caa a22 4500 477119646 CHVBK 20180405111632.0 cr unu---uuuuu 170330e19960301xx s 000 0 eng 10.1007/BF00240047 doi (NATIONALLICENCE)springer-10.1007/BF00240047 Uncoupling of mitochondrial oxidative phosphorylation alters lipid peroxidation-derived free radical production but not recovery of postischemic rat hearts and post-hypoxic endothelial cells [Elektronische Daten] [I. Blasig, B. Dickens, W. Weglicki, J. Kramer] The contribution of mitochondrial free radical production towards the initiation of lipid peroxidation (LPO) and functional injury in the post-ischemic heart is unclear. Using the isolated rat heart model, the effects of the uncoupler of mitochondrial oxidative phosphorylation dinitrophenol (DNP, 50 μM final) on post-ischemic lipid peroxidation-derived free radical production and functional recovery were assessed. Hearts were subjected to 30 min total global ischemia followed by 15 min of reperfusion in the presence of DNP. As expected, DNP enhanced oxygen consumption before (11.3 ± 0.9 μmol/min, p < 0.001) and during reperfusion (at 10 min: 7.9 ± 0.7 μumol/min), compared to the heart with control treatment (8.2 ± 0.5 and 6.7 ± 0.3, respectively). This effect was only associated with a higher incidence of ventricular tachycardia during reperfusion (80 vs. 50% for control treatment, p < 0.05). Electron spin resonance spectroscopy (ESR) and spin trapping with u.-phenyl-tert-butylnitrone (PBN, 3 mM final) were used to monitor free radical generation during reperfusion. The vascular concentration of PBN-radical adducts (untreated: 6.4 ±1.0 nM, at 10 min) decreased in the presence of DNP (1.7 ± 0.4 nM, p < 0.01). The radical concentration inversely correlated with myocardial oxygen consumption. Total liberation of free radical adducts during the initial 10 min of reperfusion was reduced by DNP (0.59 ± 0.09 nmol, p < 0.01) compared to the respective control treatment (1.26 ± 0.16 nmol). Similar effects, prevention of PBN adduct formation and unchanged viability in the presence of DNP, were obtained with endothelial cells during post-hypoxic reoxygenation. Since inhibition of mitochondrial phosphorylation can inhibit the formation of LPO-derived free radicals after an ischemic/hypoxic interval, mitochondria may represent an important source of free radicals capable of initiating lipid peroxidative injury during reperfusion/reoxygenation. (Mol Cell Biochem 160/161: 167-177, 1996) Kluwer Academic Publishers, 1996 ESR spin trapping nationallicence lipid radicals nationallicence mitochondrial uncoupling nationallicence oxygen consumption nationallicence myocardial reperfusion nationallicence endothelial cell reoxygenation nationallicence Blasig I. Forschungsinstitut für Molekulare Pharmakologie, Forschungsverbund Berlin e.V., Alfred-Kowalke-Str 4, D-10315, Berlin, Germany aut Dickens B. Departments of Medicine and Physiology, Division of Experimental Medicine, The George Washington University Medical Center, 2300 Eye St, N.W., 20037, Washington, D. C., USA aut Weglicki W. Departments of Medicine and Physiology, Division of Experimental Medicine, The George Washington University Medical Center, 2300 Eye St, N.W., 20037, Washington, D. C., USA aut Kramer J. Departments of Medicine and Physiology, Division of Experimental Medicine, The George Washington University Medical Center, 2300 Eye St, N.W., 20037, Washington, D. C., USA aut Molecular and Cellular Biochemistry Kluwer Academic Publishers; http://www.wkap.nl 160-161/1(1996-03-01), 167-177 0300-8177 160-161:1<167 1996 160-161 11010 https://doi.org/10.1007/BF00240047 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF00240047 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Blasig I. Forschungsinstitut für Molekulare Pharmakologie, Forschungsverbund Berlin e.V., Alfred-Kowalke-Str 4, D-10315, Berlin, Germany aut NATIONALLICENCE 700 1- Dickens B. Departments of Medicine and Physiology, Division of Experimental Medicine, The George Washington University Medical Center, 2300 Eye St, N.W., 20037, Washington, D. C., USA aut NATIONALLICENCE 700 1- Weglicki W. Departments of Medicine and Physiology, Division of Experimental Medicine, The George Washington University Medical Center, 2300 Eye St, N.W., 20037, Washington, D. C., USA aut NATIONALLICENCE 700 1- Kramer J. Departments of Medicine and Physiology, Division of Experimental Medicine, The George Washington University Medical Center, 2300 Eye St, N.W., 20037, Washington, D. C., USA aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Kluwer Academic Publishers; http://www.wkap.nl 160-161/1(1996-03-01), 167-177 0300-8177 160-161:1<167 1996 160-161 11010 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer