Studies on the antiarrhythmic actions of prostaglandins
Creators: name: Martinez, Terry T.
Publisher: name: University of British Columbia
Year: 2010

description: The antiarrhythmic actions of prostaglandins were first investigated using arrhythmias associated with cardiac ischemia in the dog and the rat. These studies were followed by investigations of the possible mechanisms of action, using rat heart tissue in intact, isolated, and cell culture preparations. Preliminary experiments in the dog revealed that prostaglandins E₂ and F₁α markedly reduced the number of premature ventricular contractions occurring within the first 25 minutes following coronary artery ligation. Prostaglandin E₂ or F₁α did not markedly alter the cardiovascular response to occlusion, making it unlikely that modulation of autonomic reflexes is a central factor in their antiarrhythmic action. Coronary ligation in the rat was used to compare the antiarrhythmic effectiveness of prostaglandins, lidocaine, and quinidine. Prostaglandins E₂, F₂β and quinidine were found to be the most effective against arrhythmias occurring within the first 25 minutes following occlusion, reducing the number of PVCs by 40 to 50 per cent. The number of flutter episodes and the number of animals dying from arrhythmias was also markedly decreased by prostaglandins E₂ and F₂β and by quinidine. Prostaglandins F₁α and A₂, and lidocaine had lesser effects. Prostaglandins had only minor effects on blood pressure or heart rate, which were not related to their antiarrhythmic activity. No significant differences were found in the infarct size with prostaglandin treatment. The effects of prostaglandins E₂, A₂ and F₂β, quinidine, and lidocaine were tested in in situ rat heart on electrically-induced flutter threshold and maximum following frequency. Flutter threshold was not changed by any of the prostaglandins tested, although lidocaine increased and quinidine decreased it. Prostaglandins caused a dose-dependent change in maximum following frequency which was usually less than 10 per cent of control. Lidocaine produced a marked increase and quinidine a marked decrease in maximum following frequency. The slight depressive action of prostaglandins does not correlate with their antidysrhythmic actions. Prostaglandins of the E, A, and F series were found to have only minimal effects on rate and force in isolated rat hearts. However, both PGE₂ and PGF₂β, delayed the loss of contractile force with time at 10⁻⁷ M. All prostaglandins tested markedly increased coronary flow rate at 10⁻⁵ M. The effects on the beating behavior of cultured rat heart cells of fourteen prostaglandins of the A, B, D., E, and F series were investigated in cultured rat heart cells. With the exception of PGF₂α, which produced a chronotropic response, prostaglandins had limited direct action in cultured rat heart cells. The effects of ouabain, calcium, potassium, dinitrophenol, and Cyanea toxin, together with prostaglandins, lidocaine, and quinidine on cultured rat heart cells were also investigated. Ouabain and calcium increased rate and fibrillatory movements, while potassium and dinitrophenol slowed rate and decreased rhythmic beating. Cyanea toxin produced a characteristic series of arrhythmogenic changes which were also used to test for antiarrhythmic activity in cultured heart cells. Lidocaine and quinidine were effective only against cellular arrhythmias caused by high calcium concentration, and prostaglandins were effective only against dinitrophenol-induced arrhythmias, indicating that there is no over-all "protective" effect of prostaglandins in cell culture.