Determination of optimal duration of mechanical unloading for failing hearts to achieve bridge to recovery in a rat heterotopic heart transplantation model.
BACKGROUND
Mechanical unloading (MU) of a failing heart using a left ventricular assist device (LVAD) can lead to "bridge to recovery" in some patients. However, it is still unknown how to determine when to withdraw assistance. We sought to determine the optimal duration of MU by investigating its short- and long-term effects using a rat model of heterotopic heart transplantation.


METHODS
Heart failure (HF) was induced in Lewis rats by ligating the left anterior descending artery. In the MU-HF groups, failing hearts were harvested and heterotopically transplanted. In the non-unloaded HF groups and the control group, hearts were not transplanted. After 2, 4 and 8 weeks, we evaluated papillary muscle function, histologic change and cardiac gene expression. Normal hearts served as the control group.


RESULTS
In the MU-HF groups, papillary muscle function improved significantly in the early period of unloading. It peaked and normalized at 4 weeks of unloading, but decreased to 50% the level of a normal heart at 8 weeks. In parallel with papillary muscle function, expression of brain natriuretic peptide (BNP) mRNA and SERCA2a mRNA normalized at 2 and 4 weeks of unloading, respectively, but deteriorated after 4 weeks. Cardiomyocyte hypertrophy was normalized at 2 weeks of unloading, but extended unloading induced cardiac atrophy. Myocardial fibrosis increased after unloading.


CONCLUSIONS
Mechanical unloading of the failing heart can help normalize cardiac function, cardiomyocyte hypertrophy and cardiac gene expression for an optimal duration (<4 weeks), but this normalization deteriorates with prolonged support.
Oriyanhan
Wunimenghe
W
Department of Cardiovascular Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Tsuneyoshi
Hiroshi
H
Nishina
Takeshi
T
Matsuoka
Satoshi
S
Ikeda
Tadashi
T
Komeda
Masashi
M
D000818:Animals; D004195:Disease Models, Animal; D004452:Echocardiography; D005500:Follow-Up Studies; D006333:Heart Failure / Q000000981:diagnostic imaging / Q000503:physiopathology / Q000628:therapy*; D016027:Heart Transplantation / Q000502:physiology*; D006352:Heart Ventricles / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology*; D006353:Heart-Assist Devices; D008297:Male; D009200:Myocardial Contraction / Q000502:physiology; D011379:Prognosis; D051381:Rats; D011917:Rats, Inbred Lew; D020127:Recovery of Function / Q000502:physiology*; D013997:Time Factors; D016042:Transplantation, Heterotopic; D016277:Ventricular Function, Left / Q000502:physiology*