QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: jpet.106.110262v1 319/3/1405    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chen, Q. Articles by Lesnefsky, E. J. Search for Related Content PubMed PubMed Citation Articles by Chen, Q. Articles by Lesnefsky, E. J.

CARDIOVASCULAR

Reversible Blockade of Electron Transport during Ischemia Protects Mitochondria and Decreases Myocardial Injury following Reperfusion

Departments of Medicine, Divisions of Cardiology (Q.C., S.M., E.J.L.) and Clinical Pharmacology (C.L.H.), and Pharmacology (C.L.H.), School of Medicine, Case Western Reserve University, Cleveland, Ohio; and Medical Service, Louis Stokes Veterans Affairs Medical Center, Cleveland, Ohio (E.J.L.)

Cardiac mitochondria sustain damage during ischemia and reperfusion, contributing to cell death. The reversible blockade of electron transport during ischemia with amobarbital, an inhibitor at the rotenone site of complex I, protects mitochondria against ischemic damage. Amobarbital treatment immediately before ischemia was used to test the hypothesis that damage to mitochondrial respiration occurs mainly during ischemia and that protection of mitochondria during ischemia leads to decreased cardiac injury with reperfusion. Langendorff-perfused Fischer-344 rat hearts were treated with amobarbital (2.5 mM) or vehicle for 1 min immediately before 25 min of global ischemia. Both groups were reperfused for 30 min without additional treatment. Subsarcolemmal (SSM) and interfibrillar (IFM) populations of mitochondria were isolated after reperfusion. Ischemia and reperfusion decreased state 3 and increased state 4 respiration rate in both SSM and IFM. Amobarbital treatment protected oxidative phosphorylation measured following reperfusion and improved the coupling of respiration. Cytochrome c content measured in SSM and IFM following reperfusion decreased in untreated, but not in amobarbital-treated, hearts. H₂O₂ release from SSM and IFM isolated from amobarbital-treated hearts during reperfusion was markedly decreased. Amobarbital treatment before ischemia improved recovery of contractile function (percentage of preischemic developed pressure: untreated 51 ± 4%, n = 12; amobarbital 70 ± 4%, n = 11, p < 0.01) and substantially reduced infarct size (untreated 32 ± 2%, n = 7; amobarbital 13 ± 2%, n = 7, p < 0.01). Thus, mitochondrial damage occurs mainly during ischemia rather than during reperfusion. Reperfusion in the setting of preserved mitochondrial respiratory function attenuates the mitochondrial release of reactive oxygen species, enhances contractile recovery, and decreases myocardial infarct size.

Address correspondence to: Dr. Edward J. Lesnefsky, Cardiology Section, Medical Service 111(W), Louis Stokes VA Medical Center, 10701 East Boulevard, Cleveland, OH 44106. E-mail: edward.lesnefsky{at}case.edu

This article has been cited by other articles:

				Q. Sun, Z. Kang, J. Cai, W. Liu, Y. Liu, J. H. Zhang, P. J. Denoble, H. Tao, and X. Sun Hydrogen-Rich Saline Protects Myocardium Against Ischemia/Reperfusion Injury in Rats Experimental Biology and Medicine, October 1, 2009; 234(10): 1212 - 1219. [Abstract] [Full Text] [PDF]

				M. L. Hudes, J. C. McCann, and B. N. Ames Unusual clustering of coefficients of variation in published articles from a medical biochemistry department in India FASEB J, March 1, 2009; 23(3): 689 - 703. [Abstract] [Full Text] [PDF]

				U. B. Hendgen-Cotta, M. W. Merx, S. Shiva, J. Schmitz, S. Becher, J. P. Klare, H.-J. Steinhoff, A. Goedecke, J. Schrader, M. T. Gladwin, et al. Nitrite reductase activity of myoglobin regulates respiration and cellular viability in myocardial ischemia-reperfusion injury PNAS, July 22, 2008; 105(29): 10256 - 10261. [Abstract] [Full Text] [PDF]

				Q. Chen, S. Moghaddas, C. L. Hoppel, and E. J. Lesnefsky Ischemic defects in the electron transport chain increase the production of reactive oxygen species from isolated rat heart mitochondria Am J Physiol Cell Physiol, February 1, 2008; 294(2): C460 - C466. [Abstract] [Full Text] [PDF]

				M. Aldakkak, D. F. Stowe, Q. Chen, E. J. Lesnefsky, and A. K.S. Camara Inhibited mitochondrial respiration by amobarbital during cardiac ischaemia improves redox state and reduces matrix Ca2+ overload and ROS release Cardiovasc Res, January 15, 2008; 77(2): 406 - 415. [Abstract] [Full Text] [PDF]

				N. M. Hadzimichalis, S. S. Baliga, R. Golfetti, K. M. Jaques, B. L. Firestein, and G. F. Merrill Acetaminophen-mediated cardioprotection via inhibition of the mitochondrial permeability transition pore-induced apoptotic pathway Am J Physiol Heart Circ Physiol, December 1, 2007; 293(6): H3348 - H3355. [Abstract] [Full Text] [PDF]

				J. W. Elrod, J. W. Calvert, J. Morrison, J. E. Doeller, D. W. Kraus, L. Tao, X. Jiao, R. Scalia, L. Kiss, C. Szabo, et al. Hydrogen sulfide attenuates myocardial ischemia-reperfusion injury by preservation of mitochondrial function PNAS, September 25, 2007; 104(39): 15560 - 15565. [Abstract] [Full Text] [PDF]

				S. Shiva, M. N. Sack, J. J. Greer, M. Duranski, L. A. Ringwood, L. Burwell, X. Wang, P. H. MacArthur, A. Shoja, N. Raghavachari, et al. Nitrite augments tolerance to ischemia/reperfusion injury via the modulation of mitochondrial electron transfer J. Exp. Med., September 3, 2007; 204(9): 2089 - 2102. [Abstract] [Full Text] [PDF]

				C. Tanaka-Esposito, Q. Chen, S. Moghaddas, and E. J. Lesnefsky Ischemic preconditioning does not protect via blockade of electron transport J Appl Physiol, August 1, 2007; 103(2): 623 - 628. [Abstract] [Full Text] [PDF]

				C. Dezfulian, N. Raat, S. Shiva, and M. T. Gladwin Role of the anion nitrite in ischemia-reperfusion cytoprotection and therapeutics Cardiovasc Res, July 15, 2007; 75(2): 327 - 338. [Abstract] [Full Text] [PDF]