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Endothelial function after prolonged coronary artery oxygen persufflation in a rabbit model of heart preservation

^a Department of Pharmacology, University of Cologne, Gleueler Strasse 24, 50931 Cologne, Germany
^b Institute for Experimental Medicine, University of Cologne, Cologne, Germany

^* Corresponding author. Tel.: +49-221-478-6064; fax: +49-221-478-5022
stefan.herzig{at}uni-koeln.de

Coronary oxygen persufflation may serve as a means to improve storage conditions and organ preservation time for cardiac transplantation. We examined whether coronary oxygen persufflation and prolonged preservation time alter the endothelium-dependent relaxation of isolated coronary arteries. Isolated rabbit hearts were subjected to four different protocols: control (no preservation), 3 h cold storage in Bretschneider's solution, 18 h cold storage in Bretschneider's or University of Wisconsin solution, combined with coronary oxygen persufflation. After 2 h parabiotic reperfusion, intramural segments of coronary arteries were isolated and isometric tension was recorded using a small-vessel myograph. Endothelial function was examined using carbachol and substance P, applied after vessel constriction using high (30 mmol/l) K⁺ or U 46.619, a thromboxane receptor agonist. In another series, coronary flow was measured after Bretschneider's ±18 h coronary oxygen persufflation, or in freshly isolated, retrogradely perfused Langendorff hearts. Flow responses to substance P, acetylcholine or bradykinin were recorded. In saline-reperfused intact hearts no change in the normal effects of endothelium-dependent relaxants was detected after 18 h, irrespective of coronary oxygen persufflation. However, after isolation of the resistance vessels endothelium-dependent relaxation was abolished after long-term preservation and persufflation. Similar results were obtained after mechanical removal of the endothelium using control hearts. Short-term preservation without persufflation resulted in relaxations similar to those in non-preserved control hearts. Long-term preservation of rabbit heart including coronary oxygen persufflation results in unchanged endothelium-dependent relaxation in intact heart, but abolishes the endothelium-dependent relaxation after isolation of the vessels.

Key Words: Coronary oxygen persufflation; Rabbit heart; Endothelium; Coronary relaxation