Circulation Research, Vol 70, 223-233, Copyright © 1992 by American Heart Association

ARTICLES

Blockade of ATP-sensitive potassium channels prevents myocardial preconditioning in dogs

GJ Gross and JA Auchampach
Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee 53226.

Single or multiple brief periods of ischemia (preconditioning) have been shown to protect the myocardium from infarction after a subsequent more prolonged ischemic insult. To test the hypothesis that preconditioning is the result of opening ATP-sensitive potassium (KATP) channels, a selective KATP channel antagonist, glibenclamide, was administered before or immediately after preconditioning in barbital- anesthetized open-chest dogs subjected to 60 minutes of left circumflex coronary artery (LCX) occlusion followed by 5 hours of reperfusion. Preconditioning was elicited by 5 minutes of LCX occlusion followed by 10 minutes of reperfusion before the 60-minute occlusion period. Glibenclamide (0.3 mg/kg i.v.) or vehicle was given 10 minutes before the initial ischemic insult in each of four groups. In a fifth group, glibenclamide was administered immediately after preconditioning. In a final series (group 6), a selective potassium channel opener, RP 52891 (10 micrograms/kg bolus and 0.1 micrograms/mg/min i.v.) was started 10 minutes before occlusion and continued throughout reperfusion. Transmural myocardial blood flow was measured at 30 minutes of occlusion, and infarct size was determined by triphenyltetrazolium staining and expressed as a percent of the area at risk. There were no significant differences in hemodynamics, collateral blood flow, or area at risk between groups. The ratio of infarct size to area at risk in the control group (28 +/- 6%) was not different from the group pretreated with glibenclamide in the absence of preconditioning (31 +/- 6%). Preconditioning produced a marked reduction (p less than 0.002) in infarct size (28 +/- 6% to 6 +/- 2%), whereas glibenclamide administered before or immediately after preconditioning completely abolished the protective effect (28 +/- 6% and 30 +/- 8%, respectively). RP 52891 also produced a significant (p less than 0.03) reduction (28 +/- 6% to 13 +/- 3%) in infarct size. These results suggest that myocardial preconditioning in the canine heart is mediated by activation of KATP channels and that these channels may serve an endogenous myocardial protective role.

This article has been cited by other articles:

				G. Ambrosio, M. Del Pinto, I. Tritto, G. Agnelli, M. Bentivoglio, C. Zuchi, F. A. Anderson, J. M. Gore, J. Lopez-Sendon, A. Wyman, et al. Chronic nitrate therapy is associated with different presentation and evolution of acute coronary syndromes: insights from 52 693 patients in the Global Registry of Acute Coronary Events Eur. Heart J., November 10, 2009; (2009) ehp457v1. [Abstract] [Full Text] [PDF]

				E. Golomb, A. Nyska, and H. Schwalb Occult Cardiotoxicity--Toxic Effects on Cardiac Ischemic Tolerance Toxicol Pathol, August 1, 2009; 37(5): 572 - 593. [Abstract] [Full Text] [PDF]

				S. Yasuda, H. Kobayashi, M. Iwasa, I. Kawamura, S. Sumi, B. Narentuoya, T. Yamaki, H. Ushikoshi, K. Nishigaki, K. Nagashima, et al. Antidiabetic drug pioglitazone protects the heart via activation of PPAR-{gamma} receptors, PI3-kinase, Akt, and eNOS pathway in a rabbit model of myocardial infarction Am J Physiol Heart Circ Physiol, May 1, 2009; 296(5): H1558 - H1565. [Abstract] [Full Text] [PDF]

				A. M. Arruda-Olson, R. K. Patch III, C. L. Leibson, A. Vella, R. L. Frye, S. A. Weston, J. M. Killian, and V. L. Roger Effect of Second-Generation Sulfonylureas on Survival in Patients With Diabetes Mellitus After Myocardial Infarction Mayo Clin. Proc., January 1, 2009; 84(1): 28 - 33. [Abstract] [Full Text] [PDF]

				J. R. Klune, T. R. Billiar, and A. Tsung HMGB1 preconditioning: therapeutic application for a danger signal? J. Leukoc. Biol., March 1, 2008; 83(3): 558 - 563. [Abstract] [Full Text] [PDF]

				Z. Sun, X. Zhang, K. Ito, Y. Li, R. A. Montgomery, S. Tachibana, and G. M. Williams Amelioration of oxidative mitochondrial DNA damage and deletion after renal ischemic injury by the KATP channel opener diazoxide Am J Physiol Renal Physiol, March 1, 2008; 294(3): F491 - F498. [Abstract] [Full Text] [PDF]

				A. Redel, M. Lange, V. Jazbutyte, C. Lotz, T. M. Smul, N. Roewer, and F. Kehl Activation of Mitochondrial Large-Conductance Calcium-Activated K+ Channels via Protein Kinase A Mediates Desflurane-Induced Preconditioning Anesth. Analg., February 1, 2008; 106(2): 384 - 391. [Abstract] [Full Text] [PDF]

				P. Ferdinandy, R. Schulz, and G. F. Baxter Interaction of Cardiovascular Risk Factors with Myocardial Ischemia/Reperfusion Injury, Preconditioning, and Postconditioning Pharmacol. Rev., December 1, 2007; 59(4): 418 - 458. [Abstract] [Full Text] [PDF]

				S. Kasama, T. Toyama, H. Sumino, H. Kumakura, Y. Takayama, S. Ichikawa, T. Suzuki, and M. Kurabayashi Long-Term Nicorandil Therapy Improves Cardiac Sympathetic Nerve Activity After Reperfusion Therapy in Patients with First Acute Myocardial Infarction J. Nucl. Med., October 1, 2007; 48(10): 1676 - 1682. [Abstract] [Full Text] [PDF]

				S. P. Loukogeorgakis, R. Williams, A. T. Panagiotidou, S. K. Kolvekar, A. Donald, T. J. Cole, D. M. Yellon, J. E. Deanfield, and R. J. MacAllister Transient Limb Ischemia Induces Remote Preconditioning and Remote Postconditioning in Humans by a KATP Channel Dependent Mechanism Circulation, September 18, 2007; 116(12): 1386 - 1395. [Abstract] [Full Text] [PDF]

				A. J. Chicco, M. S. Johnson, C. J. Armstrong, J. M. Lynch, R. T. Gardner, G. S. Fasen, C. P. Gillenwater, and R. L. Moore Sex-specific and exercise-acquired cardioprotection is abolished by sarcolemmal KATP channel blockade in the rat heart Am J Physiol Heart Circ Physiol, May 1, 2007; 292(5): H2432 - H2437. [Abstract] [Full Text] [PDF]

				S. Kasama, T. Toyama, T. Hatori, H. Sumino, H. Kumakura, Y. Takayama, S. Ichikawa, T. Suzuki, and M. Kurabayashi Effects of Intravenous Atrial Natriuretic Peptide on Cardiac Sympathetic Nerve Activity and Left Ventricular Remodeling in Patients With First Anterior Acute Myocardial Infarction J. Am. Coll. Cardiol., February 13, 2007; 49(6): 667 - 674. [Abstract] [Full Text] [PDF]

				R. C. Kukreja Mechanism of reactive oxygen species generation after opening of mitochondrial KATP channels Am J Physiol Heart Circ Physiol, November 1, 2006; 291(5): H2041 - H2043. [Full Text] [PDF]

				N. P. Riksen, Z. Zhou, W. J.G. Oyen, R. Jaspers, B. P. Ramakers, R. M.H.J. Brouwer, O. C. Boerman, N. Steinmetz, P. Smits, and G. A. Rongen Caffeine Prevents Protection in Two Human Models of Ischemic Preconditioning J. Am. Coll. Cardiol., August 15, 2006; 48(4): 700 - 707. [Abstract] [Full Text] [PDF]

				K. Nithipatikom, J. M. Moore, M. A. Isbell, J. R. Falck, and G. J. Gross Epoxyeicosatrienoic acids in cardioprotection: ischemic versus reperfusion injury Am J Physiol Heart Circ Physiol, August 1, 2006; 291(2): H537 - H542. [Abstract] [Full Text] [PDF]

				P. Valensi and G. Slama Review: Sulphonylureas and cardiovascular risk: facts and controversies The British Journal of Diabetes & Vascular Disease, July 1, 2006; 6(4): 159 - 165. [Abstract] [PDF]

				L. Tritapepe, V. De Santis, D. Vitale, M. Santulli, A. Morelli, I. Nofroni, P. E. Puddu, M. Singer, and P. Pietropaoli Preconditioning effects of levosimendan in coronary artery bypass grafting--a pilot study Br. J. Anaesth., June 1, 2006; 96(6): 694 - 700. [Abstract] [Full Text] [PDF]

				G. J. Grover Mitochondrial ATP-sensitive potassium channels and mitochondrial protein kinase C: sometimes it's good to have a close neighbor Am J Physiol Heart Circ Physiol, May 1, 2006; 290(5): H1752 - H1753. [Full Text] [PDF]

				G. Roseborough, D. Gao, L. Chen, M. A. Trush, S. Zhou, G. M. Williams, and C. Wei The Mitochondrial K-ATP Channel Opener, Diazoxide, Prevents Ischemia-Reperfusion Injury in the Rabbit Spinal Cord Am. J. Pathol., May 1, 2006; 168(5): 1443 - 1451. [Abstract] [Full Text] [PDF]

				D. K. Das and N. Maulik Resveratrol in cardioprotection: a therapeutic promise of alternative medicine. Mol. Interv., February 1, 2006; 6(1): 36 - 47. [Abstract] [Full Text] [PDF]

				J.-S. Bian, Q. C. Yong, T.-T. Pan, Z.-N. Feng, M. Y. Ali, S. Zhou, and P. K. Moore Role of Hydrogen Sulfide in the Cardioprotection Caused by Ischemic Preconditioning in the Rat Heart and Cardiac Myocytes J. Pharmacol. Exp. Ther., February 1, 2006; 316(2): 670 - 678. [Abstract] [Full Text] [PDF]

				A. Hassouna, M. Loubani, B. M. Matata, A. Fowler, N. B. Standen, and M. Galinanes Mitochondrial dysfunction as the cause of the failure to precondition the diabetic human myocardium Cardiovasc Res, February 1, 2006; 69(2): 450 - 458. [Abstract] [Full Text] [PDF]

				A. D. T. Costa, C. L. Quinlan, A. Andrukhiv, I. C. West, M. Jaburek, and K. D. Garlid The direct physiological effects of mitoKATP opening on heart mitochondria Am J Physiol Heart Circ Physiol, January 1, 2006; 290(1): H406 - H415. [Abstract] [Full Text] [PDF]

				J. E. Davies, S. B. Digerness, C. R. Killingsworth, C. Zaragoza, C. R. Katholi, R. K. Justice, S. P. Goldberg, and W. L. Holman Multiple Treatment Approach to Limit Cardiac Ischemia-Reperfusion Injury Ann. Thorac. Surg., October 1, 2005; 80(4): 1408 - 1416. [Abstract] [Full Text] [PDF]

				D. A Brown, J. M Lynch, C. J Armstrong, N. M Caruso, L. B Ehlers, M. S Johnson, and R. L Moore Susceptibility of the heart to ischaemia-reperfusion injury and exercise-induced cardioprotection are sex-dependent in the rat J. Physiol., April 15, 2005; 564(2): 619 - 630. [Abstract] [Full Text] [PDF]

				G. J. Gross Sildenafil and Endothelial Dysfunction in Humans Circulation, February 15, 2005; 111(6): 721 - 723. [Full Text] [PDF]

				M. A. Moses, P. D. Addison, P. C. Neligan, H. Ashrafpour, N. Huang, M. Zair, A. Rassuli, C. R. Forrest, G. J. Grover, and C. Y. Pang Mitochondrial KATP channels in hindlimb remote ischemic preconditioning of skeletal muscle against infarction Am J Physiol Heart Circ Physiol, February 1, 2005; 288(2): H559 - H567. [Abstract] [Full Text] [PDF]

				T. Yorozuya, N. Adachi, K. Dote, K. Nakanishi, Y. Takasaki, and T. Arai Enhancement of Na+,K+-ATPase and Ca2+-ATPase activities in multi-cycle ischemic preconditioning in rabbit hearts Eur. J. Cardiothorac. Surg., November 1, 2004; 26(5): 981 - 987. [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]

				M.W. Broadhead, R.K. Kharbanda, M.J. Peters, and R.J. MacAllister KATP Channel Activation Induces Ischemic Preconditioning of the Endothelium in Humans In Vivo Circulation, October 12, 2004; 110(15): 2077 - 2082. [Abstract] [Full Text] [PDF]

				J. F. LaDisa Jr., J. G. Krolikowski, P. S. Pagel, D. C. Warltier, and J. R. Kersten Cardioprotection by glucose-insulin-potassium: dependence on KATP channel opening and blood glucose concentration before ischemia Am J Physiol Heart Circ Physiol, August 1, 2004; 287(2): H601 - H607. [Abstract] [Full Text] [PDF]

				R. A. Kloner and S. H. Rezkalla Cardiac protection during acute myocardial infarction: Where do we stand in 2004? J. Am. Coll. Cardiol., July 21, 2004; 44(2): 276 - 286. [Abstract] [Full Text] [PDF]

				R. D. Rainbow, D. Lodwick, D. Hudman, N. W. Davies, R. I. Norman, and N. B. Standen SUR2A C-terminal fragments reduce KATP currents and ischaemic tolerance of rat cardiac myocytes J. Physiol., June 15, 2004; 557(3): 785 - 794. [Abstract] [Full Text] [PDF]

				C.-M. Cao, Q. Xia, J. Tu, M. Chen, S. Wu, and T.-M. Wong Cardioprotection of Interleukin-2 Is Mediated via {kappa}-Opioid Receptors J. Pharmacol. Exp. Ther., May 1, 2004; 309(2): 560 - 567. [Abstract] [Full Text] [PDF]

				M. A. Deja, K. S. Golba, M. Kolowca, K. Widenka, J. Biernat, and S. Wos Diazoxide provides protection to human myocardium in vitro that is concentration dependent Ann. Thorac. Surg., January 1, 2004; 77(1): 226 - 232. [Abstract] [Full Text] [PDF]

				J J Meier, B Gallwitz, W E Schmidt, A Mugge, and M A Nauck Is impairment of ischaemic preconditioning by sulfonylurea drugs clinically important? Heart, January 1, 2004; 90(1): 9 - 12. [Abstract] [Full Text] [PDF]

				O. Oldenburg, Q. Qin, T. Krieg, X.-M. Yang, S. Philipp, S. D. Critz, M. V. Cohen, and J. M. Downey Bradykinin induces mitochondrial ROS generation via NO, cGMP, PKG, and mitoKATP channel opening and leads to cardioprotection Am J Physiol Heart Circ Physiol, January 1, 2004; 286(1): H468 - H476. [Abstract] [Full Text] [PDF]

				D. V. Cancherini, L. G. Trabuco, N. A. Reboucas, and A. J. Kowaltowski ATP-sensitive K+ channels in renal mitochondria Am J Physiol Renal Physiol, December 1, 2003; 285(6): F1291 - F1296. [Abstract] [Full Text]

				D. M. YELLON and J. M. DOWNEY Preconditioning the Myocardium: From Cellular Physiology to Clinical Cardiology Physiol Rev, October 1, 2003; 83(4): 1113 - 1151. [Abstract] [Full Text] [PDF]

				G. J. Gross and J. N. Peart KATP channels and myocardial preconditioning: an update Am J Physiol Heart Circ Physiol, August 7, 2003; 285(3): H921 - H930. [Abstract] [Full Text] [PDF]

				G. Taimor Mitochondria as common endpoints in early and late preconditioning Cardiovasc Res, August 1, 2003; 59(2): 266 - 267. [Full Text] [PDF]

				J. A. Auchampach, Z.-D. Ge, T. C. Wan, J. Moore, and G. J. Gross A3 adenosine receptor agonist IB-MECA reduces myocardial ischemia-reperfusion injury in dogs Am J Physiol Heart Circ Physiol, July 11, 2003; 285(2): H607 - H613. [Abstract] [Full Text] [PDF]

				H. Matsuo, S. Watanabe, T. Segawa, S. Yasuda, T. Hirose, M. Iwama, S. Tanaka, T. Yamaki, Y. Matsuno, M. Tomita, et al. Evidence of pharmacologic preconditioning during PTCA by intravenous pretreatment with ATP-sensitive K+ channel opener nicorandil Eur. Heart J., July 2, 2003; 24(14): 1296 - 1303. [Abstract] [Full Text] [PDF]

				E. o. Cosar and C. J. O'Connor Hibernation, Stunning, and Preconditioning: Historical Perspective, Current Concepts, Clinical Applications, and Future Implications Seminars in Cardiothoracic and Vascular Anesthesia, June 1, 2003; 7(2): 115 - 140. [Abstract] [PDF]

				S. K. Jain, R. B. Schuessler, and J. E. Saffitz Mechanisms of Delayed Electrical Uncoupling Induced by Ischemic Preconditioning Circ. Res., May 30, 2003; 92(10): 1138 - 1144. [Abstract] [Full Text] [PDF]

				Y. Nakae, W.-M. Kwok, Z. J. Bosnjak, and M. T. Jiang Isoflurane activates rat mitochondrial ATP-sensitive K+ channels reconstituted in lipid bilayers Am J Physiol Heart Circ Physiol, May 1, 2003; 284(5): H1865 - H1871. [Abstract] [Full Text] [PDF]

				F. Kehl, P. S. Pagel, J. G. Krolikowski, W. Gu, W. Toller, D. C. Warltier, and J. R. Kersten Isoflurane Does Not Produce a Second Window of Preconditioning Against Myocardial Infarction In Vivo Anesth. Analg., November 1, 2002; 95(5): 1162 - 1168. [Abstract] [Full Text] [PDF]

				G. J. Grover, A. J. D'Alonzo, R. B. Darbenzio, C. S. Parham, T. A. Hess, and M. S. Bathala In Vivo Characterization of the Mitochondrial Selective KATP Opener (3R)-trans-4-((4-Chlorophenyl)-N-(1H-imidazol-2-ylmethyl)dimethyl-2H-1-benzopyran-6-carbonitril Monohydrochloride (BMS-191095): Cardioprotective, Hemodynamic, and Electrophysiological Effects J. Pharmacol. Exp. Ther., October 1, 2002; 303(1): 132 - 140. [Abstract] [Full Text] [PDF]

				L. M. Schwartz, T. S. Welch, and M. S. Crago Cardioprotection by multiple preconditioning cycles does not require mitochondrial KATP channels in pigs Am J Physiol Heart Circ Physiol, October 1, 2002; 283(4): H1538 - H1544. [Abstract] [Full Text] [PDF]

				H. Ogita, K. Node, H. Asanuma, S. Sanada, Y. Liao, S. Takashima, M. Asakura, H. Mori, Y. Shinozaki, M. Hori, et al. Amelioration of ischemia- and reperfusion-induced myocardial injury by the selective estrogen receptor modulator, raloxifene, in the canine heart J. Am. Coll. Cardiol., September 4, 2002; 40(5): 998 - 1005. [Abstract] [Full Text] [PDF]

				D. J. Caparrelli, S. M. Cattaneo II, B. T. Bethea, J. G. Shake, C. Eberhart, M. E. Blue, E. Marban, M. V. Johnston, W. A. Baumgartner, and V. L. Gott Pharmacological preconditioning ameliorates neurological injury in a model of spinal cord ischemia Ann. Thorac. Surg., September 1, 2002; 74(3): 838 - 845. [Abstract] [Full Text] [PDF]

				O. Oldenburg, M. V Cohen, D. M Yellon, and J. M Downey Mitochondrial KATP channels: role in cardioprotection Cardiovasc Res, August 15, 2002; 55(3): 429 - 437. [Abstract] [Full Text] [PDF]

				R. Rajashree, J. C. Koster, K. P. Markova, C. G. Nichols, and P. A. Hofmann Contractility and ischemic response of hearts from transgenic mice with altered sarcolemmal KATP channels Am J Physiol Heart Circ Physiol, August 1, 2002; 283(2): H584 - H590. [Abstract] [Full Text] [PDF]

				Z. Ren, Q. Yang, H. Storm Floten, and G.-W. He Hypoxic preconditioning in coronary microarteries: role of EDHF and K+ channel openers Ann. Thorac. Surg., July 1, 2002; 74(1): 143 - 148. [Abstract] [Full Text] [PDF]

				Y. Ohnuma, T. Miura, T. Miki, M. Tanno, A. Kuno, A. Tsuchida, and K. Shimamoto Opening of mitochondrial KATP channel occurs downstream of PKC-epsilon activation in the mechanism of preconditioning Am J Physiol Heart Circ Physiol, July 1, 2002; 283(1): H440 - H447. [Abstract] [Full Text] [PDF]

				H. Liu, H. Y. Zhang, X. Zhu, Z. Shao, and Z. Yao Preconditioning blocks cardiocyte apoptosis: role of KATP channels and PKC-epsilon Am J Physiol Heart Circ Physiol, April 1, 2002; 282(4): H1380 - H1386. [Abstract] [Full Text] [PDF]

				P. S. Pagel, J. G. Krolikowski, F. Kehl, B. Mraovic, J. R. Kersten, and D. C. Warltier The Role of Mitochondrial and Sarcolemmal KATP Channels in Canine Ethanol-Induced Preconditioning In Vivo Anesth. Analg., April 1, 2002; 94(4): 841 - 848. [Abstract] [Full Text] [PDF]

				R. Schulz, M. V Cohen, M. Behrends, J. M Downey, and G. Heusch Signal transduction of ischemic preconditioning Cardiovasc Res, November 1, 2001; 52(2): 181 - 198. [Full Text] [PDF]

				J. An, S. G. Varadarajan, E. Novalija, and D. F. Stowe Ischemic and anesthetic preconditioning reduces cytosolic [Ca2+] and improves Ca2+ responses in intact hearts Am J Physiol Heart Circ Physiol, October 1, 2001; 281(4): H1508 - H1523. [Abstract] [Full Text] [PDF]

				T. Miura, S. Kawamura, H. Tatsuno, Y. Ikeda, S. Mikami, H. Iwamoto, T. Okamura, M. Iwatate, M. Kimura, Y. Dairaku, et al. Ischemic Preconditioning Attenuates Cardiac Sympathetic Nerve Injury via ATP-Sensitive Potassium Channels During Myocardial Ischemia Circulation, August 28, 2001; 104(9): 1053 - 1058. [Abstract] [Full Text] [PDF]

				H. Liu, B. C. McPherson, and Z. Yao Preconditioning attenuates apoptosis and necrosis: role of protein kinase C{epsilon} and -{delta} isoforms Am J Physiol Heart Circ Physiol, July 1, 2001; 281(1): H404 - H410. [Abstract] [Full Text] [PDF]

				G. J. Grover, A. J. D'Alonzo, K. D. Garlid, R. Bajgar, N. J. Lodge, P. G. Sleph, R. B. Darbenzio, T. A. Hess, M. A. Smith, P. Paucek, et al. Pharmacologic Characterization of BMS-191095, a Mitochondrial KATP Opener with No Peripheral Vasodilator or Cardiac Action Potential Shortening Activity J. Pharmacol. Exp. Ther., June 1, 2001; 297(3): 1184 - 1192. [Abstract] [Full Text]

				R. A. Ockaili, P. Bhargava, and R. C. Kukreja Chemical preconditioning with 3-nitropropionic acid in hearts: role of mitochondrial KATP channel Am J Physiol Heart Circ Physiol, May 1, 2001; 280(5): H2406 - H2411. [Abstract] [Full Text] [PDF]

				Y. Toyoda, S. Levitsky, and J. D. McCully Opening of mitochondrial ATP-sensitive potassium channels enhances cardioplegic protection Ann. Thorac. Surg., April 1, 2001; 71(4): 1281 - 1288. [Abstract] [Full Text] [PDF]

				B. P. Lipton, J. B. Delcarpio, and K. H. McDonough Effects of Endotoxin on Neutrophil-Mediated Ischemia/Reperfusion Injury in the Rat Heart In Vivo Experimental Biology and Medicine, April 1, 2001; 226(4): 320 - 327. [Abstract] [Full Text]

				P. Spallarossa, M. Schiavo, P. Rossettin, S. Cordone, L. Olivotti, R. Cordera, and C. Brunelli Sulfonylurea Treatment of Type 2 Diabetic Patients Does Not Reduce the Vasodilator Response to Ischemia Diabetes Care, April 1, 2001; 24(4): 738 - 742. [Abstract] [Full Text]

				G. Vassort Adenosine 5'-Triphosphate: a P2-Purinergic Agonist in the Myocardium Physiol Rev, April 1, 2001; 81(2): 767 - 806. [Abstract] [Full Text] [PDF]

				J. R. Kersten, M. W. Montgomery, T. Ghassemi, E. R. Gross, W. G. Toller, P. S. Pagel, and D. C. Warltier Diabetes and hyperglycemia impair activation of mitochondrial KATP channels Am J Physiol Heart Circ Physiol, April 1, 2001; 280(4): H1744 - H1750. [Abstract] [Full Text] [PDF]

				K. Mackay and D. Mochly-Rosen Arachidonic acid protects neonatal rat cardiac myocytes from ischaemic injury through {epsilon} protein kinase C Cardiovasc Res, April 1, 2001; 50(1): 65 - 74. [Abstract] [Full Text] [PDF]

				P. Bogaty, J. G. Kingma, J. Guimond, P. Poirier, L. Boyer, L. Charbonneau, and G. R. Dagenais Myocardial perfusion imaging findings and the role of adenosine in the warm-up angina phenomenon J. Am. Coll. Cardiol., February 1, 2001; 37(2): 463 - 469. [Abstract] [Full Text] [PDF]

				Z. Ren, Q. Yang, H. S. Floten, A. P. Furnary, A. P.C. Yim, and G.-W. He ATP-sensitive potassium channel openers may mimic the effects of hypoxic preconditioning on the coronary artery Ann. Thorac. Surg., February 1, 2001; 71(2): 642 - 647. [Abstract] [Full Text] [PDF]

				E. R. Gross, M. Gare, W. G. Toller, J. R. Kersten, D. C. Warltier, and P. S. Pagel Ethanol Enhances the Functional Recovery of Stunned Myocardium Independent of KATP Channels in Dogs Anesth. Analg., February 1, 2001; 92(2): 299 - 305. [Abstract] [Full Text] [PDF]

				S. Sanada, M. Kitakaze, H. Asanuma, K. Harada, H. Ogita, K. Node, S. Takashima, Y. Sakata, M. Asakura, Y. Shinozaki, et al. Role of mitochondrial and sarcolemmal KATP channels in ischemic preconditioning of the canine heart Am J Physiol Heart Circ Physiol, January 1, 2001; 280(1): H256 - H263. [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]

				Y. Toyoda, I. Friehs, R. A. Parker, S. Levitsky, and J. D. McCully Differential role of sarcolemmal and mitochondrial KATP channels in adenosine-enhanced ischemic preconditioning Am J Physiol Heart Circ Physiol, December 1, 2000; 279(6): H2694 - H2703. [Abstract] [Full Text] [PDF]

				H. Takano, X.-L. Tang, and R. Bolli Differential role of KATP channels in late preconditioning against myocardial stunning and infarction in rabbits Am J Physiol Heart Circ Physiol, November 1, 2000; 279(5): H2350 - H2359. [Abstract] [Full Text] [PDF]

				P. S. Pagel, W. G. Toller, E. R. Gross, M. Gare, J. R. Kersten, and D. C. Warltier KATP channels mediate the beneficial effects of chronic ethanol ingestion Am J Physiol Heart Circ Physiol, November 1, 2000; 279(5): H2574 - H2579. [Abstract] [Full Text] [PDF]

				W. Tang, M. H. Weil, S. Sun, A. Pernat, and E. Mason KATP channel activation reduces the severity of postresuscitation myocardial dysfunction Am J Physiol Heart Circ Physiol, October 1, 2000; 279(4): H1609 - H1615. [Abstract] [Full Text] [PDF]

				W. G. Pyle, T. D. Smith, and P. A. Hofmann Cardioprotection with kappa -opioid receptor stimulation is associated with a slowing of cross-bridge cycling Am J Physiol Heart Circ Physiol, October 1, 2000; 279(4): H1941 - H1948. [Abstract] [Full Text] [PDF]

				G. J. Gross and R. M. Fryer Mitochondrial KATP Channels : Triggers or Distal Effectors of Ischemic or Pharmacological Preconditioning? Circ. Res., September 15, 2000; 87(6): 431 - 433. [Full Text] [PDF]

				T. Pain, X.-M. Yang, S. D. Critz, Y. Yue, A. Nakano, G. S. Liu, G. Heusch, M. V. Cohen, and J. M. Downey Opening of Mitochondrial KATP Channels Triggers the Preconditioned State by Generating Free Radicals Circ. Res., September 15, 2000; 87(6): 460 - 466. [Abstract] [Full Text] [PDF]

				E. J. Tanhehco, K. Yasojima, P. L. McGeer, E. G. McGeer, and B. R. Lucchesi Preconditioning reduces myocardial complement gene expression in vivo Am J Physiol Heart Circ Physiol, September 1, 2000; 279(3): H1157 - H1165. [Abstract] [Full Text] [PDF]

				T. Zhao, L. Xi, J. Chelliah, J. E. Levasseur, and R. C. Kukreja Inducible Nitric Oxide Synthase Mediates Delayed Myocardial Protection Induced by Activation of Adenosine A1 Receptors : Evidence From Gene-Knockout Mice Circulation, August 22, 2000; 102(8): 902 - 907. [Abstract] [Full Text] [PDF]

				T. Sato, N. Sasaki, B. O'Rourke, and E. Marban Adenosine Primes the Opening of Mitochondrial ATP-Sensitive Potassium Channels : A Key Step in Ischemic Preconditioning? Circulation, August 15, 2000; 102(7): 800 - 805. [Abstract] [Full Text] [PDF]

				G. R. Gaudette, I. B. Krukenkamp, A. E. Saltman, H. Horimoto, and S. Levitsky Preconditioning with PKC and the ATP-sensitive potassium channels: a codependent relationship Ann. Thorac. Surg., August 1, 2000; 70(2): 602 - 608. [Abstract] [Full Text] [PDF]

				A. E. Saltman, G. R. Gaudette, S. Levitsky, and I. B. Krukenkamp Amrinone preconditioning in the isolated perfused rabbit heart Ann. Thorac. Surg., August 1, 2000; 70(2): 609 - 613. [Abstract] [Full Text] [PDF]

				R. M. Fryer, A. K. Hsu, H. Nagase, and G. J. Gross Opioid-Induced Cardioprotection against Myocardial Infarction and Arrhythmias: Mitochondrial versus Sarcolemmal ATP-Sensitive Potassium Channels J. Pharmacol. Exp. Ther., August 1, 2000; 294(2): 451 - 457. [Abstract] [Full Text]

				B. J. Pomerantz, T. N. Robinson, T. D. Morrell, J. K. Heimbach, A. Banerjee, and A. H. Harken Selective mitochondrial adenosine triphosphate-sensitive potassium channel activation is sufficient to precondition human myocardium J. Thorac. Cardiovasc. Surg., August 1, 2000; 120(2): 387 - 392. [Abstract] [Full Text] [PDF]

				R. A. Hopper, C. R. Forrest, H. Xu, A. Zhong, W. He, J. Rutka, P. Neligan, and C. Y. Pang Role and mechanism of PKC in ischemic preconditioning of pig skeletal muscle against infarction Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2000; 279(2): R666 - R676. [Abstract] [Full Text] [PDF]

				M. Kawasuji, M. Ikeda, N. Sakakibara, S. Fujii, S. Tomita, and Y. Watanabe Near-infrared monitoring of myocardial oxygenation during ischemic preconditioning Ann. Thorac. Surg., June 1, 2000; 69(6): 1806 - 1810. [Abstract] [Full Text] [PDF]

				T. Sato, N. Sasaki, J. Seharaseyon, B. O'Rourke, and E. Marban Selective Pharmacological Agents Implicate Mitochondrial but Not Sarcolemmal KATP Channels in Ischemic Cardioprotection Circulation, May 23, 2000; 101(20): 2418 - 2423. [Abstract] [Full Text] [PDF]

				J. R. Kersten, W. G. Toller, E. R. Gross, P. S. Pagel, and D. C. Warltier Diabetes abolishes ischemic preconditioning: role of glucose, insulin, and osmolality Am J Physiol Heart Circ Physiol, April 1, 2000; 278(4): H1218 - H1224. [Abstract] [Full Text] [PDF]

				T. L. V. Hoek, L. B. Becker, Z.-H. Shao, C.-Q. Li, and P. T. Schumacker Preconditioning in Cardiomyocytes Protects by Attenuating Oxidant Stress at Reperfusion Circ. Res., March 17, 2000; 86(5): 541 - 548. [Abstract] [Full Text] [PDF]

				H. H. Chen, K. Y. Oh, A. Terzic, and J. C. Burnett Jr. The modulating actions of sulfonylurea on atrial natriuretic peptide release in experimental acute heart failure Eur J Heart Fail, March 1, 2000; 2(1): 33 - 40. [Abstract] [Full Text] [PDF]

				S. Ghosh, N. B Standen, and M. Galinanes Evidence for mitochondrial KATP channels as effectors of human myocardial preconditioning Cardiovasc Res, March 1, 2000; 45(4): 934 - 940. [Abstract] [Full Text] [PDF]

				T. Matsubara, S. Minatoguchi, H. Matsuo, K. Hayakawa, T. Segawa, Y. Matsuno, S. Watanabe, M. Arai, Y. Uno, M. Kawasaki, et al. Three minute, but not one minute, ischemia and nicorandil have a preconditioning effect in patients with coronary artery disease J. Am. Coll. Cardiol., February 1, 2000; 35(2): 345 - 351. [Abstract] [Full Text] [PDF]

				W. Matar, T. M. Nosek, D. Wong, and J.-M. Renaud Pinacidil suppresses contractility and preserves energy but glibenclamide has no effect during muscle fatigue Am J Physiol Cell Physiol, February 1, 2000; 278(2): C404 - C416. [Abstract] [Full Text] [PDF]

				M. Nakamura, N.-P. Wang, Z.-Q. Zhao, J. N Wilcox, V. Thourani, R. A Guyton, and J. Vinten-Johansen Preconditioning decreases Bax expression, PMN accumulation and apoptosis in reperfused rat heart Cardiovasc Res, February 1, 2000; 45(3): 661 - 670. [Abstract] [Full Text] [PDF]