Role of prostaglandins in positive end-expiratory pressure-induced negative inotropism

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Abstract
Positive end-expiratory pressure (PEEP) therapy is used for treatment of hypoxemia in acute respiratory failure. PEEP is limited principally because of its adverse effect on cardiac output, which may be due in part to a circulating negative inotropic agent(s). PEEP plasma taken from dogs pretreated with indomethacin (5 mg/kg), aspirin (200 mg/kg) or imidazole (25 mg .cntdot. kg-1 .cntdot. h-1) were tested by use of an isolated isometrically contracting rat papillary muscle bioassay. The PEEP plasma of untreated control dogs resulted in a depression of the peak developed tension (DTmax) from 5.45 .+-. 0.78 to 4.82 .+-. 0.72 g (P < 0.001). PEEP plasma from any of the pretreated dogs did not show depression in DTmax. PEEP increased 6-keto prostaglandin F1.alpha. (PGF1.alpha.) (stable metabolite of PGI2) levels from 0.076 to 0.130 ng/ml (P < 0.01) and increased thromboxane B2 (TXB2) (stable metabolite of TXA2) levels from 0.088 to 0.211 ng/ml (P < 0.05). TXB2 production was inhibited in the pretreated groups, but 6-keto PGF1.alpha. increased only in the imidazole group (.PI. < 0.01). The in vitro addition of indomethacin, aspirin, imidazole or PGI2 did not cause a depression of DTmax, and even at 1 ng/ml, TXB2 caused only minimal DTmax depression. It is unlikely that TXB2 is the direct causative agent. PEEP plasma from an isolated perfused lung lobe did not reduce DTmax. Prostaglandins apparently are related to the negative inotropic agent(s) induced by PEEP. Thromboxanes are indirect mediators.