(Circulation. 1995;91:1814-1823.)
© 1995 American Heart Association, Inc.
Articles |
Myocardial High-Energy Phosphate and Substrate Metabolism in Swine With Moderate Left Ventricular Hypertrophy
From the Cardiology Section (B.M.M, S.S., J.G., G.G.S., J.A.W.) and Magnetic Resonance Unit (M.W.W.), San Francisco (Calif) Department of Veterans Affairs Medical Center; the Department of Medicine and the Cardiovascular Research Institute (B.M.M., J.G., G.G.S., J.A.W., M.W.W.), University of California, San Francisco; and the Department of Pathology (M.D.M., F.C.W.), University of California, San Diego.
Correspondence to Barry M. Massie, MD, Cardiology Section (111C), Department of Veterans Affairs Medical Center, 4150 Clement St, San Francisco, CA 94121.
Background Although left ventricular hypertrophy (LVH) is frequently associated with impaired coronary vasodilator reserve, it is uncertain whether this leads to myocardial ischemia under physiological conditions. The goal of the present study was to determine whether swine with moderate LVH exhibit metabolic evidence of ischemia when myocardial oxygen requirements are increased.
Methods and Results Myocardial metabolism was evaluated in an open-chest anesthetized preparation at baseline and during dobutamine infusion in 13 adolescent pigs with moderate LVH induced by supravalvular aortic banding and 12 age-matched control pigs. Transmural myocardial blood flow was quantified with radioactive microspheres; the ratio of phosphocreatine to ATP (PCr/ATP) in the anterior LV free wall was measured by 31P–nuclear magnetic resonance; and anterior wall lactate release was quantified from the arterial-coronary venous difference in 14C- or 13C-labeled lactate. In a subset of 5 animals from each group, the metabolic fate of exogenous glucose was determined from the transmyocardial difference in 6-14C-glucose and its metabolites 14C-lactate and 14CO2. Coronary reserve, as assessed by the ratio of blood flow during adenosine infusion to baseline blood flow, was significantly lower in the LVH pigs compared with controls (3.5±0.4 versus 5.5±0.4 mL/g · min, P<.05); however, transmural myocardial blood flow was similar in both groups of pigs, both at baseline and with dobutamine stimulation, probably reflecting the higher coronary perfusion pressure in the LVH pigs. At baseline, PCr/ATP tended to be lower in the LVH pigs (P=.09) but decreased similarly with dobutamine infusion in both groups. Isotopically measured anterior wall lactate release did not differ between the groups at baseline, nor did the increase in lactate release differ during dobutamine stimulation. The uptake of glucose, lactate, and free fatty acids did not differ between the groups in the basal state. However, during dobutamine stimulation, glucose uptake was greater in the LVH group (0.84±0.09 µmol/g · min versus 0.59±0.08 µmol/g · min, P<.05). In a subset of animals, 14C-glucose was used to assess glucose oxidation. These data showed that the LVH animals had a greater rate of glucose oxidation (0.60±0.10 versus 0.28±0.08 µmol/g · min, P<.05) and a greater rate of glucose conversion to lactate (0.20±0.04 versus 0.09±0.02 µmol/g · min, P<.05) compared with the control pigs.
Conclusions These results suggest that despite their reduced coronary vasodilator reserve and the absence of a greater rise in myocardial blood flow to compensate for a substantially higher LV double product, pigs with this model of moderate LVH do not exhibit a greater susceptibility to myocardial ischemia during dobutamine stress. However, LVH pigs exhibit significantly greater use of exogenous glucose during dobutamine stress, as evidenced by increases in both glucose oxidation and anaerobic glycolysis.
Key Words: hypertrophy • metabolism • magnetic resonance spectroscopy • ischemia
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