L-arginine during long-term ischemia: effects on cardiac function, energetic metabolism and endothelial damage.
BACKGROUND
We have evaluated the addition of L-arginine, a precursor of nitric oxide, to a cardioplegic solution (named CRMBM) designed for long-term heart preservation.


METHODS
Isolated isovolumic-perfused rat hearts (n = 22) were arrested with the CRMBM solution either with (Arg) or without L-arginine (2 mmol/L) (Arg group, n = 12, vs control group n = 10), submitted to 8 hours of cold storage (4 degrees C) in the solution, and then reperfused for 60 minutes at 37 degrees C. In 11 hearts, we evaluated the quality of cardiac preservation with P-31 magnetic resonance spectroscopy and the measure of function and cellular integrity. Endothelium-dependent and independent vasodilatations were measured in 11 other hearts, using 5-hydroxytryptamine and papaverine to assess endothelial and smooth muscle function.


RESULTS
Adding L-arginine to the cardioplegic solution improved functional recovery during reflow, as shown by the rate pressure product (31% +/- 3% for control vs 47% +/- 3% for Arg, p = 0.003) together with higher coronary flow and diminished contracture. Purine release in coronary effluents during reperfusion was lower in the Arg group. During ischemia and reflow kinetics of intracellular pH and high-energy phosphates were similar in both groups. Coronary endothelium-dependent vasodilatation was similarly impaired in both groups, but smooth muscle was less altered with L-arginine.


CONCLUSIONS
As an additive to the CRMBM cardioplegic solution, L-arginine provides a protective effect for long-term heart preservation. Our data do not show coronary endothelial protection as the prominent mechanism.
Desrois
M
M
Centre de Résonance Magnétique Biologique et Médicale, Marseille, France.
Sciaky
M
M
Lan
C
C
Cozzone
P J
PJ
Bernard
M
M
D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D002314:Cardioplegic Solutions / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000473:pathology; D004734:Energy Metabolism / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D066298:In Vitro Techniques; D008279:Magnetic Resonance Imaging; D008297:Male; D017202:Myocardial Ischemia / Q000175:diagnosis / Q000517:prevention & control*; D009926:Organ Preservation / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D012680:Sensitivity and Specificity
D002314:Cardioplegic Solutions; D001120:Arginine