L-arginine reverses low coronary reflow and enhances postischaemic recovery of cardiac mechanical function.
OBJECTIVE
To evaluate the effect of L-arginine, the physiological substrate of nitric oxide (NO), upon coronary flow (CF) and mechanical function during reperfusion following cardioplegic arrest.


METHODS
Two groups of isolated rat hearts were subjected to cardioplegic arrest for 4 h at 4 degrees C. In group 1 (n = 10) cardioplegic arrest was followed by 4 consecutive periods of reperfusion with Krebs buffer (control), Krebs plus L-lysine (1 mmol/1), Krebs plus L-arginine (1 mmol/1) and Krebs plus L-NGmonomethylarginine (L-NMMA), a specific inhibitor of NO synthesis, (0.5 mmol/1). In group 2, hearts (n = 8) were perfused by Krebs, then L-NMMA, during both pre- and postischaemic periods. In group 3, hearts (n = 8) were perfused by Krebs, then L-arginine (1, 2 and 4 mmol/1). In group 4 (n = 5), NO released into the perfusate was measured before ischaemia and during reperfusion.


RESULTS
In group 1, L-arginine enhanced the postischaemic CF (ml/min +/- s.e.m.) from 15.0 +/- 0.4 to 17.2 +/-0.4. This was reduced by L-NMMA to 11.3 +/- 0.3. Postischaemic cardiac output (% of preischaemic value +/- s.e.m.) was increased from 55.8 +/- 2.4 to 80.1 +/- 2.5 by L-arginine and dropped to 54.3 +/- 2.3 with L-NMMA. In group 2, the pre- and postischaemic loss of coronary flow (CF) by L-NMMA was 51% and 31% respectively. In group 3, L-arginine did not modify CF. In group 4 the preischaemic level of NO (in nmol/ml/min) in the coronary effluent, measured by chemiluminescence, was 14.84 +/- 0.83 and dropped significantly (P < 0.05) to levels ranging from 3.80 +/- 0.56 to 4.75 +/- 0.51 during the postischaemic period.


CONCLUSIONS
Exogenous administration of L-arginine improves low coronary reflow and postischaemic mechanical function.
Amrani
M
M
National Heart and Lung Institute, Harefield Hospital, Middlesex, UK.
Chester
A H
AH
Jayakumar
J
J
Schyns
C J
CJ
Yacoub
M H
MH
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects*; D006321:Heart / Q000187:drug effects / Q000503:physiopathology*; D006324:Heart Arrest, Induced; D008297:Male; D017202:Myocardial Ischemia / Q000503:physiopathology; D015425:Myocardial Reperfusion; D009569:Nitric Oxide / Q000037:antagonists & inhibitors; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D019323:omega-N-Methylarginine
D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine