Effects of ventricular unloading on apoptosis and atrophy of cardiac myocytes.
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.


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.
Schena
Stefano
S
Department of Surgery, University of Miami, Miami, Florida 33136, USA.
Kurimoto
Yoshihiko
Y
Fukada
Johji
J
Tack
Ivan
I
Ruiz
Phillip
P
Pang
Manhui
M
Striker
Liliane J
LJ
Aitouche
Abdelouahab
A
Pham
Si M
SM
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001284:Atrophy; D016027:Heart Transplantation; D006353:Heart-Assist Devices; D008297:Male; D023421:Models, Animal; D032383:Myocytes, Cardiac / Q000473:pathology* / Q000502:physiology*; D009929:Organ Size / Q000502:physiology; D051381:Rats; D011912:Rats, Inbred ACI; D016276:Ventricular Function / Q000502:physiology