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

Background: The significance of cellular viability in human valve allografts for functional clinical longevity continues to be debated. Meaningful tests for this biological entity are therefore in demand to quantify the relative merits of graft origin and procurement techniques. The valve leaflet endothelium is recognized as a particularly sensitive target to noxes and its continued ability to produce prostacyclin (PGI-2) after explantation has been suggested as indicating viability. Objective: Graft ischemic history and species differences were therefore studied in human and porcine valve leaflets by the measurement of endothelial prostacyclin production, post-explantational, basal and after stimulation with bradykinin. Methods: Four groups of aortic valve donors were established. Fresh human heart-beating donors (h-HBD), cadaveric human donors (h-NHBD) processed within 24 h, fresh porcine donors (p-HBD) and cadaveric porcine donors (p- NHBD) also processed within 24 h. Leaflets were separately incubated at 37°C for successive periods of 30 min up to 5 h in Earle's Medium 199. After 240 min PGI-2 production was stimulated by 10 μM bradykinin. Postincubational release was stopped with indomethacin 10 μg/ml. Prostacyclin production was measured as 6-kPGF1a using an ELISA. Results: Initial PGI-2 production is significantly 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 maintained. After PGI-2 stimulation species differences dominate again while ischemic 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 cellular integrity may be misleading. Valid data are obtained only if the natural time-course and reaction to stimulation of PGI-2 production are duely recognized and species differences in the response to mechanical and ischemic stress are considered.