Electrophysiological and arrhythmogenic effects of platelet activating factor during normal perfusion, myocardial ischaemia and reperfusion in the guinea‐pig

Abstract

Platelet activating factor (PAF) is often used to study the effects of platelet activation. While direct myocardial electrophysiological effects of PAF have been described in superfused myocardial tissue, little is known about its actions on the whole heart. The cellular electrophysiological and arrhythmogenic effects of PAF (10−11 m, 10−10 m and 10−9 m) were studied during normal perfusion, global myocardial ischaemia and reperfusion in Langendorff‐perfused guinea‐pig hearts at 32°C. PAF (10−9 m) increased the incidence of ventricular fibrillation during ischaemia and reduced action potential duration (APD) during normal perfusion and early myocardial ischaemia (10−9 m and 10−10 m). PAF also reduced refractory period (RP) during normal perfusion (10−9 m) and early ischaemia (10−9 m and 10−10 m). PAF prevented recovery of APD (10−9 m) and RP (10−9 m and 10−10 m) during reperfusion. PAF at a concentration of 10−11 m had no electrophysiological effects. PAF (10−9 m) increased the QRS width of the electrocardiogram during late ischaemia while 10−10 m PAF raised pacing threshold during late ischaemia. Perfusion pressure was increased, and developed tension decreased by 10−9 m PAF. These results demonstrate that PAF has direct myocardial electrophysiological effects in the whole heart which occur during normal perfusion and are capable of augmenting the effects of myocardial ischaemia, but are independent of the presence of platelets.

Ability to Induce Atrial Fibrillation in the Peri-operative Period Is Associated with Phosphorylation-dependent Inhibition of TWIK Protein-related Acid-sensitive Potassium Channel 1 (TASK-1)

“…Exogenous PAF caused ventricular tachycardias in Langendorff-perfused rat hearts (29) and potentiated ischemia-induced arrhythmias in Langendorff-perfused guinea pig hearts (30). In mice, overexpression of the PAF receptor (PAFR) as a transgene resulted in increased sensitivity to PAF-induced arrhythmias (31).…”

Left regional cardiac perfusion in vitro with platelet‐activating factor, norepinephrine and K+ reveals that ischaemic arrhythmias are caused by independent effects of endogenous ‘mediators’ facilitated by interactions, and moderated by paradoxical antagonism

“…Several separate pieces of evidence support this. For example, PAF accumulates in the ischaemic myocardium ( Berti et al ., 1990 ), exogenously applied PAF worsens the severity of low‐flow global ischaemia‐induced VF ( Flores & Sheridan, 1990 ), and the PAF antagonist BN‐50739 protects against ischaemia‐induced VF when delivered to the left (and subsequently ischaemic) coronary bed ( Baker & Curtis, 1999 ). However, these data all have their limitations.…”

Effects of the PAF antagonists BN50726 and BN50739 on arrhythmogenesis and extent of necrosis during myocardial ischaemia/reperfusion in rabbits

“…The exact mechanism through which PAF mediates these effects is not clear. Direct myocardial actions, which are known to be arrhythmogenic (Tamargo et al, 1985;Stahl et al, 1988;Flores & Sheridan, 1990) may be important, together with the activation of platelets and/or white cells (Wainwright et al, 1989;Chakrabarty et al, 1991a). Koltai et al (1991a) recently commented on the complexity of the actions of PAF in the whole animal.…”

“…Release of platelet activating factor (PAF) from the ischaemic myocardium has been demonstrated experimentally and in man (Lotner et al, 1980;Annable et al, 1985;Zimmerman et al, 1985;Montrucchio et al, 1986;Sisson et al, 1987). Experimental studies have shown that PAF increases myocardial necrosis and arrhythmogenesis (Mickelson et al, 1988;Chakrabarty et al, 1991a) during myocardial ischaemia and that it has direct myocardial cellular electrophysiological and arrhythmogenic effects (Flores & Sheridan, 1990). Recent studies have shown that PAF antagonists have opposite actions, reducing the incidence of arrhythmias and preventing necrosis during ischaemia and reperfusion (Wainwright et al, 1989;Chakrabarty et al, 1991a;Koltai et al, 1991a).…”