© 1996 American Heart Association, Inc.
Articles |
No Prevention of Ischemic Preconditioning by the Protein Kinase C Inhibitor Staurosporine in Swine
Abteilung fur Pathophysiologie, Zentrum fur Innere Medizin des Universitatsklinikum Essen (Germany).
Correspondence to Prof Dr Gerd Heusch, FESC, FACC, Abteilung fur Pathophysiologie, Zentrum fur Innere Medizin, Universitatsklinikum Essen, Hufelandstraße 55, 45122 Essen, Germany.
The delay of infarct size development by ischemic preconditioning involves the activation of protein kinase C in rats and rabbits. In dogs the role of protein kinase C in ischemic preconditioning is controversial. We investigated whether or not the activation of protein kinase C is a prerequisite for ischemic preconditioning in swine. Swine were used, since they are large mammals and since infarct development in this species, due to the lack of an innate collateral circulation, is similar to that in humans. In 20 enflurane-anesthetized swine, the proximal left anterior descending coronary artery was cannulated and perfused from an extracorporeal circuit. The impact of continuous intracoronary infusion of 10-7 mol/L staurosporine, a potent protein kinase C inhibitor, on global and regional myocardial function (sonomicrometry), subendocardial blood flow (ENDO, microspheres), and infarct size (IS, triphenyltetrazolium chloride staining after 120 minutes of reperfusion) was analyzed. Staurosporine (10-7 mol/L) abolished the 1.6-fold increase in coronary arterial resistance in response to 10-6 mol/L IC 4ß-phorbol 12-myristate 13-acetate, a potent protein kinase C activator. In the presence of staurosporine, 90 minutes of low-flow ischemia at an ENDO of 0.05±0.04 (mean±SD) mL·min-1·g-1 resulted in an IS of 12.5±8.6% (n=10) of the area at risk. Also, in the presence of staurosporine, ischemic preconditioning by a cycle of 10 minutes of low-flow ischemia followed by 15 minutes reperfusion before the 90 minutes sustained ischemic period (ENDO, 0.05±0.03 mL·min-1·g-1) reduced IS to 3.3±3.4% (n=10, P<.05). The protein kinase C inhibitor staurosporine does not prevent ischemic preconditioning in swine.
Key Words: myocardial ischemia • reperfusion • ischemic preconditioning • protein kinase C • staurosporine • swine
This article has been cited by other articles:
 |
|
 |
|
  X. Zhu, B. Liu, S. Zhou, Y.-R. Chen, Y. Deng, J. L. Zweier, and G. He Ischemic preconditioning prevents in vivo hyperoxygenation in postischemic myocardium with preservation of mitochondrial oxygen consumption Am J Physiol Heart Circ Physiol, September 1, 2007; 293(3): H1442 - H1450. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Kohro, Q. H. Hogan, D. C. Warltier, and Z. J. Bosnjak Protein Kinase C Inhibitors Produce Mitochondrial Flavoprotein Oxidation in Cardiac Myocytes Anesth. Analg., November 1, 2004; 99(5): 1316 - 1322. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Hassouna, B. M. Matata, and M. Galinanes PKC-{epsilon} is upstream and PKC-{alpha} is downstream of mitoKATP channels in the signal transduction pathway of ischemic preconditioning of human myocardium Am J Physiol Cell Physiol, November 1, 2004; 287(5): C1418 - C1425. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Weinbrenner, F. Schulze, L. Sarvary, and R. H Strasser Remote preconditioning by infrarenal aortic occlusion is operative via {delta}1-opioid receptors and free radicals in vivo in the rat heart Cardiovasc Res, February 15, 2004; 61(3): 591 - 599. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Zaugg, E. Lucchinetti, M. Uecker, T. Pasch, and M. C. Schaub Anaesthetics and cardiac preconditioning. Part I. Signalling and cytoprotective mechanisms Br. J. Anaesth., October 1, 2003; 91(4): 551 - 565. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Singh and H. K. Saini Resident Cardiac Mast Cells and Ischemia-Reperfusion Injury Journal of Cardiovascular Pharmacology and Therapeutics, June 1, 2003; 8(2): 135 - 148. [Abstract] [PDF]
|
|
|
|
|
|
S. Belosjorow, I. Bolle, A. Duschin, G. Heusch, and R. Schulz TNF-alpha antibodies are as effective as ischemic preconditioning in reducing infarct size in rabbits Am J Physiol Heart Circ Physiol, March 1, 2003; 284(3): H927 - H930. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Ladilov, H. Maxeiner, C. Wolf, C. Schafer, K. Meuter, and H. M. Piper Role of protein phosphatases in hypoxic preconditioning Am J Physiol Heart Circ Physiol, September 1, 2002; 283(3): H1092 - H1098. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Tanoue, P. Herijgers, B. Meuris, E. Verbeken, V. Leunens, M. Lox, and W. Flameng Ischemic preconditioning reduces unloaded myocardial oxygen consumption in an in-vivo sheep model* Cardiovasc Res, August 15, 2002; 55(3): 633 - 641. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. A. Kloner and R. B. Jennings Consequences of Brief Ischemia: Stunning, Preconditioning, and Their Clinical Implications: Part 2 Circulation, December 18, 2001; 104(25): 3158 - 3167. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G.-Y. Wang, S. Wu, J.-M. Pei, X.-C. Yu, and T.-M. Wong {kappa}- but not {delta}-opioid receptors mediate effects of ischemic preconditioning on both infarct and arrhythmia in rats Am J Physiol Heart Circ Physiol, January 1, 2001; 280(1): H384 - H391. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Castelnovo, C. Dosquet, A. Gaudric, J. Sahel, and D. Hicks Human Platelet Suspension Stimulates Porcine Retinal Glial Proliferation and Migration In Vitro Invest. Ophthalmol. Vis. Sci., February 1, 2000; 41(2): 601 - 609. [Abstract] [Full Text]
|
|
|
|
|
|
A. Gysembergh, S. Lemaire, C. Piot, C. Sportouch, S. Richard, R. A. Kloner, and K. Przyklenk Pharmacological manipulation of Ins(1,4,5)P3 signaling mimics preconditioning in rabbit heart Am J Physiol Heart Circ Physiol, December 1, 1999; 277(6): H2458 - H2469. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. R.C. Dekker, R. Coronel, E. VanBavel, J. A.E. Spaan, and T. Opthof Intracellular Ca2+ and delay of ischemia-induced electrical uncoupling in preconditioned rabbit ventricular myocardium Cardiovasc Res, October 1, 1999; 44(1): 101 - 112. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Ping, J. Zhang, Y.-T. Zheng, R. C. X. Li, B. Dawn, X.-L. Tang, H. Takano, Z. Balafanova, and R. Bolli Demonstration of Selective Protein Kinase C–Dependent Activation of Src and Lck Tyrosine Kinases During Ischemic Preconditioning in Conscious Rabbits Circ. Res., September 17, 1999; 85(6): 542 - 550. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Takeo and Y. Nasa Role of energy metabolism in the preconditioned heart - a possible contribution of mitochondria Cardiovasc Res, July 1, 1999; 43(1): 32 - 43. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Z. Simkhovich, K. Przyklenk, and R. A. Kloner Role of protein kinase C as a cellular mediator of ischemic preconditioning: a critical review Cardiovasc Res, October 1, 1998; 40(1): 9 - 22. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Zhao, O. Renner, L. Wightman, P. H. Sugden, L. Stewart, A. D. Miller, D. S. Latchman, and M. S. Marber The Expression of Constitutively Active Isotypes of Protein Kinase C to Investigate Preconditioning J. Biol. Chem., September 4, 1998; 273(36): 23072 - 23079. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. A. Kloner, R. Bolli, E. Marban, L. Reinlib, and E. Braunwald Medical and Cellular Implications of Stunning, Hibernation, and Preconditioning : An NHLBI Workshop Circulation, May 19, 1998; 97(18): 1848 - 1867. [Full Text] [PDF]
|
|
|
|
|
|
L. R. C. Dekker, H. Rademaker, J. T. Vermeulen, T. Opthof, R. Coronel, J. A. E. Spaan, and M. J. Janse Cellular Uncoupling During Ischemia in Hypertrophied and Failing Rabbit Ventricular Myocardium : Effects of Preconditioning Circulation, May 5, 1998; 97(17): 1724 - 1730. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Miura, T. Miura, S. Kawamura, M. Goto, J. Sakamoto, A. Tsuchida, M. Matsuzaki, and K. Shimamoto Effect of protein kinase C inhibitors on cardioprotection by ischemic preconditioning depends on the number of preconditioning episodes Cardiovasc Res, March 1, 1998; 37(3): 700 - 709. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. R.C Dekker Toward the heart of ischemic preconditioning Cardiovasc Res, January 1, 1998; 37(1): 14 - 20. [Full Text] [PDF]
|
|
|
|
|
|
D. M Yellon, G. F Baxter, D. Garcia-Dorado, G. Heusch, and M. S Sumeray Ischaemic preconditioning: present position and future directions Cardiovasc Res, January 1, 1998; 37(1): 21 - 33. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Liu, W. D. Gao, B. O'Rourke, and E. Marban Priming effect of adenosine on KATP currents in intact ventricular myocytes: implications for preconditioning Am J Physiol Heart Circ Physiol, October 1, 1997; 273(4): H1637 - H1643. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Ping, J. Zhang, Y. Qiu, X.-L. Tang, S. Manchikalapudi, X. Cao, and R. Bolli Ischemic Preconditioning Induces Selective Translocation of Protein Kinase C Isoforms {epsilon} and {eta} in the Heart of Conscious Rabbits Without Subcellular Redistribution of Total Protein Kinase C Activity Circ. Res., September 19, 1997; 81(3): 404 - 414. [Abstract] [Full Text]
|
|
|
|
|
|
E. Giannella, H.-C. Mochmann, and R. Levi Ischemic Preconditioning Prevents the Impairment of Hypoxic Coronary Vasodilatation Caused by Ischemia/Reperfusion : Role of Adenosine A1/A3 and Bradykinin B2 Receptor Activation Circ. Res., September 19, 1997; 81(3): 415 - 422. [Abstract] [Full Text]
|
|
|
|
|
|
G. Brooks and D. J. Hearse Role of Protein Kinase C in Ischemic Preconditioning: Player or Spectator? Circ. Res., September 1, 1996; 79(3): 628 - 631. [Full Text]
|
|