Release of platelet-activating factor from ischemic-reperfused rabbit heart

Abstract

This study shows that platelet-activating factor (PAF) is released in significant amounts (10.9 +/- 12.8 ng/min) during the initial reperfusion of the ischemic-isolated rabbit heart. When reperfusion was performed in the presence of autologous rabbit platelets, the electrical and mechanical alterations characteristic of this phase were significantly worsened. These alterations were antagonized by pretreatment of rabbit platelets with a PAF receptor antagonist (SDZ 63-675), suggesting a contribution of PAF released during reperfusion in the cardiac dysfunction. To discriminate whether the effect of PAF was platelet dependent, infusion of PAF (10-40 ng) was performed in nonischemic rabbit hearts perfused with or without autologous platelets. Although the effect of PAF per se was minimal, in the presence of platelets PAF induced a biphasic effect characterized by a transient positive inotropism followed by a dose-dependent decrease in coronary flow, negative inotropism, reduction of action potential duration, and conduction arrhythmias. These effects were abolished by pretreatment of platelets with SDZ 63-675, suggesting a PAF receptor-mediated platelet activation. In addition, a relative contribution of histamine, thromboxanes, and leukotrienes released from activated platelets was inferred by experiments performed with pyrilamine and cimetidine, imidazole, and FPL 55712, respectively.

A KATP channel opener inhibited myocardial reperfusion action potential shortening and arrhythmias

“…Previously we demonstrated the reliability of this recording method in our model (Workman et al, 2000). Moreover, a period of similar reperfusion-induced early action potential shortening has been reported by others in the hearts of various species, including pig (Coronel et al, 1992), guinea pig (Culling et al, 1984;Penny and Sheridan, 1983), rabbit (Montrucchio et al, 1989), and rat (Perchenet and Kreher, 1995). In each of those studies, however, repolarisation was measured first after a full 1 min of reperfusion.…”

“…In these hearts, in marked contrast to the controls, however, there was no further shortening of repolarisation during reperfusion. In several previous studies of action potentials during post-ischaemic reperfusion, arrhythmias were only seen during reperfusion if (and often immediately after) repolarisation had shortened (Coronel et al, 1992;Culling et al, 1984;Montrucchio et al, 1989;Penny and Sheridan, 1983;Perchenet and Kreher, 1995). Moreover, those interventions which inhibited these arrhythmias, such as reducing the duration of prior ischaemia (Coronel et al, 1992), preceding it with an episode of ischaemic preconditioning (Coronel et al, 1992;Perchenet and Kreher, 1995), or using various pharmacological treatments (Culling et al, 1984) all resulted in an inhibition of the acute action potential shortening during reperfusion.…”

“…The time course of action potential changes that occur during post-ischaemic reperfusion has been studied previously in intact hearts of several species. It is generally accepted that there is a rapid and transient shortening of repolarisation in pigs (Coronel et al, 1992), guinea pigs (Culling et al, 1984;Penny and Sheridan, 1983) and rabbits (Montrucchio et al, 1989). Only limited data is available from the rat (Perchenet and Kreher, 1995), but in that study action potentials were recorded only after 1 min of reperfusion and beyond, but repolarisation also transiently shortened.…”

Effects of endothelin‐1 on vascular permeability in the conscious rat: interactions with platelet‐activating factor

“…Enhanced plasma levels of endothelin-1 have recently been reported in pathological conditions, including ischaemia (Yasuda et al, 1990;Watanabe et al, 1990) and endotoxin shock (Morel et al, 1989) when enhanced blood PAF levels can also be detected (Doebber et al, 1985;Filep et al, 1989;Montrucchio et al, 1989;M6zes et al, 1989). Since PAF and endothelin-1 exert opposite effects on the vascular tone in most vascular beds (PAF is usually a vasodilator while endothelin-1 is a vasoconstrictor), one might assume that they could modify each other's effects on vascular permeability.…”

“…Elevated plasma concentrations of endothelin-1 and PAF have been reported under the same pathological conditions including ischaemia Mozes et al, 1989;Montrucchio et al, 1989;Yasuda et al, 1990;Watanabe et al, 1990) and endotoxin shock (Doebber et al, 1985;Morel et al, 1989). Since enhanced plasma extravasation is a characteristic feature of these conditions, it can be postulated that endothelin-1 and PAF could act together to modulate vascular permeability.…”