Backtable heat-enhanced preconditioning: a simple and effective means of improving function of heart transplants

Abstract

Background. Cardiac harvest teams are usually committed to immediately transfer the explanted donor heart into its cold storage solution. We tested the opposite hypothesis that a brief prestorage episode of heat-enhanced ischemic preconditioning could be protective. Methods. Fifty-three isolated isovolumic rat hearts underwent 4 hours of cold (4°C) storage in the Celsior preservation solution and 2 hours of reperfusion. Control hearts were immediately immersed after arrest. In the 3 treated groups, 2 customized thermal probes were first applied onto the left ventricular free wall of the explanted heart at 22°C, 37°C or 42.5°C for 15 minutes before immersion. Each of the selected temperatures were monitored at the probe-tissue interface by a thermocouple. Results. Whereas base line end-diastolic pressure was set at ≠ 8 mm Hg in all groups, it increased during reperfusion (mean ± SEM) to 28 ± 3, 27 ± 3, 17 ± 1, and 18 ± 2 mm Hg in control, 22°C, 37°C and 42.5°C-heated hearts, respectively (37°C and 42.5°C: p < 0.05 versus controls and 22°C). Slopes of pressure-volume curves featured similar patterns. Likewise, reperfusion dP/dT (mm Hg/s −1) was significantly lower in control and 22°C hearts (1,119 ± 114 and 1,076 ± 125, respectively) than in those undergoing prestorage heating to 37°C and 42.5°C (1,545 ± 109 and 1,719 ± 111, p < 0.05 and p < 0.01 versus controls and 22°C, respectively). Western blot analysis of LV samples did not demonstrate any upregulation of HSP 72 in either group. Conversely, the involvement of preconditioning was evidenced by the loss of protection in the 42.5°C-heated hearts when, in 2 additional groups, the storage solution was supplemented with either the protein kinase C and tyrosine kinase inhibitors chelerythrine (5 μmol/L) and genistein (50 μmol/L) or the mitochondrial K ATP channel inhibitor 5-hydroxydecanoate (200 μmol/L). Conclusions. A brief period of postexplant ischemia with enhancement by topical heating (“backtable preconditioning”) could be a simple and effective means of improving the functional recovery of heart transplants.