Effects of University of Wisconsin solution on endothelium-dependent coronary artery relaxation in the rat

Abstract

University of Wisconsin (UW) solution has been reported to enhance myocardial preservation in heart transplantation. To evaluate the effects of UW solution on coronary artery endothelial function, we designed experiments to compare UW solution with a standard crystalloid hyperkalemic cardioplegic solution (CHCS). Isolated rat hearts were studied in a modified Langendorff apparatus for coronary endothelial function. Groups 1 and 2 were perfused with 4 °C CHCS (24 mmol/L of KCl) and UW solution, respectively, for 10 minutes at a pressure of 80 cm H 2O, whereas group 3 underwent warm ischemia for 10 minutes. Groups 4 and 5 were perfused with and stored for 4 hours in cold (4 °C) CHCS and UW solution, respectively. Group 6 underwent 4 hours of topical cooling (4 °C) without any cardioplegic perfusion. All groups had 6 hearts each. Endothelium-dependent relaxation and endothelium-independent relaxation of the coronary arteries were tested by infusing 5-hydroxytryptamine (5HT) (10 −6 mol/L) and sodium nitroprusside (10 −5 mol/L), respectively, before and after perfusion with and storage in one of the two cardioplegic solutions. The coronary vasodilatation induced by 5HT and sodium nitroprusside was not altered in hearts perfused with (group 1) or perfused with and stored in CHCS (group 4). Coronary flow increase after 5HT infusion was significantly decreased in hearts perfused with (group 2) (before, 35% ± 10%; after, 13% ± 10%; p < 0.01) or perfused with and stored in UW solution (group 5) (before, 34% ± 5%; after, −5% ± 12%), indicating severe endothelial dysfunction. In the latter group, coronary flow increase with sodium nitroprusside was also decreased, a finding suggesting smooth muscle damage (before, 84% ± 35%; after, 30% ± 15%). Coronary arteries of hearts having 4 hours of cold ischemia alone (group 6) had a significant decrease only in flow response to 5HT stimulation (before, 60% ± 23%; after, 24% ± 12%). These experiments suggest that perfusion with and storage in UW solution does not preserve endothelium-dependent coronary relaxation in the isolated rat heart.