L-Arginine administration prevents reperfusion-induced cardiomyocyte hypercontracture and reduces infarct size in the pig.
OBJECTIVE
Stimulation of cGMP synthesis protects cardiomyocytes against reoxygenation-induced hypercontracture. The purpose of this study was to determine whether L-arginine supplementation has a protective effect against reperfusion-induced hypercontracture and necrosis in the intact animal.


METHODS
Twenty-four Large-White pigs were randomized to receive either 100 mg/kg of L-arginine i.v. or vehicle 10 min before 48 min of coronary occlusion and 2 h of reperfusion. Hemodynamic variables, coronary blood flow and myocardial segment length changes (piezoelectric crystals) were monitored. Postmortem studies included quantification of myocardium at risk (in vivo fluorescein), infarct size (triphenyltetrazolium reaction), myocardial myeloperoxidase activity and histological analysis. Systemic, coronary vein, and myocardial cGMP concentration were measured in additional animals.


RESULTS
Administration of L-arginine had no significant effect in hemodynamics or coronary blood flow. During reperfusion, myocardial cGMP content was reduced in the LAD as compared to control myocardium (P=0.02). L-Arginine increased myocardial cGMP content and caused a transient increase in plasma cGMP concentration during the initial minutes of reperfusion (P=0.02). The reduction in end-diastolic segment length induced by reperfusion, reflecting hypercontracture, was less pronounced in the L-arginine group (P=0.02). Infarct size was smaller in pigs receiving L-arginine (47.9+/-7.2% of the area at risk) than in controls (62.9+/-4.9%, P=0.047). There were no differences between groups in leukocyte accumulation in reperfused myocardium (P=0.80).


CONCLUSIONS
L-Arginine supplementation reduces myocardial necrosis secondary to in situ ischemia-reperfusion by a direct protective effect against myocyte hypercontracture.
Padilla
F
F
Department of Cardiology, Hospital General Universitario Vall d'Hebron, Barcelona, Spain.
Garcia-Dorado
D
D
Agulló
L
L
Inserte
J
J
Paniagua
A
A
Mirabet
S
S
Barrabés
J A
JA
Ruiz-Meana
M
M
Soler-Soler
J
J
D000704:Analysis of Variance; D000818:Animals; D001120:Arginine / Q000097:blood / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D006152:Cyclic GMP / Q000097:blood; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D011897:Random Allocation; D013552:Swine
D001120:Arginine; D009195:Peroxidase; D006152:Cyclic GMP