Myocardial High-Energy Phosphate and Substrate Metabolism in Swine With Moderate Left Ventricular Hypertrophy

Abstract

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 31 P–nuclear magnetic resonance; and anterior wall lactate release was quantified from the arterial-coronary venous difference in 14 C- or 13 C-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- 14 C-glucose and its metabolites 14 C-lactate and 14 CO 2 . 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, 14 C-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.