Systemic Effects Of Thromboxanes Released By Positive Endexpiratory Pressure

Positive end-expiratory pressure (PEEP) stimulates prostaglandin production at the same time that cardiovascular functions are altered. This study explores a possible regulatory role for prostaglandins to mediate cardiovascular functions and other effects of PEEP. Eight healthy volunteers breathed against 10 cm H₂O PEEP for 15 min. There was a mean increase in functional residual capacity of 838 ml (p < 0.001); the stable metabolite of the vasoconstricting and pro-aggregating agent thromboxane A₂, thromboxane B₂, rose from 0.03 to 0.09 ng/ml (p < 0.03). ADP induced platelet aggregation increased from 35 to 48% (p < 0.03); plasma 5-hydroxytryptamine increased from 45 to 57 ng/ml (p < 0.005); and diastolic pressure rose from 73 to 93 mm Hg (p < 0.005). A circulating agent which depressed myocardial function was detected by in-vitro assays. PEEPplasma decreased: (1) developed tension of a rat papillary muscle (p < 0.005); (2) Ca⁺⁺-ATPase activity of two rat myocardial subfractions, myofibrils (p < 0.005) and sarcoplasmic reticulum (p < 0.03); (3) succinate dehydrogenase activity (p < 0.05) of mitochondria isolated from rat heart. There was no change in concentration of the stable metabolite of prostacyclin, 6-keto-PGF_1α. Treatment of volunteers with 650 mg aspirin 12 h prior to PEEP reduced baseline thromboxane B₂ concentration from 0.03 to 0.002 ng/ml (p < 0.005). During PEEP these lowered thromboxane B₂ levels were unchanged as was cardiovascular function and platelet sensitivity to ADP induced aggregation. This study shows that a short period of PEEP produces sufficient thromboxanes to effect significantly cardiovascular and platelet functions, which are preventable with aspirin.