Skip to main content
Top
Published in: Basic Research in Cardiology 4/2006

01-07-2006 | REPORT

No loss of cardioprotection by postconditioning in connexin 43-deficient mice

Authors: Gerd Heusch, Astrid Büchert, Sandra Feldhaus, Rainer Schulz

Published in: Basic Research in Cardiology | Issue 4/2006

Login to get access

Abstract

In situ hearts and isolated cardiomyocytes from heterozygous connexin 43-deficient (Cx43+/−) mice cannot be protected by ischemic preconditioning or diazoxide. We have now addressed the role of connexin 43 in ischemic postconditioning (PC). Wild type (WT) and Cx43+/−mice were subjected to 30 min coronary occlusion and 120 min reperfusion, with and without a PC protocol of three cycles of 10 s coronary occlusion/10 s reperfusion. Infarct size (TTC staining) was reduced by PC from 54±5 to 37±3% of area at risk in WT. Likewise, infarct size was reduced by PC from 53±4 to 34±3% of area at risk in Cx43+/−. We conclude that connexin 43 is no prerequisite for PC’s protection. To this end, the signal transduction of ischemic preconditioning and postconditioning differs.
Literature
1.
go back to reference Boengler K, Dodoni G, Ruiz-Meana M, Cabestrero A, Rodriguez-Sinovas A, Garcia-Dorado D, Gres P, Di Lisa F, Heusch G, Schulz R (2005) Connexin 43 in cardiomyocyte mitochondria and its increase by ischemic preconditioning. Cardiovasc Res 67:234–244PubMedCrossRef Boengler K, Dodoni G, Ruiz-Meana M, Cabestrero A, Rodriguez-Sinovas A, Garcia-Dorado D, Gres P, Di Lisa F, Heusch G, Schulz R (2005) Connexin 43 in cardiomyocyte mitochondria and its increase by ischemic preconditioning. Cardiovasc Res 67:234–244PubMedCrossRef
2.
go back to reference Bolli R, Patel BS, Jeroudi MO, Lai EK, McCay PB (1988) Demonstration of free radical generation in “stunned” myocardium of intact dogs with the use of the spin trap a-phenyl N-tert-butyl nitrone. J Clin Invest 82:476–485PubMedCrossRef Bolli R, Patel BS, Jeroudi MO, Lai EK, McCay PB (1988) Demonstration of free radical generation in “stunned” myocardium of intact dogs with the use of the spin trap a-phenyl N-tert-butyl nitrone. J Clin Invest 82:476–485PubMedCrossRef
3.
5.
go back to reference Hausenloy DJ, Tsang A, Yellon DM (2005) The reperfusion injury salvage kinase pathway: a common target for both ischemic preconditioning and postconditioning. Trends Cardiovasc Med 15:69–75PubMedCrossRef Hausenloy DJ, Tsang A, Yellon DM (2005) The reperfusion injury salvage kinase pathway: a common target for both ischemic preconditioning and postconditioning. Trends Cardiovasc Med 15:69–75PubMedCrossRef
6.
go back to reference Heinzel FR, Luo Y, Li X, Boengler K, Buechert A, García-Dorado D, Di Lisa F, Schulz R, Heusch G (2005) Impairment of diazoxide-induced formation of reactive oxygen species and loss of cardioprotection in connexin 43 deficient mice. Circ Res 97:583–586PubMedCrossRef Heinzel FR, Luo Y, Li X, Boengler K, Buechert A, García-Dorado D, Di Lisa F, Schulz R, Heusch G (2005) Impairment of diazoxide-induced formation of reactive oxygen species and loss of cardioprotection in connexin 43 deficient mice. Circ Res 97:583–586PubMedCrossRef
7.
8.
go back to reference Kin H, Zhao Z-Q, Sun H-Y, Wang N-P, Corvera JS, Halkos ME, Kerendi F, Guyton RA, Vinten-Johansen J (2004) Postconditioning attenuates myocardial ischemia-reperfusion injury by inhibiting events in the early minutes of reperfusion. Cardiovasc Res 62:74–85PubMedCrossRef Kin H, Zhao Z-Q, Sun H-Y, Wang N-P, Corvera JS, Halkos ME, Kerendi F, Guyton RA, Vinten-Johansen J (2004) Postconditioning attenuates myocardial ischemia-reperfusion injury by inhibiting events in the early minutes of reperfusion. Cardiovasc Res 62:74–85PubMedCrossRef
9.
go back to reference Li X, Heinzel FR, Boengler K, Schulz R, Heusch G (2004) Role of connexin 43 in ischemic preconditioning does not involve intercellular communications through gap junctions. J Mol Cell Cardiol 36:161–163PubMedCrossRef Li X, Heinzel FR, Boengler K, Schulz R, Heusch G (2004) Role of connexin 43 in ischemic preconditioning does not involve intercellular communications through gap junctions. J Mol Cell Cardiol 36:161–163PubMedCrossRef
10.
go back to reference Penna C, Rastaldo R, Mancardi D, Raimondo S, Cappello S, Gattullo D, Losano G, Pagliario P (2006) Post-conditioning induced cardioprotection requires signaling through a redox-sensitive mechanism, mitochondrial ATP-sensitive K+ channel and protein kinase C activation. Basic Res Cardiol 101:180–189PubMedCrossRef Penna C, Rastaldo R, Mancardi D, Raimondo S, Cappello S, Gattullo D, Losano G, Pagliario P (2006) Post-conditioning induced cardioprotection requires signaling through a redox-sensitive mechanism, mitochondrial ATP-sensitive K+ channel and protein kinase C activation. Basic Res Cardiol 101:180–189PubMedCrossRef
11.
go back to reference Schulz R, Cohen MV, Behrends M, Downey JM, Heusch G (2001) Signal transduction of ischemic preconditioning. Cardiovasc Res 52:181–198PubMedCrossRef Schulz R, Cohen MV, Behrends M, Downey JM, Heusch G (2001) Signal transduction of ischemic preconditioning. Cardiovasc Res 52:181–198PubMedCrossRef
12.
13.
go back to reference Schwanke U, Konietzka I, Duschin A, Li X, Schulz R, Heusch G (2002) No ischemic preconditioning in heterozygous connexin43-deficient mice. Am J Physiol Heart Circ Physiol 283:H1740–H1742PubMed Schwanke U, Konietzka I, Duschin A, Li X, Schulz R, Heusch G (2002) No ischemic preconditioning in heterozygous connexin43-deficient mice. Am J Physiol Heart Circ Physiol 283:H1740–H1742PubMed
14.
go back to reference Schwanke U, Li X, Schulz R, Heusch G (2003) No ischemic preconditioning in heterozygous connexin 43-deficient mice: a further in vivo study. Basic Res Cardiol 98:181–182PubMed Schwanke U, Li X, Schulz R, Heusch G (2003) No ischemic preconditioning in heterozygous connexin 43-deficient mice: a further in vivo study. Basic Res Cardiol 98:181–182PubMed
15.
go back to reference Staat P, Rioufol G, Piot C, Cottin Y, Cung TT, L’Huillier I, Aupetit J-F, Bonnefoy E, Finet G, Andre-Fouet X, Ovize M (2005) Postconditioning the human heart. Circulation 112:2143–2148PubMedCrossRef Staat P, Rioufol G, Piot C, Cottin Y, Cung TT, L’Huillier I, Aupetit J-F, Bonnefoy E, Finet G, Andre-Fouet X, Ovize M (2005) Postconditioning the human heart. Circulation 112:2143–2148PubMedCrossRef
16.
go back to reference Yang X-M, Proctor JB, Cui L, Krieg T, Downey JM, Cohen MV (2004) Multiple, brief coronary occlusions during early reperfusion protect hearts by targeting cell signaling pathways. J Am Coll Cardiol 44:1103–1110PubMedCrossRef Yang X-M, Proctor JB, Cui L, Krieg T, Downey JM, Cohen MV (2004) Multiple, brief coronary occlusions during early reperfusion protect hearts by targeting cell signaling pathways. J Am Coll Cardiol 44:1103–1110PubMedCrossRef
17.
go back to reference Yellon DM, Downey JM (2003) Preconditioning the myocardium: from cellular physiology to clinical cardiology. Physiol Rev 83:1113–1151PubMed Yellon DM, Downey JM (2003) Preconditioning the myocardium: from cellular physiology to clinical cardiology. Physiol Rev 83:1113–1151PubMed
18.
go back to reference Zhao Z-Q, Corvera JS, Halkos ME, Kerendi F, Wang N-P, Guyton RA, Vinten-Johansen J (2003) Inhibition of myocardial injury by ischemic postconditioning during reperfusion: comparison with ischemic preconditioning. Am J Physiol Heart Circ Physiol 285:H579–H588PubMed Zhao Z-Q, Corvera JS, Halkos ME, Kerendi F, Wang N-P, Guyton RA, Vinten-Johansen J (2003) Inhibition of myocardial injury by ischemic postconditioning during reperfusion: comparison with ischemic preconditioning. Am J Physiol Heart Circ Physiol 285:H579–H588PubMed
Metadata
Title
No loss of cardioprotection by postconditioning in connexin 43-deficient mice
Authors
Gerd Heusch
Astrid Büchert
Sandra Feldhaus
Rainer Schulz
Publication date
01-07-2006
Publisher
Steinkopff-Verlag
Published in
Basic Research in Cardiology / Issue 4/2006
Print ISSN: 0300-8428
Electronic ISSN: 1435-1803
DOI
https://doi.org/10.1007/s00395-006-0589-0

Other articles of this Issue 4/2006

Basic Research in Cardiology 4/2006 Go to the issue