tcv-309 and Ventricular-Fibrillation

This swine model was designed to elucidate the role of platelet-activating factor in regional myocardial ischemia-reperfusion injury.. In groups 1 and 2 (n = 12 each), the left anterior descending coronary artery was ligated for 60 minutes to induce regional myocardial ischemia followed by 6 hours of reperfusion. Group 1 received the platelet-activating factor antagonist TCV-309 before ischemia, whereas group 2 did not. Group 3 (n = 3) had a sham operation.. Animals in group 2 exhibited significant (p < 0.05) hemodynamic instability and myocardial depression during the reperfusion period. Despite preventive measures, 7 of the 12 animals experienced severe dysrhythmias in the form of atrial and ventricular fibrillation leading to cardiac arrest. In contrast, animals in group 1 in whom the effects of platelet-activating factor were blocked by the specific platelet-activating factor receptor antagonist TCV-309 were hemodynamically stable and had significantly (p < 0.05) better myocardial function. This significant difference in global myocardial function between the groups was observed in the presence of similar morphologic findings and regional myocardial function.. These results suggest that platelet-activating factor has a definite influence on global myocardial dysfunction associated with regional myocardial ischemia-reperfusion injury.

Topics: Animals; Arrhythmias, Cardiac; Atrial Fibrillation; Blood Pressure; Cardiac Output; Cardiac Volume; Disease Models, Animal; Female; Heart Arrest; Hemodynamics; Isoquinolines; Myocardial Contraction; Myocardial Infarction; Myocardial Ischemia; Myocardial Reperfusion Injury; Myocardium; Neutrophils; Platelet Activating Factor; Platelet Aggregation Inhibitors; Pyridinium Compounds; Random Allocation; Stroke Volume; Swine; Tetrahydroisoquinolines; Ventricular Fibrillation; Ventricular Function

We investigated the effects of a platelet-activating-factor antagonist TCV-309, an antagonist of metabolites of ischemia, on arrhythmias and functional recovery during in-situ reperfusion in dogs.. Open-chest anesthetized dogs were subjected to ligation of the left anterior coronary artery. Ischemia was maintained for 20 min after which reperfusion was allowed. A cardiac surface ECG was recorded continuously with the II limb lead. Monophasic action potential, left ventricular segment shortening measured by sonomicrometer, and left ventricular pressure were recorded simultaneously under atrial pacing (group A, n = 14). In a second group of dogs, TCV-309 (1 mg/kg) was administered before coronary artery occlusion (group B, n = 12). The hearts were constantly paced through the right atrium at 120 beats/min throughout all experiments. Measurements were continuously obtained from before drug administration to 30 min after reperfusion.. The 90% repolarization time of monophasic action potentials in group B revealed significant recovery compared with group A until the fifth minute after reperfusion (P < 0.02). Reduction of severe ventricular arrhythmias was observed during reperfusion in group B (P < 0.05). The percentage segment shortening and left ventricular pressure did not differ significantly between the groups.. The platelet-activating-factor antagonist had beneficial effects on arrhythmias but not on functional recovery during reperfusion after brief coronary artery occlusion in situ in dogs.

Topics: Action Potentials; Animals; Cardiac Pacing, Artificial; Dogs; Electrocardiography; Isoquinolines; Myocardial Contraction; Myocardial Reperfusion Injury; Platelet Activating Factor; Pyridinium Compounds; Tachycardia, Ventricular; Tetrahydroisoquinolines; Ventricular Fibrillation; Ventricular Function, Left