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


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.


CONCLUSIONS
This study showed that the novel modified HTK-1 solution improved myocardial contractility and relaxation after heart transplantation.
Koch
A
A
Department of Cardiac Surgery, University of Heidelberg, Heidelberg, Germany. Achim_Koch@med.uni-heidelberg.de
Radovits
T
T
Loganathan
S
S
Sack
F-U
FU
Karck
M
M
Szabó
G B
GB
D000227:Adenine Nucleotides / Q000378:metabolism; D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D001794:Blood Pressure; D005947:Glucose; D006339:Heart Rate; D016027:Heart Transplantation / Q000379:methods* / Q000502:physiology; D006639:Histidine / Q000494:pharmacology; D008353:Mannitol; D017202:Myocardial Ischemia; D019188:Organ Preservation Solutions; D011189:Potassium Chloride; D011343:Procaine; D051381:Rats; D011917:Rats, Inbred Lew; D016042:Transplantation, Heterotopic
D000227:Adenine Nucleotides; C039984:Bretschneider cardioplegic solution; C120612:N(alpha)-acetylhistidine methyl ester; D019188:Organ Preservation Solutions; D008353:Mannitol; D006639:Histidine; D011343:Procaine; D011189:Potassium Chloride; D001120:Arginine; D005947:Glucose