title: Quantitative PET imaging detects early metabolic remodeling in a mouse model of pressure-overload left ventricular hypertrophy in vivo.
abstract: We proposed that metabolic remodeling in the form of increased uptake of the myocardial glucose analog (18)F-FDG precedes and triggers the onset of severe contractile dysfunction in pressure-overload left ventricular hypertrophy in vivo. To test this hypothesis, we used a mouse model of transverse aortic constriction (TAC) together with PET and assessed serial changes in cardiac metabolism and function over 7 d.
  
  
  METHODS
  Scans of 16 C57BL/6 male mice were obtained using a small-animal PET device under sevoflurane anesthesia. A 10-min transmission scan was followed by a 60-min dynamic (18)F-FDG PET scan with cardiac and respiratory gating. Blood glucose levels were measured before and after the emission scan. TAC and sham surgeries were performed after baseline imaging. Osmotic mini pumps containing either propranolol (5 mg/kg/d) or vehicle alone were implanted subcutaneously at the end of surgery. Subsequent scans were taken at days 1 and 7 after surgery. A compartment model, in which the blood input function with spillover and partial-volume corrections and the metabolic rate constants in a 3-compartment model are simultaneously estimated, was used to determine the net myocardial (18)F-FDG influx constant, Ki. The rate of myocardial glucose utilization, rMGU, was also computed. Estimations of the ejection fractions were based on the high-resolution gated PET images.
  
  
  RESULTS
  Mice undergoing TAC surgery exhibited an increase in the Ki (580%) and glucose utilization the day after surgery, indicating early adaptive response. On day 7, the ejection fraction had decreased by 24%, indicating a maladaptive response. Average Ki increases were not linearly associated with increases in rMGU. Ki exceeded rMGU by 29% in the TAC mice. TAC mice treated with propranolol attenuated the rate of (18)F-FDG uptake, diminished mismatch between Ki and rMGU (9%), and rescued cardiac function.
  
  
  CONCLUSIONS
  Metabolic maladaptation precedes the onset of severe contractile dysfunction. Both are prevented by treatment with propranolol. The early detection of metabolic remodeling may offer a metabolic target for modulation of hypertrophy.
authors: Department of Physics, University of Virginia, Charlottesville, VA 22908, USA.
authors: Min
authors: M
authors: Zhong
authors: Clayton E
authors: CE
authors: Alonso
authors: Heinrich
authors: H
authors: Taegtmeyer
authors: Bijoy K
authors: BK
authors: Kundu
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005947:Glucose / Q000378:metabolism; D017379:Hypertrophy, Left Ventricular / Q000000981:diagnostic imaging* / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D049268:Positron-Emission Tomography; D011312:Pressure / Q000009:adverse effects*; D055425:Respiratory-Gated Imaging Techniques; D013318:Stroke Volume; D013997:Time Factors; D020257:Ventricular Remodeling
chemical_list: D005947:Glucose