Platelet activating factor alters receptor-coupled function in the isolated perfused rat heart.
Sepsis induces primary myocardial dysfunction. Yet, both hyper- and hypodynamic cardiac states characterize the sepsis syndrome, suggesting a modulatory role of septic mediators. Platelet activating factor (PAF), implicated in the pathogenesis of sepsis, is an endogenous phospholipid with diverse intracellular and extracellular effects. The purpose of this study was to investigate the influence of PAF (1) upon basal mechanical function of the heart, (2) upon receptor-coupled function of the heart, and (3) on basal and stimulated myocardial function at differing concentrations. In order to focus on the relationship between PAF and cardiac mechanical function, rat hearts were isolated and crystalloid perfused using a modified Langendorf preparation. Separate hearts received intracoronary vehicle (5% ethanol, 2.5% BSA) or PAF (20 or 40 microM) as a bolus, followed 10 min later by 0.25 microM isoproterenol (beta-receptor agonist) infusion over 3 min. Both 20 and 40 microM PAF produced a rapid decrease in rate pressure product (RPP = HR X LVDPmax) relative to control (P < 0.05). The depressive effect of PAF upon basal myocardial function did not persist and by 10 min RPP was not different (P > 0.05) among the groups. Isoproterenol infusion increased (P < 0.05) RPP in all groups. However, hearts pretreated with 20 microM PAF demonstrated a greater (P < 0.05) response to beta-adrenergic stimulation relative to vehicle-pretreated controls. This amplified response to isoproterenol was not observed with pretreatment at a higher concentration of PAF (40 microM, P > 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Bensard
D D
DD
Department of Surgery, University of Colorado Health Sciences Center, Denver 80262.
Anderson
B O
BO
Banerjee
A
A
Nelson
D W
DW
Poggetti
R S
RS
Berens
R L
RL
Harken
A H
AH
D000818:Animals; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D010477:Perfusion; D010972:Platelet Activating Factor / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000502:physiology*
D010972:Platelet Activating Factor; D011943:Receptors, Adrenergic, beta; D007545:Isoproterenol