Myocardial infarct size is smaller in dogs with pacing-induced heart failure

Hoskins, Darrell E.; Ignasiak, Diane P.; Saganek, Lori J.; Gallagher, Kim P.; Peterson, Janet T.

doi:10.1016/0008-6363(96)00028-4

Cited by 9 publications

(6 citation statements)

References 40 publications

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“…Our findings that CHF cells have improved ischemia tolerance are corroborated by the results of Hoskins et al (15) showing that dogs with pacing-induced failing heart had much smaller infarcts than control animals after ischemia-reperfusion. Thus, despite different pathological stimuli (pacing vs. postinfarction heart failure) and different biological levels (whole heart vs. isolated cardiomyocytes), these two studies show the same phenomenon of better ischemic tolerance of failing myocardium.…”

Section: Discussionsupporting

confidence: 89%

Cardiomyocytes from postinfarction failing rat hearts have improved ischemia tolerance

Sharikabad

Aronsen²,

Haugen³

et al. 2009

American Journal of Physiology-Heart and Circulatory Physiology

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Altered myocardial Ca(2+) and Na(+) handling in congestive heart failure (CHF) may be expected to decrease the tolerance to ischemia by augmenting reperfusion Ca(2+) overload. The aim of the present study was to investigate tolerance to hypoxia-reoxygenation by measuring enzyme release, cell death, ATP level, and cell Ca(2+) and Na(+) in cardiomyocytes from failing rat hearts. CHF was induced in Wistar rats by ligation of the left coronary artery during isoflurane anesthesia, after which cardiac failure developed within 6 wk. Isolated cardiomyocytes were cultured for 24 h and subsequently exposed to 4 h of hypoxia and 2 h of reoxygenation. Cell damage was measured as lactate dehydrogenase (LD) release, cell death as propidium iodide uptake, and ATP by firefly luciferase assay. Cell Ca(2+) and Na(+) were determined with radioactive isotopes, and free intracellular Ca(2+) concentration ([Ca(2+)](i)) with fluo-3 AM. CHF cells showed less increase in LD release and cell death after hypoxia-reoxygenation and had less relative reduction in ATP level after hypoxia than sham cells. CHF cells accumulated less Na(+) than sham cells during hypoxia (117 vs. 267 nmol/mg protein). CHF cells maintained much lower [Ca(2+)](i) than sham cells during hypoxia (423 vs. 1,766 arbitrary units at 4 h of hypoxia), and exchangeable Ca(2+) increased much less in CHF than in sham cells (1.4 vs. 6.7 nmol/mg protein) after 120 min of reoxygenation. Ranolazine, an inhibitor of late Na(+) current, significantly attenuated both the increase in exchangeable Ca(2+) and the increase in LD release in sham cells after reoxygenation. This supports the suggestion that differences in Na(+) accumulation during hypoxia cause the observed differences in Ca(2+) accumulation during reoxygenation. Tolerance to hypoxia and reoxygenation was surprisingly higher in CHF than in sham cardiomyocytes, probably explained by lower hypoxia-mediated Na(+) accumulation and subsequent lower Ca(2+) accumulation in CHF after reoxygenation.

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Section: Discussionsupporting

confidence: 89%

Cardiomyocytes from postinfarction failing rat hearts have improved ischemia tolerance

Sharikabad

Aronsen²,

Haugen³

et al. 2009

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

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“…There is little doubt that ischemia becomes much more arrhythmogenic in the failing heart, in humans and in animal models (Chakko et al 1989; Bril, Forest, and Gout 1991). When infarct size in the nonpreconditioned heart is measured, there are studies that show decreased (Hoskins et al 1996) or unaltered infarct size (Miki et al 2000) in heart failure, depending on the experimental model.…”

Section: Physiologic and Pathologic States Of Altered Ischemic Tolerancementioning

confidence: 99%

Occult Cardiotoxicity—Toxic Effects on Cardiac Ischemic Tolerance

2009

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The outcome of cardiac ischemic events depends not only on the extent and duration of the ischemic stimulus but also on the myocardial intrinsic tolerance to ischemic injury. Cardiac ischemic tolerance reflects myocardial functional reserves that are not always used when the tissue is appropriately oxygenated. Ischemic tolerance is modulated by ubiquitous signal transduction pathways, transcription factors and cellular enzymes, converging on the mitochondria as the main end effector. Therefore, drugs and toxins affecting these pathways may impair cardiac ischemic tolerance without affecting myocardial integrity or function in oxygenated conditions. Such effect would not be detected by current toxicological studies but would considerably influence the outcome of ischemic events. The authors refer to such effect as "occult cardiotoxicity." In this review, the authors summarize current knowledge about main mechanisms that determine cardiac ischemic tolerance, methods to assess it, and the effects of drugs and toxins on it. The authors offer a view that low cardiac ischemic tolerance is a premorbid status and, therefore, that occult cardiotoxicity is a significant potential source of cardiac morbidity. The authors propose that toxicologic assessment of compounds would include the assessment of their effect on cardiac ischemic tolerance.

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“…DeVan and colleagues demonstrated that traditional cardiovascular risk factors, such as advanced age, are associated with a greater magnitude and delayed recovery from endothelial IR-injury in humans 3 . Also experimental studies suggest that the presence of cardiovascular risk factors or disease is associated with exaggerated IR-injury 2,4,5 , although some studies suggest otherwise 6,7 . Accordingly, we examined the hypothesis that HF patients demonstrate an increased endothelial IR-injury compared to healthy peers in vivo.…”

Section: Introductionmentioning

confidence: 99%