Age-related effects of Platelet Activating Factor (PAF) in the isolated perfused rat heart

Abstract

Platelet Activating Factor (PAF) is a phospholipid that has been implicated as an important mediator of anaphylactic cardiac dysfunction and involved in the toxic effects of the ischaemia-reperfusion process. In the elderly, these phenomena are thought to be exaggerated by the age-related changes in response to several chemical factors and myocardial ischaemia. We evaluated the effects of PAF (acetyl-o-alkyl-l-phosphatidylcholine) on left ventricular systolic (LVSP) and diastolic (LVDP) pressure, coronary flow rate (CFR) and heart rate (HR) in adult (6 months, AH) and senescent (24 months, SH) rat hearts. The perfusion of PAF (10 −8, 10 −7 and 10 −6 m) induced a concentration-related reduction of LVSP, CFR and HR and a linear increase in LVDP. Contractile modifications were more pronounced in senescent hearts: LVSP decreased ( P < 0.01) and LVDP increased with respect to younger animals ( P < 0.01 vs. AH). This negative inotropic effect was also present in electrically paced hearts. PAF produced conduction arrhythmias ranging from second-degree atrio-ventricular conduction block to cardiac standstill both in adult and senescent hearts; at a higher dose (10 −6 m), cardiac standstill appeared after 96.5 ± 15.3 s in adult hearts and after 45.5 ± 17.6 s in senescent hearts ( P < 0.01). Lyso-PAF did not modify while specific PAF antagonist compounds CV-3988 inhibited all electromechanical responses both in adult and senescent hearts. These data suggest that age influences the effect of PAF on contractile parameters, coronary flow and conduction arrhythmias by acting on receptors, whose function is unaffected by age.