The role of the L-arginine/nitric oxide (NO) pathway in myocardial ischaemic/reperfusion injury remains controversial in experimental animal models. The aim of the present studies was to investigate the role of this pathway in the human myocardium. Myocardial specimens from right atrial appendages of patients undergoing elective coronary bypass graft surgery were incubated in crystalloid buffer at 37 °C and subjected to 120 min of simulated ischaemia followed by 120 min of reoxygenation. Tested drugs were added 15 min before ischaemia, and maintained during ischaemia and throughout reoxygenation. Ischaemia resulted in severe myocardial damage, as assessed by the leakage of lactate dehydrogenase (LDH) into the incubation medium and by the capacity of the tissue to reduce 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) to formazan product. L-Arginine (10 mM), a precursor of NO, significantly decreased LDH leakage (from 9.0±0.6 to 5.3±0.3 units/g wet wt; P < 0.05), but had no effect on MTT reduction or oxygen consumption. D-Arginine (10 mM), NG-nitro-L-arginine methyl ester (L-NAME; 0.5 mM), an NO synthase inhibitor, and S-nitroso-N-acetylpenicillamine (at 1, 100, 500 and 1000 µM), an NO donor, had no significant effects on the measured indices, and L-NAME did not reverse the protection afforded by L-arginine against LDH leakage. In addition, the formation of nitrotyrosine was not influenced by ischaemia/reoxygenation alone or by the agents investigated. In conclusion, these data suggest that L-arginine affords modest protection against ischaemic/reoxygenation injury of the human myocardium, an action that is NO-independent, and that NO metabolism does not play a significant role in this model.
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November 07 2000
Role of the l-arginine/nitric oxide pathway in ischaemic/reoxygenation injury of the human myocardium
Jin-Gang ZHANG;
Jin-Gang ZHANG
1
1Department of Surgery/Division of Cardiac Surgery, University of Leicester, Glenfield Hospital, Leicester LE3 9QP, U.K.
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Manuel GALIÑANES
1Department of Surgery/Division of Cardiac Surgery, University of Leicester, Glenfield Hospital, Leicester LE3 9QP, U.K.
Correspondence: Professor Manuel Galiñanes (e-mail [email protected]).
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Publisher: Portland Press Ltd
Received:
March 24 2000
Revision Received:
May 24 2000
Accepted:
August 07 2000
Online ISSN: 1470-8736
Print ISSN: 0143-5221
The Biochemical Society and the Medical Research Society © 2000
2000
Clin Sci (Lond) (2000) 99 (6): 497–504.
Article history
Received:
March 24 2000
Revision Received:
May 24 2000
Accepted:
August 07 2000
Citation
Jin-Gang ZHANG, Manuel GALIÑANES; Role of the l-arginine/nitric oxide pathway in ischaemic/reoxygenation injury of the human myocardium. Clin Sci (Lond) 1 December 2000; 99 (6): 497–504. doi: https://doi.org/10.1042/cs0990497
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