested to explain the antiarrhythmic action of fish oils include the incorporation and modification of cell membrane structure by (n-3) polyunsaturated fatty acids, their direct effect on calcium channels and cardiomyocytes and their role in eicosanoid metabolism. Other mechanisms that are currently being investigated include the role of (n-3) polyunsaturated fatty acids in cell signalling mediated through phosphoinositides and their effect on various enzymes and receptors. This article reviews these mechanisms and the antiarrhythmic studies using (n-3) polyunsaturated fatty acids.
Exposure to the n-3 polyunsaturated fatty acid docosahexaenoic acid impairs alpha1-adrenoceptor-mediated contractile responses and inositol phosphate formation in rat cardiomyocytes
Reithmann C.; Scheininger C.; Bulgan T.; Werdan K.
Medizinische Klinik I, Klinikum Grosshadern, Universitat Munchen, Marchioninistrasse 15, D-81377 Munchen Germany
Naunyn-Schmiedeberg's Archives of Pharmacology (Germany), 1996, 354/2 (109-119)
The beneficial effects of n-3 polyunsaturated fatty acids of fish oil in the prevention of fatal arrhythmias in myocardial ischemia were suggested to be at least in part mediated by a modulation of dihydropyridine-sensitive L-type calcium channels. As cardiac alpha1-adrenoceptor stimulation has been suggested to have no significant effect on L-type calcium channels, the aim of this study using cultured neonatal rat cardiomyocytes was to investigate whether chronic n-3 polyunsaturated fatty acid exposure may have an influence on alpha1-adrenoceptor-induced positive inotropic effects and induction of arrhythmias. Pretreatment of the rat cardiomyocytes for 3 days in the presence of the n-3 polyunsaturated fish oil-derived fatty acid docosahexaenoic acid (60 micromol/l) markedly decreased alpha1-adrenoceptor-stimulated increase in contraction velocity and induction of arrhythmias. The increase in contraction velocity of the cardiomyocytes induced by the beta-adrenoceptor agonist isoprenaline was also markedly reduced by the n-3 fatty acid pretreatment. Basal contractile amplitude and spontaneous beating frequency of the cardiomyocytes were not significantly altered by the docosahexaenoic acid exposure. The pretreatment of the rat cardiomyocytes for 3 days in the presence of docosahexaenoic acid (60 micromol/l) decreased alpha1-adrenoceptor-stimulat ed formation of the calcium-mobilizing second messenger IP3 and its metabolites IP2 and IP1 by 55%. The depression of IP3 formation by docosahexaenoic acid treatment was not mediated by a decreased uptake of myo-inositol into the cardiomyocytes nor by a decreased synthesis of phosphatidylinositol bisphosphate (PIP2), the substrate of phospholipase C. The level of glycerol-3-phosphate, an important substrate of the phosphoinositide cycle, was unaltered by the docosahexaenoic acid pretreatment. Receptor binding studies revealed that the dissociation constant and maximal binding capacity of the alpha1-adrenoceptor antagonist (3H)prazosin was unchanged by the n-3 polyunsaturated fatty acid exposure. beta-Adrenoceptor- and forskolin-stimulated adenylyl cyclase activities were not diminished by the docosahexaenoic acid pretreatment. Chronic exposure of the cardiomyocytes to the n-6 polyunsaturated fatty acid arachidon ic acid (60 micromol/l) did neither significantly alter alpha1-adrenoceptor-induced inositol phosphate formation nor alpha1-adrenoceptor-stimulated increase in contraction velocity. The results presented show that chronic n-3 polyunsaturated fatty acid pretreatment of rat cardiomyocytes leads to a marked impairment of alpha1-adrenoceptor-induced positive inotropic effects and induction of arrhythmias concomitant with a n-3 fatty acid-induced decrease in IP3 formation. This derangement of the phosphoinositide pathway by chronic n-3 fatty acid exposure may, thus, contribute to the beneficial effects of fish oil-derived fatty acids in the prevention of fatal arrhythmias in myocardial ischemia.
Selenium deficiency associated with cardiac dysfunction in three patients with chronic respiratory failure
To Y.; Koshino T.; Kubo M.; Yoshizawa A.; Kudo K.; Kabe J.
Japanese Journal of Thoracic Diseases (Japan), 1996, 34/12 (1406-1410)
We encountered three patients with chronic respiratory failure who had heart failure of cardiac arrhythmias and low levels of serum selenium. All three had tracheostomies and had received long-term parenteral nutrition that had not included selenium. All three also had refractory cardiac dysfunction, which was manifested in edema, heart failure, and various tachycardias. We suspected that selenium deficiency had caused their cardiac dysfunction. Serum selenium concentrations were found to be much lower than normal in all three, so 100 microg/day of selenium was administered in addition to their tube feedings. Cardiac function improved after replacement of selenium. These cases show the need for preventing selenium deficiency in patients with chronic respiratory failure during long-term administration of parenteral nutrition.
Fish oil and other nutritional adjuvants for treatment of congestive heart failure
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.
Evidence on the participation of the 3',5'-cyclic AMP pathway in the non-genomic action of 1,25-dihydroxy-vitamin D3 in cardiac muscle.
Selles J; Boland R
Mol Cell Endocrinol (Netherlands) Dec 1991, 82 (2-3) p229-35
Several studies have suggested that vitamin D plays a role in cardiovascular function. It has been recently shown that in vitro treatment of vitamin D-deficient chick cardiac muscle with physiological concentrations of 1,25-dihydroxy-vitamin D3 (1,25(OH)2D3) induces a rapid (1-10 min) increase of tissue 45Ca uptake which can be suppressed by Ca channel blockers. The hormone simultaneously stimulated heart microsomal membrane protein phosphorylation. Experiments were performed to investigate the existence of a relationship between these changes and to obtain information about the mechanism involved in 1,25(OH)2D3-induced modifications in cardiac protein phosphorylation. Dibutyryl cyclic AMP (10 microM) and forskolin (10 microM), known activators of the cAMP pathway, produced time courses of changes in 45Ca uptake by chick heart tissue similar to 1,25(OH)2D3 (10(-10) M). Analogously to the hormone, the effects of both compounds were abolished by nifedipine (30 microM) and verapamil (10 microM). In agreement with these observations, 1,25(OH)2D3 significantly increased (34-70%) heart muscle cAMP levels within 1-10 min of treatment. In addition, 1,25(OH)2D3 and forskolin caused similar changes in cardiac microsomal membrane protein phosphorylation (e.g. stimulation in 43 kDa and 55 kDa proteins). These changes were also evidenced by direct exposure of isolated heart microsomes to 1,25(OH)2D3, suggesting a direct membrane action of the hormone. The fast effects of 1,25(OH)2D3 on dihydropyridine-sensitive cardiac muscle Ca uptake could be reproduced in primary-cultured myocytes isolated from chick embryonic heart. Furthermore, the effects of the hormone could be suppressed by a specific protein kinase A inhibitor. These results suggest that 1,25(OH)2D3 affect s heart cell calcium metabolism through regulation of Ca channel activity mediated by the cAMP pathway.
1,25(OH)2 vitamin D3, and retinoic acid antagonize endothelin-stimulated hypertrophy of neonatal rat cardiac myocytes.
Wu J; Garami M; Cheng T; Gardner DG
Department of Medicine, University of California, San Francisco, 94143, USA.
J Clin Invest (United States) Apr 1 1996, 97 (7) p1577-88
1,25(OH)2 Vitamin D3 (VD3) and retinoic acid (RA) function as ligands for nuclear receptors which regulate transcription. Though the cardiovascular system is not thought to represent a classical target for these ligands, it is clear that both cardiac myocytes and vascular smooth muscle cells respond to these agents with changes in growth characteristics and gene expression. In this study we demonstrate that each of these ligands suppresses many of the phenotypic correlates of endothelin-induced hypertrophy in a cultured neonatal rat cardiac ventriculocyte model. Each of these agents reduced endothelin-stimulated ANP secretion in a dose-dependent fashion and the two in combination proved to be more effective than either agent used alone (VD3: 49%; RA:52%; VD3 + RA:80% inhibition). RA, at concentrations known to activate the retinoid X receptor, and, to a lesser extent, VD3 effected a reduction in atrial natriuretic peptide, brain natriuretic peptide, and alpha-skeletal actin mRNA levels. Similar inhibition (VD3:30%; RA:33%; VD3 + RA:59% inhibition) was demonstrated when cells transfected with reporter constructs harboring the relevant promoter sequences were treated with VD3 and/or RA for 48 h. These effects were not accompanied by alterations in endothelin-induced c-fos, c-jun, or c-myc gene expression, suggesting either that the inhibitory locus responsible for the reduction in the mRNA levels lies distal to the activation of the immediate early gene response or that the two are not mechanistically coupled. Both VD3 and RA also reduced [3H]leucine incorporation (VD3:30%; RA:33%; VD3 + RA:45% inhibition) in endothelin-stimulated ventriculocytes and, once again, the combination of the two was more effective than either agent used in isolation. Finally, 1,25(OH)2 vitamin D3 abrogated the increase in cell size seen after endothelin treatment. These findings suggest that the liganded vitamin D and retinoid receptors are capable of modulating the hypertrophic process in vitro and that agents acting through these or similar signaling pathways may be of value in probing the molecular mechanisms underlying hypertrophy.
[Effect of vitamin E deficiency on the development of cardiac arrhythmias as affected by acute ischemia]
Belkina LM; Arkhipenko IuV; Dzhaparidze LM; Saltykova VA; Meerson FZ
Biull Eksp Biol Med (USSR) Nov 1986, 102 (11) p530-2
Malonic dialdehyde content was increased by 53% in the myocardium of male Wistar rats (250-300 g) devoid of vitamin E for 2 months, as compared to the control rats (animals receiving an optimal amount of vitamin E). Transitory ischemia (10 min) with subsequent reoxygenation (5 min) was induced during open heart surgery under urethan anesthesia. Ischemia was induced by the occlusion of the descending branch of the left coronary artery. In ischemic rats with vitamin E deficiency the incidence of ventricular fibrillation, tachycardia, extrasystoles and the additive duration of arrhythmias were significantly increased as compared to the control.
Antioxidant protection against adrenaline-induced arrhythmias in rats with chronic heart hypertrophy.
Kirshenbaum LA; Gupta M; Thomas TP; Singal PK
Division of Cardiovascular Sciences, St Boniface General Hospital Research Centre, Winnipeg, Manitoba.
Can J Cardiol (Canada) Mar 1990, 6 (2) p71-4
Effects of vitamin E on adrenaline-induced arrhythmias were examined in rats with chronic heart hypertrophy subsequent to narrowing of the abdominal aorta. After 60 weeks of pressure overload, the rats showed an increase of about 21% in heart/body weight ratio and a small but significant rise in left ventricular end diastolic pressure (LVEDP) (sham control 1.7 +/- 0.67 mmHg; hypertrophy 7.1 +/- 2.7 mmHg) without any change in left ventricular peak systolic pressure (LVSP). Intravenous infusion of adrenaline caused rhythm disorders in a dose-dependent manner and pathological arrhythmias (occurrence of six premature ventricular complexes/min) were observed at doses of 2.9 +/- 0.6 and 3.8 +/- 1.0 micrograms/kg of the drug in control and hypertrophy animals, respectively. Administration of two doses of vitamin E (50 mg/kg intraperitoneally), given 24 h and 1 h before adrenaline infusion, significantly increased the amount of adrenaline required to produce pathological arrhythmias (control 8.0 +/- 3.0; hypertrophy 7.7 +/- 2.0 micrograms/kg). Vitamin E pretreatment did not have any detrimental effect on the pressure readings nor did it have any influence on adrenaline-induced pressure changes. The data suggest that a combination therapy with vitamin E may allow therapeutic use of higher concentrations of adrenaline required to improve function in failing hearts with a reduced risk of arrhythmias
The antiarrhythmic effects of taurine alone and in combination with magnesium sulfate on ischemia/reperfusion arrhythmia
Yi K.-M.; Wang G.-X.
Dept. of Pharmacology, Tianjin Medical College, Tianjin 300070 China
Chinese Pharmacological Bulletin (China), 1994, 10/5 (358-362)
The effect of tauring (Taur) alone and in combination with magnesium sulfate (MgSO4) on ischemia/reperfusion arrhythmia was investigated. The arrhythmia as produced by coronary artery occlusion for 10 min followed by reperfusion. In addition, the present study also observed the effect of MgSO4 alone and in combination with Taur on hemodynamics. The results showed that Taur (50 mg . kg-1) and MgSO4 (25 mg . kg-1) had partly antiarrhythmic effect. Taur (100, 150mg. kg-1) MgSO4 (50, 100mg. kg-1) had significantly antiarrhythmic effect. Taur (50 mg. kg-1) combined with MgSO4 (25 mg. kg-1) shortened the duration of ventricular tachycardia (VT) more than that either drug did alone. The hypotensive effect of MgSO4 (25 mg. kg-1) was not increased by coadministration of Taur, but the myocardial oxygen consumption was reduced. These findings indicate that Taur in combination with MgSO4 is more effect on reperfusion arrhythmia, and that the mechanism of antiarrhythmic effect of Taur and MgSO4 may be involved in the effect of defence on myocardium.
The effects of antioxidants on reperfusion dysrhythmias
Kovacs P.; Baricova L.; Kovalova M.; Dostal J.; Stankovicova T.; Svec P.
Katedra Farmakologie a Toxikologie, Farmaceuticka Fakulta, Univerzita Komenskeho, Kalinciakova 8, 832 32 Bratislava Slovak Republic
Ceska a Slovenska Farmacie (Czech Republic), 1995, 44/5 (257-260)
The present study aims to investigate the effects of the lipophilic antioxidant Trolox C (a vitamin E analogue) and stobadine, a scavenger of free oxygen radicals, on reperfusion dysrhythmias. Experiments were performed on isolated perfused rat hearts subjected to global stop-flow ischaemia followed by reperfusion. Trolox C (10-4 mol.l-1) and stobadine (10-5 mol.l-1) were infused immediately prior to ischaemia. Trolox C (10-4 mol.l-1) and stobadine (10-5 mol.l-1) decreased the incidence and duration of reperfusion-induced dysrhythmias (quantified by the dysrhythmia score) in comparison to the ischaemic-reperfusion damaged hearts. There was an improvement in the recovery of contraction force and left ventricular diastolic pressure in Trolox or stobadine pretreated hearts. No significant changes in coronary flow resistance were observed. The results suggest that both substances protect the myocardium during ischaemic-reperfusion injury probably by affecting the generation and activity of reactive oxygen species.
Protective effects of all-trans-retinoic acid against cardiac arrhythmias induced by isoproterenol, lysophosphatidylcholine or ischemia and reperfusion
Kang JX; Leaf A
Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.
J Cardiovasc Pharmacol (United States) Dec 1995, 26 (6) p943-8
Previous studies have shown that free polyunsaturated fatty acids (PUFA) reduce the excitability of cardiac myocytes and exert antiarrhythmic effects. Therefore, we hypothesized that retinoic acid (RA, vitamin A acid), which has structural characteristics similar to those of PUFA, may have similar antiarrhythmic effects. To test this hypothesis, we used an isolated, spontaneously beating, neonatal rat cardiac myocyte preparation to examine the effects of RA, added to the perfusion solution, on the cell contraction and arrhythmias induced by isoproterenol (ISO) or lysophosphatidylcholine (LPC). All-trans-RA (10-20 microM) induced a marked and reversible reduction in the contraction rate of the cell in 2-5 min without changing the amplitude of the contractions. Superfusion of the myocytes with either ISO (3 microM) or LPC (5 microM) induced sustained tachyarrhythmias characterized by spasmodic contractures and fibrillation. Addition of 15-20 microM all-trans-RA to the perfusion solution effectively prevented as well as terminated the arrhythmias induced by ISO and LPC. Furthermore, in a whole-animal model of arrhythmia in which the left anterior descending coronary artery (LAD) of the anesthetized rat was occluded for 15 min followed by reperfusion, both the incidence and severity of ventricular tachycardia and fibrillation (VT, VF) were significantly reduced during the ischemic and reperfusion periods by intravenous infusion of all-trans-RA. In contrast, other analogues, including retinol and retinal, and other fat-soluble vitamins, including vitamin D, E, and K, did not have such effects. Our results demonstrate that all-trans-RA can produce antiarrhythmic effects similar to those of PUFA, suggesting a novel role of RA as a potential antiarrhythmic agent.
Effects of dietary supplementation with alpha-tocopherol on myocardial infarct size and ventricular arrhythmias in a dog model of ischemia-reperfusion
Sebbag L; Forrat R; Canet E; Renaud S; Delaye J; de Lorgeril M
Institut National pour la Sante et la Recherche Medicale (INSERM), Unit 63, Lyon, France.
J. Am. Coll. Cardiol. (USA), 1994, 24/6 (1580-1585)
Objectives. We investigated whether dietary supplementation with the antioxidant vitamin alpha-tocopherol (500 mg daily) might reduce lethal ventricular arrhythmias and infarct size.
Background. Previous studies suggested that dietary supplementation with alpha-tocopherol may be associated with a reduced risk of ischemic heart disease. However, the mechanism of this protection remains unknown.
Methods. Beagle dogs were randomized to either a supplemented or a control group. Because of the low mortality rate in the supplemented group, five dogs were added to the control group. After 2 months, dogs were anesthetized and underwent a 2-h coronary artery occlusion and 6-h reperfusion. Plasma vitamin E, retinol and malondialdehyde concentrations were assessed in all dogs.
Results. Fourteen dogs (11 of 25 control vs. 3 of 19 supplemented dogs, p < 0.05) developed ventricular fibrillation during either ischemia or reperfusion. Malondialdehyde concentrations were higher in dogs that subsequently developed arrhythmias (2.7 plus or minus 0.2 micromol/liter, mean plus or minus SEM) compared with dogs that did not (2.1 plus or minus 0.2 micromol/liter, p = 0.03). Among survivors with significant ischemia, infarct size was larger in supplemented (n = 12, 58.5 plus or minus 3.3% of area at risk) than in control (n = 11, 41.9 plus or minus 6.5%, p < 0.04) dogs. In addition, for a given collateral flow, supplemented dogs (n = 16) developed larger infarct size than control dogs (n = 15, p < 0.001, analysis of covariance).
Conclusions. The data suggest that dietary alpha-tocopherol supplementation prevented lethal ventricular arrhythmias associated with ischemia and reperfusion. However, its influence on infarct size and long-term prognosis warrants further inve stigation.
Magnesium flux during and after open heart operations in children.
Satur CM, Stubington SR, Jennings A, Newton K, Martin PG, Gebitekin C, Walker DR
Department of Cardiothoracic Surgery, Killingbeck Hospital, Leeds, United Kingdom.
Ann Thorac Surg (United States) Apr 1995, 59 (4) p921-7
Hypomagnesemia and depletion of the body's magnesium stores is known to be associated with an increased incidence of both cardiac arrhythmias and neurological irritability. In a two-part prospective study we have evaluated whether magnesium deficiency is a significant occurrence in children treated in the intensive care unit after open heart operations, and subsequently have sought to identify how intraoperative metabolic changes were related to the resultant findings. In 41 children studied after operation the plasma magnesium concentration showed a significant decrease from 0.92 mmol/L (10th to 90th centile, 0.71 to 1.15 mmol/L) immediately after operation to 0.77 mmol/L (0.65 to 0.91 mmol/L) on the following morning. The subsequent change in grouped values was not significant but 14 (34.2%) and 7 (17.1%) possessed values of less than 0.7 mmol/L and 0.6 mmol/L, respectively. The occurrence of cardiac arrhythmias was not statistically related to the occurrence of hypomagnesemia. In 21 children perioperative changes in extracellular and tissue magnesium, potassium, and calcium content were measured. It was found that hemodilution with a prime low in magnesium caused a reduction from a median of 0.81 mmol/L to 0.61 mmol/L (p < 0.01). Plasma potassium level, however, was elevated from 3.7 mmol/L to 4.15 mmol/L (p < 0.05) and the ionized calcium content from 1.17 mmol/L (1.07 to 1.25 mmol/L) to 1.49 mmol/L (1.25 to 2.56 mmol/L) (p = 0.0009). The myocardial content of magnesium did not change significantly but skeletal muscle content was depleted from 6.75 mumol/g (2.85 to 8.35 mumol/g) to 5.65 mumol/g (2.45 to 7.2 mumol/g) (p < 0.01)
Sino-atrial Wenckebach conduction in thyrotoxic periodic paralysis: a case report.
Chia BL, Lee KH, Cheah JS
Department of Medicine, National University Hospital, National University of Singapore.
Int J Cardiol (Ireland) Jan 6 1995, 47 (3) p285-9
A 28-year-old male presented with thyrotoxic periodic paralysis. On admission to hospital the serum potassium level was 1.4 mmol/l. The ECG showed classical features of hypokalaemia. In addition, sino-atrial block with Wenckebach conduction was also present. With the normalization of the serum potassium, the ECG became completely normal and showed no evidence of any arrhythmia .
A possible beneficial effect of selenium administration in antiarrhythmic therapy.
New York Medical College, N.Y. 10025-6421.
J Am Coll Nutr (United States) Oct 1994, 13 (5) p496-8
OBJECTIVE: The following review of the literature on the importance of Selenium (Se) in myocardial homeostasis and of the pharmacology of this trace metal, represents an attempt to search, without prejudice to other possible explanations, for a rationale of a beneficial effect of Se substitution as an adjuvant to antiarrhythmic therapy.
BACKGROUND: For several years, in the early 1980s, I had to deal with the problem of a serious ventricular arrhythmia (non-sustained and sustained ventricular tachycardia) which was remarkably resistant to a battery of the most potent antiarrhythmic agents. Eventually, dramatic improvement, lasting for a period of 8 years, was achieved with Flecainide, which, however, left unsolved the episodic occurrence of disabling ventricular bigemini. Over the most recent period of 1 year and 8 months, there was a sudden and unexplained return to unbroken normal sinus rhythm. Among the multiplicity of possible reasons for this fortunate development, the concurrent introduction of Se substitution appeared as the most obvious, though very tentative explanation. Substitution of this trace metal preceded the extinction of ventricular bigemini by 1 week and actually represented the sole modification of otherwise reasonably standardized conditions of antiarrhythmic therapy, life style and diet. (25 Refs.)
Omega-3 fatty acids and prevention of ventricular fibrillation.
Medical Services, Massachusetts General Hospital, Charlestown, MA 02129, USA.
Prostaglandins Leukot Essent Fatty Acids 1995 Feb-Mar;52(2-3):197-8
Interest in the potential cardiovascular benefits of omega-3 long chain polyunsaturated fatty acids has been largely focused on possible antiatherothrombotic effects. In addition, however, definitive antiarrhythmic effects of these dietary omega-3 fatty acids have been reported by Charnock & McLennan. Our studies commenced with the observation that two of these fatty acids, eicosapentaenoic (C20:5n-3, EPA) and docosahexaenoic acid (C22:6n-3, DHA) prevented contracture and fibrillation of isolated neonatal cardiac myocytes when exposed to toxic levels of ouabain (0.1 mM). This protection was associated with prevention of excessively high intracellular calcium concentrations in the myocyte. Further, it was shown that these fatty acids modulate calcium currents through L-type calcium channels and that the effect occurs within a few minutes of adding EPA or DHA to the medium perfusing the cultured cardiac myocytes. Infusing an emulsion of the omega-3 fatty acids intravenously just prior to compression of a coronary artery in a conscious, prepared dog will prevent the expected subsequent ischemia-induced ventricular fibrillation. (9 Refs.)
[Effect of anti-arrhythmia drugs on the beta2 receptor-dependent adenyl cyclase system of lymphocytes in patients with cardiac rhythm disorders]
Krasnikova TL, Iurkova VB, Ku'zmina MM, Ku'lginskaia IV, Sokolov SF, Golitsyn SI, Chernousova TV, Svet EA, Mazaev AV
Kardiologiia (USSR) Jul 1989, 29 (7) p25-9
The authors analyzed the density of beta 2-adrenoreceptors, their affinity for catecholamines and activity of peripheral lymphocyte adenylate cyclase in healthy donors and patients with frequent ventricular premature contraction (VPC) in their pretreatment state and during short-term ethmosine or allapinine therapy. The density of beta 2-adrenoreceptors was increased by 43%, whereas guanylimidodiphosphate- or forskolin-induced stimulation of adenylate cyclase was decreased in the lymphocytes of VPC patients as compared to those of healthy donors. Ethmosine therapy failed to produce any changes in the density and affinity of the receptors for catecholamines. Allapinine caused a 47% reduction in beta 2-adrenoreceptor density and a 10(2)-10(3)-fold decrease in receptor affinity for 1-isoproterenol. After discontinuation of allapinine, the changes in beta 2-adrenoreceptor density and affinity for catecholamines remained on days 3 and 7, respectively. The clinical effect of both ethmosine and allapinine was accompanied by an increase in lymphocyte adenylate cyclase activity.