Effects of the PAF antagonists BN50726 and BN50739 on arrhythmogenesis and extent of necrosis during myocardial ischaemia/reperfusion in rabbits.
1. The effects of two novel platelet activating factor (PAF) antagonists BN50726 and BN50739 on arrhythmias, haemodynamics and extent of necrosis during myocardial ischaemia and reperfusion were investigated in anaesthetized rabbits subjected to coronary artery ligation. 2. BN50739 reduced heart rate prior to coronary artery occlusion (P < 0.005) but had no other significant haemodynamic effects at this time. BN50739 and BN50726 did not significantly alter heart rate or blood pressure during 30 min of ischaemia or 30 min of reperfusion, compared to control hearts. 3. BN50739 and BN50726 had no effect on the incidence of arrhythmias during ischaemia. BN50726 significantly reduced the incidence of reperfusion ventricular fibrillation compared to controls (0% v 40%, P < 0.05), and improved survival (80% v 39%, P < 0.05). Similar trends were observed with BN50739. 4. BN50726 reduced the extent of necrosis compared to control hearts (18 +/- 2% v 30 +/- 3%, P < 0.01). A similar trend was observed with BN50739. 5. These results demonstrate that PAF antagonism with BN50726 attenuates reperfusion-induced arrhythmias and preserves myocardium in the early phase of ischaemia, independently of haemodynamic effects.
Chakrabarty
S
S
Academic Cardiology Unit, St Mary's Hospital Medical School, London.
Fluck
D S
DS
Flores
N A
NA
Sheridan
D J
DJ
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000503:physiopathology*; D001381:Azepines / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D004562:Electrocardiography / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D009203:Myocardial Infarction / Q000503:physiopathology; D017202:Myocardial Ischemia / Q000473:pathology / Q000503:physiopathology*; D015428:Myocardial Reperfusion Injury / Q000473:pathology / Q000503:physiopathology*; D009336:Necrosis / Q000139:chemically induced / Q000473:pathology; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D011817:Rabbits; D058924:Thienopyridines; D014230:Triazoles / Q000494:pharmacology*
D001381:Azepines; D010972:Platelet Activating Factor; D058924:Thienopyridines; D014230:Triazoles; C061327:BN 50726; C064509:BN 50739