Calcitonin gene-related peptide-induced preconditioning improves preservation with cardioplegia

Our recent work has shown that calcitonin gene-related peptide (CGRP) may play an important role in mediation of ischemic preconditioning. Therefore, we tested the hypothesis that CGRP-induced preconditioning protects against myocardial damage after prolonged cardioplegic arrest in isolated rat hearts.

Six groups were studied: the control, ischemic preconditioning, and CGRP-pretreated groups for both 4- and 8-hour hypothermic ischemia. All hearts were arrested using St. Thomas Hospital cardioplegia, and then reperfused with normothermic Krebs-Henseleit solution for 60 minutes after the 4- or 8-hour hypothermic ischemic period. Hearts were subjected to two cycles of 5-minute ischemia and 10-minute reperfusion in the ischemic preconditioning group. In the CGRP-pretreated group, Krebs-Henseleit solution containing CGRP (5 x 10(-9) mol/L) was substituted for the ischemic period.

At 30 minutes of reperfusion after 4-hour storage, left ventricular pressure (mm Hg) and its first derivative (dp/dtmax, mm Hg/s) in the control, ischemic preconditioning, and CGRP groups were 65.2 +/- 5.93 and 1,170 +/- 119, 94.13 +/- 4.93 and 1,825 +/- 145.83, and 85.47 +/- 4.17 and 1,900 +/- 123.13, respectively (p < 0.01). After 8-hour storage, left ventricular pressure (mm Hg) and dp/dtmax (mm Hg/s) in the same groups were 51.07 +/- 5.83 and 815 +/- 107.17, 83.47 +/- 6.54 and 1,480 +/- 120.91, and 84.8 +/- 8.49 and 1,396 +/- 126.16 (p < 0.01). Ischemic preconditioning and CGRP-induced preconditioning also significantly reduced the release of myocardial enzymes.

The present studies suggest that ischemic preconditioning protects against ischemia-reperfusion injury even after 8 hours of hypothermic preservation in isolated rat hearts, and that CGRP exerts preconditioning-like cardioprotection.