6-ketoprostaglandin-f1-alpha and Ventricular-Fibrillation

To investigate the role of catecholamine and prostacyclin in ischemia reperfusion-induced ventricular fibrillation, experiments were performed in rat hearts using methods of radioimmunoassay and fluorohistochemistry. Regional myocardial ischemia was induced by ligation of the left coronary artery followed by reperfusion. In the ischemia reperfusion group, ventricular fibrillation during reperfusion took place in 78% of the hearts. In the group pretreated with captopril, the incidence of ventricular fibrillation decreased significantly (65.5%). In comparison with the ischemia reperfusion group, myocardial catecholamine content and 6-keto-PGF1 alpha of the captopril group were significantly increased (P < 0.01) while thromboxane B2 (TxB2) and TxB2/6-keto-PGF1 alpha were decreased (P < 0.01). In Ang II group, infusion of angiotensin II reversed the protective effect of captopril and restored the incidence of ventricular fibrillation (85%), while myocardial catecholamine content was not different from the ischemia reperfusion group (P > 0.05). Above results suggest that reduction of the incidence of ischemia reperfusion-induced ventricular fibrillation by captopril may be due to its inhibition on angiotensin II production with consequent reduction of the release of myocardial catecholamine, suppression of TxB2 and promotion of PGI2 synthesis.

Topics: 6-Ketoprostaglandin F1 alpha; Angiotensin-Converting Enzyme Inhibitors; Animals; Captopril; Catecholamines; Male; Myocardial Reperfusion Injury; Rats; Rats, Sprague-Dawley; Thromboxane B2; Ventricular Fibrillation

It was found, that adaptation of rats to cold and physical exercise prevented ventricular fibrillation, caused by the occlusion of the left anterior coronary artery. An adaptation to cold only or to physical exercise do not prevent ventricular arrhythmias. An significant increase of prostacyclin/thromboxane index in plasma and heats was estimated in rats adapted to cold and physical exercise in relation to control non-adapted group in condition of functional rest or acute myocardial ischemia. It was assumed that an increase of prostacyclin/thromboxane ratio has a significant role in antiarrhythmic action of adaptation.

Topics: 6-Ketoprostaglandin F1 alpha; Adaptation, Physiological; Animals; Cardiac Complexes, Premature; Cold Temperature; Coronary Disease; Disease Models, Animal; Male; Rats; Swimming; Thromboxane B2; Ventricular Fibrillation

The effects of a new thromboxane A2 synthetase inhibitor (DP-1904) on electrical stability of the heart were tested in anesthetized, open chest dogs. The incidence of spontaneous ventricular arrhythmias, ventricular refractory period and ventricular fibrillation threshold (VFT) during ligation of the left anterior descending coronary artery (LAD) for 180 min and after reperfusion were measured as indices of stability. Ventricular fibrillation and ventricular tachycardia occurred spontaneously after ligation of LAD in 56% of 9 control dogs and 29% of 7 dogs which received intravenous DP-1904 (100 mg) before ligation of LAD (n.s.). In the control group, the ventricular refractory period decreased in the ischemic region; consequently, the difference in refractory period duration between the ischemic and non-ischemic regions (i.e., dispersion) increased 30 min after coronary ligation (7 +/- 9 ms vs 32 +/- 17 ms, p less than 0.05). The dispersion at 30 min after coronary ligation, though, was not affected in the DP-1904 treated group (2 +/- 4 ms vs 10 +/- 9 ms, n.s.). The VFT (determined with pulse trains) decreased from 28 +/- 5 mA to 15 +/- 11 mA (p less than 0.05) 30 min after coronary ligation in the control group, but was not affected (30 +/- 0 mA vs 27 +/- 4 mA) in the DP-1904 group. The plasma concentration of thromboxane B2 decreased after DP-1904 administration (baseline vs 30 min after coronary ligation: 475 +/- 165 pg/ml vs 165 +/- 74 pg/ml, n = 3, p less than 0.05), while the concentration of 6-keto-prostaglandin F1 alpha increased gradually. In conclusion, DP-1904 prevents a decline in electrical stability in the ischemic region of the canine heart during coronary occlusion.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Coronary Disease; Coronary Vessels; Dogs; Electrophysiology; Female; Heart Rate; Heart Ventricles; Imidazoles; Ligation; Male; Naphthalenes; Refractory Period, Electrophysiological; Reperfusion; Tetrahydronaphthalenes; Thromboxane B2; Thromboxane-A Synthase; Ventricular Fibrillation

Reperfusion of ischemic tissue is responsible for production of metabolites with deleterious local vascular effects. Thromboxane A2, a potent vasoconstrictor and platelet aggregator, has been implicated as a mediator of the "reperfusion injury." We studied the effect of an experimental thromboxane synthetase inhibitor, OKY-046, on coronary sinus thromboxane levels, ventricular irritability, myocardial contractility, infarct salvage, and histologic features of reperfusion. Sixteen sheep were randomized to OKY-046, 3 mg/kg, or saline vehicle before 3-hour occlusion and subsequent reperfusion of the left anterior descending artery. The OKY group demonstrated less ventricular irritability as measured by incidence of ventricular fibrillation and necessity for countershock to reverse tachyarrhythmias. Coronary sinus thromboxane levels were significantly lower in the OKY group compared with the control group. There is additional evidence to suggest that OKY increases infarct salvage and attenuates histologic features of microcirculatory damage.

Topics: 6-Ketoprostaglandin F1 alpha; Acrylates; Animals; Coronary Circulation; Coronary Disease; Disease Models, Animal; Methacrylates; Microcirculation; Myocardial Contraction; Random Allocation; Sheep; Thromboxane B2; Thromboxane-A Synthase; Ventricular Fibrillation

The administration of the thromboxane synthetase inhibitor UK38485, 3 mg/kg i.v. 30 min prior to occlusion of the LAD in chloralose-anaesthetized dogs reduced the number of extrasystoles that occurred in the first 30 min of ischaemia from 832 +/- 158 in controls to 193 +/- 126 (P less than 0.01). VF induced by the release of the occlusion after 40 min was also markedly reduced from seven out of nine in controls to two out of seven in the drug group. UK38485 did not alter blood gases or haemodynamics prior to LAD occlusion and the changes in PO2, PCO2 and pH in blood draining from the ischaemic myocardium during occlusion were similar in control and drug-treated dogs. The haemodynamic changes induced by coronary artery occlusion were attenuated by UK38485. This drug also prevented the thromboxane release that normally occurs during acute myocardial ischaemia but did not suppress prostacyclin release. These results provide further evidence in support of the hypothesis that thromboxane is arrhythmogenic during acute myocardial ischaemia and is a particularly important contributory factor in reperfusion-induced VF.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Arrhythmias, Cardiac; Arteries; Blood; Carbon Dioxide; Coronary Vessels; Dogs; Female; Hemodynamics; Hydrogen-Ion Concentration; Ligation; Male; Oxygen; Perfusion; Thromboxane A2; Thromboxane B2; Thromboxane-A Synthase; Thromboxanes; Ventricular Fibrillation