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This Article Full Text Full Text (PDF) All Versions of this Article: 295/5/H2098    most recent 00471.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Qanud, K. Articles by Recchia, F. A. PubMed PubMed Citation Articles by Qanud, K. Articles by Recchia, F. A.

Reverse changes in cardiac substrate oxidation in dogs recovering from heart failure

¹Department of Physiology, New York Medical College, Valhalla, New York; ²Department of Medicine, Division of Cardiovascular Medicine, Henry Ford Hospital, Detroit, Michigan; ³Division of Cardiology, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland; and ⁴Sector of Medicine, Scuola Superiore Sant'Anna, Pisa, Italy

Submitted 6 May 2008 ; accepted in final form 16 September 2008

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 wk. 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 (FFAs) 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 ± 0.2 g/kg, P < 0.05). HF increased glucose oxidation (76.8 ± 19.7 nmol·min^–1·g^–1) and decreased FFA oxidation (20.7 ± 6.4 nmol·min^–1·g^–1), compared with normal dogs (24.5 ± 6.3 and 51.7 ± 9.6 nmol·min^–1·g^–1, respectively), and reversed to normal values at 10 days of recovery (25.4 ± 6.0 and 46.6 ± 6.7 nmol·min^–1·g^–1, 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 was significantly decreased during recovery compared with that in 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.

dilated cardiomyopathy; fatty acids; glucose; tachypacing