Endothelial prostacyclin (PGI-2) production of human and porcine valve allografts related to ischemic history

Background: The significance of cellular viability in human valve allograft s for functional clinical longevity continues to be debated. Meaningful tes ts for this biological entity are therefore in demand to quantify the relat ive merits of graft origin and procurement techniques, The valve leaflet en dothelium is recognized as a particularly sensitive target to noxes and its continued ability to produce prostacyclin (PGI-2) after explantation has b een suggested as indicating viability. Objective: Graft ischemic history an d species differences were therefore studied in human and porcine valve lea flets by the measurement of endothelial prostacyclin production, post-expla ntational, basal and after stimulation with bradykinin, Methods: Four group s of aortic valve donors were established. Fresh human heart-beating donors (h-HBD), cadaveric human donors (h-NHBD) processed within 24 h, fresh porc ine donors (p-HBD) and cadaveric porcine donors (p-NHBD) also processed wit hin 24 h, Leaflets were separately incubated at 37 degrees C for successive periods of 30 min up to 5 h in Earle's Medium 199. After 240 min PGI-2 pro duction was stimulated by 10 mu M bradykinin, Postincubational release was stopped with indomethacin 10 mu g/ml. Prostacyclin production was measured as 6-kPGF1a using an ELISA. Results: Initial PGI-2 production is significan tly higher in porcine than in human grafts and in both species enhanced by previous warm ischemia. While baseline species differences disappear during progressive incubation, differences resulting from graft history are maint ained. After PGI-2 stimulation species differences dominate again while isc hemic history has no effect. Conclusion: Ischemia and surgical manipulation are stimulators of endothelial PGI-2 production in both human and porcine allografts and, therefore, a correlation of this metabolic activity with ce llular integrity may be misleading. Valid data are obtained only if the nat ural time-course and reaction to stimulation of PGI-2 production are duely recognized and species differences in the response to mechanical and ischem ic stress are considered. (C) 1998 Elsevier Science B.V, All rights reserve d.