Role of the L-arginine/nitric oxide pathway in ischaemic/reoxygenation injury of the human myocardium.
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 degrees 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), N(G)-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 microM), 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.
Zhang
J G
JG
Department of Surgery/Division of Cardiac Surgery, University of Leicester, Glenfield Hospital, Leicester LE3 9QP, UK.
Galiñanes
M
M
D000704:Analysis of Variance; D001120:Arginine / Q000187:drug effects / Q000502:physiology*; D046508:Culture Techniques; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005562:Formazans / Q000378:metabolism; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D015428:Myocardial Reperfusion Injury / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009603:Nitroso Compounds / Q000494:pharmacology; D013778:Tetrazolium Salts / Q000378:metabolism; D014022:Tissue Survival / Q000187:drug effects; D014443:Tyrosine / Q000032:analysis
D004791:Enzyme Inhibitors; D005562:Formazans; D020030:Nitric Oxide Donors; D009603:Nitroso Compounds; D013778:Tetrazolium Salts; D009569:Nitric Oxide; D014443:Tyrosine; D001120:Arginine; D007770:L-Lactate Dehydrogenase; D019331:NG-Nitroarginine Methyl Ester