(Circulation. 2000;102:3032.)
© 2000 American Heart Association, Inc.
Clinical Investigation and Reports |
Inhibition of the Sodium-Hydrogen Exchanger With Cariporide to Prevent Myocardial Infarction in High-Risk Ischemic Situations
Main Results of the GUARDIAN Trial
Background—The transmembrane sodium/hydrogen exchanger maintains myocardial cell pH integrity during myocardial ischemia but paradoxically may precipitate cell necrosis. The development of cariporide, a potent and specific inhibitor of the exchanger, prompted this investigation of the potential of the drug to prevent myocardial cell necrosis.
Methods and Results—A total of 11 590 patients with unstable angina or non–ST-elevation myocardial infarction (MI) or undergoing high-risk percutaneous or surgical revascularization were randomized to receive placebo or 1 of 3 doses of cariporide for the period of risk. The trial failed to document benefit of cariporide over placebo on the primary end point of death or MI assessed after 36 days. Doses of 20 and 80 mg every 8 hours had no effect, whereas a dose of 120 mg was associated with a 10% risk reduction (98% CI 5.5% to 23.4%, P=0.12). With this dose, benefit was limited to patients undergoing bypass surgery (risk reduction 25%, 95% CI 3.1% to 41.5%, P=0.03) and was maintained after 6 months. No effect was seen on mortality. The rate of Q-wave MI was reduced by 32% across all entry diagnostic groups (2.6% versus 1.8%, P=0.03), but the rate of non–Q-wave MI was reduced only in patients undergoing surgery (7.1% versus 3.8%, P=0.005). There were no increases in clinically serious adverse events.
Conclusions—No significant benefit of cariporide could be demonstrated across a wide range of clinical situations of risk. The trial documented safety of the drug and suggested that a high degree of inhibition of the exchanger could prevent cell necrosis in settings of ischemia-reperfusion.
Key Words: ischemia • myocardial infarction • cardiopulmonary bypass • necrosis • cariporide
This article has been cited by other articles:
 |
|
 |
|
  J. Inserte, J. A. Barrabes, V. Hernando, and D. Garcia-Dorado Orphan targets for reperfusion injury Cardiovasc Res, July 15, 2009; 83(2): 169 - 178. [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]
|
|
|
|
 |
|
 S. E. McAllister, M. A. Moses, K. Jindal, H. Ashrafpour, N. J. Cahoon, N. Huang, P. C. Neligan, C. R. Forrest, J. E. Lipa, and C. Y. Pang Na+/H+ exchange inhibitor cariporide attenuates skeletal muscle infarction when administered before ischemia or reperfusion J Appl Physiol, January 1, 2009; 106(1): 20 - 28. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. K. Kaba, J. Schultz, F.-Y. Law, C. T. Lefort, G. Martel-Gallegos, M. Kim, R. E. Waugh, J. Arreola, and P. A. Knauf Inhibition of Na+/H+ exchanger enhances low pH-induced L-selectin shedding and {beta}2-integrin surface expression in human neutrophils Am J Physiol Cell Physiol, November 1, 2008; 295(5): C1454 - C1463. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. R. Schelling and B. G. Abu Jawdeh Regulation of cell survival by Na+/H+ exchanger-1 Am J Physiol Renal Physiol, September 1, 2008; 295(3): F625 - F632. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. W. Stone Angioplasty Strategies in ST-Segment-Elevation Myocardial Infarction: Part II: Intervention After Fibrinolytic Therapy, Integrated Treatment Recommendations, and Future Directions Circulation, July 29, 2008; 118(5): 552 - 566. [Full Text] [PDF]
|
|
|
|
 |
|
 MEND-CABG II Investigators* Efficacy and Safety of Pyridoxal 5'-Phosphate (MC-1) in High-Risk Patients Undergoing Coronary Artery Bypass Graft Surgery: The MEND-CABG II Randomized Clinical Trial JAMA, April 16, 2008; 299(15): 1777 - 1787. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. M. Mentzer Jr, C. Bartels, R. Bolli, S. Boyce, G. D. Buckberg, B. Chaitman, A. Haverich, J. Knight, P. Menasche, M. L. Myers, et al. Sodium-Hydrogen Exchange Inhibition by Cariporide to Reduce the Risk of Ischemic Cardiac Events in Patients Undergoing Coronary Artery Bypass Grafting: Results of the EXPEDITION Study Ann. Thorac. Surg., April 1, 2008; 85(4): 1261 - 1270. [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]
|
|
|
|
 |
|
 P. A. Grayburn and J. W. Choi Advances in the assessment of no-reflow after successful primary percutaneous coronary intervention for acute ST-segment elevation myocardial infarction: now that we can diagnose it, what do we do about it? J. Am. Coll. Cardiol., February 5, 2008; 51(5): 566 - 568. [Full Text] [PDF]
|
|
|
|
 |
|
 I. George and M. C. Oz Myocardial Revascularization after Acute Myocardial Infarction Card. Surg. Adult, January 1, 2008; 3(2008): 669 - 696. [Full Text]
|
|
|
|
 |
|
 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. Tardif, M. Carrier, D. E. Kandzari, R. Emery, R. Cote, T. Heinonen, M. Zettler, V. Hasselblad, M.-C. Guertin, R. A. Harrington, et al. Effects of pyridoxal-5'-phosphate (MC-1) in patients undergoing high-risk coronary artery bypass surgery: Results of the MEND-CABG randomized study J. Thorac. Cardiovasc. Surg., June 1, 2007; 133(6): 1604 - 1611. [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]
|
|
|
|
 |
|
 K. Imahashi, F. Mraiche, C. Steenbergen, E. Murphy, and L. Fliegel Overexpression of the Na+/H+ exchanger and ischemia-reperfusion injury in the myocardium Am J Physiol Heart Circ Physiol, May 1, 2007; 292(5): H2237 - H2247. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. G. Perez, M. R. Piaggio, I. L. Ennis, C. D. Garciarena, C. Morales, E. M. Escudero, O. H. Cingolani, G. Chiappe de Cingolani, X.-P. Yang, and H. E. Cingolani Phosphodiesterase 5A Inhibition Induces Na+/H+ Exchanger Blockade and Protection Against Myocardial Infarction Hypertension, May 1, 2007; 49(5): 1095 - 1103. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. R. Schmidt, M. Smerup, I. E. Konstantinov, M. Shimizu, J. Li, M. Cheung, P. A. White, S. B. Kristiansen, K. Sorensen, V. Dzavik, et al. Intermittent peripheral tissue ischemia during coronary ischemia reduces myocardial infarction through a KATP-dependent mechanism: first demonstration of remote ischemic perconditioning Am J Physiol Heart Circ Physiol, April 1, 2007; 292(4): H1883 - H1890. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. E. Cingolani and I. L. Ennis Sodium-Hydrogen Exchanger, Cardiac Overload, and Myocardial Hypertrophy Circulation, March 6, 2007; 115(9): 1090 - 1100. [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]
|
|
|
|
|
|
N. Maekawa, J.-i. Abe, T. Shishido, S. Itoh, B. Ding, V. K. Sharma, S.-S. Sheu, B. C. Blaxall, and B. C. Berk Inhibiting p90 Ribosomal S6 Kinase Prevents Na+-H+ Exchanger-Mediated Cardiac Ischemia-Reperfusion Injury Circulation, May 30, 2006; 113(21): 2516 - 2523. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Castella, G. D. Buckberg, and S. Saleh Diastolic dysfunction in stunned myocardium: a state of abnormal excitation-contraction coupling that is limited by Na+-H+ exchange inhibition Eur. J. Cardiothorac. Surg., April 1, 2006; 29(Suppl_1): S107 - S114. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Additional Information JAMA, March 15, 2006; 295(11): E1 - E6. [Full Text] [PDF]
|
|
|
|
|
|
J. Herrmann Peri-procedural myocardial injury: 2005 update Eur. Heart J., December 1, 2005; 26(23): 2493 - 2519. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. Yang and G.-W. He Effect of Cardioplegic and Organ Preservation Solutions and Their Components on Coronary Endothelium-Derived Relaxing Factors Ann. Thorac. Surg., August 1, 2005; 80(2): 757 - 767. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Ross, R. J. Gibbons, G. W. Stone, R. A. Kloner, R. W. Alexander, and for the AMISTAD-II Investigators A Randomized, Double-Blinded, Placebo-Controlled Multicenter Trial of Adenosine as an Adjunct to Reperfusion in the Treatment of Acute Myocardial Infarction (AMISTAD-II) J. Am. Coll. Cardiol., June 7, 2005; 45(11): 1775 - 1780. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Kevelaitis, A. A. Qureshi, C. Mouas, F. Marotte, S. Kevelaitiene, M. Avkiran, and P. Menasche Na+/H+ exchange inhibition in hypertrophied myocardium subjected to cardioplegic arrest: an effective cardioprotective approach Eur. J. Cardiothorac. Surg., January 1, 2005; 27(1): 111 - 116. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Lee, N. S. Visen, N. S. Dhalla, H. D. Le, M. Isaac, P. Choptiany, G. Gross, A. Omelchenko, T. Matsuda, A. Baba, et al. Inhibitory Profile of SEA0400 [2-[4-[(2,5-Difluorophenyl)methoxy]phenoxy]-5-ethoxyaniline] Assessed on the Cardiac Na+-Ca2+ Exchanger, NCX1.1 J. Pharmacol. Exp. Ther., November 1, 2004; 311(2): 748 - 757. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Bolli, L. Becker, G. Gross, R. Mentzer Jr, D. Balshaw, and D. A. Lathrop Myocardial Protection at a Crossroads: The Need for Translation Into Clinical Therapy Circ. Res., July 23, 2004; 95(2): 125 - 134. [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]
|
|
|
|
|
|
E. D. Verrier, S. K. Shernan, K. M. Taylor, F. Van de Werf, M. F. Newman, J. C. Chen, M. Carrier, A. Haverich, K. J. Malloy, P. X. Adams, et al. Terminal Complement Blockade With Pexelizumab During Coronary Artery Bypass Graft Surgery Requiring Cardiopulmonary Bypass: A Randomized Trial JAMA, May 19, 2004; 291(19): 2319 - 2327. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Fujii, M. Avkiran, and D. J Chambers Experimental studies on myocardial protection with intermittent cross-clamp fibrillation: additive effect of the sodium-hydrogen exchanger inhibitor, cariporide Ann. Thorac. Surg., April 1, 2004; 77(4): 1398 - 1407. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Eefting, B. Rensing, J. Wigman, W. J. Pannekoek, W. M. Liu, M. J. Cramer, D. J Lips, and P. A Doevendans Role of apoptosis in reperfusion injury Cardiovasc Res, February 15, 2004; 61(3): 414 - 426. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. M. Stevens, M. Salik Jahania, R. M. Mentzer Jr, and R. D. Lasley Sodium-hydrogen exchange inhibition attenuates in vivo porcine myocardial stunning Ann. Thorac. Surg., February 1, 2004; 77(2): 651 - 657. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Eichler, M. J. Bechtel, S. Klaus, M. Heringlake, M. Hernandez, K. Toerber, K.-F. Klotz, and C. Bartels Na+/H+exchange inhibitor cariporide: effects on respiratory dysfunction after cardiopulmonary bypass Perfusion, January 1, 2004; 19(1): 33 - 40. [Abstract] [PDF]
|
|
|
|
|
|
L. Chen, C. X. Chen, X. T. Gan, N. Beier, W. Scholz, and M. Karmazyn Inhibition and reversal of myocardial infarction-induced hypertrophy and heart failure by NHE-1 inhibition Am J Physiol Heart Circ Physiol, January 1, 2004; 286(1): H381 - H387. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Nicolini, C. Beghi, C. Muscari, A. Agostinelli, A. M. Budillon, I. Spaggiari, and T. Gherli Myocardial protection in adult cardiac surgery: current options and future challenges Eur. J. Cardiothorac. Surg., December 1, 2003; 24(6): 986 - 993. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. M. Yarbrough, R. Mukherjee, G. P. Escobar, J. W. Hendrick, J. A. Sample, K. B. Dowdy, J. E. McLean, J. T. Mingoia, F. A. Crawford Jr, and F. G. Spinale Modulation of calcium transport improves myocardial contractility and enzyme profiles after prolonged ischemia-reperfusion Ann. Thorac. Surg., December 1, 2003; 76(6): 2054 - 2061. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Pernow, F. Bohm, E. Beltran, and A. Gonon L-Arginine protects from ischemia-reperfusion-induced endothelial dysfunction in humans in vivo J Appl Physiol, December 1, 2003; 95(6): 2218 - 2222. [Abstract] [Full Text]
|
|
|
|
|
|
Y. Teshima, M. Akao, S. P. Jones, and E. Marban Cariporide (HOE642), a Selective Na+-H+ Exchange Inhibitor, Inhibits the Mitochondrial Death Pathway Circulation, November 4, 2003; 108(18): 2275 - 2281. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. S. Corvera, Z.-Q. Zhao, L. S. Schmarkey, S. L. Katzmark, J. M. Budde, C. D. Morris, T. Ehring, R. A. Guyton, and J. Vinten-Johansen Optimal dose and mode of delivery of Na+/H+ exchange-1 inhibitor are critical for reducing postsurgical ischemia-reperfusion injury Ann. Thorac. Surg., November 1, 2003; 76(5): 1614 - 1622. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Castella, G. D. Buckberg, S. Saleh, Z. Tan, and L. J. Ignarro A new role for cardioplegic buffering: should acidosis or calcium accumulation be counteracted to salvage jeopardized hearts? J. Thorac. Cardiovasc. Surg., November 1, 2003; 126(5): 1442 - 1448. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. M. Yarbrough, R. Mukherjee, G. P. Escobar, J. T. Mingoia, J. A. Sample, J. W. Hendrick, K. B. Dowdy, J. E. McLean, R. E. Stroud, and F. G. Spinale Direct inhibition of the sodium/hydrogen exchanger after prolonged regional ischemia improves contractility on reperfusion independent of myocardial viability J. Thorac. Cardiovasc. Surg., November 1, 2003; 126(5): 1489 - 1497. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H.E. Cingolani, I.L. Ennis, and S.M. Mosca NHE-1 and NHE-6 Activities: Ischemic and Reperfusion Injury Circ. Res., October 17, 2003; 93(8): 694 - 696. [Full Text] [PDF]
|
|
|
|
|
|
Y. Wang, J. W. Meyer, M. Ashraf, and G. E. Shull Mice With a Null Mutation in the NHE1 Na+-H+ Exchanger Are Resistant to Cardiac Ischemia-Reperfusion Injury Circ. Res., October 17, 2003; 93(8): 776 - 782. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. C. Herrmann Optimizing outcomes in ST-segment elevation myocardial infarction J. Am. Coll. Cardiol., October 15, 2003; 42(8): 1357 - 1359. [Full Text] [PDF]
|
|
|
|
|
|
D. G. Rabkin, S. E. Cabreriza, F. H. Cheema, A. A. Hill, L. J. Curtis, R. R. Sciacca, R. S. Mosca, and H. M. Spotnitz Cariporide is cardioprotective after iatrogenic ventricular fibrillation in the intact swine heart Ann. Thorac. Surg., October 1, 2003; 76(4): 1264 - 1269. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Gavard, B. R. Chaitman, S. Sakai, K. Stocke, N. Danchin, L. Erhardt, R. Gallo, E. Chi, A. Jessel, and P. Theroux Prognostic significance of elevated creatine kinase MB after coronary bypass surgery and after an acute coronary syndrome: results from the GUARDIAN trial J. Thorac. Cardiovasc. Surg., September 1, 2003; 126(3): 807 - 813. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. M. Mentzer Jr Does size matter? What is your infarct rate after coronary artery bypass grafting? J. Thorac. Cardiovasc. Surg., August 1, 2003; 126(2): 326 - 328. [Full Text] [PDF]
|
|
|
|
|
|
S. W. Boyce, C. Bartels, R. Bolli, B. Chaitman, J. C. Chen, E. Chi, A. Jessel, D. Kereiakes, J. Knight, L. Thulin, et al. Impact of sodium-hydrogen exchange inhibition by cariporide on death or myocardial infarction in high-risk CABG surgery patients: results of the CABG surgery cohort of the GUARDIAN study J. Thorac. Cardiovasc. Surg., August 1, 2003; 126(2): 420 - 427. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K.W. Lee and G.Y.H. Lip The role of omega-3 fatty acids in the secondary prevention of cardiovascular disease QJM, July 1, 2003; 96(7): 465 - 480. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K.-H. Mak and D. P. Faxon Clinical studies on coronary revascularization in patients with type 2 diabetes Eur. Heart J., June 2, 2003; 24(12): 1087 - 1103. [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]
|
|
|
|
|
|
D. G. Rabkin, S. E. Cabreriza, J. C. LaCorte, A. D. Weinberg, L. Coku, R. Walsh, R. Mosca, and H. M. Spotnitz Sodium-hydrogen exchange inhibition preserves ventricular function after ventricular fibrillation in the intact swine heart J. Thorac. Cardiovasc. Surg., June 1, 2003; 125(6): 1499 - 1509. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. J. Reshkin, A. Bellizzi, R. A. Cardone, M. Tommasino, V. Casavola, and A. Paradiso Paclitaxel Induces Apoptosis via Protein Kinase A- and p38 Mitogen-activated Protein-dependent Inhibition of the Na+/H+ Exchanger (NHE) NHE Isoform 1 in Human Breast Cancer Cells Clin. Cancer Res., June 1, 2003; 9(6): 2366 - 2373. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Castella, G. D. Buckberg, and Z. Tan Blood cardioplegic protection in profoundly damaged hearts: role of Na+-H+ exchange inhibition during pretreatment or during controlled reperfusion supplementation Ann. Thorac. Surg., April 1, 2003; 75(4): 1238 - 1245. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. G Allen and X.-H. Xiao Role of the cardiac Na+/H+ exchanger during ischemia and reperfusion Cardiovasc Res, March 15, 2003; 57(4): 934 - 941. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Avkiran and R. S Haworth Regulatory effects of G protein-coupled receptors on cardiac sarcolemmal Na+/H+ exchanger activity: signalling and significance Cardiovasc Res, March 15, 2003; 57(4): 942 - 952. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A Baartscheer, C.A Schumacher, M.M.G.J van Borren, C.N.W Belterman, R Coronel, and J.W.T Fiolet Increased Na+/H+-exchange activity is the cause of increased [Na+]i and underlies disturbed calcium handling in the rabbit pressure and volume overload heart failure model Cardiovasc Res, March 15, 2003; 57(4): 1015 - 1024. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. P. Magee, G. Deshmukh, M. P. Deninno, J. C. Sutt, J. G. Chapman, and W. R. Tracey Differing cardioprotective efficacy of the Na+/Ca2+ exchanger inhibitors SEA0400 and KB-R7943 Am J Physiol Heart Circ Physiol, March 1, 2003; 284(3): H903 - H910. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. M. Mentzer Jr, R. D. Lasley, A. Jessel, and M. Karmazyn Intracellular sodium hydrogen exchange inhibition and clinical myocardial protection Ann. Thorac. Surg., February 1, 2003; 75(2): S700 - 708. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Muraki, C. D. Morris, J. M. Budde, Z.-Q. Zhao, R. A. Guyton, and J. Vinten-Johansen Blood cardioplegia supplementation with the sodium-hydrogen ion exchange inhibitor cariporide to attenuate infarct size and coronary artery endothelial dysfunction after severe regional ischemia in a canine model J. Thorac. Cardiovasc. Surg., January 1, 2003; 125(1): 155 - 164. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. S. Cox Jr, S. J. Allen, H. Sauer, and G. A. Laine Improved Myocardial Function Using a Na+/H+ Exchanger Inhibitor During Cardioplegic Arrest and Cardiopulmonary Bypass Chest, January 1, 2003; 123(1): 187 - 194. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. M. Mentzer Jr., M. S. Jahania, and R. D. Lasley Myocardial Protection Card. Surg. Adult, January 1, 2003; 2(2003): 413 - 438. [Full Text]
|
|
|
|
|
|
M. Castella, G. D. Buckberg, Z. Tan, and L. J. Ignarro Myocyte and endothelial effects of preconditioning the jeopardized heart by inhibiting Na+/H+ exchange J. Thorac. Cardiovasc. Surg., December 1, 2002; 124(6): 1113 - 1121. [Abstract] [Full Text]
|
|
|
|
 |
|
 S.-r. Wann, M. H. Weil, S. Sun, W. Tang, and T. Yu Cariporide for Pharmacologic Defibrillation After Prolonged Cardiac Arrest Journal of Cardiovascular Pharmacology and Therapeutics, September 1, 2002; 7(3): 161 - 169. [Abstract] [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]
|
|
|
|
|
|
S. C. Smith Jr, D. Faxon, W. Cascio, H. Schaff, T. Gardner, A. Jacobs, S. Nissen, and R. Stouffer Prevention Conference VI: Diabetes and Cardiovascular Disease: Writing Group VI: Revascularization in Diabetic Patients Circulation, May 7, 2002; 105 (18): e165 - e169. [Full Text] [PDF]
|
|
|
|
|
|
K. Shinagawa, H. Mitamura, S. Ogawa, and S. Nattel Effects of inhibiting Na+/H+-exchange or angiotensin converting enzyme on atrial tachycardia-induced remodeling Cardiovasc Res, May 1, 2002; 54(2): 438 - 446. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Avkiran and M. S. Marber Na+/h+ exchange inhibitors for cardioprotective therapy: progress, problems and prospects J. Am. Coll. Cardiol., March 6, 2002; 39(5): 747 - 753. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. K Snabaitis, D. J Hearse, and M. Avkiran Regulation of sarcolemmal Na+/H+ exchange by hydrogen peroxide in adult rat ventricular myocytes Cardiovasc Res, February 1, 2002; 53(2): 470 - 480. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Zeymer, H. Suryapranata, J. P. Monassier, G. Opolski, J. Davies, G. Rasmanis, G. Linssen, U. Tebbe, R. Schroder, R. Tiemann, et al. The Na+/H+ exchange inhibitor eniporide as an adjunct to early reperfusion therapy for acute myocardial infarction: Results of the evaluation of the safety and cardioprotective effects of eniporide in acute myocardial infarction (ESCAMI) trial J. Am. Coll. Cardiol., November 15, 2001; 38(6): 1644 - 1650. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. B. A. Menown and A. A. J. Adgey Cardioprotective therapy and sodium-hydrogen exchange inhibition: current concepts and future goals J. Am. Coll. Cardiol., November 15, 2001; 38(6): 1651 - 1653. [Full Text] [PDF]
|
|
|
|
 |
|
 N. Danchin Recent advances in cardioprotection during myocardial revascularization procedures: benefit of a metabolic intervention Eur. Heart J. Suppl., November 1, 2001; 3(suppl_O): O21 - O25. [Abstract] [PDF]
|
|