title: Reverse changes in cardiac substrate oxidation in dogs recovering from heart failure.
abstract: 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.
authors.affiliation: Department of Physiology, New York Medical College, Valhalla, NY 10595, USA.
authors.forename: Khaled
authors.initials: K
authors.lastname: Qanud
authors.forename: Mohammed
authors.initials: M
authors.lastname: Mamdani
authors.forename: Martino
authors.initials: M
authors.lastname: Pepe
authors.forename: Ramzi J
authors.initials: RJ
authors.lastname: Khairallah
authors.forename: John
authors.initials: J
authors.lastname: Gravel
authors.forename: Biao
authors.initials: B
authors.lastname: Lei
authors.forename: Sachin A
authors.initials: SA
authors.lastname: Gupte
authors.forename: Victor G
authors.initials: VG
authors.lastname: Sharov
authors.forename: Hani N
authors.initials: HN
authors.lastname: Sabbah
authors.forename: William C
authors.initials: WC
authors.lastname: Stanley
authors.forename: Fabio A
authors.initials: FA
authors.lastname: Recchia
mesh_terms: D000154:Aconitate Hydratase / Q000378:metabolism; D042964:Acyl-CoA Dehydrogenase / Q000378:metabolism; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D002304:Cardiac Pacing, Artificial; D002950:Citrate (si)-Synthase / Q000378:metabolism; D004195:Disease Models, Animal; D004285:Dogs; D004734:Energy Metabolism; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006333:Heart Failure / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology*; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D008929:Mitochondria, Heart / Q000201:enzymology / Q000378:metabolism*; D009200:Myocardial Contraction; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D010084:Oxidation-Reduction; D020127:Recovery of Function; D013997:Time Factors; D014463:Ultrasonography; D020257:Ventricular Remodeling
chemical_list: D000318:Adrenergic beta-Agonists; D005230:Fatty Acids, Nonesterified; D042964:Acyl-CoA Dehydrogenase; D002950:Citrate (si)-Synthase; D000154:Aconitate Hydratase; D005947:Glucose