Only Hibernating Myocardium Invariably Shows Early Recovery After Coronary Revascularization

Shivalkar, Bharati; Maes, Alex; Borgers, M.; Ausma, Jannie; Scheys, Ilse; Nuyts, Johan; Mortelmans, Luc; Flameng, Willem

doi:10.1161/01.cir.94.3.308

Cited by 129 publications

(52 citation statements)

References 28 publications

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“…These results are qualitatively and quantitatively similar to the results of the present study in which FDG uptake during insulin clamp was the same in hibernating and normal regions. Thus, the finding of homogeneous FDG uptake during insulin clamp by Marinho et al 4 and the present study support a role of regional fibrosis as the explanation for reduced FDG uptake in some clinical studies, as suggested by Shilvalkar et al 10 Increased FDG uptake in the fasting state has been speculated to reflect alterations in myocardial glucose utilization, resulting in altered glucose transporter expression and increased transport capacity. Quantification of mRNA from biopsies of patients with hibernating myocardium has demonstrated induction of the glucose transporter primarily responsible for basal glucose uptake, GLUT1, with no change in the other major myocardial glucose transporter, GLUT4.…”

Section: Fallavollita Heterogeneity Of Fdg In Hibernating Myocardiumsupporting

confidence: 88%

Spatial Heterogeneity in Fasting and Insulin-Stimulated ¹⁸ F-2-Deoxyglucose Uptake in Pigs With Hibernating Myocardium

Fallavollita

2000

Circulation

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Background-Previous studies of hibernating myocardium in the fasting state have shown regionally increased 18 F-2-deoxyglucose (FDG) uptake with a marked transmural gradient. We hypothesized that this adaptation to chronic ischemia might be associated with altered maximal FDG uptake. Methods and Results-Pigs were instrumented with a 1.5-mm proximal left anterior descending artery (LAD) stenosis.Studies were conducted 106Ϯ4 days later on anesthetized animals with complete LAD occlusion and anteroapical dysfunction. In fasting animals (nϭ9), FDG uptake in dysfunctional LAD regions was 2-fold higher than in normally perfused myocardium (7.9Ϯ1.2 versus 4.0Ϯ0.5mol ⅐ min Ϫ1 ⅐ 100 g Ϫ1 , PϽ0.05), with a pronounced transmural gradient (endocardial/epicardial ratio 2.56Ϯ0.19 versus 1.25Ϯ0.03, PϽ0.05). Euglycemic, hyperinsulinemic clamp (insulin clamp, nϭ8) produced a 5-to 9-fold increase in FDG uptake, but there was no longer a regional difference in accumulation (LAD, 37.8Ϯ4.2 versus normal, 36.4Ϯ5.1 mol ⅐ min Ϫ1 ⅐ 100 g Ϫ1 , PϭNS) and the transmural distribution was uniform. FDG uptake in the fasting state varied inversely with coronary flow during vasodilation. In contrast, during insulin clamp there was no relation between FDG uptake and vasodilated flow, resulting in a reduced spatial heterogeneity in individual samples (relative dispersionϭSD/mean; fasting, 52Ϯ5% versus insulin, 24Ϯ2%, PϽ0.05). Conclusions-In the fasting state, FDG uptake in pigs with hibernating myocardium was heterogeneous and was increased in dysfunctional regions with a marked transmural gradient and high spatial heterogeneity. In contrast, FDG uptake was more homogeneously distributed during insulin clamp with (1) uptake in dysfunctional myocardium similar to remote normal regions, (2) uniform transmural distribution, and (3)

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Section: Fallavollita Heterogeneity Of Fdg In Hibernating Myocardiumsupporting

confidence: 88%

Spatial Heterogeneity in Fasting and Insulin-Stimulated ¹⁸ F-2-Deoxyglucose Uptake in Pigs With Hibernating Myocardium

Fallavollita

2000

Circulation

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“…Nevertheless, the extent of infarction was trivial, indicating that this is essentially a model of heart failure from viable dysfunctional myocardium arising from chronic episodes of reversible ischemia. In support of reversible dysfunction, our finding of 16.5% connective tissue in the LAD distribution is within the range (11-24%) reported in patients with hibernating myocardium that improved function after revascularization (13,23,32). The results of the present investigation would not be substantively different even if animals with Ͼ1% infarction were excluded.…”

supporting

confidence: 82%

Ischemic cardiomyopathy in pigs with two-vessel occlusion and viable, chronically dysfunctional myocardium

Fallavollita

Canty

2002

American Journal of Physiology-Heart and Circulatory Physiology

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Fallavollita, James A. and John M. Canty, Jr. Ischemic cardiomyopathy in pigs with two-vessel occlusion and viable, chronically dysfunctional myocardium. Am J Physiol Heart Circ Physiol 282: H1370-H1379, 2002; 10.1152/ajpheart.00138.2001.-A chronic left anterior descending coronary artery (LAD) stenosis leads to the development of hibernating myocardium with severe regional hypokinesis but normal global ventricular function after 3 mo. We hypothesized that two-vessel occlusion would accelerate the progression to hibernating myocardium and lead to global left ventricular (LV) dysfunction and heart failure. Pigs were instrumented with a fixed 1.5-mm constrictor on the proximal LAD and circumflex arteries. After 2 mo, there were no overt signs of right-heart failure and triphenyl tetrazolium chloride infarction was trivial (1.4 Ϯ 0.1% of the LV). Compared with shams, regional function [myocardial systolic excursion (⌬WT); 2.1 Ϯ 0.3 vs. 4.6 Ϯ 0.4 mm, P Ͻ 0.05] and resting perfusion (0.90 Ϯ 0.13 vs. 1.32 Ϯ 0.09 ml ⅐ min Ϫ1 ⅐ g Ϫ1 , P Ͻ 0.05) were reduced, consistent with hibernating myocardium. Pulmonary systolic (45.9 Ϯ 3.3 vs. 36.5 Ϯ 2.2 mmHg, P Ͻ 0.05) and wedge pressures (19.1 Ϯ 1.6 vs. 11.2 Ϯ 0.9 mmHg, P Ͻ 0.05) were increased with global ventricular dysfunction (ejection fraction 43 Ϯ 2 vs. 50 Ϯ 2%, P Ͻ 0.05). Early LV remodeling was present with increased cavity size and mass. Reductions in sarcoplasmic reticulum Ca 2ϩ -ATPase and phospholamban were confined to the dysfunctional LAD region with no change in calsequestrin. Thus combined stenoses of the LAD and circumflex arteries accelerate the development of hibernating myocardium and result in compensated heart failure. hibernating myocardium; stunned myocardium; pigs; collaterals; heart failure; ischemic cardiomyopathy ISCHEMIC CARDIOMYOPATHY is an increasingly prevalent cause of death and disability from cardiovascular disease (20). Unfortunately, major deficiencies exist in our understanding of how chronic coronary artery disease progresses to symptomatic left ventricular (LV) dysfunction due to the lack of experimental animal models where the progression of physiological, cellular, and molecular responses can be evaluated longitudinally. Although some patients develop heart failure due to muscle loss and replacement fibrosis in association with large or multiple myocardial infarcts (1, 6, 29), pathological studies support the view that many patients have global LV dysfunction, disproportionately severe in relationship to the amount of replacement fibrosis identified at postmortem exam (3, 31). Two of the factors that could contribute to this dissociation include a chronic depression in myocyte contractile function due to alterations in sarcoplasmic reticulum (SR) function and LV remodeling with diffuse interstitial connective tissue proliferation and myocyte cell dropout due to apoptosis (28). An additional explanation for the dissociation between the severity of LV dysfunction and fixed structural changes could be reversible contractile dysfunction arisi...

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“…Studies described above and many others [123][124][125][126][127][128][129][130][131][132][133][134] support the concept of hibernating myocardium as originally defined. However, one limitation of these clinical studies is that in general they do not track reduced flow and reduced function in a chronic manner, that is, at multiple time points before revascularization.…”

Section: Time Course Of Recovery Of Hibernating Myocardiummentioning

confidence: 83%

Medical and Cellular Implications of Stunning, Hibernation, and Preconditioning

et al. 1998

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Only Hibernating Myocardium Invariably Shows Early Recovery After Coronary Revascularization

Abstract: Multivariate analysis identifies hibernating myocardium showing early postrevascularization recovery, as opposed to viable but myolytic myocardium with no early recovery. Postrevascularization recovery can be predicted (combination of low REF and high MET) by noninvasive techniques.

Cited by 129 publications

References 28 publications

Spatial Heterogeneity in Fasting and Insulin-Stimulated ¹⁸ F-2-Deoxyglucose Uptake in Pigs With Hibernating Myocardium

Spatial Heterogeneity in Fasting and Insulin-Stimulated ¹⁸ F-2-Deoxyglucose Uptake in Pigs With Hibernating Myocardium

Ischemic cardiomyopathy in pigs with two-vessel occlusion and viable, chronically dysfunctional myocardium

Medical and Cellular Implications of Stunning, Hibernation, and Preconditioning

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Only Hibernating Myocardium Invariably Shows Early Recovery After Coronary Revascularization

Abstract: Multivariate analysis identifies hibernating myocardium showing early postrevascularization recovery, as opposed to viable but myolytic myocardium with no early recovery. Postrevascularization recovery can be predicted (combination of low REF and high MET) by noninvasive techniques.

Cited by 129 publications

References 28 publications

Spatial Heterogeneity in Fasting and Insulin-Stimulated 18 F-2-Deoxyglucose Uptake in Pigs With Hibernating Myocardium

Spatial Heterogeneity in Fasting and Insulin-Stimulated 18 F-2-Deoxyglucose Uptake in Pigs With Hibernating Myocardium

Ischemic cardiomyopathy in pigs with two-vessel occlusion and viable, chronically dysfunctional myocardium

Medical and Cellular Implications of Stunning, Hibernation, and Preconditioning

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Product

Resources

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Spatial Heterogeneity in Fasting and Insulin-Stimulated ¹⁸ F-2-Deoxyglucose Uptake in Pigs With Hibernating Myocardium

Spatial Heterogeneity in Fasting and Insulin-Stimulated ¹⁸ F-2-Deoxyglucose Uptake in Pigs With Hibernating Myocardium