Circulation Research. 2004;95:125-134
doi: 10.1161/01.RES.0000137171.97172.d7
doi: 10.1161/01.RES.0000137171.97172.d7
© 2004 American Heart Association, Inc.
Special Article |
Myocardial Protection at a Crossroads
The Need for Translation Into Clinical Therapy
From the Heart Research Program, Division of Heart and Vascular Diseases, National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health & Human Services, Bethesda, Md.
Correspondence to David A. Lathrop, PhD, Leader, Arrhythmia, Ischemia, and Sudden Cardiac Death, Scientific Research Group, Heart Research Program, Division of Heart and Vascular Diseases, National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health & Human Services, Bethesda, MD 20892. E-mail LathropD{at}nhlbi.nih.gov
Over the past 30 years, hundreds of experimental interventions (both pharmacologic and nonpharmacologic) have been reported to protect the ischemic myocardium in experimental animals; however, with the exception of early reperfusion, none has been translated into clinical practice. The National Heart, Lung, and Blood Institute convened a working group to discuss the reasons for the failure to translate potential therapies for protecting the heart from ischemia and reperfusion and to recommend new approaches to accomplish this goal. The Working Group concluded that cardioprotection in the setting of acute myocardial infarction, cardiac surgery, and cardiac arrest is at a crossroads. Present basic research approaches to identify cardioprotective therapies are inefficient and counterproductive. For 3 decades, significant resources have been invested in single-center studies that have often yielded inconclusive results. A new paradigm is needed to obviate many of the difficulties associated with translation of basic science findings. The Working Group urged a new focus on translational research that emphasizes efficacy and clinically relevant outcomes, and recommended the establishment of a system for rigorous preclinical testing of promising cardioprotective agents with clinical trial-like approaches (ie, blinded, randomized, multicenter, and adequately powered studies using standardized methods). A national preclinical research consortium would enable rational translation of important basic science findings into clinical use. The Working Group recommended that the National Institutes of Health proactively intervene to remedy current problems that impede translation of cardioprotective therapies. Their specific recommendations include the establishment of a preclinical consortium and the performance of 2 clinical studies that are likely to demonstrate effectiveness (phase III clinical trials of adenosine in acute myocardial infarction and cardiac surgery).
Key Words: basic science • myocardial ischemia • reperfusion injury • ischemic heart disease • cardiac surgery • cardioprotection • research translation
This article has been cited by other articles:
 |
|
 |
|
  H. Q. Ly, K. E. Kip, and J.-F. Tanguay Superoxygen Therapy: A Bayesian Breath of Fresh Air for Myocardial Salvage Circ Cardiovasc Interv, October 1, 2009; 2(5): 363 - 365. [Full Text] [PDF]
|
|
|
|
 |
|
 Q. Sun, Z. Kang, J. Cai, W. Liu, Y. Liu, J. H. Zhang, P. J. Denoble, H. Tao, and X. Sun Hydrogen-Rich Saline Protects Myocardium Against Ischemia/Reperfusion Injury in Rats Experimental Biology and Medicine, October 1, 2009; 234(10): 1212 - 1219. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. W. Stone, J. L. Martin, M.-J. de Boer, M. Margheri, E. Bramucci, J. C. Blankenship, D. C. Metzger, R. J. Gibbons, B. S. Lindsay, B. H. Weiner, et al. Effect of Supersaturated Oxygen Delivery on Infarct Size After Percutaneous Coronary Intervention in Acute Myocardial Infarction Circ Cardiovasc Interv, October 1, 2009; 2(5): 366 - 375. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M.A. H. Talukder, J. L. Zweier, and M. Periasamy Targeting calcium transport in ischaemic heart disease Cardiovasc Res, August 17, 2009; (2009) cvp264v2. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Granfeldt, D. J. Lefer, and J. Vinten-Johansen Protective ischaemia in patients: preconditioning and postconditioning Cardiovasc Res, July 15, 2009; 83(2): 234 - 246. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. M. Osipov, M. P. Robich, J. Feng, R. T. Clements, Y. Liu, H. P. Glazer, J. Wagstaff, C. Bianchi, and F. W. Sellke Effect of thrombin fragment (TP508) on myocardial ischemia-reperfusion injury in hypercholesterolemic pigs J Appl Physiol, June 1, 2009; 106(6): 1993 - 2001. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. N. Peart and J. P. Headrick Clinical cardioprotection and the value of conditioning responses Am J Physiol Heart Circ Physiol, June 1, 2009; 296(6): H1705 - H1720. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Mihov, N. Bogdanov, B. Grenacher, M. Gassmann, G. Zund, A. Bogdanova, and R. Tavakoli Erythropoietin protects from reperfusion-induced myocardial injury by enhancing coronary endothelial nitric oxide production Eur. J. Cardiothorac. Surg., May 1, 2009; 35(5): 839 - 846. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 U. Abdel-Rahman, P. Risteski, K. Tizi, S. Kerscher, S. Bejati, K. Zwicker, M. Scholz, U. Brandt, and A. Moritz Hypoxic reoxygenation during initial reperfusion attenuates cardiac dysfunction and limits ischemia-reperfusion injury after cardioplegic arrest in a porcine model J. Thorac. Cardiovasc. Surg., April 1, 2009; 137(4): 978 - 982. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. M. Osipov, C. Bianchi, R. T. Clements, J. Feng, Y. Liu, S.-H. Xu, M. P. Robich, J. Wagstaff, and F. W. Sellke Thrombin Fragment (TP508) Decreases Myocardial Infarction and Apoptosis After Ischemia Reperfusion Injury. Ann. Thorac. Surg., March 1, 2009; 87(3): 786 - 793. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Murphy and D. A. Eisner Regulation of Intracellular and Mitochondrial Sodium in Health and Disease Circ. Res., February 13, 2009; 104(3): 292 - 303. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Timmers, J. P.S. Henriques, D. P.V. de Kleijn, J. H. DeVries, H. Kemperman, P. Steendijk, C. W.J. Verlaan, M. Kerver, J. J. Piek, P. A. Doevendans, et al. Exenatide reduces infarct size and improves cardiac function in a porcine model of ischemia and reperfusion injury. J. Am. Coll. Cardiol., February 10, 2009; 53(6): 501 - 510. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. G. Webb, R. Williams, and M. S. Marber Lizard spit and reperfusion injury. J. Am. Coll. Cardiol., February 10, 2009; 53(6): 511 - 513. [Full Text] [PDF]
|
|
|
|
 |
|
 G. Heusch, K. Boengler, and R. Schulz Cardioprotection: Nitric Oxide, Protein Kinases, and Mitochondria Circulation, November 4, 2008; 118(19): 1915 - 1919. [Full Text] [PDF]
|
|
|
|
|
|
N. C. Moss, R.-H. Tang, M. Willis, W. E. Stansfield, A. S. Baldwin, and C. H. Selzman Inhibitory kappa B kinase-beta is a target for specific nuclear factor kappa B-mediated delayed cardioprotection. J. Thorac. Cardiovasc. Surg., November 1, 2008; 136(5): 1274 - 1279. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Feng, H. Zhao, X. Xu, E. S. Buys, M. J. Raher, J. C. Bopassa, H. Thibault, M. Scherrer-Crosbie, U. Schmidt, and W. Chao Innate immune adaptor MyD88 mediates neutrophil recruitment and myocardial injury after ischemia-reperfusion in mice Am J Physiol Heart Circ Physiol, September 1, 2008; 295(3): H1311 - H1318. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. G. Yamazaki, D. Romero-Perez, M. Barraza-Hidalgo, M. Cruz, M. Rivas, B. Cortez-Gomez, G. Ceballos, and F. Villarreal Short- and long-term effects of (-)-epicatechin on myocardial ischemia-reperfusion injury Am J Physiol Heart Circ Physiol, August 1, 2008; 295(2): H761 - H767. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Kasama, M. Furuya, T. Toyama, S. Ichikawa, and M. Kurabayashi Effect of atrial natriuretic peptide on left ventricular remodelling in patients with acute myocardial infarction Eur. Heart J., June 2, 2008; 29(12): 1485 - 1494. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Murphy and C. Steenbergen Mechanisms Underlying Acute Protection From Cardiac Ischemia-Reperfusion Injury Physiol Rev, April 1, 2008; 88(2): 581 - 609. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. H. Talukder, A. Kalyanasundaram, L. Zuo, M. Velayutham, Y. Nishijima, M. Periasamy, and J. L. Zweier Is reduced SERCA2a expression detrimental or beneficial to postischemic cardiac function and injury? Evidence from heterozygous SERCA2a knockout mice Am J Physiol Heart Circ Physiol, March 1, 2008; 294(3): H1426 - H1434. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Inserte, I. Barba, V. Hernando, A. Abellan, M. Ruiz-Meana, A. Rodriguez-Sinovas, and D. Garcia-Dorado Effect of acidic reperfusion on prolongation of intracellular acidosis and myocardial salvage Cardiovasc Res, March 1, 2008; 77(4): 782 - 790. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. C. Huffman, S. E. Koch, and K. L. Butler Coronary effluent from a preconditioned heart activates the JAK-STAT pathway and induces cardioprotection in a donor heart Am J Physiol Heart Circ Physiol, January 1, 2008; 294(1): H257 - H262. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. E. Baker, J. Su, A. Hsu, Y. Shi, M. Zhao, J. L. Strande, X. Fu, H. Xu, A. Eis, R. Komorowski, et al. Human thrombopoietin reduces myocardial infarct size, apoptosis, and stunning following ischaemia/reperfusion in rats Cardiovasc Res, January 1, 2008; 77(1): 44 - 53. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Jahangir, S. Sagar, and A. Terzic Aging and cardioprotection J Appl Physiol, December 1, 2007; 103(6): 2120 - 2128. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Zaugg Is protection by inhalation agents volatile? Controversies in cardioprotection Br. J. Anaesth., November 1, 2007; 99(5): 603 - 606. [Full Text] [PDF]
|
|
|
|
|
|
K. Meurrens, S. Ruf, G. Ross, R. Schleef, K. von Holt, and K.-D. Schluter Smoking accelerates the progression of hypertension-induced myocardial hypertrophy to heart failure in spontaneously hypertensive rats Cardiovasc Res, November 1, 2007; 76(2): 311 - 322. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. D. McEvoy, S. T. Reeves, J. G. Reves, and F. G. Spinale Aprotinin in Cardiac Surgery: A Review of Conventional and Novel Mechanisms of Action Anesth. Analg., October 1, 2007; 105(4): 949 - 962. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. H. Talukder, A. Kalyanasundaram, X. Zhao, L. Zuo, P. Bhupathy, G. J. Babu, A. J. Cardounel, M. Periasamy, and J. L. Zweier Expression of SERCA isoform with faster Ca2+ transport properties improves postischemic cardiac function and Ca2+ handling and decreases myocardial infarction Am J Physiol Heart Circ Physiol, October 1, 2007; 293(4): H2418 - H2428. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. C. Moss, W. E. Stansfield, M. S. Willis, R.-H. Tang, and C. H. Selzman IKKbeta inhibition attenuates myocardial injury and dysfunction following acute ischemia-reperfusion injury Am J Physiol Heart Circ Physiol, October 1, 2007; 293(4): H2248 - H2253. [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]
|
|
|
|
 |
|
 D. M. Yellon and D. J. Hausenloy Myocardial Reperfusion Injury N. Engl. J. Med., September 13, 2007; 357(11): 1121 - 1135. [Full Text] [PDF]
|
|
|
|
|
|
J. C. Quindry, K. L. Hamilton, J. P. French, Y. Lee, Z. Murlasits, N. Tumer, and S. K. Powers Exercise-induced HSP-72 elevation and cardioprotection against infarct and apoptosis J Appl Physiol, September 1, 2007; 103(3): 1056 - 1062. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Liu, R. B. Marchase, and J. C. Chatham Increased O-GlcNAc levels during reperfusion lead to improved functional recovery and reduced calpain proteolysis Am J Physiol Heart Circ Physiol, September 1, 2007; 293(3): H1391 - H1399. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Liu, Y. Huang, P. Pokreisz, P. Vermeersch, G. Marsboom, M. Swinnen, E. Verbeken, J. Santos, M. Pellens, H. Gillijns, et al. Nitric Oxide Inhalation Improves Microvascular Flow and Decreases Infarction Size After Myocardial Ischemia and Reperfusion J. Am. Coll. Cardiol., August 21, 2007; 50(8): 808 - 817. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. B. Granger and M. R. Patel The Search for Myocardial Protection: Is There Still Hope? J. Am. Coll. Cardiol., July 31, 2007; 50(5): 406 - 408. [Full Text] [PDF]
|
|
|
|
|
|
C. Dezfulian, N. Raat, S. Shiva, and M. T. Gladwin Role of the anion nitrite in ischemia-reperfusion cytoprotection and therapeutics Cardiovasc Res, July 15, 2007; 75(2): 327 - 338. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. E. Stansfield, N. C. Moss, M. S. Willis, R. Tang, and C. H. Selzman Proteasome Inhibition Attenuates Infarct Size and Preserves Cardiac Function in a Murine Model of Myocardial Ischemia-Reperfusion Injury Ann. Thorac. Surg., July 1, 2007; 84(1): 120 - 125. [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]
|
|
|
|
|
|
A. Lerman, D. R. Holmes, J. Herrmann, and B. J. Gersh Microcirculatory dysfunction in ST-elevation myocardial infarction: cause, consequence, or both? Eur. Heart J., April 1, 2007; 28(7): 788 - 797. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Wang, H. Fraser, S. G. Lloyd, J. J. McVeigh, L. Belardinelli, and J. C. Chatham A Comparison between Ranolazine and CVT-4325, a Novel Inhibitor of Fatty Acid Oxidation, on Cardiac Metabolism and Left Ventricular Function in Rat Isolated Perfused Heart during Ischemia and Reperfusion J. Pharmacol. Exp. Ther., April 1, 2007; 321(1): 213 - 220. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Wang, C. Zaragoza, and W. Holman Sodium-Hydrogen Exchange Inhibition and {beta}-Blockade Additively Decrease Infarct Size Ann. Thorac. Surg., March 1, 2007; 83(3): 1121 - 1127. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. V. Pierre, C. Yang, Z. Yuan, J. Seminerio, C. Mouas, K. D. Garlid, P. Dos-Santos, and Z. Xie Ouabain triggers preconditioning through activation of the Na+,K+-ATPase signaling cascade in rat hearts Cardiovasc Res, February 1, 2007; 73(3): 488 - 496. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Bolli Preconditioning: a paradigm shift in the biology of myocardial ischemia Am J Physiol Heart Circ Physiol, January 1, 2007; 292(1): H19 - H27. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. P. Taylor, M. E. Olsen, and J. W. Starnes Improved postischemic function following acute exercise is not mediated by nitric oxide synthase in the rat heart Am J Physiol Heart Circ Physiol, January 1, 2007; 292(1): H601 - H607. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Doukas, W. Wrasidlo, G. Noronha, E. Dneprovskaia, R. Fine, S. Weis, J. Hood, A. DeMaria, R. Soll, and D. Cheresh Phosphoinositide 3-kinase {gamma}/{delta} inhibition limits infarct size after myocardial ischemia/reperfusion injury PNAS, December 26, 2006; 103(52): 19866 - 19871. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E K Iliodromitis, S Kyrzopoulos, I A Paraskevaidis, K G Kolocassides, S Adamopoulos, G Karavolias, and D T Kremastinos Increased C reactive protein and cardiac enzyme levels after coronary stent implantation. Is there protection by remote ischaemic preconditioning? Heart, December 1, 2006; 92(12): 1821 - 1826. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. W. Bar, D. Tzivoni, M. T. Dirksen, A. Fernandez-Ortiz, G. R. Heyndrickx, J. Brachmann, J. H.C. Reiber, N. Avasthy, J. Tatsuno, M. Davies, et al. Results of the first clinical study of adjunctive CAldaret (MCC-135) in patients undergoing primary percutaneous coronary intervention for ST-Elevation Myocardial Infarction: the randomized multicentre CASTEMI study Eur. Heart J., November 1, 2006; 27(21): 2516 - 2523. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Theilmeier, C. Schmidt, J. Herrmann, P. Keul, M. Schafers, I. Herrgott, J. Mersmann, J. Larmann, S. Hermann, J. Stypmann, et al. High-Density Lipoproteins and Their Constituent, Sphingosine-1-Phosphate, Directly Protect the Heart Against Ischemia/Reperfusion Injury In Vivo via the S1P3 Lysophospholipid Receptor Circulation, September 26, 2006; 114(13): 1403 - 1409. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. George, G.-H. Yi, A. R. Schulman, B. T. Morrow, Y. Cheng, A. Gu, G. Zhang, M. C. Oz, D. Burkhoff, and J. Wang A polymerized bovine hemoglobin oxygen carrier preserves regional myocardial function and reduces infarct size after acute myocardial ischemia Am J Physiol Heart Circ Physiol, September 1, 2006; 291(3): H1126 - H1137. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. J. Thuerauf, M. Marcinko, N. Gude, M. Rubio, M. A. Sussman, and C. C. Glembotski Activation of the Unfolded Protein Response in Infarcted Mouse Heart and Hypoxic Cultured Cardiac Myocytes Circ. Res., August 4, 2006; 99(3): 275 - 282. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. L. Butler, L. C. Huffman, S. E. Koch, H. S. Hahn, and J. K. Gwathmey STAT-3 activation is necessary for ischemic preconditioning in hypertrophied myocardium Am J Physiol Heart Circ Physiol, August 1, 2006; 291(2): H797 - H803. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Takeda, M. Akao, M. Matsumoto-Ida, M. Kato, H. Takenaka, Y. Kihara, T. Kume, A. Akaike, and T. Kita Serofendic Acid, a Novel Substance Extracted From Fetal Calf Serum, Protects Against Oxidative Stress in Neonatal Rat Cardiac Myocytes J. Am. Coll. Cardiol., May 2, 2006; 47(9): 1882 - 1890. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Zweier and M.A. H. Talukder The role of oxidants and free radicals in reperfusion injury Cardiovasc Res, May 1, 2006; 70(2): 181 - 190. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. Li, Y. Guo, W. Tan, A. B. Stein, B. Dawn, W.-J. Wu, X. Zhu, X. Lu, X. Xu, T. Siddiqui, et al. Gene therapy with iNOS provides long-term protection against myocardial infarction without adverse functional consequences Am J Physiol Heart Circ Physiol, February 1, 2006; 290(2): H584 - H589. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Bolli and A. Abdel-Latif No Pain, No Gain: The Useful Function of Angina Circulation, December 6, 2005; 112(23): 3541 - 3543. [Full Text] [PDF]
|
|
|
|
|
|
J. Tan, Z. Ma, L. Han, R. Du, L. Zhao, X. Wei, D. Hou, B. H. Johnstone, M. R. Farlow, and Y. Du Caffeic acid phenethyl ester possesses potent cardioprotective effects in a rabbit model of acute myocardial ischemia-reperfusion injury Am J Physiol Heart Circ Physiol, November 1, 2005; 289(5): H2265 - H2271. [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]
|
|
|
|
|
|
M. Juhaszova, C. Rabuel, D. B. Zorov, E. G. Lakatta, and S. J. Sollott Protection in the aged heart: preventing the heart-break of old age? Cardiovasc Res, May 1, 2005; 66(2): 233 - 244. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G.-C. Fan, X. Ren, J. Qian, Q. Yuan, P. Nicolaou, Y. Wang, W. K. Jones, G. Chu, and E. G. Kranias Novel Cardioprotective Role of a Small Heat-Shock Protein, Hsp20, Against Ischemia/Reperfusion Injury Circulation, April 12, 2005; 111(14): 1792 - 1799. [Abstract] [Full Text] [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]
|
|
|
|
|
|
J. S. Karliner Symbols within words: Have we neglected the AdeNOsine A2 receptor? Cardiovasc Res, March 1, 2005; 65(4): 763 - 765. [Full Text] [PDF]
|
|