Why Do We Still Not Have Cardioprotective Drugs?
- 1 January 2009
- journal article
- review article
- Published by Japanese Circulation Society in Circulation Journal
- Vol. 73 (7), 1171-1177
- https://doi.org/10.1253/circj.cj-09-0338
Abstract
Despite thousands of publications describing agents that limit infarct size in animals, all we have available today is reperfusion therapy. In this review, we examine why these drugs have not been translated into clinical practice. Many of the first interventions tested in clinical trials were very controversial in animal trials and their actual efficacy is still in question. Interventions based on the preconditioning mechanism have been very reproducible in animals, but clinical testing of them has just begun. Only approximately 25% of reperfused patients have infarcts large enough to put them at risk of heart failure and would require additional treatment. Inclusion of the 75% of patients with small infarcts in treatment groups has greatly diluted the significance of data in past clinical trials. Size of the risk zone has emerged as a reliable way to identify the vulnerable 25%. Recent small-scale clinical trials using risk stratification algorithms have shown clear infarct size limitation using ischemic and pharmacological postconditioning, confirming that the human heart responds like hearts of animal models. Most cardioprotectants have been studied in healthy animals, but recent studies indicate that aging and diabetes, common in coronary patients, do interfere with preconditioning-based interventions in animals. Clearly more study is needed to identify which interventions are adversely affected by comorbidities.Keywords
This publication has 46 references indexed in Scilit:
- Infarct limitation by a protein kinase G activator at reperfusion in rabbit hearts is dependent on sensitizing the heart to A2b agonists by protein kinase CAmerican Journal of Physiology-Heart and Circulatory Physiology, 2008
- Protein kinase C protects preconditioned rabbit hearts by increasing sensitivity of adenosine A2b-dependent signaling during early reperfusionJournal of Molecular and Cellular Cardiology, 2007
- The pH Hypothesis of PostconditioningCirculation, 2007
- Ability of mechanical reperfusion to salvage myocardium in patients with acute myocardial infarction presenting beyond 12 hours after onset of symptomsAmerican Heart Journal, 2006
- Comparison Between Nicorandil and Magnesium as an Adjunct Cardioprotective Agent to Percutaneous Coronary Intervention in Acute Anterior Myocardial InfarctionCirculation Journal, 2004
- Grade III Ischemia on Presentation with Acute Myocardial Infarction Predicts Rapid Progression of Necrosis and Less Myocardial Salvage with ThrombolysisCardiology, 2002
- Aging Reduces the Cardioprotective Effect of Ischemic Preconditioning in the Rat HeartJournal of Molecular and Cellular Cardiology, 2000
- Infarct Size Limitation by a New Na-H Exchange Inhibitor, Hoe 642: Difference From Preconditioning in the Role of Protein Kinase CJournal of the American College of Cardiology, 1997
- Effect of adenosine therapy at reperfusion on myocardial infarct size in dogsCardiovascular Research, 1996
- Factors Influencing Infarct Size Following Experimental Coronary Artery OcclusionsCirculation, 1971