Hearts at Rest May Recover from Heart Failure

Structural changes in heart muscle cells following heart failure (HF) are not permanent, and can be reversed by allowing the heart to rest, according to a new study.

Researchers at the Harefield Heart Science Centre (HHSC; London, United Kingdom) and Imperial College London (ICL; United Kingdom) induced HF in rats by left coronary artery ligation for 12 weeks; the failing hearts were then mechanically unloaded for 4 weeks by heterotopic abdominal heart transplantation (HF-UN), a microsurgical technique for vascular anastomosis, whereby the donor's thoracic aorta is connected end-to-side to the recipient's infrarenal abdominal aorta, and the donor's pulmonary artery is connected to the recipient's inferior vena cava. The researchers aim was to reduce transverse (t)-tubule system disruption, which occurs early in HF.

The researchers found that HF-UN reversed the t-tubule density reduction observed by HF in isolated left ventricular myocytes. The deterioration in the regularity of the t-tubule system in HF was also reversed in HF-UN, as demonstrated by scanning ion conductance microscopy that showed the reappearance of normal surface striations, and electron microscopy that revealed recovery of normal t-tubule micro-architecture. According to the researchers, the process is similar to that of using a left ventricle assist device (LVAD) to boost heart function and reduce strain on the left ventricle, thus helping the heart muscle similarly recover. The study was published early online on April 2, 2012, in the European Journal of Heart Failure.

“This is the first demonstration that this important form of remodeling of heart muscle cells induced by heart failure is reversible,” said lead author Michael Ibrahim, PhD, of the HHSC laboratory of cell electrophysiology. “If we can discover the molecular mechanisms for these changes, it might be possible to induce recovery without a serious procedure like having an LVAD implanted.”

The transverse (t)-tubule system is a deep invagination of the sarcolemma found in skeletal and cardiac muscle cells. These invaginations allow depolarization of the membrane to quickly penetrate to the interior of the cell. The system guarantees the proximity of the triggers for Ca2+ induced Ca2+ release (CICR), a process whereby calcium can trigger release of further calcium from the muscle sarcoplasmic reticulum, which is critical for contraction in cardiomyocytes.

Related Links:
Harefield Heart Science Centre
Imperial College London