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Review ArticleReview Article

Interaction of Cardiovascular Risk Factors with Myocardial Ischemia/Reperfusion Injury, Preconditioning, and Postconditioning

Peter Ferdinandy, Rainer Schulz and Gary F. Baxter
Pharmacological Reviews December 2007, 59 (4) 418-458; DOI: https://doi.org/10.1124/pr.107.06002
Peter Ferdinandy
Cardiovascular Research Group, Department of Biochemistry, University of Szeged, Szeged, Hungary (P.F.); Pharmahungary Group, Szeged, Hungary (P.F.); Institut für Pathophysiologie, Zentrum für Innere Medizin, Universitasklinikum Essen, Universität Duisburg-Essen, Essen, Germany (R.S.); and Division of Pharmacology, Welsh School of Pharmacy, Cardiff University, Cardiff, UK (G.F.B.)
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Rainer Schulz
Cardiovascular Research Group, Department of Biochemistry, University of Szeged, Szeged, Hungary (P.F.); Pharmahungary Group, Szeged, Hungary (P.F.); Institut für Pathophysiologie, Zentrum für Innere Medizin, Universitasklinikum Essen, Universität Duisburg-Essen, Essen, Germany (R.S.); and Division of Pharmacology, Welsh School of Pharmacy, Cardiff University, Cardiff, UK (G.F.B.)
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Gary F. Baxter
Cardiovascular Research Group, Department of Biochemistry, University of Szeged, Szeged, Hungary (P.F.); Pharmahungary Group, Szeged, Hungary (P.F.); Institut für Pathophysiologie, Zentrum für Innere Medizin, Universitasklinikum Essen, Universität Duisburg-Essen, Essen, Germany (R.S.); and Division of Pharmacology, Welsh School of Pharmacy, Cardiff University, Cardiff, UK (G.F.B.)
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Abstract

Therapeutic strategies to protect the ischemic myocardium have been studied extensively. Reperfusion is the definitive treatment for acute coronary syndromes, especially acute myocardial infarction; however, reperfusion has the potential to exacerbate lethal tissue injury, a process termed “reperfusion injury.” Ischemia/reperfusion injury may lead to myocardial infarction, cardiac arrhythmias, and contractile dysfunction. Ischemic preconditioning of myocardium is a well described adaptive response in which brief exposure to ischemia/reperfusion before sustained ischemia markedly enhances the ability of the heart to withstand a subsequent ischemic insult. Additionally, the application of brief repetitive episodes of ischemia/reperfusion at the immediate onset of reperfusion, which has been termed “postconditioning,” reduces the extent of reperfusion injury. Ischemic pre- and postconditioning share some but not all parts of the proposed signal transduction cascade, including the activation of survival protein kinase pathways. Most experimental studies on cardioprotection have been undertaken in animal models, in which ischemia/reperfusion is imposed in the absence of other disease processes. However, ischemic heart disease in humans is a complex disorder caused by or associated with known cardiovascular risk factors including hypertension, hyperlipidemia, diabetes, insulin resistance, atherosclerosis, and heart failure; additionally, aging is an important modifying condition. In these diseases and aging, the pathological processes are associated with fundamental molecular alterations that can potentially affect the development of ischemia/reperfusion injury per se and responses to cardioprotective interventions. Among many other possible mechanisms, for example, in hyperlipidemia and diabetes, the pathological increase in reactive oxygen and nitrogen species and the use of the ATP-sensitive potassium channel inhibitor insulin secretagogue antidiabetic drugs and, in aging, the reduced expression of connexin-43 and signal transducer and activator of transcription 3 may disrupt major cytoprotective signaling pathways thereby significantly interfering with the cardioprotective effect of pre- and postconditioning. The aim of this review is to show the potential for developing cardioprotective drugs on the basis of endogenous cardioprotection by pre- and postconditioning (i.e., drug applied as trigger or to activate signaling pathways associated with endogenous cardioprotection) and to review the evidence that comorbidities and aging accompanying coronary disease modify responses to ischemia/reperfusion and the cardioprotection conferred by preconditioning and postconditioning. We emphasize the critical need for more detailed and mechanistic preclinical studies that examine car-dioprotection specifically in relation to complicating disease states. These are now essential to maximize the likelihood of successful development of rational approaches to therapeutic protection for the majority of patients with ischemic heart disease who are aged and/or have modifying comorbid conditions.

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Pharmacological Reviews: 59 (4)
Pharmacological Reviews
Vol. 59, Issue 4
1 Dec 2007
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Review ArticleReview Article

Interaction of Cardiovascular Risk Factors with Myocardial Ischemia/Reperfusion Injury, Preconditioning, and Postconditioning

Peter Ferdinandy, Rainer Schulz and Gary F. Baxter
Pharmacological Reviews December 1, 2007, 59 (4) 418-458; DOI: https://doi.org/10.1124/pr.107.06002

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Review ArticleReview Article

Interaction of Cardiovascular Risk Factors with Myocardial Ischemia/Reperfusion Injury, Preconditioning, and Postconditioning

Peter Ferdinandy, Rainer Schulz and Gary F. Baxter
Pharmacological Reviews December 1, 2007, 59 (4) 418-458; DOI: https://doi.org/10.1124/pr.107.06002
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  • Article
    • Abstract
    • I. Introduction
    • II. Introduction to Endpoints of Ischemia/Reperfusion Injury and Experimental Approaches to Cardioprotection
    • III. Animal Models and Human Studies of Cardioprotective Strategies
    • IV. Effects of Major Risk Factors on Ischemia/Reperfusion Injury and Cardioprotective Strategies
    • V. Conclusions and Perspectives
    • Acknowledgments
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