Myocardial protection with the use of L-arginine and N-alpha-acetyl-histidine

Transplant Proc. 2009 Jul-Aug;41(6):2592-4. doi: 10.1016/j.transproceed.2009.06.150.

Abstract

Objective: 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.

Materials and methods: 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.

Results: 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.

Conclusion: This study showed that the novel modified HTK-1 solution improved myocardial contractility and relaxation after heart transplantation.

MeSH terms

  • Adenine Nucleotides / metabolism
  • Animals
  • Arginine / pharmacology*
  • Blood Pressure
  • Glucose
  • Heart Rate
  • Heart Transplantation / methods*
  • Heart Transplantation / physiology
  • Histidine / pharmacology
  • Mannitol
  • Myocardial Ischemia
  • Organ Preservation Solutions
  • Potassium Chloride
  • Procaine
  • Rats
  • Rats, Inbred Lew
  • Transplantation, Heterotopic

Substances

  • Adenine Nucleotides
  • Bretschneider cardioplegic solution
  • N(alpha)-acetylhistidine methyl ester
  • Organ Preservation Solutions
  • Mannitol
  • Histidine
  • Procaine
  • Potassium Chloride
  • Arginine
  • Glucose