Circulation. 2001;104:2981-2989
doi: 10.1161/hc4801.100038
doi: 10.1161/hc4801.100038
(Circulation. 2001;104:2981.)
© 2001 American Heart Association, Inc.
Clinical Cardiology: New Frontiers |
Consequences of Brief Ischemia: Stunning, Preconditioning, and Their Clinical Implications
Part 1
From the Heart Institute, Good Samaritan Hospital, Keck School of Medicine, University of Southern California, Los Angeles (R.A.K.), and the Pathology Department, Duke University Medical Center, Durham, NC (R.B.J.).
Correspondence to Robert A. Kloner, MD, PhD, Heart Institute, Good Samaritan Hospital, 1225 Wilshire Blvd, Los Angeles, CA 90017. E-mail rkloner{at}goodsam.org
In experimental studies in the dog, total proximal coronary artery occlusions of up to 15 minutes result in reversible injury, meaning that the myocytes survive this insult. The 15 minutes of ischemia, however, induce numerous changes in the myocardium, including certain monuments to the brief episode of ischemia that may persist for days. One of these monuments is stunned myocardium, which represents "prolonged postischemic contractile dysfunction of myocardium salvaged by reperfusion." The mechanism of stunning involves generation of oxygen radicals as well as alteration in calcium homeostasis and possibly alteration in contractile protein structure. Stunning has been observed in several clinical scenarios, including after percutaneous transluminal coronary angioplasty, unstable angina, stress-induced ischemia, after thrombolysis, and after cardiopulmonary bypass. Oxygen radical scavengers and calcium channel blockers have been shown to enhance function of stunned myocardium in experimental studies, and in a few clinical studies, calcium channel blockers have been shown to ameliorate stunning. Although brief periods of ischemia can contribute to prolonged left ventricular dysfunction and even heart failure, they paradoxically play a cardioprotective role. Episodes of ischemia as short as 5 minutes, followed by reperfusion, protect the heart from a subsequent longer coronary artery occlusion by markedly reducing the amount of necrosis that results from the test episode of ischemia. This phenomenon, called ischemic preconditioning, has been observed in virtually every species in which it has been studied and is a powerful cardioprotective effect. The mechanism of ischemic preconditioning involves both triggers and mediators and involves complex second messenger pathways that appear to involve such components as adenosine, adenosine receptors, the epsilon isoform of protein kinase C, the ATP-dependent potassium channels, as well as others, including a paradoxical protective role of oxygen radicals. Both an early and a late phase of preconditioning have been described, and the mechanisms underlying their induction are under investigation. That preconditioning may occur in humans is suggested by the observations that repetitive balloon inflations in the coronary artery are associated with progressively less chest pain, ST-segment elevation, lactate production, the protective effects of preinfarction angina, the anginal "warm-up phenomenon," and studies performed on human cardiac biopsies that show metabolic properties suggesting preconditioning. Development of pharmacological agents that stimulate second messenger pathways thought to be involved in preconditioning, but without causing ischemia, could result in novel approaches to treating ischemia. Hence, on one hand, brief episodes of ischemia can have a negative effect on the heart: stunning; and on the other hand, they have a protective effect: preconditioning. The future challenge is how to minimize the stunning phenomenon and maximize the preconditioning phenomenon in clinical practice.
Key Words: ischemia • myocardial stunning • reperfusion • myocardial infarction
This article has been cited by other articles:
 |
|
 |
|
  S. Nakamura, M. Kimura, C. Goto, K. Noma, M. Yoshizumi, K. Chayama, Y. Kihara, and Y. Higashi Cigarette Smoking Abolishes Ischemic Preconditioning-Induced Augmentation of Endothelium-Dependent Vasodilation Hypertension, April 1, 2009; 53(4): 674 - 681. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. S. Halvorsen, A. Espinoza, L. A. Fleischer, O. J. Elle, L. Hoff, R. Lundblad, H. Skulstad, T. Edvardsen, H. Ihlen, and E. Fosse Feasibility of a three-axis epicardial accelerometer in detecting myocardial ischemia in cardiac surgical patients. J. Thorac. Cardiovasc. Surg., December 1, 2008; 136(6): 1496 - 1502. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. B. West, G. Rokosh, D. Obal, M. Velayutham, Y.-T. Xuan, B. G. Hill, R. J. Keith, J. Schrader, Y. Guo, D. J. Conklin, et al. Cardiac Myocyte-Specific Expression of Inducible Nitric Oxide Synthase Protects Against Ischemia/Reperfusion Injury by Preventing Mitochondrial Permeability Transition Circulation, November 4, 2008; 118(19): 1970 - 1978. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Czibik, Z. Wu, G. P. Berne, M. Tarkka, J. Vaage, J. Laurikka, O. Jarvinen, and G. Valen Human adaptation to ischemia by preconditioning or unstable angina: involvement of nuclear factor kappa B, but not hypoxia-inducible factor 1 alpha in the heart Eur. J. Cardiothorac. Surg., November 1, 2008; 34(5): 976 - 984. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. R. Egan, T. L. Butler, A. D. Cole, A. Aharonyan, D. Baines, N. Street, M. Navaratnam, O. Biecker, C. Zazulak, C. G. Au, et al. Myocardial ischemia is more important than the effects of cardiopulmonary bypass on myocardial water handling and postoperative dysfunction: A pediatric animal model. J. Thorac. Cardiovasc. Surg., November 1, 2008; 136(5): 1265 - 1273.e2. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Ashrafian and H. Watkins Exercise-induced ventricular dysfunction in hypertrophic cardiomyopathy: stunning by any other name? Heart, October 1, 2008; 94(10): 1251 - 1253. [Full Text] [PDF]
|
|
|
|
 |
|
 M. Yenari, K. Kitagawa, P. Lyden, and M. Perez-Pinzon Metabolic Downregulation: A Key to Successful Neuroprotection? Stroke, October 1, 2008; 39(10): 2910 - 2917. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. T. Clements, G. Smejkal, N. R. Sodha, A. R. Ivanov, J. M. Asara, J. Feng, A. Lazarev, S. Gautam, V. Senthilnathan, K. R. Khabbaz, et al. Pilot Proteomic Profile of Differentially Regulated Proteins in Right Atrial Appendage Before and After Cardiac Surgery Using Cardioplegia and Cardiopulmonary Bypass Circulation, September 30, 2008; 118(14_suppl_1): S24 - S31. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Ban, A. J. Cooper, S. Samuel, A. Bhatti, M. Patel, S. Izumo, J. M. Penninger, P. H. Backx, G. Y. Oudit, and R. G. Tsushima Phosphatidylinositol 3-Kinase {gamma} Is a Critical Mediator of Myocardial Ischemic and Adenosine-Mediated Preconditioning Circ. Res., September 12, 2008; 103(6): 643 - 653. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. G. Friedrich Tissue characterization of acute myocardial infarction and myocarditis by cardiac magnetic resonance. J. Am. Coll. Cardiol. Img., September 1, 2008; 1(5): 652 - 662. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. D. O'Brien and S. E. Howlett Simulated ischemia-induced preconditioning of isolated ventricular myocytes from young adult and aged Fischer-344 rat hearts Am J Physiol Heart Circ Physiol, August 1, 2008; 295(2): H768 - H777. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Morimoto, M. Hirose, M. Takahashi, M. Kawaguchi, H. Ise, P. E. Kolattukudy, M. Yamada, and U. Ikeda MCP-1 induces cardioprotection against ischaemia/reperfusion injury: role of reactive oxygen species Cardiovasc Res, June 1, 2008; 78(3): 554 - 562. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. T. Clements, N. R. Sodha, J. Feng, S. Mieno, M. Boodhwani, B. Ramlawi, C. Bianchi, and F. W. Sellke Phosphorylation and translocation of heat shock protein 27 and alphaB-crystallin in human myocardium after cardioplegia and cardiopulmonary bypass. J. Thorac. Cardiovasc. Surg., December 1, 2007; 134(6): 1461 - 1470.e3. [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]
|
|
|
|
 |
|
 J. R Triana, M. Yanagihashi, and D. F Larson Mathematical modeling of buffers used in myocardial preservation Perfusion, September 1, 2007; 22(5): 353 - 362. [Abstract] [PDF]
|
|
|
|
 |
|
 H. Morimoto, M. Takahashi, Y. Shiba, A. Izawa, H. Ise, M. Hongo, K. Hatake, K. Motoyoshi, and U. Ikeda Bone Marrow-Derived CXCR4+ Cells Mobilized by Macrophage Colony-Stimulating Factor Participate in the Reduction of Infarct Area and Improvement of Cardiac Remodeling after Myocardial Infarction in Mice Am. J. Pathol., September 1, 2007; 171(3): 755 - 766. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Heinze, C. Rosemann, C. Weber, G. Heinrichs, L. Bahlmann, M. Misfeld, M. Heringlake, and W. Eichler A single prophylactic dose of pentoxifylline reduces high dependency unit time in cardiac surgery -- a prospective randomized and controlled study Eur. J. Cardiothorac. Surg., July 1, 2007; 32(1): 83 - 89. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Kimura, K. Ueda, C. Goto, D. Jitsuiki, K. Nishioka, T. Umemura, K. Noma, M. Yoshizumi, K. Chayama, and Y. Higashi Repetition of Ischemic Preconditioning Augments Endothelium-Dependent Vasodilation in Humans: Role of Endothelium-Derived Nitric Oxide and Endothelial Progenitor Cells Arterioscler Thromb Vasc Biol, June 1, 2007; 27(6): 1403 - 1410. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. T. Dirksen, G. J. Laarman, M. L. Simoons, and D. J.G.M. Duncker Reperfusion injury in humans: A review of clinical trials on reperfusion injury inhibitory strategies Cardiovasc Res, June 1, 2007; 74(3): 343 - 355. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. W. van Laake, R. Hassink, P. A. Doevendans, and C. Mummery Heart repair and stem cells J. Physiol., December 1, 2006; 577(2): 467 - 478. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Cai and G. L. Semenza Is 15-min Ischemia too Lethal to Be an Ischemic Preconditioning Stimulus? Circ. Res., November 10, 2006; 99(10): e86 - e86. [Full Text] [PDF]
|
|
|
|
 |
|
 G. S. Werner, R. Surber, M. Ferrari, M. Fritzenwanger, and H. R. Figulla The functional reserve of collaterals supplying long-term chronic total coronary occlusions in patients without prior myocardial infarction Eur. Heart J., October 2, 2006; 27(20): 2406 - 2412. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Lunde, S. Solheim, S. Aakhus, H. Arnesen, M. Abdelnoor, T. Egeland, K. Endresen, A. Ilebekk, A. Mangschau, J. G. Fjeld, et al. Intracoronary injection of mononuclear bone marrow cells in acute myocardial infarction. N. Engl. J. Med., September 21, 2006; 355(12): 1199 - 1209. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Ganitkevich, S. Reil, B. Schwethelm, T. Schroeter, and K. Benndorf Dynamic Responses of Single Cardiomyocytes to Graded Ischemia Studied by Oxygen Clamp in On-Chip Picochambers Circ. Res., July 21, 2006; 99(2): 165 - 171. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. T. Mangano, Y. Miao, I. C. Tudor, C. Dietzel, for the Investigators of the Multicenter Study of, and and the Ischemia Research and Education Foundation Post-Reperfusion Myocardial Infarction: Long-Term Survival Improvement Using Adenosine Regulation With Acadesine J. Am. Coll. Cardiol., July 4, 2006; 48(1): 206 - 214. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Disruption of the ventricular myocardial force-frequency relationship after cardiac surgery in children: noninvasive assessment by means of tissue Doppler imaging. J. Thorac. Cardiovasc. Surg., March 1, 2006; 131(3): 625 - 631.
|
|
|
|
|
|
Z. Cai and G. L. Semenza PTEN Activity Is Modulated During Ischemia and Reperfusion: Involvement in the Induction and Decay of Preconditioning Circ. Res., December 9, 2005; 97(12): 1351 - 1359. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. Morariu, B. G. Loef, L. P. H. J. Aarts, G. W. Rietman, G. Rakhorst, W. van Oeveren, and A. H. Epema Dexamethasone: Benefit and Prejudice for Patients Undergoing On-Pump Coronary Artery Bypass Grafting: A Study on Myocardial, Pulmonary, Renal, Intestinal, and Hepatic Injury Chest, October 1, 2005; 128(4): 2677 - 2687. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Gozal, J. Raphael, J. Rivo, E. Berenshtein, M. Chevion, and B. Drenger Isoflurane does not mimic ischaemic preconditioning in decreasing hydroxyl radical production in the rabbit Br. J. Anaesth., October 1, 2005; 95(4): 442 - 447. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. G. De Hert, F. Turani, S. Mathur, and D. F. Stowe Cardioprotection with Volatile Anesthetics: Mechanisms and Clinical Implications Anesth. Analg., June 1, 2005; 100(6): 1584 - 1593. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A.-L. Bulteau, K. C. Lundberg, M. Ikeda-Saito, G. Isaya, and L. I. Szweda Reversible redox-dependent modulation of mitochondrial aconitase and proteolytic activity during in vivo cardiac ischemia/reperfusion PNAS, April 26, 2005; 102(17): 5987 - 5991. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. L. Hale and R. A. Kloner Acetaminophen and Myocardial Stunning after Transient Ischemia in Rabbit Hearts Journal of Cardiovascular Pharmacology and Therapeutics, April 1, 2005; 10(2): 121 - 129. [Abstract] [PDF]
|
|
|
|
|
|
B. Dawn, A. B. Stein, K. Urbanek, M. Rota, B. Whang, R. Rastaldo, D. Torella, X.-L. Tang, A. Rezazadeh, J. Kajstura, et al. Cardiac stem cells delivered intravascularly traverse the vessel barrier, regenerate infarcted myocardium, and improve cardiac function PNAS, March 8, 2005; 102(10): 3766 - 3771. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Jagathesan, P. A. Kaufmann, S. D. Rosen, O. E. Rimoldi, F. Turkeimer, R. Foale, and P. G. Camici Assessment of the Long-Term Reproducibility of Baseline and Dobutamine-Induced Myocardial Blood Flow in Patients with Stable Coronary Artery Disease J. Nucl. Med., February 1, 2005; 46(2): 212 - 219. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Srivastava, M. Spite, J. O. Trent, M. B. West, Y. Ahmed, and A. Bhatnagar Aldose Reductase-catalyzed Reduction of Aldehyde Phospholipids J. Biol. Chem., December 17, 2004; 279(51): 53395 - 53406. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Penna, P. Pagliaro, R. Rastaldo, F. Di Pancrazio, G. Lippe, D. Gattullo, D. Mancardi, M. Samaja, G. Losano, and I. Mavelli F0F1 ATP synthase activity is differently modulated by coronary reactive hyperemia before and after ischemic preconditioning in the goat Am J Physiol Heart Circ Physiol, November 1, 2004; 287(5): H2192 - H2200. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. K. Eltzschig and C. D. Collard Vascular ischaemia and reperfusion injury Br. Med. Bull., October 19, 2004; 70(1): 71 - 86. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Conti, C. Carrozza, E. Capoluongo, M. Volpe, F. Crea, C. Zuppi, and F. Andreotti Insulin-Like Growth Factor-1 as a Vascular Protective Factor Circulation, October 12, 2004; 110(15): 2260 - 2265. [Full Text] [PDF]
|
|
|
|
|
|
T. A. Khan, C. Bianchi, P. Voisine, J. Feng, J. Baker, M. Hart, M. Takahashi, G. Stahl, and F. W. Sellke Reduction of myocardial reperfusion injury by aprotinin after regional ischemia and cardioplegic arrest J. Thorac. Cardiovasc. Surg., October 1, 2004; 128(4): 602 - 608. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Depre, S.-J. Kim, A. S. John, Y. Huang, O. E. Rimoldi, J. R. Pepper, G. D. Dreyfus, V. Gaussin, D. J. Pennell, D. E. Vatner, et al. Program of Cell Survival Underlying Human and Experimental Hibernating Myocardium Circ. Res., August 20, 2004; 95(4): 433 - 440. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Wei, X. Wang, P. Kuukasjarvi, J. Laurikka, T. Rinne, E.-L. Honkonen, and M. Tarkka Bradykinin preconditioning in coronary artery bypass grafting Ann. Thorac. Surg., August 1, 2004; 78(2): 492 - 497. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Mayr, B. Metzler, Y.-L. Chung, E. McGregor, U. Mayr, H. Troy, Y. Hu, M. Leitges, O. Pachinger, J. R. Griffiths, et al. Ischemic preconditioning exaggerates cardiac damage in PKC-{delta} null mice Am J Physiol Heart Circ Physiol, August 1, 2004; 287(2): H946 - H956. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. G. Barra, A. J. Crottogini, P. Willshaw, E. C. Lascano, and R. H. Pichel Contribution of myocardium hydraulic skeleton to left ventricular wall interaction and synergy in dogs Am J Physiol Heart Circ Physiol, August 1, 2004; 287(2): H896 - H904. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. R Eberli Stunned myocardium--an unfinished puzzle Cardiovasc Res, August 1, 2004; 63(2): 189 - 191. [Full Text] [PDF]
|
|
|
|
|
|
M. Zimarino, S. Gallina, M. Di Fulvio, M. Di Mauro, G. Di Giammarco, R. De Caterina, and A. M. Calafiore Intraoperative ischemia and long-term events after minimally invasive coronary surgery Ann. Thorac. Surg., July 1, 2004; 78(1): 135 - 141. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Michiels Physiological and Pathological Responses to Hypoxia Am. J. Pathol., June 1, 2004; 164(6): 1875 - 1882. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Nishino, T. Miura, T. Miki, J. Sakamoto, Y. Nakamura, Y. Ikeda, H. Kobayashi, and K. Shimamoto Ischemic preconditioning activates AMPK in a PKC-dependent manner and induces GLUT4 up-regulation in the late phase of cardioprotection Cardiovasc Res, February 15, 2004; 61(3): 610 - 619. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Wang, M. Wei, P. Kuukasjarvi, J. Laurikka, O. Jarvinen, T. Rinne, E.-L. Honkonen, and M. Tarkka Novel pharmacological preconditioning with diazoxide attenuates myocardial stunning in coronary artery bypass grafting Eur. J. Cardiothorac. Surg., December 1, 2003; 24(6): 967 - 973. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. B. Foster, T. Noguchi, P. VanBuren, A. M. Murphy, and J. E. Van Eyk C-Terminal Truncation of Cardiac Troponin I Causes Divergent Effects on ATPase and Force: Implications for the Pathophysiology of Myocardial Stunning Circ. Res., November 14, 2003; 93(10): 917 - 924. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. J. Duncker, P. D. Verdouw, M. Suzuki, T. Saito, T. Sato, M. Tamagawa, T. Miki, S. Seino, and H. Nakaya Cardioprotective Effect of Diazoxide Is Mediated by Activation of Sarcolemmal but not Mitochondrial ATP-Sensitive Potassium Channels in Mice * Response Circulation, August 12, 2003; 108 (6): e44 - e44. [Full Text] [PDF]
|
|
|
|
|
|
Z.-Q. Zhao, J. S. Corvera, M. E. Halkos, F. Kerendi, N.-P. Wang, R. A. Guyton, and J. Vinten-Johansen Inhibition of myocardial injury by ischemic postconditioning during reperfusion: comparison with ischemic preconditioning Am J Physiol Heart Circ Physiol, August 1, 2003; 285(2): H579 - H588. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Thomas, S. B. Haudek, T. Koroglu, M. F. Tsen, D. D. Bryant, D. J. White, D. F. Kusewitt, J. W. Horton, and B. P. Giroir IRAK1 deletion disrupts cardiac Toll/IL-1 signaling and protects against contractile dysfunction Am J Physiol Heart Circ Physiol, August 1, 2003; 285(2): H597 - H606. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z.-Q. Z.-Q. Zhao, C. D. Morris, J. M. Budde, N.-P. N.-P. Wang, S. Muraki, H.-Y. H.-Y. Sun, and R. A. Guyton Inhibition of myocardial apoptosis reduces infarct size and improves regional contractile dysfunction during reperfusion Cardiovasc Res, July 1, 2003; 59(1): 132 - 142. [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]
|
|
|
|
|
|
J. D. Dowell, M. Rubart, K. B.S. Pasumarthi, M. H. Soonpaa, and L. J. Field Myocyte and myogenic stem cell transplantation in the heart Cardiovasc Res, May 1, 2003; 58(2): 336 - 350. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Depre, L. Wang, J. E. Tomlinson, V. Gaussin, M. Abdellatif, J. N. Topper, and S. F. Vatner Characterization of pDJA1, a cardiac-specific chaperone found by genomic profiling of the post-ischemic swine heart Cardiovasc Res, April 1, 2003; 58(1): 126 - 135. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Verma, P. W.M. Fedak, R. D. Weisel, J. Butany, V. Rao, A. Maitland, R.-K. Li, B. Dhillon, and T. M. Yau Fundamentals of Reperfusion Injury for the Clinical Cardiologist Circulation, May 21, 2002; 105(20): 2332 - 2336. [Full Text] [PDF]
|
|