The pericardium as a source of prostacyclin in the dog, ox and rat.

Cyclo-oxygenase products of arachidonic acid metabolism formed by the pericardium and epicardial surface of dog heart were identified and quantitated by radioimmunoassay after separation by high-pressure liquid chromatography. Pieces of parietal pericardium, of dog, ox and rat, when incubated in vitro produced mainly 6-keto-PGF1 alpha, with lesser amounts of PGE2, PGF2 alpha and thromboxane B2. Biosynthesis of all prostanoids increased during incubation of the parietal pericardium of each species with arachidonic acid, but 6-keto-PGF1 alpha was still the major metabolite. When slices of dog heart were incubated with arachidonic acid (1 microgram/ml) the rates of 6-keto-PGF1 alpha formation by the parietal pericardium was much greater than that of the myocardium and endocardium. Epicardial slices appeared to be intermediate in 6-keto-PGF1 alpha formation. The hearts of anesthetized dogs were also irrigated in situ with Krebs' solution, and during the first 5 min of epicardial irrigation the pericardial fluid leaving the heart again contained high levels of 6-keto-PGF1 alpha, with lesser amounts of the other prostanoids. Addition of arachidonic acid (3 micrograms/ml) to the irrigating fluid caused an increase in all measured prostanoid levels, although 6-keto-PGF1 alpha remained the predominant metabolite. In contrast, intravenous infusion of isoproterenol selectively increased the release of 6-keto-PGF1 alpha from the irrigated heart. It is concluded that the pericardium and epicardium continuously release prostacyclin into the pericardial fluid, and that the increased release of this substance observed when cardiac workload increases derives mainly from these membranous sources. This raises the interesting possibility that pericardial prostacyclin might influence coronary vascular tone and chemoreflexes which arise from the epicardium during myocardial ischemia.