[Circulating negative inotropic substance produced by the lung, affected by prostaglandin and thromboxane]

The Lung is capable of the synthesis and the release of prostaglandins responded to a number of pathophysiological stimuli, which may impair myocardial performance. Present study was undertaken to determine the release of circulating negative inotropic substance(s) from the lung and whether or not blockage of prostanoid synthesis, or infusion of prostaglandin are related to the production of this substance(s). Sixteen isolated left lower lobes were divided into 3 groups: (1) untreated, isolated blood-perfused lungs (n = 5), (2) prostaglandin I2, 1 microgram/min, continuously added to the perfusate (n = 6), and (3) five lobes pretreated with ibuprofen (12.5 mg/kg) in addition to 1 microgram/min prostaglandin I2. Perfusion of an isolated lobe with heparinized whole blood caused thrombocytopenia. The plasma 4 hours after perfusion led to the generation of a humoral agent(s) that reduced developed tension (Tpd) of a papillary muscle (p less than 0.05), and Ca++ -and Mg++-ATPase of sarcoplasmic reticulum (SR) (p less than 0.01). With prostaglandin I2, thromboxane B2 rose from 0.076 to 0.362 ng/ml at a level higher than control (p less than 0.05). The plasma significantly lowered SR-ATPase and myofibril-Mg++-ATPase activities and further reduced papillary muscle Tpd. By pretreatment with ibuprofen, adverse prostaglandin I2 effects were eliminated. The observation suggests that the lung produces prostaglandin related negative inotropic substance(s) that may reduced contractility, affected by energy availability.