Occlusion and reperfusion-induced arrhythmias in rats: involvement of platelets and effects of calcium antagonists.
The role of blood platelets in ischemia- and reperfusion-induced arrhythmias and the efficacy of three calcium blocking drugs (verapamil, diltiazem, and nicardipine) in preventing the arrhythmias were investigated. Using anesthetized rats, we measured platelet count (Pc) continuously in vivo with a Technicon autocounter. Thromboxane B2 (TxB2) and 6-keto-PGF1 alpha levels in blood from coronary sinus were determined by radioimmunoassay (RIA). Myocardial ischemia and arrhythmias were monitored from lead I ECG during and after occlusion of the left anterior descending coronary artery (LAD) for 7 min. Ischemia-induced arrhythmias were mainly ventricular ectopic contractions (VECs), whereas reperfusion produced VECs, ventricular tachycardia (VT), and reversible and irreversible ventricular fibrillation (VF). Both ischemia and reperfusion decreased platelet count and increased TxB2 level in blood from the coronary sinus. The effects of the CEBs were determined at two dose levels (0.1 and 0.3 mg/kg). Each calcium entry blocker (CEB), at both dose levels, significantly inhibited ischemia-induced arrhythmias. Verapamil and diltiazem significantly reduced reperfusion-induced VECs, prevented VT and irreversible VF, and reduced the number of animals with reversible VF. Nicardipine in preventing arrhythmias was not very effective at either dose. The CEBs also inhibited both ischemia- and reperfusion-induced decreases in PC with a moderate increase (up to 7%) as compared with levels in sham-operated controls. The CEBs also significantly reduced TxB2 levels in blood from the coronary sinus. These results indicate that ischemia and postischemic reperfusion both induce platelet aggregation in rats. Aggregating platelets release biologically active substances including thromboxane A2 (TxA2) which exacerbates existing ischemia and facilitates generation of arrhythmias. CEBs inhibit platelet aggregation and TxA2 release and enhance PGI2 synthesis, thereby preventing arrhythmias.
School of Pharmacy, Robert Gordon's Institute of Technology, Schoolhill, Aberdeen, Poland.
J
J
Swies
E K
EK
Omogbai
G M
GM
Smith
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000503:physiopathology*; D001157:Arterial Occlusive Diseases / Q000503:physiopathology*; D001792:Blood Platelets / Q000502:physiology*; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004562:Electrocardiography; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D015425:Myocardial Reperfusion; D010976:Platelet Count / Q000187:drug effects; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D013929:Thromboxane B2 / Q000097:blood
D002121:Calcium Channel Blockers; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha