Ventricular pacing attenuates but does not reverse cardiac atrophy and an isomyosin shift in the rat heart

Abstract

The heterotopically transplanted rat heart (TH) undergoes rapid muscle atrophy and a concurrent shift from alpha- to beta-myosin heavy chain (MHC) by 1 wk after surgery. In the current experiments, TH were continuously paced (420 beats/min) for 1 wk beginning 24 h after surgery or for 1 wk beginning 14 days after surgery to determine the role of increased heart rate in preventing or reversing cardiac atrophy. Left ventricular (LV) wet weight (283 vs. 256 mg paced vs. nonpaced) and protein content (32 vs. 23 mg paced vs. nonpaced, P < 0.05) were significantly elevated in TH paced 1 wk after surgery but were unchanged (211 vs. 198 mg and 24 vs. 23 mg LV wet wt and protein content, respectively) in TH paced 2 wk after surgery. Total cardiac protein synthesis in the TH paced immediately after surgery was increased compared with the corresponding nonpaced hearts (5.6 vs. 4.0 mg.mg LV wet wt-1.day-1, P < 0.05), while in the TH, where pacing was initiated 2 wk after surgery, it was unchanged (3.6 vs. 3.7 mg.mg LV wet wt-1.day-1). Fractional synthesis rate was elevated in TH and was not altered by pacing. Pacing the TH also attenuated the shift in alpha-MHC in the first 7 days after surgery but did not reverse the shift 2 wk later. The increase in protein synthesis combined with an unchanged fractional synthesis rate suggests that pacing attenuates cardiac mass by decreasing protein degradation and that once the atrophic process is established, neither synthesis rate nor isomyosin shift can be altered by continuous pacing.