Cardioprotective-Mimetics Reduce Myocardial Infarct Size in Animals Resistant to Ischemic Preconditioning

Gumina, Richard J.; Schultz, Jo El J.; Moore, Jeanine; Beier, Norbert; Schelling, Pierre; Gross, Garrett J.

doi:10.1007/s10557-005-3693-8

Cited by 9 publications

(11 citation statements)

References 26 publications

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“…Numerous triggers have been identified as being able to elicit and reproduce the effects of IPC [21]. The role of K(ATP) channels as mediators of the cardioprotective effects of preconditioning has been based on the observations that potassium channel openers duplicate these effects, whereas potassium channel blockers eliminate them [22].…”

Section: Discussionmentioning

confidence: 99%

“…Brief episodes of ischemia render the heart more resistant to subsequent ischemia whose mechanism appears to be mainly due to the activation of ATP-sensitive K + [K(ATP)] channels [2]. Some studies [3][4][5][6] offer a better understanding of the features of this protective effect and its molecular mechanisms. Much attention has been focused recently on the role of mitochondrial K(ATP) channels and the permeability transition pore that seem to play a major role in the progression toward irreversible cellular injury [7,8].…”

Section: Introductionmentioning

confidence: 99%

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Effect of a hypoglycemic agent on ischemic preconditioning in patients with type 2 diabetes and stable angina pectoris

Hueb

Uchida²,

Gersh³

et al. 2007

Coronary Artery Disease

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effect of a hypoglycemic agent on ischemic preconditioning in patients with type 2 diabetes and stable angina pectoris

Hueb

Uchida²,

Gersh³

et al. 2007

Coronary Artery Disease

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“…Infarct size is a standard marker of cell injury following permanent ischemia-reperfusion (9). A majority of cells die in the infarcted myocardium due to increased sarcolemmal permeability, ATP depletion, and loss of Ca 2ϩ homeostasis (33), whereas many cells at the infarct border zone undergo apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Chronic preconditioning: a novel approach for cardiac protection

Wang

Ahmad

Wang

et al. 2007

American Journal of Physiology-Heart and Circulatory Physiology

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Ischemic preconditioning is the most powerful protective mechanism known against lethal ischemia. Unfortunately, the protection lasts for only a few hours. Here we tested the hypothesis that the heart can be kept in a preconditioned state for constant protection against ischemia. In this study we chose BMS-191095 (BMS), a highly selective opener of mitochondrial ATP-sensitive K(+) (mitoK(ATP)) channels. BMS (1 mg/kg ip) was administered to rats every 24 h until 96 h. In other groups, BMS plus wortmannin (WTN, 15 microg/kg ip), an inhibitor of the phosphatidylinositol 3-kinase (PI3-K), or BMS plus 5-hydroxydecanoic acid (5-HD, 5 mg/kg ip), an inhibitor of mitoK(ATP), or BMS plus N(omega)-nitro-L-arginine methyl ester (L-NAME) (30 microg/kg ip), an inhibitor of nitric oxide (NO) synthase, were administered to rats. Rats were then subjected to 30-min left anterior descending coronary artery occlusion and 120-min reperfusion. Cardiac function, infarct size, pathological changes, and apoptosis were assessed at the end of treatments. Saline-treated hearts displayed marked contractile dysfunction and underwent pathological changes. BMS-treated rats showed significant improvement in cardiac function, and infarct size was significantly reduced in BMS-treated hearts. However, protection by BMS was abolished by 5-HD, WTN, or L-NAME. These data demonstrate that hearts can be chronically preconditioned and retain their ability to remain resistant against lethal ischemia and that this protection is mediated by activation of mitoK(ATP) via NO and PI3-K/Akt signaling pathways.

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“…Furthermore, Garcia-Dorado and colleagues (76) reported that the activation of the cGMP/PKG pathway is upstream of delayed normalization of intracellular pH upon reperfusion via PKG-dependent inhibition of Na ϩ /H ϩ -exchange. This indicates that the pre-and postconditioning mechanisms differ substantially because the Na ϩ /H ϩ exchange inhibition seems distant from cardioprotection that is induced by ischemic preconditioning (55).…”

Section: Role Of Transient Reperfusion In the Postconditioning Mechanmentioning

confidence: 99%

Pathophysiology of myocardial reperfusion injury: preconditioning, postconditioning, and translational aspects of protective measures

Shoji

Komuro

Kitakaze

2011

American Journal of Physiology-Heart and Circulatory Physiology

331

270

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Sanada S, Komuro I, Kitakaze M. Pathophysiology of myocardial reperfusion injury: preconditioning, postconditioning, and translational aspects of protective measures. Am J Physiol Heart Circ Physiol 301: H1723-H1741, 2011. First published August 19, 2011; doi:10.1152/ajpheart.00553.2011.-Heart diseases due to myocardial ischemia, such as myocardial infarction or ischemic heart failure, are major causes of death in developed countries, and their number is unfortunately still growing. Preliminary exploration into the pathophysiology of ischemia-reperfusion injury, together with the accumulation of clinical evidence, led to the discovery of ischemic preconditioning, which has been the main hypothesis for over three decades for how ischemia-reperfusion injury can be attenuated. The subcellular pathophysiological mechanism of ischemia-reperfusion injury and preconditioninginduced cardioprotection is not well understood, but extensive research into components, including autacoids, ion channels, receptors, subcellular signaling cascades, and mitochondrial modulators, as well as strategies for modulating these components, has made evolutional progress. Owing to the accumulation of both basic and clinical evidence, the idea of ischemic postconditioning with a cardioprotective potential has been discovered and established, making it possible to apply this knowledge in the clinical setting after ischemia-reperfusion insult. Another a great outcome has been the launch of translational studies that apply basic findings for manipulating ischemia-reperfusion injury into practical clinical treatments against ischemic heart diseases. In this review, we discuss the current findings regarding the fundamental pathophysiological mechanisms of ischemiareperfusion injury, the associated protective mechanisms of ischemic pre-and postconditioning, and the potential seeds for molecular, pharmacological, or mechanical treatments against ischemia-reperfusion injury, as well as subsequent adverse outcomes by modulation of subcellular signaling mechanisms (especially mitochondrial function). We also review emerging translational clinical trials and the subsistent clinical comorbidities that need to be overcome to make these trials applicable in clinical medicine. calcium overload; reactive oxygen species; mitochondria; transition pore; comorbidities; clinical trials WHAT DO WE KNOW ABOUT ischemia-reperfusion injury? Because the morbidity and mortality due to ischemic heart diseases have come to the fore in developed countries and are still increasing, it is critically important, both scientifically and socially, to know how cardioprotection is achieved in ischemic myocardium. In fact, in the clinical setting, the application of coronary thrombolysis or immediate percutaneous coronary intervention for faster recanalization has been shown to dramatically improve the outcomes of patients with acute or chronic myocardial ischemia due to impaired coronary blood supply. This finding is founded on the premise that a shorter period of index ischemia...

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Cardioprotective-Mimetics Reduce Myocardial Infarct Size in Animals Resistant to Ischemic Preconditioning

Abstract: IPC resistance occurs in this canine model of ischemia-reperfusion injury. However, in spite of IPC resistance, hearts can still be pharmacologically protected by direct application of the K(ATP) channel opener bimakalim or the NHE inhibitor EMD 85131.

Cited by 9 publications

References 26 publications

Effect of a hypoglycemic agent on ischemic preconditioning in patients with type 2 diabetes and stable angina pectoris

Effect of a hypoglycemic agent on ischemic preconditioning in patients with type 2 diabetes and stable angina pectoris

Chronic preconditioning: a novel approach for cardiac protection

Pathophysiology of myocardial reperfusion injury: preconditioning, postconditioning, and translational aspects of protective measures

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