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Title: The pathophysiological role of the endogenous opioid system in myocardial ischaemia and cardiac failure
Author: Oldroyd, Keith G.
ISNI:       0000 0001 3456 438X
Awarding Body: University of Aberdeen
Current Institution: University of Aberdeen
Date of Award: 1992
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The endogenous opioid system may be involved in the pathogenesis of arrhythmias and produce deleterious haemodynamic effects in patients with myocardial ischaemia and/or cardiac failure. Plasma concentrations of β-endorphin, a potent opioid peptide, were elevated in 31/42 patients with acute myocardial infarction, 3/18 with unstable angina, 3/34 with chronic heart failure, 8/28 with acute heart failure and 10/14 with cardiogenic shock. (Met)enkephalin levels were generally normal. There was no independent statistical relationship between β-endorphin concentrations after myocardial infarction and the incidence of cardiac arrhythmias. In isolated myocardium, the opioid antagonists naloxone and nalmafene, and morphine, an agonist, all produced Class III antiarrhythmic effects. Naloxone enhanced the reduction in maximum upstroke velocity produced by hyperkalaemia and post-repolarization refractoriness developed. During myocardial ischaemia the Class III effects of naloxone were gradually lost but both racemic naloxone (active at opioid receptors) and d-naloxone (inactive) reduced the rate of rise of extracellular potassium concentration and preserved resting membrane potential. The fall in maximum upstroke velocity during ischaemia was enhanced by both compounds suggesting an additional Class I effect. In human studies, despite employing high doses of naloxone, it was only possible to show a minor prolongation of repolarization. In patients with coronary heart disease, naloxone administered by both intracoronary and intravenous routes had no effect on coronary blood flow. In patients with heart failure naloxone had no significant effects on a range of haemodynamic parameters, exercise performance or levels of dyspnoea and fatigue.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Opioid peptides