TY - JOUR
T1 - Nitroglycerin as a nitric oxide donor accelerates lipid peroxidation but preserves ventricular function in a canine model of orthotopic heart transplantation
AU - Tanoue, Y.
AU - Morita, S.
AU - Ochiai, Y.
AU - Haraguchi, N.
AU - Tominaga, R.
AU - Kawachi, Y.
AU - Yasui, H.
N1 - Funding Information:
All animals received humane care in compliance with the “Principles of Laboratory Animal Care” formulated by the National Society for Medical Research and the “Guide for the Care and Use of Laboratory Animals” prepared by the Institute of Laboratory Animal Resources and published by the National Institutes of Health (NIH Publication No. 86-23, revised 1985). This experiment was reviewed by the Committee of the Ethics on Animal Experiment in the Faculty of Medicine, Kyushu University, and carried out under the control of the Guidelines for Animal Experimentation in the Faculty of Medicine, Kyushu University and The Law (No. 105) and Notification (No. 6) of the Government.
PY - 1999
Y1 - 1999
N2 - Background: Nitric oxide has cardioprotective effects through several mechanisms. However, nitric oxide may have deleterious effects in the presence of superoxide because it is converted to peroxynitrite, which then initiates lipid peroxidation. Using a canine model of orthotopic heart transplantation, we examined whether adding an organic nitric oxide donor, nitroglycerin, to preservation solution elicits lipid peroxidation after reperfusion and causes deleterious effects on coronary endothelial function and left ventricular function. Methods and results: The donor heart was preserved for 24 hours in cold University of Wisconsin solution with nitroglycerin (0.1 mg/mL) supplementation (group NTG, n = 8) or in standard University of Wisconsin solution (group C, n = 8). After reperfusion, changes of coronary resistance were measured during the infusion of acetylcholine (0.1 mg/min)and of sodium nitroprusside (1 mg/min), and percent coronary relaxation was calculated. Left ventricular function was evaluated by pressure-volume relations with the use of a conductance catheter, thereby deriving the slopes of end-systolic pressure-volume relation, stroke work- end-diastolic volume relation, and maximum rate of change of left ventricular pressure-end-diastolic volume relation. Serum lipid peroxide level was measured. Percent coronary relaxation was similar for the 2 groups. The slopes of end-systolic pressure-volume relation, stroke work-end-diastolic volume relation, and maximum rate of change of left ventricular pressure-end- diastolic volume relation in group NTG were significantly higher than those in group C. On the other side, serum lipid peroxide level in group NTG was significantly higher than that in group C. Conclusions: Nitroglycerin may have detrimental effects evidenced by the increase in lipid peroxidation, which implied peroxynitrite formation. However, the overall effect of nitroglycerin was cardioprotective. Although the exact mechanism is yet to be clarified, the superb cardioprotective effect of nitroglycerin overwhelms the exaggeration of lipid peroxidation.
AB - Background: Nitric oxide has cardioprotective effects through several mechanisms. However, nitric oxide may have deleterious effects in the presence of superoxide because it is converted to peroxynitrite, which then initiates lipid peroxidation. Using a canine model of orthotopic heart transplantation, we examined whether adding an organic nitric oxide donor, nitroglycerin, to preservation solution elicits lipid peroxidation after reperfusion and causes deleterious effects on coronary endothelial function and left ventricular function. Methods and results: The donor heart was preserved for 24 hours in cold University of Wisconsin solution with nitroglycerin (0.1 mg/mL) supplementation (group NTG, n = 8) or in standard University of Wisconsin solution (group C, n = 8). After reperfusion, changes of coronary resistance were measured during the infusion of acetylcholine (0.1 mg/min)and of sodium nitroprusside (1 mg/min), and percent coronary relaxation was calculated. Left ventricular function was evaluated by pressure-volume relations with the use of a conductance catheter, thereby deriving the slopes of end-systolic pressure-volume relation, stroke work- end-diastolic volume relation, and maximum rate of change of left ventricular pressure-end-diastolic volume relation. Serum lipid peroxide level was measured. Percent coronary relaxation was similar for the 2 groups. The slopes of end-systolic pressure-volume relation, stroke work-end-diastolic volume relation, and maximum rate of change of left ventricular pressure-end- diastolic volume relation in group NTG were significantly higher than those in group C. On the other side, serum lipid peroxide level in group NTG was significantly higher than that in group C. Conclusions: Nitroglycerin may have detrimental effects evidenced by the increase in lipid peroxidation, which implied peroxynitrite formation. However, the overall effect of nitroglycerin was cardioprotective. Although the exact mechanism is yet to be clarified, the superb cardioprotective effect of nitroglycerin overwhelms the exaggeration of lipid peroxidation.
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U2 - 10.1016/S0022-5223(99)70195-9
DO - 10.1016/S0022-5223(99)70195-9
M3 - Article
C2 - 10469974
AN - SCOPUS:0032887185
VL - 118
SP - 547
EP - 556
JO - Journal of Thoracic and Cardiovascular Surgery
JF - Journal of Thoracic and Cardiovascular Surgery
SN - 0022-5223
IS - 3
ER -