The specificity of prostaglandin E2 (PGE2) in reducing coronary vascular resistance: A comparison with adenosine.

Experiments were performed on the isolated, electrically driven guinea-pig heart, perfused at constant rate. All animals were pretreated with reserpine. Myocardial contractile force (MCF), coronary perfusion pressure (CPP) and myocardial oxygen consumption (QO2) were monitored continuously. Both adenosine (ADO) and PGE2 produced a concentration-dependent decrease in the CPP. The ED50 (50% of maximum response) was 2.1 +/- 0.6 X 10(-9)M for PGE2 but 40 +/- 7 X 10(-9)M for ADO (P less than 0.01) at 1.8 mM Ca(e). This coronary vasodilation was independent of the external Ca-concentration, which was varied between 0.55-9.0 mM. PGE2 had no effect on MCF or QO2 and the effect of ADO was only slight. There was no evidence that any action of ADO could be inhibited by simultaneously applied PGE2. The results provide evidence for the specific coronary vasodilating action of PGE2 which in this system is about 20 times as effective as adenosine.

Increase in the coronary vascular resistance by indomethacin in the isolated guinea pig heart preparation in the absence of changes in mechanical performance and oxygen consumption.

Experiments were performed in isolated guinea pig hearts, perfused at constant volume. Left ventricular pressure, left ventricular dp/dtmax, coronary vascular pressure and coronary venous pO2 were measured continuously. Indomethacin (1.4 X 10(-6) M) increased coronary vascular resistance by 15% over control (p less than 0.01) without altering the myocardial contractile force. When PGE2 (1.4 X10(-8) M) was subsequently added, it abolished the indomethacin action and lowered the coronary vascular resistance below the pre-indomethacin control value. This increase in coronary vascular resistance caused by indomethacin was also seen when the animals were pretreated with reserpine and/or the adrenoceptor blocking agents phenoxybenzamine and propranolol, but was prevented completely by previous addition of PGE2 (1.4 X 10(-7) M). The results provide evidence for possible involvement of endogenous prostaglandin-like substances in the maintenance of coronary vascular resistance in the isolated guinea pig heart.

Inotropic actions of lignocaine and phenytoin.

1. The inotropic effects of two antiarrhythmic drugs, lignocaine and phenytoin, were studied in electrically driven isolated rabbit atrial preparations. The time-effect relationship of each drug was investigated with different concentrations and frequencies of stimulation.2. The effects of time of exposure, drug concentration and heart rate on the development of beat alterations (cessation of beat, skipped beat, alternating variation of force of contraction and extrasystole) were also studied.3. When the chronotropic effects of both drugs were prevented, the inotropic effects were positive or negative depending on the concentration of drug, time of exposure and frequency of stimulation.4. At concentrations higher than those obtained in the blood of man on maintenance doses, alteration of the beat occurred but was consistent with the peak blood concentrations immediately after the injection of standard clinical doses. The time of onset of beat alteration shortened when either drug concentration or frequency of stimulation was increased.5. The beat alteration produced by antiarrhythmic drugs can account for various adverse effects associated with their clinical use. These effects include transient ventricular tachycardia and extrasystole during and shortly after injection of drug, ventricular tachycardia, ventricular fibrillation and cardiac arrest due either to excessive dose or to persistent tachyarrhythmia if the dose is not excessive.