Passive mechanical containment with the Acorn Cardiac Support Device in dogs with heart failure improved cardiomyocyte contraction, downregulated stretch response proteins, and attenuated hypertrophy.
Does passive mechanical ventricular containment with the Acorn Cardiac Support Device reverse molecular and cellular abnormalities in a canine model of heart failure?
Passive mechanical containment of the failing left ventricle with the Acorn CSD reverses chronic molecular and cellular abnormalities, including stretch response protein expression and myocyte hypertrophy, in a canine model of heart failure.
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 Ca2+-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 alpha/beta mitogen-activated protein kinase), increased myocyte hypertrophy, reduced SERCA2a activity with unchanged affinity for calcium, reduced proportion of mRNA gene expression for alpha-MHC, and increased proportion of beta-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 alpha- and beta-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.
Sabbah et al. (Tue,) conducted a other in Heart failure (n=18). Acorn Cardiac Support Device (CSD) vs. Untreated heart failure controls and normal dogs was evaluated on Expression of cardiac stretch response proteins, myocyte hypertrophy, SERCA2a activity, and MHC mRNA gene expression. Passive mechanical containment with the Acorn Cardiac Support Device in dogs with heart failure improved cardiomyocyte contraction, downregulated stretch response proteins, and attenuated hypertrophy.