Copyright © 2007, European Society of Cardiology
Reperfusion injury in humans: A review of clinical trials on reperfusion injury inhibitory strategies
aAmsterdam Department of Interventional Cardiology, Onze Lieve Vrouwe Gasthuis, Amsterdam, The Netherlands
bDepartment of Cardiology, Erasmus Medical Center, Rotterdam, The Netherlands
* Corresponding author. Department of Cardiology, Onze Lieve Vrouwe Gasthuis, Oosterpark 9, 1090 HM Amsterdam, The Netherlands. Tel.: +31 20 5993032; fax: +31 20 5993120. Email address: g.j.laarman{at}olvg.nl
The principal therapy in patients with myocardial infarction to limit infarct size is myocardial reperfusion by mechanical or pharmacological intervention. Reperfusion has been proposed to cause myocardial injury beyond that caused by the preceding ischaemia, termed "reperfusion injury" (RI). While the precise mechanism of RI is still incompletely understood, a large number of clinical studies have been performed over the past decade targeting some of the postulated mechanisms of RI. These clinical studies were based on experimental data demonstrating significant myocardial salvage. Nevertheless, clinical benefits were absent or very limited. The purpose of this review is to provide an overview of the various strategies that inhibit RI and to discuss potential mechanisms that may contribute to the discrepancy between the promising pre-clinical data and the rather disappointing results obtained from prospective clinical trials. There are numerous differences between the experimental models and clinical studies, including the fact that experimental studies typically use abrupt occlusion and reperfusion protocols in animals with previously healthy myocardium that apparently do not predict the therapeutic efficacy of novel cardioprotective agents in a clinical setting with pre-existing progressive coronary disease, intermittent coronary occlusion, and relatively late reperfusion. However, discrepancies also exist between experimental studies. Future experimental studies of reperfusion injury should use models that mimic the clinical situation more closely. Furthermore, future large clinical trials should only be performed in cases where the drug under investigation proved to reduce RI in a series of well-designed (possibly multicenter) experimental studies and in clinical trials with predefined subgroups.
KEYWORDS Reperfusion injury; Review; Experimental; Clinical; Acute myocardial infarction; Reperfusion
Time for primary review 31 days
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M.A. H. Talukder, J. L. Zweier, and M. Periasamy Targeting calcium transport in ischaemic heart disease Cardiovasc Res, December 1, 2009; 84(3): 345 - 352. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 A. S. Wechsler and J. Y. Kresh Of Mice and Men (and Effects of Gene Silencing) Circulation, September 22, 2009; 120(12): 1027 - 1028. [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
 |
|
 J. Ganame, G. Messalli, S. Dymarkowski, F. E. Rademakers, W. Desmet, F. Van de Werf, and J. Bogaert Impact of myocardial haemorrhage on left ventricular function and remodelling in patients with reperfused acute myocardial infarction Eur. Heart J., June 2, 2009; 30(12): 1440 - 1449. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Majidi, A. S. Kosinski, S. M. Al-Khatib, M. E. Lemmert, L. Smolders, A. van Weert, J. H.C. Reiber, D. Tzivoni, F. W.H.M. Bar, H. J.J. Wellens, et al. Reperfusion ventricular arrhythmia 'bursts' predict larger infarct size despite TIMI 3 flow restoration with primary angioplasty for anterior ST-elevation myocardial infarction Eur. Heart J., April 1, 2009; 30(7): 757 - 764. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. C. Wu Fighting the "Fire" of Myocardial Reperfusion Injury: How to Define Success? J. Am. Coll. Cardiol., February 24, 2009; 53(8): 730 - 731. [Full Text] [PDF]
|
|
|
|
|
|
D. Atar, P. Petzelbauer, J. Schwitter, K. Huber, B. Rensing, J. D. Kasprzak, C. Butter, L. Grip, P. R. Hansen, T. Suselbeck, et al. Effect of Intravenous FX06 as an Adjunct to Primary Percutaneous Coronary Intervention for Acute ST-Segment Elevation Myocardial Infarction: Results of the F.I.R.E. (Efficacy of FX06 in the Prevention of Myocardial Reperfusion Injury) Trial J. Am. Coll. Cardiol., February 24, 2009; 53(8): 720 - 729. [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]
|
|
|
|
|
|
Z. Cai, H. Zhong, M. Bosch-Marce, K. Fox-Talbot, L. Wang, C. Wei, M. A. Trush, and G. L. Semenza Complete loss of ischaemic preconditioning-induced cardioprotection in mice with partial deficiency of HIF-1{alpha} Cardiovasc Res, February 1, 2008; 77(3): 463 - 470. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Carles, J. Dellamonica, J. Roux, D. Lena, J. Levraut, J. F. Pittet, P. Boileau, and M. Raucoules-Aime Sevoflurane but not propofol increases interstitial glycolysis metabolites availability during tourniquet-induced ischaemia reperfusion Br. J. Anaesth., January 1, 2008; 100(1): 29 - 35. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Kaneda Complex Roles of Endothelial Shear Stress in Vascular Remodeling Response J. Am. Coll. Cardiol., November 27, 2007; 50(22): 2171 - 2171. [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]
|
|