Variability of contractile reserve in hibernating myocardium: dependence on the method of inotropic stimulation

Malm, Brian

doi:10.1016/s0008-6363(02)00599-0

Cited by 20 publications

(35 citation statements)

References 24 publications

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“…Blood flow measurements were determined at rest and during pharmacological vasodilation with adenosine (0.9 mg/kg per minute IV with phenylephrine coinfused to prevent hypotension) using fluorescent microspheres. 8 Echocardiography was used to assess regional wall thickening in the hibernating LAD and normally perfused remote regions. 8 End diastole was defined at the peak of the R wave and end systole was evaluated at minimum left ventricular (LV) chamber volume.…”

Section: Methodsmentioning

confidence: 99%

“…8 Echocardiography was used to assess regional wall thickening in the hibernating LAD and normally perfused remote regions. 8 End diastole was defined at the peak of the R wave and end systole was evaluated at minimum left ventricular (LV) chamber volume. The animals were allowed to recover and tissue sampling was performed at least 3 days after pharmacological stimulation.…”

Section: Methodsmentioning

confidence: 99%

“…4 -6 We recently used a porcine model that progresses from stunned to chronic hibernating myocardium 7 to demonstrate a similar attenuation of regional function during graded ␤-adrenergic stimulation. 8 Although the increase in flow was attenuated in the presence of a critical LAD stenosis, intrinsic adaptive responses in hibernating myocardium prevented the development of ischemia, as reflected by increased subendocardial function in the absence of lactate production during submaximal ␤-adrenergic stimulation. 9 These results suggest that hibernating myocardium operates at a lower point of the supply/demand relation than normal myocardium to limit an energetic imbalance during increases in external myocardial workload.…”

mentioning

confidence: 99%

“…13 Such effects would be predicted to lead to an attenuated rather than accentuated contractile response to sympathetic stimulation and are consistent with in vivo observations in swine with hibernating myocardium. 8,9,14 We, therefore, hypothesized that the attenuated metabolic and functional response to submaximal ␤-adrenergic stimulation in pigs with hibernating myocardium arises from a regional downregulation in ␤-adrenergic adenylyl cyclase coupling. To test this, we assessed in vitro ␤-receptor density and affinity, stimulated cAMP production, and changes in regional G-protein expression in swine.…”

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confidence: 99%

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Regional Desensitization of β-Adrenergic Receptor Signaling in Swine With Chronic Hibernating Myocardium

Iyer

Canty²

2005

Circulation Research

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Abstract-Contractile reserve during submaximal ␤-adrenergic stimulation is attenuated in patients and swine with hibernating myocardium. We tested the hypothesis that this arises as a regional adaptive response in ␤-adrenergic adenylyl cyclase coupling. Pigs (nϭ8) were studied 3 months after instrumentation with a left anterior descending artery (LAD) Key Words: ␤-receptors Ⅲ hibernating myocardium Ⅲ chronic ischemic heart disease Ⅲ adenylyl cyclase M yocardial viability is an important determinant of prognosis in ischemic heart disease and is frequently identified by an increase in regional function in response to ␤-adrenergic stimulation. 1-3 Unfortunately, a significant number of patients have limited contractile reserve when viability is present as assessed by nuclear techniques. The absence of contractile reserve appears to be particularly common in the subset of patients with hibernating myocardium where resting perfusion and function are both reduced, as compared with those with chronic stunning, where function is reduced and resting perfusion is normal. 4 -6 We recently used a porcine model that progresses from stunned to chronic hibernating myocardium 7 to demonstrate a similar attenuation of regional function during graded ␤-adrenergic stimulation. 8 Although the increase in flow was attenuated in the presence of a critical LAD stenosis, intrinsic adaptive responses in hibernating myocardium prevented the development of ischemia, as reflected by increased subendocardial function in the absence of lactate production during submaximal ␤-adrenergic stimulation. 9 These results suggest that hibernating myocardium operates at a lower point of the supply/demand relation than normal myocardium to limit an energetic imbalance during increases in external myocardial workload. The adaptations responsible for the attenuated contractile response to ␤-adrenergic stimulation have not been established.One potential adaptation that could explain the attenuated contractile reserve is a regional reduction in ␤-adrenergic responsiveness arising from repetitive reversible ischemia. Although no previous studies have evaluated ␤-receptor signaling in chronic hibernating myocardium, stunned myocardium has been reported to have increased ␤-receptor density, little change in ␤-receptor-mediated cAMP production, and an accentuated contractile response. 10,11 Although this is similar to the denervation hypersensitivity seen following transmural myocardial infarction, these findings have not been reproduced by others. 12 Importantly, Shan et al actually demonstrated a reduction in ␤-adrenergic surface density in needle biopsies from humans with hibernating myocardium. 13 Such effects would be predicted to lead to an attenuated rather than accentuated contractile response to sympathetic stimulation and are consistent with in vivo observations in swine with hibernating myocardium. 8,9,14 We, therefore, hypothesized that the attenuated metabolic and functional response to submaximal ␤-adrenergic stimulation in pigs with hibernati...

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Regional Desensitization of β-Adrenergic Receptor Signaling in Swine With Chronic Hibernating Myocardium

Iyer

Canty²

2005

Circulation Research

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“…10 Regional wall thickening and global LV function were assessed using 2D echocardiography (GE System 5). 14 …”

Section: Physiological Substrate Preceding Scdmentioning

confidence: 99%

Hibernating Myocardium

Canty¹,

Suzuki²,

Banas³

et al. 2004

Circulation Research

142

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Abstract-The inability to reproduce spontaneous ventricular fibrillation in an animal model of chronic coronary artery disease has limited advances in understanding mechanisms of sudden cardiac death (SCD). Swine with hibernating myocardium arising from a chronic left anterior descending coronary artery (LAD) occlusion have a high rate of SCD that parallels the poor clinical survival of medically treated patients with hibernating myocardium. Kaplan-Meier analysis (nϭ426) demonstrated a cumulative mortality of 49% after 5 months that was almost entirely attributable to spontaneous SCD. Using implantable loop recorders, ventricular fibrillation was documented as the arrhythmic mechanism of death in all animals (nϭ10) and was usually preceded by ventricular tachycardia (nϭ8). Physiological studies before SCD (nϭ7) demonstrated total LAD occlusion and collateral-dependent myocardium (nϭ5), excluding acute occlusion as a major trigger of arrhythmia. The physiological substrate of hibernating myocardium was present before SCD, with reductions in LAD perfusion (SCD 0.79Ϯ0.13 versus 0.80Ϯ0.08 mL/min per g) and wall thickening (SCD 28Ϯ3% versus 22Ϯ3%) that were similar to survivors (nϭ14). Triphenyltetrazolium chloride infarcts among animals with SCD were infrequent (4 of 32) and small, averaging 4.6% of LV mass. Histology (nϭ4) showed postmortem changes but no acute inflammation nor contraction band necrosis. These data support the notion that hibernating myocardium is a pathophysiological substrate at high risk of SCD. This is independent of changes in functional stenosis severity, acute myocardial necrosis, or fibrotic scar. Thus, regional adaptations that promote myocyte survival in the setting of chronic repetitive ischemia result in a substrate with enhanced vulnerability to lethal arrhythmias and SCD.

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Spatial heterogeneity of endocardial voltage amplitude in viable, chronically dysfunctional myocardium

Fallavollita

Valeti

Oza

et al. 2004

Basic Research in Cardiology

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Our data demonstrates significant regional and spatial heterogeneity of endocardial voltage and NOGA-derived linear shortening in normal and viable dysfunctional myocardium, with large confidence intervals for individual measurements. Even though the absence of necrosis in this model precludes assessment of the sensitivity and specificity of NOGA mapping to identify infarction, our findings highlight important methodological limitations in using electromechanical mapping to determine viability.

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Variability of contractile reserve in hibernating myocardium: dependence on the method of inotropic stimulation

Cited by 20 publications

References 24 publications

Regional Desensitization of β-Adrenergic Receptor Signaling in Swine With Chronic Hibernating Myocardium

Regional Desensitization of β-Adrenergic Receptor Signaling in Swine With Chronic Hibernating Myocardium

Hibernating Myocardium

Spatial heterogeneity of endocardial voltage amplitude in viable, chronically dysfunctional myocardium

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