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Published on: December 2, 2014
Effects of ventricular unloading on apoptosis and atrophy of cardiac myocytes
Stefano Schena1, Yoshihiko Kurimoto, Johji Fukada
1Department of Surgery, University of Miami, Miami, Florida 33136, USA.
Insights
Ventricular unloading reduces heart mass primarily through reversible cellular atrophy, not irreversible myocyte death. This suggests potential for functional recovery after ventricular assist device support.
Area of Science:
- Cardiovascular Science
- Regenerative Medicine
- Cardiac Physiology
Background:
- Ventricular unloading leads to decreased cardiac ventricular mass.
- Myocyte loss can result from reversible atrophy or irreversible apoptosis.
- Investigating the mechanisms of myocyte loss in response to unloading is crucial.
Purpose of the Study:
- To investigate the effects of ventricular unloading on cardiac myocyte atrophy and apoptosis.
- To compare these effects in working and nonworking heart transplant models.
- To determine the primary mechanism of myocardial weight reduction.
Main Methods:
- Utilized rat heterotopic heart transplantation models (working and nonworking).
- Assessed apoptosis using TUNEL assay, caspase-3 activity, and electron microscopy.
- Quantified cellular atrophy via the cytoplasmic index (CI).
Main Results:
- Nonworking hearts showed greater ventricular mass reduction than working hearts.
- Apoptosis and caspase-3 activity increased in both groups but were similar between models.
- Cellular atrophy, measured by CI, was significantly greater in nonworking grafts.
Conclusions:
- Cellular atrophy, a reversible process, is the main driver of myocardial weight reduction after ventricular unloading.
- Ventricular unloading may not cause permanent myocyte loss, preserving potential for functional recovery.
- Findings have implications for ventricular assist device therapy and cardiac rehabilitation.
Background:
Ventricular unloading decreases cardiac ventricular mass. This loss of ventricular mass can be due to either atrophy (a reversible process) or apoptosis (an irreversible process) of the cardiac myocytes. We investigated the effect of ventricular unloading on atrophy and apoptosis of cardiac myocytes, using working and nonworking transplant heart models in rats.
Materials And Methods:
ACI rats underwent heterotopic heart transplantation with two different techniques to create working and nonworking cardiac grafts. Cardiac grafts were harvested at different time points after transplantation. TUNEL, caspase-3 assay, and electron microscopy were used to assess the degree of apoptosis while cellular atrophy was estimated by calculation of the cytoplasmic index (CI = mean sectional cytoplasmic area/nucleus).
Results:
Ventricular mass reduction was more pronounced in nonworking than in working hearts (P < 0.05). Apoptotic index and caspase-3 activities increased in both groups, peaking at 3 days after transplantation, but were not significantly different between the two models. The cytoplasmic index was significantly lower in nonworking than in working grafts (P < 0.05).
Conclusions:
These data suggest that cellular atrophy is the primary mechanism that accounts for myocardial weight reduction following ventricular unloading. The inference is that ventricular unloading by ventricular assist devices may not cause permanent loss of cardiac myocytes, thus allowing for functional recovery.
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