Ginkgolide B protects isolated hearts against arrhythmias induced by ischemia but not reperfusion.
The effect of ginkgolide B (BN 52021), a specific platelet-activating factor (PAF) antagonist, applied in doses of 1.5, 3.0, 6.0 X 10(-5) and 1.2 X 10(-4) mol/l, in comparison to that of metoprolol (10(-5) mol/l) and diltiazem (10(-7) mol/l), two widely used antiarrhythmic agents, on ischemia- and reperfusion-induced arrhythmias and heart functions, such as heart rate (HR), coronary flow (CF), aortic flow (AF), left ventricular developed pressure (LVDP), its first derivative (LVdp/dtmax), and left ventricular end-diastolic pressure (LVEDP) in isolated working rat hearts was examined. BN 52021 caused a dose-related protection against dysrhythmias, such as ventricular fibrillation, ventricular tachycardia, and premature ventricular beats induced by ischemia (30 min ligation of the left anterior descending coronary artery). The antiarrhythmic effect of BN 52021 given in a dose of 6.0 X 10(-5) mol/l was comparable to that of diltiazem and superior to the activity of metoprolol. None of the drugs influenced reperfusion-induced rhythm disturbances. BN 52021 did not alter heart functions, while metoprolol reduced (LVEDP only, and diltiazem increased CF, decreased AF, LVDP, and LVdp/dtmax during regional ischemia, indicating a negative inotropic effect. The antiarrhythmic effect of BN 52021 appears to be related to an antagonism of an increase in slow calcium influx induced by PAF in myocardial cells. Similarly to the mechanism of action of established antiarrhythmic drugs, BN 52021 can presumably prevent the re-entry mechanism involved in the development of ischemia-induced rhythm disturbances.
Koltai
M
M
Institut Henri Beaufour, Le Plessis-Robinson, France.
Tosaki
A
A
Hosford
D
D
Braquet
P
P
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000503:physiopathology*; D004110:Diltiazem / Q000494:pharmacology; D004224:Diterpenes; D046934:Ginkgolides; D006334:Heart Function Tests; D007783:Lactones / Q000494:pharmacology*; D008297:Male; D008790:Metoprolol / Q000494:pharmacology; D015425:Myocardial Reperfusion; D010477:Perfusion; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D051381:Rats; D011919:Rats, Inbred Strains; D015427:Reperfusion Injury / Q000503:physiopathology*
D004224:Diterpenes; D046934:Ginkgolides; D007783:Lactones; D010972:Platelet Activating Factor; C045856:ginkgolide B; D004110:Diltiazem; D008790:Metoprolol