An investigation into the characteristics of reperfusion‐induced arrhythmias in the anaesthetized rat and their susceptibility to antiarrhythmic agents

1 The aim of the present studies was to examine the effects of nitric oxide donors on arrhythmias induced by coronary artery occlusion and reperfusion, and on cardiac cyclic nucleotides. Experiments were performed in pentobarbitone-anaesthetized rats prepared for occlusion of the left coronary artery.2 Sodium nitroprusside (0.1, 0.3 and I jg kg-' minm) had no significant effects on the incidence of ventricular tachycardia, total ventricular fibrillation or the mortality resulting from 25 min of acute myocardial ischaemia when compared with values in controls. In addition, there was no alteration in the number of ventricular premature beats that occurred in survivors. 3 3-Morpholinosydnonimine-N-ethylcarbamide (SIN-1, 10, 20 and 40 jig kg-' min-') caused marked hypotension but did not alter the incidence or severity of ischaemia-induced arrhythmias. In rats subject to abrupt reperfusion after 5 min of myocardial ischaemia, lower doses of 3 and O jig kg-min-') still caused significant reductions in systolic and diastolic blood pressure but were devoid of antiarrhythmic activity. 4 In separate experiments in sham-operated rats, sodium nitroprusside (1lag kg-' min-'), isosorbide dinitrate (30 and 60 tg kg' min-') and SIN-1 (20 and 40 fg kg' min') had no significant effects on cardiac cyclic GMP content. 5These results indicate that nitric oxide donors do not alter arrhythmias induced by acute coronary artery occlusion or reperfusion in anaesthetized rats. Although increases in total cardiac cyclic GMP could not be detected, the results suggest that, at least in the rat, cyclic GMP does not influence these arrhythmias.

Section: Discussionmentioning

confidence: 99%

Failure of nitric oxide donors to alter arrhythmias induced by acute myocardial ischaemia or reperfusion in anaesthetized rats

Barnes

Coker

1995

“…It was necessary to infuse DPI since its duration of action as reflected by heart rate decrease and ECG effects in rats is transient lasting for only about 15min after bolus injection. Other antiarrhythmics found to be effective in this model (Kane et al, 1984) include lignocaine (class I) and melperone (class III). The class III effects of melperone were described by Platou et al Doses of aconitine required to induce arrhythmias in anaesthetized rats were increased following pretreatment with DPI.…”

Section: Discussionmentioning

confidence: 99%

“…Evaluation ofreperfusion-inducedarrhythmias Within seconds of releasing the occlusion, ventricular tachycardia (VT) occurs and often degenerates into ventricular fibrillation (VF) (Kane et al, 1984). This is not always a terminal event in rats, since spontaneous reversion to sinus rhythm can occur.…”

Section: Introductionmentioning

confidence: 99%

Antiarrhythmic effects of DPI 201‐106

Scholtysik¹,

Williams²

1986

“…Reperfusion-induced arrhythmias in the rat were chosen since sodium channel blocking agents have consistently shown activity against this type of arrhythmia in the rat heart, both in vivo and in vitro, whereas in most studies to date, calcium channel blockers, especially the more specific dihydropyridines, have not proved effective (Bergey et al, 1982;Winslow et al, 1983;Manning et al, 1983;Kane et al, 1984).…”

Section: Introductionmentioning

confidence: 99%

Comparative antiarrhythmic and electrophysiological effects of drugs known to inhibit calmodulin (TFP, W7 and bepridil)

Barron¹,

Marshall²,

Martorana³

et al. 1986

The potential antiarrhythmic and electrophysiological actions of drugs known to inhibit calmodulin, i.e. trifluoperazine (TFP) and N‐(6‐aminohexyl)‐5‐chloro‐1‐naphthalene sulphonamide (W7) have been compared with bepridil, whose antiarrhythmic actions have previously been ascribed to blockade of the fast inward sodium current in cardiac tissue. Like bepridil, both TFP and W7 reduced the severity of arrhythmias evoked by 30 min of coronary artery occlusion in tha anaesthetized rat. TFP (2.5–10 mg kg−1, i.v.), W7 (2.5–10 mg kg−1, i.v.) and bepridil (1–5 mg kg−1, i.v.) also antagonized the development of ventricular fibrillation induced by 5 min of occlusion followed by reperfusion. All three drugs also reduced mortality. TFP and bepridil also reduced the incidence of reperfusion‐induced ventricular tachycardia whilst all 3 drugs reduced its duration. Although TFP was shown to possess α‐adrenoceptor blocking properties, the classical α‐blocker, phentolamine, failed to reduce significantly the incidence or severity of reperfusion arrhythmias. In contrast to bepridil (2–20 μM), which markedly reduced the maximum rate of depolarization (Vmax) of guinea‐pig isolated papillary muscle, W7 (5–50 μM) showed only weak effects on Vmax and was at least 10 times less potent than bepridil whilst TFP only reduced Vmax in high concentrations (40–100 μM) which lowered resting membrane potential. Unlike bepridil, neither TFP (4–40 μM) nor W7 prolonged the absolute refractory period. The results suggest that drugs which inhibit calmodulin confer protection against both ischaemia ‐ and reperfusion‐induced arrhythmias in the rat. Although the electrophysiological actions of bepridil would adequately account for its antiarrhythmic activity, the same cannot be said of W7 and especially TFP. In conclusion, calmodulin antagonism may constitute a mechanism of antiarrhythmic activity.