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

Abstract

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.

Changes in preganglionic sympathetic nerve function following chronic morphine treatment in rats

“…These include altered sensitivity to the actions of catecholamines, acetylcholine, 5-hydroxytryptamine and arachidonic acid (Schulz & Goldstein, 1973;Kromer & Steigeman, 1982;Rae & De Moraes, 1983;Dai et al, 1985;Martin & Takemori, 1986) and altered responses to certain pathophysiological conditions such as acute myocardial ischaemia (Chan et al, 1987;Ko et al, 1988). The mechanisms behind such effects are not clear.…”

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

“…In the chronic study, a previously described method for inducing opiate dependence (Badawy et al, 1982;Chan et al, 1987) was adopted for chronic administration of morphine. Rats, weighing 250-300 g, were used.…”

“…It has been found in a recent study that rats undergoing chronic morphine-treatment exhibit significantly lower incidence and delayed onset of early ventricular arrhythmias during acute myocardial ischaemia (Chan et al, 1987). However, the mechanism remains unclear.…”

“…It has been shown recently that chronic administration of morphine, besides producing tolerance and physical dependence, can also induce certain physiological changes, such as decreased cardiovascular responses to sympathetic nerve stimulation (Leung et al, 1986). Therefore, it is possible that the observed decrease and delay in the development of early ventricular arrhythmias, in morphinetreated rats subjected to acute coronary artery ligation (Chan et al, 1987), may be attributed to the reduced cardiovascular responses to sympathetic excitation.…”

Arterial catecholamine levels in morphine‐treated rats subjected to sympathetic nerve stimulation

“…It has been reported that, depending on the species and opioid-exposure time, experimental animals also exhibit other physiological alterations after chronic opiate treatment which are different from those observed after acute treatment (Schulz & Goldstein, 1973; Kromer & Steigemann, 1982; Rae & De Moraes, 1983;Dai et al, 1985;Martin & Takemori, 1 Author for correspondence. 1986). Recently, it has been observed that chronically morphine-treated rats exhibit a significantly lower incidence and delayed onset of early ventricular arrhythmias, and a marked decline in ventricular noradrenaline concentration, during acute myocardial ischaemia (Chan et al, 1987;Ko et al, 1988). A previous study has shown that the cardiovascular responses to sympathetic nerve stimulation are significantly reduced following prolonged morphine administration (Leung et al, 1986b).…”