Effects of morphine on catecholamine release and arrhythmias evoked by myocardial ischaemia in rats

Abstract

1 The effects of morphine (10mgkg-' i.p.) on haemodynamics, arrhythmias and plasma and myocardial catecholamines (CA) were studied after coronary artery occlusion in anaesthetized rats. Myocardial intraneuronal CA were assessed histofluorimetrically and CA concentrations measured by high performance liquid chromatography. 2 Morphine increased blood pressure, presumably due to higher plasma noradrenaline (NA) concentrations found in morphine-treated rats. 3 Morphine increased the area ofcatecholamine-containing fluorescing neurones in the myocardium (as a percentage of total field area) 60 min after sham-operation (0.87 ± 0.07%) or occlusion (0.57 ± 0.05%) compared to untreated animals (0.67 ± 0.06 and 0.38 ± 0.03% respectively). Tissue NA content was not significantly affected by coronary occlusion and/or morphine within the first 60 min. 4 Morphine had no effect on ischaemia-induced arrhythmias. 5 Whether the higher intraneuronal NA content following morphine resulted from reduced central sympathetic outflow to the heart, presynaptic inhibition of NA release, or increased uptake due to higher plasma concentrations is unclear. Ischaemia-induced local NA release appears independent of these mechanisms, as it was unaffected by morphine.

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

“…However, reports on an association between the changes in NA levels and the onset of serious ventricular arrhythmias are conflicting (Hirche et al, 1980;Abrahamsson et al, 1982b;Daugherty et al, 1986). The present study revealed that the increase in sympathetic activity was most pronounced at 5min after coronary artery ligation, during which severe ventricular arrhythmias most often occur (Dai, 1986;Chan et al, 1987 (Addicks et al, 1987;Chan et al, 1987).…”

Morphine and Morphiceptin Increase the Threshold for Epinephrine‐induced Cardiac Arrhythmias in the Rat Through Brain Mu Opioid Receptors

“…Morphine was found to suppress the occurrence of cardiac arrhythmias produced in the dog after coronary artery ligation in studies by DeSilva et al (1978a) andPant et al (1984). Although Addicks et al (1987) reported that morphine reduced the duration of ventricular tachycardia or fibrillation after coronary artery occlusion in pentobarbitone anaesthetized rats, it was not statistically significant. Morphine increased arrhythmia threshold in unanaesthetized dog subjected to psychological stress (DeSilva et al 1978b) and increased threshold for arrhythmias from digitalis glycosides in the anaesthetized dog and guinea-pig Rabkin 1988).…”

“…Mu opioid receptor agonists such as morphine and fentanyl have been found to modulate cardiac arrhythmias but their site of action is unclear because most studies have used the systemic route of administration and were unable to differentiate a peripheral from a central nervous system (CNS) site of interaction (Leimdorfer 1955;DeSilva et al 1978a;Pant et al 1984;Addicks et al 1987; Correspondence: Dr Simon W. Rabkin, University Hospital (Shaughnessy), University of British Columbia, 4500 Oak Street, Vancouver, BC V6H 3N1, Canada. 1988, Saini et al 1988). An action in the brain is a likely possibility because the CNS actions of opioids are generally appreciated and have long been the subject of intensive investigation.…”