Magnesium suppression of early afterdepolarizations and ventricular tachyarrhythmias induced by cesium in dogs

The mechanism by which magnesium therapy suppresses some ventricular tachyarrhythmias characterized by a prolonged QT interval (e.g., torsades de pointes) is unknown. Since early afterdepolarizations have been proposed as a cause of the long QT syndrome and the related ventricular tachyarrhythmias, we hypothesized that magnesium therapy would suppress both the early afterdepolarizations and the ventricular arrhythmias. The present study was performed to test that hypothesis. Using monophasic action potentials (MAP) recorded with a contact electrode from the right ventricular endocardium to demonstrate early afterdepolarizations, cesium chloride (168 mg/kg iv) was administered before, during, and 1 to 2 hr after discontinuation of a magnesium infusion (1 to 2 mg/kg/min for 20 to 30 min). Before magnesium infusion, cesium induced early afterdepolarizations that were 49.7 +/- 1.6% (mean +/- SE) of the amplitude of the corresponding monophasic action potential. The amplitude of the early afterdepolarization decreased to 31.2 +/- 3.8% of the MAP amplitude during magnesium infusion (p less than .003) and increased to 48.0 +/- 4.0% 1 to 2 hr after termination of the magnesium infusion (p less than .003). Cesium induced sustained monomorphic ventricular tachycardia, torsades de pointes, or ventricular fibrillation in 12 of 13 dogs before magnesium infusion, and in eight of 11 dogs 1 to 2 hr after stopping infusion, but in only three of 13 dogs during magnesium infusion. Cesium prolonged the corrected QT interval from 338 +/- 16 msec (control) to 387 +/- 14 msec before (p less than .003), 356 +/- 12 msec during (p less than .003), and 406 +/- 16 msec after stopping the magnesium infusion (p less than .003).(ABSTRACT TRUNCATED AT 250 WORDS)     

Alpha-adrenoceptor stimulation and blockade modulates cesium-induced early afterdepolarizations and ventricular tachyarrhythmias in dogs

In 84 open-chest dogs, we studied the effects on early afterdepolarizations (EADs) and ventricular tachyarrhythmias (VTs) induced by cesium chloride (168 mg/kg i.v.) of alpha-adrenoceptor stimulation with phenylephrine (100 micrograms plus 0.25 microgram/kg/min i.v.) and with left ansa subclavia stimulation (LAS; 2 Hz, 4 msec, 2 mA) after propranolol (0.5 mg/kg) administration. We also studied the effects of alpha-adrenoceptor blockade with phentolamine (3 mg/kg), prazosin (25-500 micrograms/kg), yohimbine (10-500 micrograms/kg), WB 4101 (2 mg/kg), and benoxathian (2 mg/kg) during decentralized LAS. EAD amplitude, presented as a percentage of monophasic action potential amplitude, was recorded simultaneously with contact electrodes from the right and left ventricular endocardium. Phenylephrine and LAS plus propranolol increased EAD amplitude (31.5 +/- 8.8% to 47.8 +/- 9.7% and 34.8 +/- 4.1% to 46.1 +/- 6.4%, respectively) and the prevalence of VT (from three to nine of 11 dogs and from the three to five of six dogs, respectively). Prazosin produced a dose-response decrease in EAD amplitude and reduced the prevalence of VT. Yohimbine did not alter the amplitude of EADs or the prevalence of VT. WB 4101 and phentolamine reduced the amplitude of EADs produced by cesium and LAS (from 44.3 +/- 10.2% to 32.6 +/- 9.4% and from 39.8 +/- 6.9% to 30.3 +/- 6.3%, respectively) and the prevalence of VT (from eight to one of 10 dogs and from 13 to 5 of 20 dogs, respectively). Benoxathian did not alter significantly the amplitude of EADs (41.6 +/- 11.4% to 37.5 +/- 9.4%) or the prevalence of VT (from six to five of 10 dogs).(ABSTRACT TRUNCATED AT 250 WORDS)     

Pericardial prostaglandin biosynthesis prevents the increased incidence of reperfusion-induced ventricular fibrillation produced by efferent sympathetic stimulation in dogs

This study tested the hypothesis that sympathetic neural stimulation increases the prevalence of reperfusion-induced ventricular fibrillation and explored the mechanisms by which this occurs and how it may be prevented. In anesthetized, autonomically denervated dogs, we examined the effects of bilateral ansae subclaviae stimulation (SS) and of induction of pericardial biosynthesis of prostaglandins, an intervention that reduces SS effects by acting at presynaptic sites. A 5-minute occlusion of the left anterior descending coronary artery distal to the first or second diagonal branch was performed during SS. Heart rate was maintained constant by atrial pacing. In the absence of SS, one of 23 dogs developed ventricular fibrillation during occlusion, and three of the remaining 22 dogs developed ventricular fibrillation upon reperfusion. SS did not increase the prevalence of occlusion-induced ventricular fibrillation (four of 23 dogs) but increased the prevalence of reperfusion-induced ventricular fibrillation (12 of the remaining 19 dogs, p = 0.01). SS did not affect occlusion-induced decrease in local electrogram amplitude recorded from the ischemic myocardium or myocardial blood flow to the ischemic myocardium during occlusion or reperfusion. SS, however, prevented occlusion-induced increase in diastolic excitability threshold. Instillation into the pericardial cavity of arachidonic acid solution (3 micrograms/ml) resulted in release of prostacyclin, measured by radioimmunoassay as a stable metabolite 6-ketoprostaglandin F1 alpha (63.1 +/- 11.3 ng/ml, n = 11, mean +/- SEM), and of prostaglandin E2 (7.0 +/- 0.9 ng/ml, n = 11). This pericardial solution blunted SS-induced increase in mean arterial blood pressure and reduced the prevalence of ventricular fibrillation during reperfusion (six dogs to one dog, p less than 0.05). Blood flow to the ischemic myocardium remained unaffected. Indomethacin, when added to the solution (3 micrograms/ml), reversed the effects of prostaglandin release and arrhythmia development. These data indicate that efferent sympathetic stimulation during a coronary occlusion and reperfusion sequence increases the prevalence of reperfusion-induced ventricular fibrillation that is reduced by pericardial biosynthesis of prostaglandins. Pericardial prostaglandin synthesis may serve as a unique antiarrhythmic function by regulating efferent cardiac sympathetic nerve effects.     

Right versus left ventricular stimulation: influence on induction of ventricular tachyarrhythmias in dogs

The contribution of left (versus right) ventricular stimulation to the induction of ventricular tachyarrhythmias was studied in 37 dogs with chronic experimental myocardial infarction, and 17 dogs with normal hearts. Programmed stimulation of the endocardium at both ventricular apices employed an aggressive protocol of up to 7 extrastimuli. The right ventricle was the most successful site for induction of ventricular tachycardia after myocardial infarction (74% of dogs with ventricular tachycardia). Ten of 11 animals with slow ventricular tachycardia (greater than or equal to 140 msec) were inducible from the right ventricle. In contrast, left ventricular stimulation was required to induce rapid ventricular tachycardia (cycle length less than 140 msec) in 5 of 10 dogs (P less than 0.05). No animal required more than five extrastimuli from any site for induction of ventricular tachycardia. In the normal heart, ventricular fibrillation was induced most often from the right ventricle (77% of dogs) when compared with the left ventricle (47%, P less than 0.05). Ventricular tachycardia was never induced in normal animals. These results show that the right ventricular apex is the most successful site for induction of "slow" ventricular tachycardia in this canine model when using five extrastimuli. Rapid ventricular tachycardia is frequently induced from the infarcted left ventricle, but this arrhythmia may not be clinically significant. The normal right ventricle is significantly more susceptible to ventricular fibrillation than is the left ventricle, but this does not interfere with induction of ventricular tachycardia in the infarcted heart.     

Depressant effect of magnesium on early afterdepolarizations and triggered activity induced by cesium, quinidine, and 4-aminopyridine in canine cardiac Purkinje fibers

Magnesium chloride has been shown to terminate torsades de pointes in some patients with the acquired long QT syndrome. The mechanism for this effect is unknown. Recently early afterdepolarizations (EADs) and triggered activity (TA) have been proposed as causes of torsades de pointes. The purpose of the present study was to examine whether magnesium suppressed EADs that were initiated in vitro by different agents and if so its mechanism of action. TA arising from EADs was induced by quinidine (1 to 4 mumol/L, n = 5) at high temperature (38.5 to 40 degrees C), cesium chloride (5 to 12 mmol/L, n = 6), and 4-aminopyridine (1.5 to 5 mmol/L, n = 7) in canine cardiac Purkinje fibers superfused with modified Tyrode's solution (KCI = 2.7 mmol/L). MgCl2 (2 to 7 mmol/L) reversibly abolished TA and suppressed EADs. Tetrodotoxin (TTX; 1 to 5 mumol/L) also abolished TA elicited by 4-aminopyridine (n = 6). We then examined the effects of MgCl2, TTX, and verapamil on depolarization-induced automaticity by means of a single sucrose gap technique to gain insight into the mechanism of action of magnesium. MgCl2 (5 mmol/L) abolished automaticity arising from membrane potentials more negative than -70 mV and prolonged the spontaneous cycle length at less negative membrane potentials. The effects of TTX (1 to 5 mumol/L) resembled those of MgCl2. Verapamil (1 mumol/L) prolonged the cycle length of the initial automatic response at high levels of membrane potential and progressively reduced the amplitude of the subsequent automatic potentials. It abolished automaticity arising from less negative membrane potentials.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of vagal stimulation on cesium-induced early afterdepolarizations and ventricular arrhythmias in rabbits.

BACKGROUND. Previous evidence has shown that increased sympathetic tone enhances the cesium chloride (Cs)-induced early afterdepolarizations (EADs) and ventricular tachycardias (VTs). METHODS AND RESULTS. We assessed the effects of vagal stimulation on Cs-induced EADs and ventricular arrhythmias in the rabbit heart. Monophasic action potentials (MAPs) of the left ventricular endocardium were recorded simultaneously with surface ECG. Two protocols were used: 1) While in their intrinsic sinus rhythm, 11 rabbits were given three intravenous Cs injections (1 mM/kg) 20 minutes apart, and the effects of vagal stimulation on the ventricular arrhythmias thus induced were examined. 2) Under constant atrial pacing (cycle length, 250 msec), EAD amplitude was measured after Cs injection (1 mM/kg) without (five rabbits, control group) or with (four rabbits, vagal stimulation group) vagal stimulation. We observed the following. 1) Cs produced EADs and VTs of polymorphic (PVT) and monomorphic (MVT) types. During PVT, the take-off potential of repetitive premature action potentials in MAP recordings was about the same as the peak level of EADs, and during MVT, the take-off potential was the level of full repolarization. Vagal stimulation suppressed PVT but not MVT. Vagal stimulation after spontaneous termination of MVT restarted MVT of the same morphology at a rate much slower than the preceding sinus rate. 2) EAD amplitude was significantly smaller in the vagal stimulation group than in the control group. CONCLUSIONS. The results suggest that PVT originated from triggering by EADs, whereas MVT was of different origin, and that vagal stimulation suppressed PVT by decreasing the amplitude of EADs.     

Long-term reproducibility of responses to programmed cardiac stimulation in spontaneous ventricular tachyarrhythmias

Programmed electrical stimulation (PES) of the heart has been used to initiate and terminate ventricular tachyarrhythmias under controlled conditions in patients in whom these arrhythmias have occurred spontaneously. The long-term reproducibility of the response to programmed cardiac stimulation in patients with ventricular arrhythmias is unknown. Seventeen patients with previously documented spontaneously occurring ventricular tachyarrhythmias were evaluated: 5 with nonsustained ventricular tachycardia (VT), 10 with sustained VT and 2 with ventricular fibrillation. The underlying cardiac diagnosis was atherosclerotic coronary heart disease (CAD) in 11 patients, dilated cardiomyopathy in 2 patients, congenital heart disease in 1 patient and no structural heart disease in 3. All patients underwent PES in the absence of antiarrhythmic drug treatment, and patients with inducible VT underwent serial electrophysiologic-pharmacologic testing in an attempt to suppress the arrhythmia. All 17 patients were reexamined with PES at a mean of 18 months (range 2 to 42) after their initial electrophysiologic study, during which time none had a myocardial infarction or intervening cardiac surgery. Repeat electrophysiologic studies, performed in the absence of antiarrhythmic agents, were undertaken because of drug intolerance, availability of new drugs, recurrent arrhythmia or preoperative reevaluation. All 11 patients with CAD had inducible VT on both the first and second electrophysiologic evaluation. Of the 6 patients with no CAD, only 1 had inducible VT on both occasions. Thus, long-term reproducibility of PES-induced VT in patients with stable CAD appears to be high.     

Cesium chloride induced ventricular arrhythmias in dogs: three-dimensional activation patterns and their relation to the cesium dose applied

Introduction: Cesium chloride has widely been used in experimental models to produce various ventricular arrhythmias. The study was designed to evaluate whether type and mechanism of these arrhythmias are dose-dependent. Methods: In 7 dogs with acute AV-block, 60 pins containing 4 bipolar electrodes each were inserted into both ventricles to provide 240 endo-, epi- and midmyocardial recording sites. A computerized mapping system was used to determine three-dimensional activation patterns of ventricular arrhythmias induced by three injections of 1 mmol/kg cesium chloride at 20 minute intervals. Results:Out of all arrhythmias induced, 25 ventricular extrasystoles, 31 monomorphic and 47 polymorphic ventricular tachycardias were mapped. Nonsustained ventricular tachycardias were readily inducible by a single bolus of cesium chloride, whereas sustained episodes required repetitive injections (1.45 ± 0.61 vs. 2.61 ± 0.57 doses, p < 0.05). Polymorphic tachycardias were observed more commonly than monomorphic tachycardias (87 vs. 31). Initiation and maintenance of cesium induced arrhythmias were exclusively based on focal mechanisms originating from the subendocardium, irrespective of morphology and dosage. All monomorphic arrhythmias were caused by repetitive firing of single immobile foci located in either the right or the left ventricle. Bi- and multifocal mechanisms, however, were found to underlie the polymorphic episodes. Conclusions: Although there is a dose-dependence as to the sustenance of mono- or polymorphic tachycardias, this does not reflect on the three-dimensional activation pattern of cesium induced arrhythmias, which are due to mono- or multifocal activation originating from the subendocardium. Received: 6 August 1999, Returned for 1. revision: 8 October 1999, 1. Revision received: 27 October 1999, Returned for 2. Revision: 24 November 1999, 2. Revision received: 9 December 1999, Accepted: 9 December 1999     

Excitation of afferent cardiac sympathetic nerve fibers induced by vagal stimulation.

The effect of vagal stimulation on activity of afferent sympathetic nerve fibers from the dog's left ventricle has been examined. During partial constriction of the coronary artery, a brief electrical stimulation of the cervical vagus nerves resulted in a decrease in blood flow of the constricted artery, systolic bulge of the left ventricle, elevation of the ST segment of electrocardiogram and excitation of the afferent nerve fibers, which continued for up to 15 min. These changes were not produced without coronary artery constriction. Intravenous injection of phentolamine eliminated the decrease in blood flow, and suppressed systolic bulge, elevation of the ST segment and excitation of afferent fibers. Propranolol could not eliminate the decrease in blood flow while suppressed the other changes. Atropine eliminated all of these changes. The results indicate participation of adrenergic alpha-receptors in sustained decrease of coronary blood flow and excitation of afferent cardiac sympathetic nerve fibers which can be produced by a brief vagal excitation.     

Effects of angiotensin II on the cardiac responses to sympathetic nerve stimulation in dogs

In anesthetized dogs with the left cardiac sympathetic nerves and both vagal nerves intact, angiotensin II (AII) induced a substantial, dose-dependent increase in arterial blood pressure and small increments in cardiac cycle length and ventricular contractile force. In dogs in which the cardiac sympathetic and vagal nerves had been interrupted, AII produced similar increases in blood pressure and larger increases in contractile force, but it decreased the cardiac cycle length. In both groups of dogs, AII augmented substantially the positive inotropic responses to sympathetic nerve stimulation, but it enhanced the positive chronotropic responses only slightly. However, AII did not appreciably prolong the cardiac responses to sympathetic nerve stimulation, nor did it alter significantly the cardiac responses to norepinephrine infusions. Hence, at the dosage levels used, AII probably did not inhibit the neuronal uptake of norepinephrine appreciably nor did it enhance the responsiveness of the cardiac effector sites to norepinephrine. Therefore, the potentiation of the cardiac responses to sympathetic nerve stimulation by AII in these experiments was probably achieved principally by facilitating norepinephrine release from the adrenergic nerve terminals in the heart.     

Acute and long-term efficacy of propafenone in patients with sustained ventricular tachyarrhythmias: assessment with programmed ventricular stimulation

To determine the electrophysiological properties of oral propafenone, 50 patients (39 male and 11 female, aged 31 to 80 years) with sustained ventricular tachycardia or ventricular fibrillation underwent serial electrophysiological drug testing, using propafenone (750 to 900 mg daily) as the anti-arrhythmic regimen of first choice. During baseline study, all patients had inducible sustained ventricular tachyarrhythmias. After oral loading of propafenone, 37 patients (74%) remained inducible whereas 13 were rendered non-inducible. Among the still inducible patients, the mean VT rate decreased from 223 +/- 38 b.min-1 (baseline) to 172 +/- 32 b.min +/- 1 (P less than 0.001). Four patients showed an increase of VT rate during propafenone compared to the VT rate at control. Non-inducible patients were discharged on propafenone. During a mean follow-up period of 20 +/- 15 months, there were three non-fatal VT recurrences among the responders, two of them due to non-compliance. Thus, propafenone used as the anti-arrhythmic agent of first choice among patients undergoing serial electrophysiological drug testing for ventricular tachyarrhythmias proved effective in suppressing VT induction in 26%. With regard to arrhythmic events, these patients have a favourable outcome.     

OPC-88117 suppresses early and delayed afterdepolarizations and arrhythmias induced by cesium, 4-aminopyridine and digitalis in canine Purkinje fibers and in the canine heart in situ

The effects of OPC-88117, a new investigational antiarrhythmic drug, on early and delayed afterdepolarizations (EAD and DAD, respectively) were assessed in vitro in canine Purkinje fibers and in vivo in the canine right ventricle. OPC-88117 had similar electrophysiologic properties to class I antiarrhythmic agents in that it decreased Vmax. OPC-88117 decreased the amplitude and prolonged the coupling interval of DAD induced by acetylstrophanthidin. Likewise, OPC-88117 suppressed EAD induced in vitro by 4-aminopyridine. In vivo, cesium-induced EAD, ventricular arrhythmia, and atrioventricular block were suppressed by OPC-88117. In summary, OPC-88117 suppressed DAD and EAD in vitro and inhibited EAD and triggered activity in the in situ canine heart.     

Nicorandil suppresses early afterdepolarisation and ventricular arrhythmias induced by caesium chloride in rabbits in vivo.

STUDY OBJECTIVE--Outward K current of cardiac membrane has been shown to be suppressed by caesium chloride (Cs) and enhanced by nicorandil, a coronary vasodilator. The aim of this study was to assess the effects of nicorandil on the Cs induced early afterdepolarisations and associated ventricular arrhythmias in the rabbit heart in vivo. DESIGN--Intravenous bolus injections of Cs (1 mmol.kg-1) were given three times at 20 min intervals. Monophasic action potentials of the left ventricular endocardium and the ECG (lead II) were recorded simultaneously over 60 min, under the intrinsic (sinus node) cardiac rhythm. EXPERIMENTAL MATERIAL--Eight rabbits were treated with Cs alone (control group); seven other rabbits were first treated with an intravenous infusion of nicorandil (0.2 mg.kg-1) (nicorandil treated group) and the effects of Cs were then examined. MEASUREMENTS AND MAIN RESULTS--In the control group, Cs produced early afterdepolarisations, premature ventricular beats and ventricular tachycardias. The ventricular tachycardias included two different types: (1) non-sustained polymorphic ventricular tachycardia mimicking the torsade de pointes in patients with long QT syndrome; (2) sustained monomorphic ventricular tachycardia. In the nicorandil treated group, the amplitude of the early afterdepolarisations and the incidence of ventricular tachycardias were significantly less than in the control group. CONCLUSIONS--Nicorandil suppresses the early afterdepolarisations and ventricular tachyarrhythmias induced by Cs, possibly by increasing the membrane K conductance.     

Vagal and sympathetic reflexes of left ventricular origin on the efferent activity of cardiac and renal nerves on anaesthetized cats

Summary The influence of reflexes of left ventricular origin on the postganglionic sympathetic activity and heart rate was investigated in anaesthetized cats. The experiments were to clarify 1. whether there are regionally different reflex adjustments due to an activation of ventricular receptors, 2. whether an increase of left ventricular diastolic pressure, which is known to activate afferent vagal fibres, causes an inhibition of sympathetic activity, 3. whether a coronary artery occlusion can activate a pressor reflex and a depressor reflex.Left ventricular receptors were stimulated by obstruction of the aortic root, coronary artery occlusion and mechanical stretch of the ventricular wall. In animals with intact CNS, all stimuli led to an inhibition of the activity of the inferior cardiac and renal sympathetic nerves and bradycardia. These reflex effects are initiated by mechanoreceptors and abolished by vagotomy. The inhibition of sympathetic activity was equally pronounced in the cardiac and renal nerves. After coronary artery occlusion and aortic obstruction, inhibition occurred as soon as the ventricular diastolic pressure had risen about 2 mm Hg. In spinal animals both stimuli caused a sympathetic activation which was mainly restricted to the cardiac nerve. This activation is not due to mechanical changes, but rather a direct result of myocardial ischaemia. Coronary artery occlusion is able to produce both inhibition and activation of sympathetic fibres, but the activation is normally suppressed and thus seems not to be particularly important for circulatory control.

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Einfluß von Rezeptoren im linken Ventrikel auf die Aktivität sympathischer efferenter Fasern in Herz-und Nierennerven

Zusammenfassung An narkotisierten Katzen wurde der Einfluß von Rezeptoren im linken Ventrikel auf die Aktivität sympathischer efferenter Fasern in Herz-und Nierennerven untersucht. Die Versuche sollten klären, ob 1. die Aktivität in beiden Nerven in gleicher Weise beeinflußt wird, ob 2. die Hemmung der Aktivität mit einem Anstieg des diastolischen Ventrikeldrucks korreliert ist und ob 3. bei Koronarverschluß gleichzeitig hemmende und aktivierende Einflüsse auf die sympathischen Fasern wirken.Die Ventrikelrezeptoren wurden durch Koronarverschluß, Stenosierung der Aorta und Zug an der Ventrikelwand erregt. Alle Reize führten zu einer Hemmung der Sympathikusaktivität und zu Bradykardie. Als Ursache dafür kann eine Aktivierung von Mechanorezeptoren, deren Afferenzen im Vagus verlaufen, angesehen werden. Bei Koronarverschluß und Aortenstenose trat die Hemmung ein, wenn der diastolische Ventrikeldruck um 2 mm Hg angestiegen war. Unterschiede in der Hemmung der Aktivität in Herz- und Nierenversagen konnten nicht registriert werden.Im Gegensatz dazu tritt bei spinalisierten Tieren nach Koronarverschluß oder Aortenstenose stets eine Sympathikusaktivierung ein. Sie war beschränkt auf den Herzsympathikus. Wahrscheinlich ist sie nicht mechanisch bedingt, sondern eine direkte Folge der Myokardischämie. Offensichtlich ruft ein Koronarverschuß zur gleichen Zeit zwei antagonistisch wirkende Reflexe hervor, von denen der eine eine Sympathikushemmung bewirkt, der andere eine Sympathikusaktivierung. Der letztere ist im intakten Tier jedoch unterdrückt.

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With 4 figures and 2 tables

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Dedicated to the memory of Prof. Dr. Dr. h. c.W. Lochner     

Baroreflex sensitivity predicts the induction of ventricular arrhythmias by cesium chloride in rabbits.

Previous studies have shown that the autonomic nervous system plays an important role in the genesis of ventricular tachycardia (VT) in patients with long QT syndrome, and in cesium chloride (Cs)-induced VT in animals. The present study investigated whether baroreflex sensitivity predicts the induction of VT by Cs in the rabbit in vivo. Monophasic action potentials (MAPs) of the left ventricular endocardium were recorded simultaneously with the surface ECG in 27 rabbits. Rabbits were divided into 4 groups based on the Cs-induced ventricular arrhythmias: (1) no ventricular premature contractions (No-VPC group), (2) single or paired VPC (VPC group), (3) monomorphic VT (MVT group), and (4) polymorphic VT (PVT group). Baroreflex sensitivity was significantly lower in the MVT and PVT groups than in the No-VPC and VPC groups. The plasma norepinephrine concentration before Cs injection was significantly higher in the MVT group than in the other 3 groups, and the norepinephrine concentration after Cs injection was significantly higher in the MVT and PVT groups than in the No-VPC and VPC groups. Baroreflex sensitivity was negatively correlated with the norepinephrine concentration before Cs injection. These results suggest that autonomic nervous system dysfunction, as defined by reduced baroreflex sensitivity, and elevated plasma norepinephrine concentrations predict increased susceptibility to Cs-induced VT.     

Mechanism of cardiac arrhythmias induced by epinephrine in dogs with hypokalemia

To investigate the mechanism of ventricular arrhythmias induced by epinephrine in dogs with hypokalemia, 30 adult mongrel dogs were separated into a control group (n = 13) and a hypokalemia group (n = 17). In the hypokalemia group, sodium polystyrene sulfonate (5 g/kg body weight) was infused into the colon. In both groups, the serum concentrations of sodium, potassium and calcium were measured every 15 minutes for 60 minutes. The mean (+/- standard deviation) serum potassium level of the hypokalemia group decreased significantly from 3.81 +/- 0.21 to 2.92 +/- 0.36 mEq/liter; there were no significant changes in other electrolytes. After 60 minutes, epinephrine (10 micrograms/kg) was injected intravenously in the hypokalemia and control groups, and the arrhythmia ratio (the number of ventricular ectopic beats divided by the total heart rate) was calculated for 5 minutes. Each group was further classified into subgroups of dogs with an arrhythmia ratio higher or lower than 10%. An arrhythmia ratio over 10% was observed in 7.7% of the control group and 53% of the hypokalemia group. Immediately after 5 minutes of epinephrine injection, myocardial mitochondria and plasma membrane fraction were prepared from each group. Mitochondrial calcium content and phospholipase activity of plasma membrane fraction were determined. Significant increases in both mitochondrial calcium content and phospholipase activity were observed in the dogs with hypokalemia and an arrhythmia ratio greater than 10%.(ABSTRACT TRUNCATED AT 250 WORDS)