Myocardial Protection With the Use of L-arginine and N-α-acetyl-histidine

Abstract

Effective myocardial preservation is an important condition for cardiac surgery, especially in heart transplantation with long ischemia times. During ischemia and reperfusion, myocardial function is altered by cold-induced ischemic injury. Cold-induced ischemic injury is triggered by cold storage and the amino acid histidine, a main component of the storage solution histidine-tryptophan-ketoglutarate (HTK). Cold-induced ischemic injury generates free oxygen radicals in an iron-dependent way. We investigated the efficacy of new modifications with the addition of L-arginine and N-alpha-acetyl-histidine to the well-established HTK solution (Custodiol) using a rat heart transplant model. Heterotopic transplantation was performed in Lewis rats (n = 20). After 1 hour of ischemic preservation and 1 hour of reperfusion, we assessed myocardial function and energy charge potential. The modifications of HTK solution included the addition of L-arginine, partial replacement of histidine with acetyl-histidine, and reduction of chloride concentration (HTK-1). In a second group, Custodiol served as the control. After 1 hour of reperfusion, left ventricular systolic pressure (106 +/- 33 vs 69 +/- 9 mm Hg; P < .05) and minimum rate of pressure development (dP/dt) (-1388 +/- 627 vs -735 +/- 219 mm Hg/s; P < .05) were significantly higher among the HTK-1 group compared with the control group. Energy charge potential did not differ significantly between the groups. This study showed that the novel modified HTK-1 solution improved myocardial contractility and relaxation after heart transplantation.