Fall In Ventricular Fibrillation Threshold Research Articles

Opposite change with ischaemia in the antifibrillatory effects of class I and class IV antiarrhythmic drugs resulting from the alteration in ion transmembrane exchanges related to depolarization

It is known that class I antiarrhythmic drugs lose their antifibrillatory activity with severe ischaemia, whereas class IV antiarrhythmic drugs acquire such activity. Tachycardia, which is also a depolarizing factor, has recently been shown to give rise to an alteration of ion transmembrane exchanges which is particularly marked in the case of calcium. This leads one to wonder if the change in antifibrillatory activity of antiarrhythmic drugs caused by ischaemia depends on the same process. The change in antifibrillatory activity was studied in normal conditions ranging to those of severe ischaemia with a class I antiarrhythmic drug, flecainide (1.00 mg x kg(-1) plus 0.04 mg x kg(-1)x min(-1), a sodium channel blocker, and a class IV antiarrhythmic drug, verapamil (50 microg x kg(-1) plus 2 microg x kg(-1) x min(-1)), a calcium channel blocker. The experiments were performed in anaesthetized, open-chest pigs. The resulting blockade of each of these channels was assessed at the end of ischaemic periods of increasing duration (30, 60, 120, 180, 300, and 420 s) by determining the ventricular fibrillation threshold (VFT). VFT was determined by means of trains of diastolic stimuli of 100 ms duration delivered by a subepicardial electrode introduced into the myocardium (heart rate 180 beats per min). Ischaemia was induced by completely occluding the left anterior descending coronary artery. The monophasic action potential was recorded concurrently for the measurement of ventricular conduction time (VCT). The monophasic action potential duration (MAPD) varied with membrane polarization of the fibres. The blockade of sodium channels by flecainide, which normally raises VFT (7.0 +/- 0.4 to 13.8 +/- 0.8 mA, p < 0.001) and lengthens VCT (28 +/- 3 to 44 +/- 5 ms, p < 0.001), lost its effects in the course of ischaemia. This resulted in decreased counteraction of the ischaemia-induced fall of VFT and decreased aggravation of the ischaemia-induced lengthening of VCT. The blockade of calcium channels, which normally does not alter VFT (between 7.2 +/- 0.6 and 8.4 +/- 0.7 mA, n.s.) or VCT (between 30 +/- 2 and 34 +/- 3 ms, n.s.), slowed the ischaemia-induced fall of VFT. VFT required more time to reach 0 mA, thus delaying the onset of fibrillation. Membrane depolarization itself was opposed as the shortening of MAPD and the lengthening of VCT were also delayed. Consequently there is a progressive decrease in the role played by sodium channels during ischaemia in the rhythmic systolic depolarization of the ventricular fibres. This reduces or suppresses the ability of sodium channel blockers to act on excitability or conduction, and increases the role of calcium channel blockers in attenuating ischaemia-induced disorders.

Efficacy of a beta-adrenergic receptor antagonist, propranolol, in preventing ischaemic ventricular fibrillation: dependence on heart rate and ischaemia duration.

To investigate the prevention of ventricular fibrillation with a beta-adrenergic receptor (beta-AR) antagonist in anaesthetized, open-chest pigs in a model of ischaemia, intended to reproduce what happens either in anginal attack or in the first hour of infarction. Ventricular fibrillation threshold (VFT) was determined with trains of diastolic stimuli of 100 ms duration delivered by a subepicardial electrode inserted in the area subjected to ischaemia. Ischaemia was obtained by the complete occlusion of the left anterior descending coronary artery, either near its origin during brief but increasing periods (30, 60, 90, 120, 150, 180, 240, 300 s), or half-way from its origin for a much longer time (more than 60 min). During transient proximal occlusion and isoprenaline infusion (0.25 microgram/kg/min), propranolol (50 micrograms/kg plus 2 micrograms/kg/min) attenuated both tachycardia and the fall in VFT to 0 mA. The shortening of MAP duration accompanying depolarization of the fibres was concurrently slowed down, and time to fibrillation prolonged (122 +/- 15 to 262 +/- 14 s, p < 0.001). In the absence of isoprenaline infusion, propranolol exerted similar effects, but to a lesser degree, in proportion to heart rate dependent on sympathetic activity. In contrast, it became unable to raise VFT before and during ischaemia, when heart rate was kept constant by pacing. After persistent midportion occlusion, significant differences in VFT were found only at the 5th min, depending on whether heart rate was accelerated by isoprenaline (0.8 +/- 0.2 mA), left normal (1.8 +/- 0.3 mA) or slowed down by propranolol (1.6 +/- 0.3 mA). Later on, especially after 15 and 25 min of ischaemia, VFT, which was below 1.0 mA, did not appear to be influenced by the activation or blockade of beta-ARs: spontaneous fibrillations were observed in the same number in this period with or without the administration of propranolol. Beyond 30 min after occlusion, the rise in VFT, subsequent to the first irreversible cell damage, also occurred in the same way. The prevention of ischaemic ventricular fibrillation by a beta-AR antagonist, judged from VFT, is easily checked experimentally when ischaemia is only transitory, especially if sympathetic activity is high. The maintenance of VFT at a relatively high level is essentially related to the depressant effect on the sinus rate. The same animal model does not give support to an effective protection in the first hour of infarction. However, the control of heart rate may also be beneficial in these circumstances by attenuating systemic haemodynamic disorders.

Antiarrhythmic and Metabolic Effects of Indoramin During Acute Regional Ischemia and Reperfusion in Isolated Rat Heart

The antiarrhythmic effect of alpha 1-adrenoceptor antagonists during myocardial ischemia and reperfusion remains controversial. The potential antiarrhythmic properties of indoramin, an alpha 1-antagonist, were assessed in the isolated perfused rat heart during regional ischemia and during sustained reperfusion. Coronary artery ligation (CAL) decreased the ventricular fibrillation threshold (VFT) of control hearts from 9.1 +/- 1.3 (pre-CAL, mean +/- SEM) to 2.1 +/- 0.5 mA 15 min post-CAL (p less than 0.0001). Perfusion with indoramin 10(-8) M (alpha 1-receptor antagonistic concentration) started 5 min prior to CAL did not prevent the fall in VFT after CAL. Indoramin 10(-6) M prevented the fall in VFT after CAL relative to the control group. Indoramin 10(-5) M markedly increased the VFT before CAL from 9.9 +/- 1.0 to 28.6 +/- 2.9 mA (p less than 0.0001) and prevented the fall in VFT after CAL. During reperfusion, indoramin 10(-5) M decreased the incidence of spontaneous ventricular fibrillation (VF) to 1 of 6 vs. 6 of 6 in the control group (p less than 0.02). Indoramin 10(-5) M preserved adenosine triphosphate in the reperfused myocardium: 2.82 +/- 0.06 vs. 2.16 +/- 0.21 mumol/g in the control group (p less than 0.05). Specific alpha 1-antagonist properties of indoramin did not appear to be involved in the antiarrhythmic effects.

Comparative Antifibrillatory Effects of d- and dl-Sotalol in Normal and Ischaemic Ventricular Muscle of the Cat

The aim of this study was to compare the effects of d- and dl-sotalol on the ventricular fibrillation threshold (VFT) and the effective refractory period (VERP) in anaesthetized cats subjected to coronary artery occlusion. Occlusion of the left anterior descending coronary artery caused a decrease in VFT (measured in mA) (1.40 +/- 0.1 to 0.6 +/- 0.1). dl-Sotalol (1 and 5 mg kg-1) increased VFT before the induction of ischaemia (1.7 +/- 0.1 to 33.8 +/- 1.0 and 38, respectively), and the higher dose prevented the ischaemia-induced fall in VFT. d-Sotalol (1 and 5 mg kg-1) caused only small increases in VFT in normal (1.9 +/- 0.3 to 2.3 +/- 0.3 and 2.6 +/- 0.3) and ischaemic (0.8 +/- 0.1 to 1.2 +/- 0.2 and 1.3 +/- 0.2) myocardium. Both d- and dl-sotalol increased VERP measured in normal myocardium. The % changes observed with 1 and 5 mg kg-1 of the racemate (17 +/- 1 and 57 +/- 4) were significantly greater than those with the d-isomer (8 +/- 3 and 16 +/- 2). dl-Sotalol, but not d-sotalol, prevented the haemodynamic responses to 50 ng kg-1 isoprenaline. These results suggest that VFT in anaesthetized cats is markedly increased by beta-adrenoceptor blockade and only marginally increased by the direct class III antiarrhythmic action of d-sotalol.

The effect of beta-adrenergic blockade on vulnerability to ventricular fibrillation and inducibility of ventricular arrhythmia in short- and long-term feline infarction models

Previous investigation, predominantly in the short-term canine model, has documented a potent antifibrillatory effect of beta-adrenergic blockade. To determine whether the protection afforded by beta blockade is species- and model-specific, we studied 23 chloralose-anesthetized cats. Eight animals were studied over a short term and underwent serial determinations of the ventricular fibrillation (VF) threshold prior to and 1 minute after occlusion of the left anterior descending coronary artery (LAD) and immediately following reperfusion of a 10-minute occlusion. Beta-blocking doses of intravenous propranolol (P) (0.5 mg/kg) attenuated the fall in VF threshold during acute ischemia. Increasing the dose of P to 1 mg/kg did not provide further protection, nor did P protect against reperfusion VF. The other 15 animals underwent a preliminary surgical procedure during which the LAD was completely and irreversibly occluded (nine animals) or in which a sham procedure was performed (six animals). Two weeks later, we measured ventricular refractoriness at several left ventricular sites, ventricular inducibility using programmed electrical stimulation, and VF thresholds both before and after administration of intravenous P (1 mg/kg). Ventricular refractory periods in the infarcted zones were significantly increased compared with normal sites and with values obtained in sham-operated animals. In addition, VF thresholds in the infarcted animals were lower than those obtained in the sham-operated group. Before treatment, a reproducible sustained ventricular tachyarrhythmia was induced by means of programmed stimulation in seven of the nine chronically infarcted animals but in none of the sham-operated animals ( p < 0.02). P increased refractory periods in the normal and infarcted zones proportionately and significantly. After P, sustained ventricular arrhythmia was induced in only one cat in the infarcted group ( p < 0.03). This attenuated inducibility was coincident with a significant increase in VF threshold after P ( p < 0.02). Beta blockade exerts a significant electrophysiologic effect in the feline ventricle. Protection against VF induced in both short-term and long-term infarction is coincident with an increase in ventricular refractoriness and with prevention of inducibility by programmed stimulation.

The effect of thromboxane inhibition on vulnerability to ventricular fibrillation in the acute and chronic feline infarction models

Inhibition of the enzyme that synthesizes thromboxanes may protect against the development of ventricular fibrillation (VF) during acute myocardial ischemia. This study was carried out to test this hypothesis with a new thromboxane synthetase inhibitor, and to extend the studies to alternative animal models of myocardial infarction. In a series of acute experiments, 19 cats were pretreated with 10 mg/kg of U-63557A (a dose that produced >75% reduction in thromboxane B 2 [TxB 2] levels) or saline before abrupt left anterior descending coronary artery occlusion. Seven of the nine control animals suffered spontaneous VF associated with a 77% fall in VF threshold compared with the treated animals, of which 2 of 10 had spontaneous VF and in which VF threshold fell by only 45% ( p < 0.025). Despite a similar extent of TxB 2 inhibition in another set of nine animals, U-63557A failed to protect against a fall in VF threshold during coronary reperfusion. Finally, chronic changes in VF threshold and inducibility of sustained ventricular tachycardia by programmed stimulation were assessed in a group of eight animals. The lowering of VF threshold and inducibility of ventricular tachycardia seen in the control state were not influenced by treatment with U-63557A. Thus protection against infarct-related VF by TxB 2 inhibition is a property shared by more than one pharmacologic agent. Arrhythmias generated by reperfusion or induced in a more chronic setting may not be thromboxane-dependent. These results have important implications for the planning of studies designed to assess the antiarrhythmic potential of drugs that inhibit thromboxane synthesis.

Perindopril prevents fall in ventricular fibrillation threshold and in cardiac output after coronary ligation in the pig: C Muller, H Basset, L Opie. MRC Ischaemic Heart Disease Research Unit, Groote Schuur Hospital and University of Cape Town, South Africa

Perindopril prevents fall in ventricular fibrillation threshold and in cardiac output after coronary ligation in the pig: C Muller, H Basset, L Opie. MRC Ischaemic Heart Disease Research Unit, Groote Schuur Hospital and University of Cape Town, South Africa

Modulation of arachidonic acid metabolites and vulnerability to ventricular fibrillation during myocardial ischemia in the cat

To determine the relative importance of arachidonic acid pathway products on vulnerability to ventricular fibrillation (VF), we examined the effects of synthesis inhibitors and a receptor blocker acting in the cyclooxygenase (C) and lipoxygenase (L) pathways on VF thresholds in a feline model of coronary occlusion. Thresholds for the induction of VF were measured before and after a 5-minute coronary occlusion in drug-treated animals and control subjects. Animals were treated with BW755c, a dual L and C inhibitor, CGS-8515, an L inhibitor, FPL-55712, a leukotriene receptor blocker, or sulfinpyrazone, a C inhibitor. BW755c, CGS-8515, and FPL-55712 all prevented an otherwise significant fall in VF threshold during coronary occlusion ( p < 0.01) independent of an effect on effective refractory period, heart rate, or blood pressure. In contrast, sulfinpyrazone, the only compound devoid of an effect on the L pathway, did not protect against an occlusion-related fall in VF threshold. BW755c and CGS-8515 inhibited the synthesis of L and C metabolites coincident with their protection against VF ( p < 0.01). We conclude that agents that antagonize the effects of L products protect against enhanced ventriculer vuinerability during acute ischemia, whereas C inhibition alone may not afford this protection.

Arrhythmogenic action of α 1-adrenoceptor stimulation in normoxic rat ventricular myocardium: Influence of nisoldipine, reduced extracellular Ca 2+ and ryanodine

This study examines the arrhythmogenic action of alpha 1 and alpha 2-adrenoceptor stimulation in the isolated perfused rat heart. The alpha 1-agonist methoxamine in the presence of the beta 1-antagonist atenolol 10(-6) M decreased the ventricular fibrillation threshold in the normoxic rat ventricular myocardium: VFT values (mA): Control 11.2 +/- 0.5; methoxamine 10(-6) M 4.9 +/- 0.9 (P less than 0.01 vs control); methoxamine 10(-5) M 3.5 +/- 0.5 (P less than 0.01 vs control). The alpha 1-antagonist prazosin 10(-8) M prevented the methoxamine-induced fall in ventricular fibrillation threshold. The alpha 2-agonist BHT 933 (azepexole) in the presence of atenolol 10(-6) M produced no alteration in the ventricular fibrillation threshold. Methoxamine 10(-6) M to 10(-5) M had a positive inotropic effect with increased left ventricular pressure development, myocardial oxygen consumption and QT-interval; however, tissue levels of cyclic AMP remained unchanged. Methoxamine 10(-6) M did not alter heart rate, coronary flow rate or deplete tissue levels of adenosine triphosphate, phosphocreatine or glycogen. The enhanced vulnerability to ventricular fibrillation induced by methoxamine could be demonstrated only at supraphysiological extracellular calcium concentrations (2.5 mM) but not at physiological calcium concentrations (1.25 mM). The arrhythmogenic and inotropic effect of methoxamine 10(-6) M was prevented by inhibition of transsarcolemmal Ca2+ ion influx by nisoldipine 10(-8) M or by inhibition of release of Ca2+ from sarcoplasmic reticulum by ryanodine 10(-9) M to 10(-8) M. Thus in isolated normoxic rat heart preparations, activity of the alpha 1-receptor appears to mediate ventricular arrhythmogenesis but only in the setting of myocardial calcium overload. The arrhythmogenic effect of alpha 1-stimulation may be due to increased transsarcolemmal calcium influx and enhanced release of calcium from the sarcoplasmic reticulum; increased myocardial oxygen consumption secondary to greater left ventricular pressure development may contribute in part.

The influence of verapamil and its isomers on vulnerability to ventricular fibrillation during acute myocardial ischemia and adrenergic stimulation in isolated rat heart

In isolated heart preparations, dl-verapamil inhibits the increased vulnerability to ventricular fibrillation and reduces myocardial tissue levels of cyclic 3'5'-adenosine monophosphate (cyclic AMP), a proposed arrhythmogenic agent. The ventricular antiarrhythmic effect of dl-verapamil may not be mediated by selective slow channel inhibition since both d(+) and l(-) isomers display equipotent activity. Three different mechanisms may contribute to the antiarrhythmic properties of dl-verapamil: calcium channel antagonism (l(-) isomer), sodium channel inhibition (d(+) isomer) and reduced cyclic AMP accumulation. In the intact animal model, coronary artery ligation is associated with increased levels of circulating catecholamines and sympathetic neural overactivity. In isolated heart preparations, it is therefore appropriate to evaluate the influence of dl-verapamil and isomers on vulnerability to ventricular fibrillation and cyclic AMP accumulation during acute myocardial ischemia with added adrenergic stimulation. We found that dl and l(-) but not d(+)-verapamil (all 1.5 X 10(-7) M) inhibited the fall in ventricular fibrillation threshold through a mechanism not involving cyclic AMP. L(-) but not d(+) verapamil inhibited Ca2+ dependent slow responses and decreased action potential duration at 90% repolarization. We propose that the ventricular antiarrhythmic property of dl and l(-) verapamil during acute regional myocardial ischemia with added adrenergic stimulation is due to inhibition of transsarcolemmal calcium influx.

The effect of bretylium and clofilium on dispersion of refractoriness and vulnerability to ventricular fibrillation in the ischemic feline heart

Bretylium has been shown to have a pronounced antifibrillatory effect. The purpose of this study was to examine the effects of bretylium on changes in vulnerability to ventricular fibrillation (VF) and refractoriness which occur during acute myocardial infarction. Right ventricular VF thresholds and effective refractory periods (ERP) at six left ventricular sites were measured before and serially after left anterior descending coronary occlusion in chloralose-anesthetized cats. In eight untreated animals, there was a decrease in VF thresholds of 73% ( p < 0.01) immediately after occlusion and dispersion of refractoriness (DR) (maximum difference in ERP between normal and ischemic left ventricular sites) increased from 18 ± 4 to 50 ± 6 msec ( p < 0.01). Five of eight animals manifested spontaneous VF within the first minutes of occlusion but none had nonsustained VF. Pretreatment with bretylium (10 to 20 mg/kg intravenously) increased resting ERP from 181 ± 9 to 201 ± 9 msec ( p < 0.05) and VF threshold from 32 ± 5 to 85 ± 7 mA ( p < 0.001). Bretylium also prevented spontaneous VF in all eight animals and abolished occlusion-related changes in VF and DR. Fourteen animals were similarly studied using clofilium, a bretylium congener which is devoid of sympatholytic effect (no effect on blood pressure response to bilateral carotid artery occlusion). Clofilium increased resting ERP and VF thresholds at both low (0.5 mg/kg intravenously) and high doses (5 mg/kg intravenously). High- but not low-dose clofilium blunted the fall in VF threshold after coronary occlusion. In addition, DR correlated with VF threshold changes at both doses. Neither regimen prevented spontaneous VF but nonsustained VF (lasting 1 to 15 seconds) was consistently observed during testing at subthreshold currents in both bretylium and clofilium-treated animals. Class III drugs appear to prevent VF during coronary occlusion not simply by prolonging baseline refractory periods but by attenuating DR between normal and ischemic zones. This latter measurement may therefore serve as an indirect marker of vulnerability to VF. These effects are partially independent of, but may be enhanced by, a sympatholytic action.

Differential effects of O-demethyl encainide on induced and spontaneous arrhythmias in the conscious dog

Encainide is highly effective in suppressing most nonsustained ventricular arrhythmias, but there is evidence that the drug is less effective and may worsen some arrhythmias, particularly in patients with sustained ventricular tachycardia. In most patients it is likely that the major antiarrhythmic effects of encainide are mediated through a potent metabolite, O-demethyl encainide. The effects of infusions of saline solution or O-demethyl encainide on spontaneous ventricular ectopic activity and ventricular fibrillation (VF) threshold were compared in 25 dogs with a mottled myocardial infarct produced by transient coronary occlusion. Plasma levels of the metabolite above 100 ng/ml suppressed (> 92%) the spontaneous ventricular ectopic activity that occurred 48 hours after MI, whereas saline solution had no effect. In 15 dogs treated with O-demethyl encainide, the VF threshold decreased an average of 23%, from a baseline level of 23 ± 8 mA to 18 ± 9 mA (p < 0.05). There was a concentration-dependent fall in VF threshold with plasma concentrations of O-demethyl encainide above 150 ng/ml. In 2 dogs with very high plasma concentrations of the metabolite (> 1,000 ng/ml), VF was induced by right ventricular pacing alone (S 1S 1 300 ms). No change in VF threshold was observed in the 8 dogs treated with saline solution, and in each of these dogs VF could be terminated by the countershock protocol. However, in 7 of the 17 dogs treated with O-demethyl encainide, VF could not be terminated by the countershock protocol. These 7 dogs, which died from VF, had higher O-demethyl encainide levels (314 ng/ml or above) than the other 10 dogs. It is concluded that O-demethyl encainide is effective in suppressing spontaneous ventricular ectopic activity in this model of myocardial infarction, but at plasma levels higher than 150 ng/ml, the agent lowers the VF threshold and at higher levels impedes defibrillation.

Antiarrhythmic action of labetalol and its effect on adenine metabolism in the isolated rat heart

Labetalol, a combined alpha- and beta-adrenergic antagonist, was assessed for antiarrhythmic activity in the isolated perfused rat heart. Inclusion of 5.0 and 7.5 mumol/liter labetalol in the perfusate reduced the fall in ventricular fibrillation threshold and eliminated ventricular arrhythmias during the coronary occlusion period of 15 minutes. In treated hearts, levels of high energy phosphates were significantly higher and lactate, adenosine and hypoxanthine levels were lower in ischemic myocardium. Cyclic adenosine monophosphate levels were reduced in uninvolved myocardium (0.31 +/- 0.01 and 0.24 +/- 0.02 versus 0.43 +/- 0.02 nmol/g fresh weight) and in the ischemic myocardium (0.38 +/- 0.02 and 0.34 +/- 0.04 versus 0.65 +/- 0.05 nmol/g) in hearts treated respectively with 5.0 and 7.5 mumol/liter labetalol versus control hearts. When untreated hearts were perfused with 3.0 mmol/liter potassium in perfusate, all had ventricular tachycardia or fibrillation during coronary ligation and developed ventricular fibrillation after reperfusion. Labetalol, 5.0 mumol/liter, reduced ventricular tachyarrhythmias during coronary occlusion and after reperfusion, whereas labetalol, 7.5 mumol/liter, eliminated tachyarrhythmias during occlusion and reperfusion. Labetalol had potent antiarrhythmic activity in the hearts rendered uniformly prone to arrhythmias by perfusion with a low potassium solution.

Decreased vulnerability to ventricular fibrillation by vasodilator-induced baroreceptor sensitisation.

Vulnerability to ventricular fibrillation (VF) is affected by changes in systemic arterial blood pressure which are mediated through the sympathetic nervous system. We determined that small doses of a vasodilator drug can abolish the enhanced ventricular vulnerability induced by norepinephrine infusion. Noradrenaline (0.5 micrograms X kg-1 X min-1) caused a fall in ventricular fibrillation threshold from 30 to 20 mA (P less than 0.001). Pretreatment with prostaglandin E1, I2 or nitroglycerin at doses which reduced mean arterial blood pressure by 0.7 to 1.3 kPa (5 to 10 mmHg) abolished the enhanced vulnerability produced by noradrenaline. Following baroreceptor denervation, these agents no longer afforded protection against the profibrillatory action of noradrenaline. We conclude that small doses of vasodilator agents can augment ventricular electrical stability. The mechanism for this protective action appears to be a decrease in cardiac sympathetic tone resulting from vasodilatation of baroreceptor areas.

Effects of antiarrhythmic drugs on ventricular fibrillation thresholds of normal and ischaemic myocardium in the anaesthetized rat.

1 The effects of agents which produce membrane stabilization (class I), beta 1-adrenoceptor blockade (class II), prolongation of the cardiac action potential (class III) or inhibition of the slow inward current (class IV) were investigated for their ability to increase the ventricular fibrillation threshold (VFT) or to modify the fall in VFT consequent upon coronary artery ligation in the anaesthetized rat. 2 The class I agent, Org6001, increased VFT of normal myocardium and in lower doses reduced the postligation fall in VFT. 3 The class II agent, metoprolol, failed to increase VFT of normal myocardium but reduced the postligation fall. 4 The class III agent, melperone, increased VFT of both normal and ischaemic myocardium whereas the class IV agent, nifedipine failed to influence VFT in either region. 5 Bepridil (class I and IV) was similar to Org6001 and sotalol (class II and III) in that it increased VFT of normal myocardium and in lower doses reduced the postligation fall in VFT. 6 Measurement of VFT before and after coronary artery ligation in the rat constitutes a rapid and reproducible screen to detect antifibrillatory activity. 7 The results also suggest that in the rat, the low currents used (approximately 400 microA) do not release substantial quantities of catecholamines whereas these may be released by coronary artery ligation.

Experimental Coronary Occlusion in Calves: The Effect of Hyperglycæmia on Ventricular Fibrillation Threshold

Measurements of ventricular fibrillation threshold (VFT) were made in two groups of bovine calves, each weighing 25 to 30 kg, before and after ligation of the anterior descending branch of the coronary artery. In the control group, the VFT was determined before occlusion of the anterior descending coronary artery, and the observations were repeated at 20-minute intervals after occlusion. A 33% reduction in VFT was observed 20 minutes after the occlusion. Prior loading with glucose by infusion of 100 ml of 10% glucose prevented the significant fall in VFT.