Cardioprotective effect of L-arginine in myocardial ischemia and reperfusion in an isolated working rat heart model.
BACKGROUND
Studies in myocardial ischemia and reperfusion have demonstrated damage to endothelium, impaired production and release of vasoactive substances such as nitric oxide, and marked alteration in endothelium-dependent relaxatin of the coronary vasculature. This study was designed to examine the cardioprotective effect of exogenous administration of L-arginine, a precursor of nitric oxide, during ischemia and reperfusion, particularly using oxygenated crystalloid cardioplegia.


METHODS
Seventy energy-depleted isolated working rat hearts were arrested by cardioplegia and subjected to 60 min normothermic global ischemia followed by 10 min nonworking and 30 min working reperfusion (Gr 1). L-arginine (3mM or 10mM) was added to the cardioplegic solution (Gr 2,3 respectively), reperfusion (Gr 6,7 respectively), throughout the experiment (Gr 4,5 respectively), and with Nw-nitro-L-arginine methyl ester (L-NAME), a competitive inhibitor of nitric oxide synthase (Gr 8).


RESULTS
At 30 min of working heart reperfusion, compared to control all arginine containing groups (Gr 2-7) exhibited a significant improved recovery of cardiac output (64.7+/-21.2, 98.1+/-21.1, 90.9+/-11.7, 88.9+/-16.2, 83.1+/-7.4, and 90.8+/-10.6, mean +/- SD% Gr 2 to 7 respectively, vs Gr 1 36.3+/-20%, p<0.01). Significant recovery improvement was observed also in other hemodynamic parameters (coronary flow, aortic peak pressure), as well as biochemical recovery assessed by O2 consumption ratio, release of lactic dehydrogenase at reperfusion and regeneration of ATP. The L-NAME group had a significant poorer hemodynamic and biochemical recovery. L-arginine had no effect on the preischemic hemodynamic parameters.


CONCLUSIONS
These results support the cumulative data considering L-arginine as a cardioprotective agent in postischemic reperfusion injury.
Izhar
U
U
Cardiothoracic Surgery Department and Joseph Lunenfeld Cardiac Surgery Research Center Hadassah University Hospital, Jerusalem, Israel.
Schwalb
H
H
Borman
J B
JB
Merin
G
G
D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D002314:Cardioplegic Solutions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006321:Heart / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects; D066298:In Vitro Techniques; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley
D002314:Cardioplegic Solutions; D004791:Enzyme Inhibitors; D001120:Arginine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester