Cardiac Binding in Experimental Heart Failure

Vaynblat, Mikhail; Chiavarelli, Mario; Shah, Himansu R.; Ramdev, Geeta; Aron, Michelle; Zisbrod, Zvi; Cunningham, Joseph N.

doi:10.1016/s0003-4975(97)00349-4

Cited by 32 publications

(20 citation statements)

References 11 publications

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“…Even though the procedure involved extensive surgery and was plagued with technical difficulties, patients showed symptomatic improvement. 24,25 However, several experimental 26,27 and clinical 28 studies have suggested that the improvement was derived primarily from the passive girdling of the heart and not from active contraction of the skeletal muscle. Several studies in various animal models of HF have shown that progressive LV dilation can be prevented or attenuated by wrapping synthetic materials around the cardiac ventricles to elicit containment.…”

Section: Discussionmentioning

confidence: 99%

Reversal of Chronic Molecular and Cellular Abnormalities Due to Heart Failure by Passive Mechanical Ventricular Containment

Sabbah¹,

Sharov²,

Gupta³

et al. 2003

Circulation Research

102

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Abstract-Passive mechanical containment of failing left ventricle (LV) with the Acorn Cardiac Support Device (CSD) was shown to prevent progressive LV dilation in dogs with heart failure (HF) and increase ejection fraction. To examine possible mechanisms for improved LV function with the CSD, we examined the effect of CSD therapy on the expression of cardiac stretch response proteins, myocyte hypertrophy, sarcoplasmic reticulum Ca 2ϩ -ATPase activity and uptake, and mRNA gene expression for myosin heavy chain (MHC) isoforms. HF was produced in 12 dogs by intracoronary microembolization. Six dogs were implanted with the CSD and 6 served as concurrent controls. LV tissue from 6 normal dogs was used for comparison. Compared with normal dogs, untreated HF dogs showed reduced cardiomyocyte contraction and relaxation, upregulation of stretch response proteins (p21ras, c-fos, and p38 ␣/␤ mitogen-activated protein kinase), increased myocyte hypertrophy, reduced SERCA2a activity with unchanged affinity for calcium, reduced proportion of mRNA gene expression for ␣-MHC, and increased proportion of ␤-MHC. Therapy with the CSD was associated with improved cardiomyocyte contraction and relaxation, downregulation of stretch response proteins, attenuation of cardiomyocyte hypertrophy, increased affinity of the pump for calcium, and restoration of ␣-and ␤-MHC isoforms ratio. The results suggest that preventing LV dilation and stretch with the CSD promotes downregulation of stretch response proteins, attenuates myocyte hypertrophy and improves SR calcium cycling. These data offer possible mechanisms for improvement of LV function after CSD therapy. Key Words: heart failure Ⅲ myocyte hypertrophy Ⅲ sarcoplasmic reticulum Ⅲ myosin heavy chain H eart failure (HF) is a progressive disorder mediated through multiple signaling pathways. Once initiated, HF is characterized by increased neurohumoral activation and ventricular dilation. Although such compensatory changes are initially beneficial, over the long-term they cause adverse structural and functional changes collectively referred to as ventricular remodeling. Ventricular dilation also causes increased mechanical stress and myocardial stretch. Upregulation of stretch response proteins, such as p21ras, 1 c-fos, 2,3 and p38 ␣/␤ mitogen-activated protein kinase (MAPK), 4 have been shown to induce cardiomyocyte hypertrophy.The Acorn Cardiac Support Device (CSD) has been shown to halt progressive left ventricular (LV) dilation and improve ejection fraction. [5][6][7] However, the mechanism(s) underlying the improved cardiac function has not been elucidated. In the present study, we tested the hypothesis that improvement in LV systolic function in dogs with HF after long-term therapy with the CSD results, in part, from downregulation of stretch response proteins, attenuation of cardiomyocyte hypertrophy, 1-4 and improvement of sarcoplasmic reticulum (SR) calcium cycling. To further understand the mechanisms for the improvement in LV systolic function, we also explored the influence of ...

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Section: Discussionmentioning

confidence: 99%

Reversal of Chronic Molecular and Cellular Abnormalities Due to Heart Failure by Passive Mechanical Ventricular Containment

Sabbah¹,

Sharov²,

Gupta³

et al. 2003

Circulation Research

102

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“…In a study in dogs with heart failure secondary to rapid ventricular pacing, wrapping the ventricles snugly with a Marlex mesh was effective in preventing cardiac enlargement and LV functional deterioration [38]. In another study in dogs with doxorubicininduced heart failure, cardiac binding with polytetrafluoroethylene prevented LV dilation but without eliciting improvement of LV systolic function [39]. Both of these studies are limited by having performed cardiac containment prior to inducing heart failure and, therefore, are difficult to interpret in light of studies described in this review conducted using the CSD.…”

Section: Discussionmentioning

confidence: 99%

Global Left Ventricular Remodeling with the Acorn Cardiac Support Device: Hemodynamic and Angiographic Findings in Dogs with Heart Failure

Sabbah

2005

Heart Fail Rev

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Preventing progressive left ventricular (LV) remodeling is paramount in the treatment of heart failure. In recent years, several surgical approaches have been implemented with the objective of improving LV function through amelioration of progressive LV remodeling. These included surgical reduction of LV size, the so-called Batista procedure, dynamic cardiomyoplasty and mitral valve repair to limit or eliminate functional mitral regurgitation. While the Batista procedure and dynamic cardiomyoplasty have for all practical purposes been abandoned, the lessons learned from these procedures gave rise to a new generation of devices aimed at preventing progressive LV dilation and restoring LV shape by passive mechanical containment of the failing LV. One such device is the Acorn Cardiac Support Device (CSD) or the CorCap. Studies in dogs with intracoronary microembolization-induced moderate and advanced heart failure have shown that long-term monotherapy with the CSD not only prevents progressive LV dilation but, in effect, partially reverses this phenotype. These studies have also shown that the CSD restores, albeit in part, progressive LV chamber sphericity and attenuates functional mitral regurgitation. These benefits were accompanied by improvement in global LV function along with improvements of remodeling at the cellular level. The findings were largely responsible for initiating safety and feasibility clinical trials with the CSD and ultimately, the initiation of the Acorn efficacy trial that was completed in 2004. This review will focus on studies conducted in dogs with heart failure and, specifically on hemodynamic, angiographic and echocardiographic results from these studies that provided support for the CSD as a successful technology targeting "reverse LV remodeling" for the treatment of heart failure.

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“…Animal [17][18][19][20] and clinical [21,22] studies of cardiomyoplasty support a conclusion that passive external constraint by the muscle wrap may halt or even reverse remodeling of the dilated ailing heart. It has been postulated that the constraining effect of cardiomyoplasty on the left ventricle E-mail: rwalsh@acorncv.com stabilizes cardiac function by limiting left ventricular volume, thus reducing chronic dilation and decreasing diastolic strain [23].…”

Section: Introductionmentioning

confidence: 87%

Design and Features of the Acorn CorCapTM Cardiac Support Device: The Concept of Passive Mechanical Diastolic Support

Walsh

2005

Heart Fail Rev

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The Laplace equation points to the importance of ventricular wall stress as a factor in heart failure development and progression. Based on animal and clinical experience with active and passive cardiomyoplasty, a synthetic passive constraint was proposed as a means of reducing excessive wall stress, and thus assuaging disease progression. The Acorn CorCap CSD Cardiac Support Device was designed to provide passive diastolic support and serve as a constraint against chronic cardiac dilation in heart failure. Basic and uncomplicated in appearance, the device nevertheless incorporates numerous sophisticated structural and functional features intended maximize therapeutic value. The device is fabricated from medical grade multifilament polyester yarn, in a specific knit construction chosen to provide structural integrity, low physical profile, pliability for intimate contact with the epicardial surface, ease of manipulation during implantation, and anisotropic compliance characteristics to encourage beneficial reverse remodeling.

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Cardiac Binding in Experimental Heart Failure

Cited by 32 publications

References 11 publications

Reversal of Chronic Molecular and Cellular Abnormalities Due to Heart Failure by Passive Mechanical Ventricular Containment

Reversal of Chronic Molecular and Cellular Abnormalities Due to Heart Failure by Passive Mechanical Ventricular Containment

Global Left Ventricular Remodeling with the Acorn Cardiac Support Device: Hemodynamic and Angiographic Findings in Dogs with Heart Failure

Design and Features of the Acorn CorCapTM Cardiac Support Device: The Concept of Passive Mechanical Diastolic Support

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