Skeletal myoblast sheet transplantation improves the diastolic function of a pressure-overloaded right heart.
OBJECTIVE
The development of right ventricular dysfunction has become a common problem after surgical repair of complex congenital heart disease. A recent study reported that tissue-engineered skeletal myoblast sheet transplantation improves left ventricular function in patients with dilated and ischemic cardiomyopathy. Therefore myoblast sheet transplantation might also improve ventricular performance in a rat model of a pressure-overloaded right ventricle.


METHODS
Seven-week-old male Lewis rats underwent pulmonary artery banding. Four weeks after pulmonary artery banding, myoblast sheet transplantation to the right ventricle was performed in the myoblast sheet transplantation group (n = 20), whereas a sham operation was performed in the sham group (n = 20).


RESULTS
Four weeks after performing the procedure, a hemodynamic assessment with a pressure-volume loop showed a compensatory increase in systolic function in both groups. However, only the myoblast sheet transplantation group showed a significant improvement in the diastolic function: end-diastolic pressure (sham vs myoblast sheet transplantation, 10.3 +/- 3.1 vs 5.0 +/- 3.7 mm Hg; P < .001), time constant of isovolumic relaxation (11.1 +/- 2.5 vs 7.6 +/- 1.2 ms, P < .001), and end-diastolic pressure-volume relationship (16.1 +/- 4.5 vs 7.6 +/- 2.4/mL, P < .005). The right ventricular weight and cell size similarly increased in both groups. A histologic assessment demonstrated significantly suppressed ventricular fibrosis and increased capillary density in the myoblast sheet transplantation group in comparison with those in the sham group. Reverse transcription-polymerase chain reaction demonstrated an increased myocardial gene expression of hepatocyte growth factor and vascular endothelial growth factor in the myoblast sheet transplantation group but not in the sham group.


CONCLUSIONS
Skeletal myoblast sheet transplantation improved the diastolic dysfunction and suppressed ventricular fibrosis with increased capillary density in a rat model of a pressure-overloaded right ventricle. This method might become a novel strategy for the myocardial regeneration of right ventricular failure in patients with congenital heart disease.
Hoashi
Takaya
T
Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
Matsumiya
Goro
G
Miyagawa
Shigeru
S
Ichikawa
Hajime
H
Ueno
Takayoshi
T
Ono
Masamichi
M
Saito
Atsuhiro
A
Shimizu
Tatsuya
T
Okano
Teruo
T
Kawaguchi
Naomasa
N
Matsuura
Nariaki
N
Sawa
Yoshiki
Y
D000818:Animals; D003971:Diastole; D006352:Heart Ventricles / Q000473:pathology / Q000601:surgery*; D006439:Hemodynamics; D008297:Male; D032448:Myoblasts, Skeletal / Q000637:transplantation*; D051381:Rats; D011917:Rats, Inbred Lew; D023822:Tissue Engineering; D018497:Ventricular Dysfunction, Right / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D016278:Ventricular Function, Right; D017725:Ventricular Pressure