Early Ventricular Arrhythmias Arising from Acute Myocardial Ischaemia; Possible Involvement of Prostaglandins and Thromboxanes

1The effects of acute coronary artery ligation on cardiac rhythm and haemodynamics were studied in rats receiving either acute or chronic morphine-treatment. 2 In chronic opiate-treated animals, increasing concentrations of morphine sulphate were administered in drinking water over a 3 week period, and the development of morphine tolerance and dependence was verified by decreased analgesic responses to morphine in the tail-immersion test and the occurrence of naloxone-precipitated withdrawal syndromes, respectively. 3 Acute coronary artery ligation induced a decrease in blood pressure, a slight increase in heart rate, and ventricular tachycardia or fibrillation in anaesthetized rats. 4 The changes in blood pressure and heart rate following acute coronary artery ligation were not significantly altered by acute or chronic morphine administration. 5 The incidence and the time of onset of ventricular tachycardia or fibrillation were found to be significantly reduced and prolonged, respectively, in chronically morphine-treated rats, but were not significantly affected by acute morphine administration in naive animals. 6 These findings suggest that chronic morphine treatment lessens the occurrence of early ventricular arrhythmias caused by acute myocardial ischaemia in rats. The mechanism of this effect is unclear.

Section: Discussionmentioning

confidence: 99%

Effects of morphine on cardiovascular responses to acute myocardial ischaemia in rats

Chan

Dai

1987

“…In this connection it may be relevant that certain endogenous products of arachidonic acid oxidation have marked effects upon coronary vascular diameter. Coker (1982) has reviewed the evidence that during myocardial ischaemia there is a balance between a vasconstrictive effect from thromboxane A2 and a vasodilatation from concomitantly formed prostacyclin. If this is correct, a drug which selectively inhibited the formation (or action) ofthromboxane A2 would be expected to protect against the arrhythmias and other consequences of ischaemia.…”

Section: Discussionmentioning

confidence: 99%

“…A drug which was equally inhibitory of both thromboxane A2 synthesis and prostacyclin synthesis, on the other hand, would be expetced to be less protective. Coker (1982) has reviewed the evidence that the weakly protective effect of indomethacin, for example, can be accounted for in this way. In contrast, Livio et al (1980) found that sulphinpyrazone inhibited thromboxane A2 synthesis without inhibiting prostacyclin synthesis in the rat.…”

Section: Discussionmentioning

confidence: 99%

A protective effect of sulphinpyrazone against coronary occlusion‐induced shortening of myocardial refractory periods in the rat

Northover

1986

1 The hearts of anaesthetized, artificially ventilated rats were exposed, and the left coronary artery occluded. The diastolic threshold voltage for stimulation (DTV), the duration of the bipolar electrogram (DBE) and the functional refractory period (FRP) of the ischaemic area were measured at minute intervals for an hour after occlusion. 2 Coronary occlusion caused a rise in DTV, a prolongation of the DBE and a biphasic change in the FRP, with an initial prolongation phase (1-4 min) followed by a decline to below pre-occlusion values (5-15 min). 3 Episodes ofventricular tachyarrhythmia (VT) were most frequent during the period 5-15 min after the onset of occlusion of the coronary artery. This coincided with the period when FRP was minimal and the difference between DBE and FRP was maximal. 4 Pretreatment of rats with sulphinpyrazone (2.5-40mgkg-') or indomethacin (5-20mgkg-') protected against the episodes of coronary occlusion-induced VT and against the associated decline in FRP of the ischaemic muscle. Sulphinpyrazone was more effective than indomethacin in this respect and a combination of the two drugs was approximately as effective as sulphinpyrazone alone. 5 It was concluded that sulphinpyrazone protects rats against coronary occlusion-induced episodes of VT by reducing the risk of ventricular action potential re-entry. This effect is probably due to protection against the ischaemia-induced shortening of the myocardial FRP.

“…Several endogenous substances such as prostaglandins and thromboxanes (Coker, 1982), cyclic AMP (Podzuweit, 1982), endorphins (Fagbemi et al, 1982) and histamine (Dai, 1986) have also been found to be involved in the genesis of early ventricular arrhythmias resulting from acute myocardial ischaemia. It is possible that chronic opiate administration may induce changes in some of these substances which contribute to the decreased occurrence of early ventricular arrhythmias during acute myocardial ischaemia.…”

Section: Discussionmentioning

confidence: 99%

Ventricular noradrenaline concentrations in naïve and morphine‐treated rats subjected to acute myocardial ischaemia

Dai

Chan

1988

1 Ventricular noradrenaline concentrations in morphine-treated rats subjected to acute left coronary artery ligation were measured by high performance liquid chromatography with electrochemical detection. 2 In naive rats, acute left coronary artery ligation induced a significant increase in right ventricular noradrenaline concentration at 5 min and significant decreases in left ventricular noradrenaline concentration at 3 and 10 min. 3 Acute morphine treatment did not significantly alter ventricular noradrenaline concentrations in rats subjected to acute coronary artery ligation. 4 Chronic morphine treatment caused significant declines in ventricular noradrenaline concentrations in rats subjected to acute coronary artery ligation. The reductions increased with duration of opiate treatment, and were reversed by opiate withdrawal. 5 These findings indicate that there is an increase in sympathetic activity during acute myocardial ischaemia. It is suggested that chronic morphine treatment may be able to retard this response, and consequently to lessen the occurrence of early ventricular arrhythmias resulting from acute myocardial ischaemia.