Cardiopulmonary and intravascular alterations during the sustained infusion of PAF

The physiologic responses during prolonged exposure to platelet activating factor (PAF) are largely unexplored. Thus, the cardiopulmonary and intravascular effects of a sustained infusion of 1-O-hexadecyl-2-acetyl-sn-glycero-3-phosphocholine (C16:0-AGEPC; 0.159 nmole/kg/min for 120 min) were characterized in anesthetized rabbits. Within minutes, a transient period of tachypnea developed and was followed by 30 min of stable ventilation. Subsequently, both respiratory rate and tidal volume irreversibly increased. The latter pulmonary ventilatory alterations were preceded by lung mechanical changes, i.e., dynamic lung compliance (C(Ldyn)) decreased 21.6 ± 3.4% (mean ± SE) and total pulmonary resistance (R(pulm) increased 25.1 ± 8.5%. In contrast to C(Ldyn) which partially recovered during infusion, R(pulm) remained elevated throughout the study. Concurrent with these pulmonary alterations, significant cardiovascular changes also occurred. Right ventricular hypertension developed immediately and was maximal within 7.9 ± 0.9 min; this hypertension persisted throughout the infusion period but rapidly reversed thereafter. Mean arterial pressure (MAP) decreased 37.1 ± 5.8% within 31.4 ± 2.5 min and then remained at this level. The patterns and extent of alterations in left ventricular pressure, +dP/dt(max), and -dP/dt(max) paralleled the changes in MAP and were accompanied by a progressive decrease in left ventricular end-diastolic pressure. These cardiopulmonary effects of C16:0-AGEPC developed in association with prolonged thrombocytopenia and intravascular platelet activation. In contrast, C16:0-AGEPC-induced neutropenia at 5 min was reversed within 60 min and was followed by sustained neutrophilia. In combination, these data suggest that the continuous biosynthesis and release of PAF in vivo could modulate significant, persistent pathophysiological alterations. Of importance, these cardiopulmonary and intravascular effects during a sustained PAF exposure are apparently not subject to immediate tachyphylactic down-regulation.