Submitted on May 6, 2008
Revised on August 23, 2008
Accepted on September 16, 2008
Reverse changes in cardiac substrate oxidation in dogs recovering from heart failure
Khaled Qanud1, Mohammed Mamdani1, Martino Pepe1, Ramiz J Khairallah2, John Gravel1, Biao Lei2, Sachin A Gupte3, Victor G Sharov4, Hani N. Sabbah5, William C. Stanley6, and Fabio A. Recchia1*
1 New York Medical College
2 University of Maryland School of Medicine
3 University of S Alabama, College of Medicine
4 Henry Ford Heart & Vascular Institute
5 Henry Ford Hospital
6 University of Maryland-Baltimore
* To whom correspondence should be addressed. E-mail: fabio_recchia{at}nymc.edu.
When recovering from heart failure (HF), the myocardium displays a marked plasticity and can regain normal gene expression and function, however recovery of substrate oxidation capacity has not been explored. We tested whether cardiac functional recovery is matched by normalization of energy substrate utilization during post-HF recovery. HF was induced in dogs by pacing the left ventricle (LV) at 210-240 beats/min for 4 weeks. Tachycardia was discontinued and the heart was allowed to recover. An additional group was studied in HF, and healthy dogs served as controls (n=8/group). Cardiac free fatty acids (FFA) and glucose oxidation were measured with 3H-oleate and 14C-glucose. At 10 days of recovery, hemodynamic parameters returned to control values, however the contractile response to dobutamine remained depressed, LV end-diastolic volume was 28% higher than control and the heart mass to body mass ratio was increased (9.8±0.4 vs 7.5.0±0.2 g/kg, P<0.05). HF increased glucose oxidation (76.8±19.7 nmol/min/g), and decreased FFA oxidation (20.7±6.4 nmol/min/g), compared to normal dogs (24.5±6.3 and 51.7±9.6 nmol/min/g, respectively), and reversed to normal values at 10 days of recovery (25.4±6.0 and 46.6±6.7 nmol/min/g, respectively). However, similar to HF, the recovered dogs failed to increase glucose and fatty acid uptake in response to pacing stress. The activity of myocardial citrate synthase and aconitase were significantly decreased during recovery compared to control dogs (58% and 27% lower, respectively, P<0.05), indicating a persistent reduction in mitochondrial oxidative capacity. In conclusion, cardiac energy substrate utilization is normalized in the early stage of post-HF recovery at baseline, but not under stress conditions.
