Changes in sarcomeric and non-sarcomeric cytoskeletal proteins and focal adhesion molecules during clinical...

Reverse remodeling can occur after left ventricular assist device (LVAD) support, which is sufficient in some cases to allow explantation of the device without cardiac transplantation. The molecular mechanisms involved remain unknown. A specific pattern of expression of sarcomeric and non-sarcomeric proteins in the myocardium is thought to be essential for normal myocardial function. However, a detailed protein analysis of their role in recovery has not been performed previously.

Myocardial samples were collected at implantation and explantation in 7 patients with dilated cardiomyopathy who had sufficient recovery for device explantation. Western blotting and immunoprobing were used to quantitate changes in the expression of sarcomeric and cytoskeletal proteins.

At implantation, all patients (6 men and 1 woman, age [mean +/- SD] 36.1 +/- 10.4 years) were inotrope-dependent; ejection fraction (EF) was 12.6 +/- 4.6%, cardiac index (CI) was 1.66 +/- 0.5 liters/min/m2 and pulmonary capillary wedge pressure (PCWP) was 26 +/- 6 mm Hg. Mean duration of LVAD support was 333 +/- 235 days. Prior to explantation, EF (pump off for 15 minutes) was 62.7 +/- 11.4%, CI was 2.7 +/- 0.7 liters/min/m2 and PCWP was 10.9 +/- 3.5 mm Hg. At explantation, the following statistically significant increases were noted: myosin heavy chain, 1.90-fold (p < 0.05); sarcomeric actin, 1.80-fold (p < 0.05); alphaII spectrin, 1.40-fold (p = 0.05); troponin C, 1.34-fold (p < 0.05); troponin T, 2.10-fold (p < 0.05); cytoskeletal actinin, 5.16-fold (p < 0.05); and smooth muscle alpha-actin, 4.10-fold (p = 0.05). Although not significant (NS), increases were also seen for: troponin I, 1.27-fold; myosin light chain 1, 1.28-fold; tropomyosin, 1.28-fold; and sarcomeric actinin at 3.24-fold. There was a decrease in talin of 2.01-fold (p = NS) between implant and explant. Vimentin was unchanged.

Our data suggest that reverse remodeling of the myocardium parallels improvements in hemodynamic function in LVAD patients showing clinical myocardial recovery.