Abstract
Cardioprotective interventions are defined as interventions able to increase myocardial resistance to ischemia. The authors approach the issue of cardioprotection on the basis of the present knowledge about the biochemical mechanisms responsible for the injury produced by myocardial ischemia or ischemia-reperfusion. Reversible and irreversible injury are distinguished. The former is largely accounted for by the direct consequences of reduced ATP synthesis, which causes decreased ATP phosphorylation potential, acidosis and phosphate accumulation. The biochemical mechanisms leading to irreversible injury include osmotic overload, production of toxic lipid metabolites, cytosolic calcium overload, and generation of reactive oxygen species, which lead to membrane disruption, mitochondrial dysfunction and possibly to the activation of apoptotic pathways. The major effect of the classical cardioprotective agents (nitrates, beta adrenergic antagonists, calcium channel blockers) consists in affecting ATP demand/supply ratio in such a way as to delay the decrease in ATP phosphorylation potential. Other drugs have been introduced, which allegedly interfere directly with the mechanisms responsible for irreversible ischemic injury. These include 3-ketoacyl-CoA tiolase inhibitors, modulators of intracellular calcium channels, ionic exchanger inhibitors, free radical scavengers, caspase inhibitors, purinergic agonists, K+ ATP channel openers, and modulators of mitochondrial permeability transition. The results obtained with these substances in experimental models and in the clinical setting are discussed. Special attention is devoted to angiotensin converting enzyme inhibitors, whose direct cardioprotective properties has recently been demonstrated.
Keywords: Angiotensin converting enzyme inhibitors (ACEis), beta blockers, calcium antagonists, free radicals, ischemia, myocardial infarction, nitric oxide (NO), preconditioning, reperfusion
Current Medicinal Chemistry
Title: Biochemical Basis of Ischemic Heart Injury and of Cardioprotective Interventions
Volume: 14 Issue: 15
Author(s): R. Zucchi, S. Ghelardoni and S. Evangelista
Affiliation:
Keywords: Angiotensin converting enzyme inhibitors (ACEis), beta blockers, calcium antagonists, free radicals, ischemia, myocardial infarction, nitric oxide (NO), preconditioning, reperfusion
Abstract: Cardioprotective interventions are defined as interventions able to increase myocardial resistance to ischemia. The authors approach the issue of cardioprotection on the basis of the present knowledge about the biochemical mechanisms responsible for the injury produced by myocardial ischemia or ischemia-reperfusion. Reversible and irreversible injury are distinguished. The former is largely accounted for by the direct consequences of reduced ATP synthesis, which causes decreased ATP phosphorylation potential, acidosis and phosphate accumulation. The biochemical mechanisms leading to irreversible injury include osmotic overload, production of toxic lipid metabolites, cytosolic calcium overload, and generation of reactive oxygen species, which lead to membrane disruption, mitochondrial dysfunction and possibly to the activation of apoptotic pathways. The major effect of the classical cardioprotective agents (nitrates, beta adrenergic antagonists, calcium channel blockers) consists in affecting ATP demand/supply ratio in such a way as to delay the decrease in ATP phosphorylation potential. Other drugs have been introduced, which allegedly interfere directly with the mechanisms responsible for irreversible ischemic injury. These include 3-ketoacyl-CoA tiolase inhibitors, modulators of intracellular calcium channels, ionic exchanger inhibitors, free radical scavengers, caspase inhibitors, purinergic agonists, K+ ATP channel openers, and modulators of mitochondrial permeability transition. The results obtained with these substances in experimental models and in the clinical setting are discussed. Special attention is devoted to angiotensin converting enzyme inhibitors, whose direct cardioprotective properties has recently been demonstrated.
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Cite this article as:
Zucchi R., Ghelardoni S. and Evangelista S., Biochemical Basis of Ischemic Heart Injury and of Cardioprotective Interventions, Current Medicinal Chemistry 2007; 14 (15) . https://dx.doi.org/10.2174/092986707780831014
DOI https://dx.doi.org/10.2174/092986707780831014 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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