© 1995 by European Society of Cardiology
Copyright © 1995, European Society of Cardiology
L-Arginine reverses low coronary reflow and enhances postischaemic recovery of cardiac mechanical function
National Heart and Lung Institute, Harefield Hospital, Harefield, Middlesex, UB9 6JH, UK
* Corresponding author. Tel. (895)828893; Fax (895)828902.
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 °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/l), Krebs plus L-arginiae (1 mmol/l) and Krebs plus L-NGmonomethylarginine (L-NMMA), a specific inhibitor of NO synthesis, (0.5 mmol/l). 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/l). 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. Conclusion: Exogenous administration of L-arginine improves low coronary reflow and postischaemic mechanical function.
KEYWORDS L-Arginine; Nitric oxide; Endothelium; Myocardial ischemia; Reperfusion; Cardioplegia; Rat heart
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