POTENTIAL PARACRINE ROLE OF THE PERICARDIUM IN THE REGULATION OF CARDIAC-FUNCTION

Objective: Both coronary and endocardial endothelium regulate cardiac contractile function via paracrine pathways. We investigated whether p ericardial fluid (PF) and pericardial mesothelial cells (PMC) could ex ert a similar paracrine action. Methods: Both PF and PMC were extracte d from sheep pericardial space. Endothelin-1, prostaglandins and atria l natriuretic factor were measured in PF in vivo. In the other hand, P MC were grown on T-75 flasks and microcarrier beads to investigate end othelin-1, nitric oxide and prostaglandin pathways in vitro. In additi on, effects of PF and PMC effluent were tested on adult rat cardiac my ocyte contraction in vitro. Results: In vitro, cultured PMC expressed endothelin-1 mRNA but not the endothelial nitric oxide synthase III, a nd released endothelin-1 and prostaglandins. Both PF and cultured PMC superfusate induced a potent, rapidly reversible decrease in the short ening of isolated rat cardiac myocytes. This effect was not associated with changes in intracellular calcium. In vivo, prostaglandins, atria l natriuretic factor and endothelin were present in PF. A greater conc entration of atrial natriuretic factor was present in PF than in serum , suggesting molecular diffusion from the myocardium to PF. Preliminar y results show that the instillation of vasoactive agents into the per icardial space of dogs rapidly alter coronary and systemic vascular to ne, consistent with a molecular diffusion of these substances from PF into the myocardium and circulation. Conclusions: In addition to its m echanical role, the pericardium may contribute to the integration and the regulation of cardiovascular function via a paracrine mechanism. ( C) 1998 Published by Elsevier Science B.V. All rights reserved.