RRC ID 2811
Author Oriyanhan W, Tsuneyoshi H, Nishina T, Matsuoka S, Ikeda T, Komeda M.
Title Determination of optimal duration of mechanical unloading for failing hearts to achieve bridge to recovery in a rat heterotopic heart transplantation model.
Journal J. Heart Lung Transplant.
Abstract 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.
Volume 26(1)
Pages 16-23
Published 2007-1
DOI 10.1016/j.healun.2006.10.016
PII S1053-2498(06)00739-X
PMID 17234512
MeSH Animals Disease Models, Animal Echocardiography Follow-Up Studies Heart Failure / diagnostic imaging Heart Failure / physiopathology Heart Failure / therapy* Heart Transplantation / physiology* Heart Ventricles / diagnostic imaging Heart Ventricles / pathology Heart Ventricles / physiopathology* Heart-Assist Devices* Male Myocardial Contraction / physiology Prognosis Rats Rats, Inbred Lew Recovery of Function / physiology* Time Factors Transplantation, Heterotopic Ventricular Function, Left / physiology*
IF 8.578
Times Cited 49