Experimental studies for the evaluation of ischemic preconditioning mechanisms in rat heart


Experimental studies for the evaluation of ischemic preconditioning mechanisms in rat heart

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Title: Experimental studies for the evaluation of ischemic preconditioning mechanisms in rat heart
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Article_Title: Experimental studies for the evaluation of ischemic preconditioning mechanisms in rat heart
Authors: Cristian Romeo Revnic, Carmen Ginghina, Floarea Revnic, Simona Botea
Affiliation: 1 University of Medicine and Pharmacy ”Carol Davila” Bucharest, Romania
2 C.C. Iliescu Institute, Department of Cardiology Bucharest, Romania
3 „Ana Aslan” National Institute of Geriatrics and Gerontology, Department of Cell and Molecular Biology, Bucharest, Romania
4 „Victor Babes” Institute, Department of Molecular Pathology, Bucharest, Romania
Abstract: Ischemic preconditioning (IPC) induced by administration of brief episodes of ischemia-reperfusion represents a protective mechanism of the heart against prolonged episodes of ischemia. The mechanism of ischemic preconditioning is far from being elucidated; there are hypotheses involving the activation of the family of protein kinase C (PKC) and also the opening of the KATP channels. Our study was designed to investigate the involvement of KATP channels and PCK activation in the mechanism of ischemic preconditioning of rat heart perfused in Langendorff system using activators of PKC (1,2-dioctanoil-sn-glycerol -DOG) and KATP channels (cromakalim) and inhibitors of PKC (cheleritrine-CHE) and of KATP channels (glibenclamide-GLY). There was an improvement of LVDP in ischemic-preconditioned hearts also a reduction of infarct size vs. controls; using the activators and inhibitors of KATP channels and PCK, it has been demonstrated that these two are involved in the pathway of the ischemia-reperfusion mechanism.
Keywords: ischemic preconditioning, ischemia-reperfusion, infarct size, Protein kinase C, Katp channels
References: Auchampach JA; Maruyama M; Gross GJ – Cardioprotective actions of potassium channel openers – European Heart J, 89-94, 1994
Auchmpach JA; Maruyama M; Cavero I; Gross GJ – Pharmacological evidence for a role of ATP-dependent potassium channels in myocardial stunning – Circulation, 86:311-319, 1992
Baines,C.P., Goto,M., and Downey,J.M. (1997). Oxygen radicals released during ischemic preconditioning contribute to cardioprotection in the rabbit myocardium. JMol. Cell Cardiol. 29, 207-216.
Bell RM; Burns DJ – Lipid activation of protein kinase C – J Biol Chem, 266:4661-4664, 1991
Bell,R.M. and Yellon,D.M. (2003). Bradykinin limits infarction when administered as an adjunct to reperfusion in mouse heart: the role of PI3K, Akt and eNOS. J. Mol. Cell Cardiol. 35, 185-193.
Cohen,M.V. and Downey,J.M. (2008). Adenosine: trigger and mediator of cardioprotection. Basic Res Cardiol. 103, 203-215
Cole WC., McPherson CD, Sontag D. – ATP-regulated K+ channels protect the myocardium against ischemia/reperfusion damage – Circ Res, 69:571-581, 1991
Garaliene V.. Ischemic Preconditionig: Its Role in Cardiporotection; Acta medica Lituanica. 2001. T.8, Nr.3
Skrzypiec-Spring M., Bartosz Grotthus, Szeląg A. and Schulz R. Isolated heart perfusion according to Langendorff—Still viable in the new millennium. Journal of Pharmacological and Toxicological Methods Volume 55, Issue 2, March-April 2007, Pages 113-126 .
Gross,E.R. and Gross,G.J. (2006). Ligand triggers of classical preconditioning and postconditioning. Cardiovascular Research 70, 212-221.
Gross,E.R. and Gross,G.J. (2006). Ligand triggers of classical preconditioning and postconditioning. Cardiovascular Research 70, 212-221.
Gross G.J., Auchampach J.A. – Role of ATP dependent potassiun channels in myocardial ischemia – Cardiovasc Res, 26:1011-1016, 1992
Gross GJ, Auchampach JA – Blockade of ATP-sensitive potassium channels prevent myocardial preconditioning in dogs – Circ Res, 70:223-233, 1992
Hausenloy,D.J., Maddock,H.L., Baxter,G.F., and Yellon,D.M. (2002). Inhibiting mitochondrial permeability transition pore opening: a new paradigm for myocardial preconditioning? Cardiovasc Res 55, 534-543.
Hille B. – Ion channels of excitable membrane – Sinauer, Sunderland, MA, USA, 1992
Kantor PF; Coatzee WA; Dennis SC; Opie LH – Effect of glybenclamide on ischemic arryhthmias – Circulation, 76 (sullp.IV) 0065, 1987
Kawamura S., Yoshida K., Miura T., Mizukami Y., Matsuzaki M., Ischemic preconditioning translocates PKC-δ and PKC-ε, which mediate functional protection in isolated rat heart, Am J Physiol Heart Circ Physiol 275: H2266-H2271, 1998.
Kim,M.Y., Kim,M.J., Yoon,I.S., Ahn,J.H., Lee,S.H., Baik,E.J., Moon,C.H., and Jung,Y.S. (2006b).Diazoxide acts more as a PKC-epsilon activator, and indirectly activates the mitochondrial K(ATP) channel conferring cardioprotection against hypoxic injury. Br J Pharmacol 149, 1059-1070.
Langendorff O; – Untersuchungen am uberlebenden Saugethuerherzen – Pflugers Arch, 61:291-332, 1985
Liu,G.S., Thornton,J., Van Winkle,D.M., Stanley,A.W., Olsson,R.A., and Downey,J.M. (1991). Protection against infarction afforded by preconditioning is mediated by A1 adenosine receptors in rabbit heart. Circulation 84, 350-356.
Miura T., Kawamura S., Goto M., Sakamoto J., Tsuchida A.., Matsuzaki A., Shimamotoa K. Effect of protein kinase C inhibitors on cardioprotection by ischemic preconditioning depends on the number of preconditioning episodes Cardiovasc Res (1998) 37 (3): 700-709. doi: 10.1016/S0008-6363(97)00244-7.
Ferdinandy,P., Schulz,R., and Baxter,G.F. (2007). Interaction of cardiovascular risk factors with myocardial ischemia/reperfusion injury, preconditioning, and postconditioning. Pharmacol Rev. 59, 418-458.
Ferrandi,C., Ballerio,R., Gaillard,P., Giachetti,C., Carboni,S., Gross,E.R., Hsu,A.K., and Gross,G.J. (2008). Delayed cardioprotection afforded by the glycogen synthase kinase 3 inhibitor SB-216763 occurs via a. Am J Physiol Heart Circ Physiol 294, H1497-H1500.
Herbert, J. M., Augereau J.M., Gleye J., and Maffrand J.P. Chelerythrine is a potent and specific inhibitor of protein kinase C. Biochem. Biophys. Res. Commun. 172: 993-999, 1990.
Klein,H.H., Puschmann,S., Schaper,J., and Schaper,W. (1981). The mechanism of the tetrazolium reaction in identifying experimental myocardial infarction. Virchows Archiv A Pathological Anatomy and Histology 393, 287-297.
Maddock,H.L., Mocanu,M.M., and Yellon,D.M. (2002). Adenosine A(3) receptor activation protects the myocardium from reperfusion/reoxygenation injury. Am J Physiol Heart Circ Physiol 283, H1307-H1313.
Malaisse WJ; Herchuelz A – Nutritional regulation of K+ conductance: An unsettled aspect of pancreatic B-cell physiology – in “Biochemical actions of hormones”, vol IX, 69-92, Acad Press, 1982
ME Speechly-Dick, MM Mocanu, DM Yellon, Protein kinase C. Its role in ischemic preconditioning in the rat Circ. Res. 1994;75;586-590.
Murry,C.E., Jennings,R.B., and Reimer,K.A. (1986). Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation 74, 1124-1136.
Nishizuka, Y. Intracellular signaling by hydrolysis of phospholipids and activation of protein kinase C. Science 258: 607-614, 1992.
Noma A. – ATP-regulated K+ channels in cardiac muscle – Nature, 305:147-148, 1983
Li GC; Vasquez JA; Gallacher CP; Lucchesi BR – Myocardial protection with preconditioning –
Revnic C.R., Ginghina C., Nica A., Revnic F. The impact of ischemia/reperfusion upon ionic transport (Na,,K) and functional parameters in rat heart From: New approaches in coronary artery disease, Proceedings of 8th International Congress on Coronary Artery Disease,Oct.11-14,2009,Prague,Czech Republic, Medimond, International Proceedings, pp.283-286
Sanguinetti MC; Scott AL; Zingaro GJ; Siegl PKS – Cromakalim activates ATP-sensitive K+ current in cardiac muscle – Proc Natl Acad Sci USA, 85:8360-8364, 1988
Toombs CF; Moore TL; Shebuski RJ – Limitation of infarct size in the rabbit by ischemic preconditioning is reversible with glibenclamide – Cardiovasc Res, 27:617-622, 1993
Circulation, 82:609-619, 1990
Tong H., Chen W., Steenbergen C., Murphy E., Ischemic Preconditioning Activates Phosphatidylinositol-3-Kinase Upstream of Protein Kinase C. Circulation Research. 2000;87:309.
Thornton JD, Thornton CS, Sterling DL; Downey JM – Blockade of ATP-sensitive potassium channels increases infarct size but does not prevent preconditioning in rabbit hearts – Circ res, 72:44-49, 1993.
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Correspondence: Cristian Romeo Revnic, UMF Carol Davila, Bucharest, Cardiology Department, C.C. Iliescu Institute Bucharest, No. 3 Aleea Dealul Macinului Str, Bl A44, Sc.C, Ap.39 Sector 6, Zip code 77416, Email: kityrom@yahoo.com

Read full article
Article Title: Experimental studies for the evaluation of ischemic preconditioning mechanisms in rat heart
Authors: Cristian Romeo Revnic, Carmen Ginghina, Floarea Revnic, Simona Botea
Affiliation: 1 University of Medicine and Pharmacy ”Carol Davila” Bucharest, Romania
2 C.C. Iliescu Institute, Department of Cardiology Bucharest, Romania
3 „Ana Aslan” National Institute of Geriatrics and Gerontology, Department of Cell and Molecular Biology, Bucharest, Romania
4 „Victor Babes” Institute, Department of Molecular Pathology, Bucharest, Romania
Abstract: Ischemic preconditioning (IPC) induced by administration of brief episodes of ischemia-reperfusion represents a protective mechanism of the heart against prolonged episodes of ischemia. The mechanism of ischemic preconditioning is far from being elucidated; there are hypotheses involving the activation of the family of protein kinase C (PKC) and also the opening of the KATP channels. Our study was designed to investigate the involvement of KATP channels and PCK activation in the mechanism of ischemic preconditioning of rat heart perfused in Langendorff system using activators of PKC (1,2-dioctanoil-sn-glycerol -DOG) and KATP channels (cromakalim) and inhibitors of PKC (cheleritrine-CHE) and of KATP channels (glibenclamide-GLY). There was an improvement of LVDP in ischemic-preconditioned hearts also a reduction of infarct size vs. controls; using the activators and inhibitors of KATP channels and PCK, it has been demonstrated that these two are involved in the pathway of the ischemia-reperfusion mechanism.
Keywords: ischemic preconditioning, ischemia-reperfusion, infarct size, Protein kinase C, Katp channels
References: Auchampach JA; Maruyama M; Gross GJ – Cardioprotective actions of potassium channel openers – European Heart J, 89-94, 1994
Auchmpach JA; Maruyama M; Cavero I; Gross GJ – Pharmacological evidence for a role of ATP-dependent potassium channels in myocardial stunning – Circulation, 86:311-319, 1992
Baines,C.P., Goto,M., and Downey,J.M. (1997). Oxygen radicals released during ischemic preconditioning contribute to cardioprotection in the rabbit myocardium. JMol. Cell Cardiol. 29, 207-216.
Bell RM; Burns DJ – Lipid activation of protein kinase C – J Biol Chem, 266:4661-4664, 1991
Bell,R.M. and Yellon,D.M. (2003). Bradykinin limits infarction when administered as an adjunct to reperfusion in mouse heart: the role of PI3K, Akt and eNOS. J. Mol. Cell Cardiol. 35, 185-193.
Cohen,M.V. and Downey,J.M. (2008). Adenosine: trigger and mediator of cardioprotection. Basic Res Cardiol. 103, 203-215
Cole WC., McPherson CD, Sontag D. – ATP-regulated K+ channels protect the myocardium against ischemia/reperfusion damage – Circ Res, 69:571-581, 1991
Garaliene V.. Ischemic Preconditionig: Its Role in Cardiporotection; Acta medica Lituanica. 2001. T.8, Nr.3
Skrzypiec-Spring M., Bartosz Grotthus, Szeląg A. and Schulz R. Isolated heart perfusion according to Langendorff—Still viable in the new millennium. Journal of Pharmacological and Toxicological Methods Volume 55, Issue 2, March-April 2007, Pages 113-126 .
Gross,E.R. and Gross,G.J. (2006). Ligand triggers of classical preconditioning and postconditioning. Cardiovascular Research 70, 212-221.
Gross,E.R. and Gross,G.J. (2006). Ligand triggers of classical preconditioning and postconditioning. Cardiovascular Research 70, 212-221.
Gross G.J., Auchampach J.A. – Role of ATP dependent potassiun channels in myocardial ischemia – Cardiovasc Res, 26:1011-1016, 1992
Gross GJ, Auchampach JA – Blockade of ATP-sensitive potassium channels prevent myocardial preconditioning in dogs – Circ Res, 70:223-233, 1992
Hausenloy,D.J., Maddock,H.L., Baxter,G.F., and Yellon,D.M. (2002). Inhibiting mitochondrial permeability transition pore opening: a new paradigm for myocardial preconditioning? Cardiovasc Res 55, 534-543.
Hille B. – Ion channels of excitable membrane – Sinauer, Sunderland, MA, USA, 1992
Kantor PF; Coatzee WA; Dennis SC; Opie LH – Effect of glybenclamide on ischemic arryhthmias – Circulation, 76 (sullp.IV) 0065, 1987
Kawamura S., Yoshida K., Miura T., Mizukami Y., Matsuzaki M., Ischemic preconditioning translocates PKC-δ and PKC-ε, which mediate functional protection in isolated rat heart, Am J Physiol Heart Circ Physiol 275: H2266-H2271, 1998.
Kim,M.Y., Kim,M.J., Yoon,I.S., Ahn,J.H., Lee,S.H., Baik,E.J., Moon,C.H., and Jung,Y.S. (2006b).Diazoxide acts more as a PKC-epsilon activator, and indirectly activates the mitochondrial K(ATP) channel conferring cardioprotection against hypoxic injury. Br J Pharmacol 149, 1059-1070.
Langendorff O; – Untersuchungen am uberlebenden Saugethuerherzen – Pflugers Arch, 61:291-332, 1985
Liu,G.S., Thornton,J., Van Winkle,D.M., Stanley,A.W., Olsson,R.A., and Downey,J.M. (1991). Protection against infarction afforded by preconditioning is mediated by A1 adenosine receptors in rabbit heart. Circulation 84, 350-356.
Miura T., Kawamura S., Goto M., Sakamoto J., Tsuchida A.., Matsuzaki A., Shimamotoa K. Effect of protein kinase C inhibitors on cardioprotection by ischemic preconditioning depends on the number of preconditioning episodes Cardiovasc Res (1998) 37 (3): 700-709. doi: 10.1016/S0008-6363(97)00244-7.
Ferdinandy,P., Schulz,R., and Baxter,G.F. (2007). Interaction of cardiovascular risk factors with myocardial ischemia/reperfusion injury, preconditioning, and postconditioning. Pharmacol Rev. 59, 418-458.
Ferrandi,C., Ballerio,R., Gaillard,P., Giachetti,C., Carboni,S., Gross,E.R., Hsu,A.K., and Gross,G.J. (2008). Delayed cardioprotection afforded by the glycogen synthase kinase 3 inhibitor SB-216763 occurs via a. Am J Physiol Heart Circ Physiol 294, H1497-H1500.
Herbert, J. M., Augereau J.M., Gleye J., and Maffrand J.P. Chelerythrine is a potent and specific inhibitor of protein kinase C. Biochem. Biophys. Res. Commun. 172: 993-999, 1990.
Klein,H.H., Puschmann,S., Schaper,J., and Schaper,W. (1981). The mechanism of the tetrazolium reaction in identifying experimental myocardial infarction. Virchows Archiv A Pathological Anatomy and Histology 393, 287-297.
Maddock,H.L., Mocanu,M.M., and Yellon,D.M. (2002). Adenosine A(3) receptor activation protects the myocardium from reperfusion/reoxygenation injury. Am J Physiol Heart Circ Physiol 283, H1307-H1313.
Malaisse WJ; Herchuelz A – Nutritional regulation of K+ conductance: An unsettled aspect of pancreatic B-cell physiology – in “Biochemical actions of hormones”, vol IX, 69-92, Acad Press, 1982
ME Speechly-Dick, MM Mocanu, DM Yellon, Protein kinase C. Its role in ischemic preconditioning in the rat Circ. Res. 1994;75;586-590.
Murry,C.E., Jennings,R.B., and Reimer,K.A. (1986). Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation 74, 1124-1136.
Nishizuka, Y. Intracellular signaling by hydrolysis of phospholipids and activation of protein kinase C. Science 258: 607-614, 1992.
Noma A. – ATP-regulated K+ channels in cardiac muscle – Nature, 305:147-148, 1983
Li GC; Vasquez JA; Gallacher CP; Lucchesi BR – Myocardial protection with preconditioning –
Revnic C.R., Ginghina C., Nica A., Revnic F. The impact of ischemia/reperfusion upon ionic transport (Na,,K) and functional parameters in rat heart From: New approaches in coronary artery disease, Proceedings of 8th International Congress on Coronary Artery Disease,Oct.11-14,2009,Prague,Czech Republic, Medimond, International Proceedings, pp.283-286
Sanguinetti MC; Scott AL; Zingaro GJ; Siegl PKS – Cromakalim activates ATP-sensitive K+ current in cardiac muscle – Proc Natl Acad Sci USA, 85:8360-8364, 1988
Toombs CF; Moore TL; Shebuski RJ – Limitation of infarct size in the rabbit by ischemic preconditioning is reversible with glibenclamide – Cardiovasc Res, 27:617-622, 1993
Circulation, 82:609-619, 1990
Tong H., Chen W., Steenbergen C., Murphy E., Ischemic Preconditioning Activates Phosphatidylinositol-3-Kinase Upstream of Protein Kinase C. Circulation Research. 2000;87:309.
Thornton JD, Thornton CS, Sterling DL; Downey JM – Blockade of ATP-sensitive potassium channels increases infarct size but does not prevent preconditioning in rabbit hearts – Circ res, 72:44-49, 1993.
*Correspondence: Cristian Romeo Revnic, UMF Carol Davila, Bucharest, Cardiology Department, C.C. Iliescu Institute Bucharest, No. 3 Aleea Dealul Macinului Str, Bl A44, Sc.C, Ap.39 Sector 6, Zip code 77416, Email: kityrom@yahoo.com