Myocardial oxygenation at high workstates in hearts with left ventricular hypertrophy

Robert J Bache, Jianyi J Zhang, Yo Murakami, Yi Zhang, Yong K. Cho, Helmut Merkle, Guangrong Gong, Arthur H From, Kamil Ugurbil

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Abstract

Background: High cardiac workloads produced by catecholamine infusion result in loss of myocardial phosphocreatine (PCr) and accumulation of inorganic phosphate (Pi) which are more prominent in hearts with left ventricular hypertrophy (LVH) than in normal hearts. Since ischemia can cause changes in phosphorylated compounds similar to those during catecholamine stimulation, this study tested the hypothesis that the exaggerated depletion of PCr and accumulation of Pi during high workloads in LVH is the result of impaired myocyte oxygenation. Methods and results: 31P- and 1H-NMR spectroscopy were used to determine myocardial high energy phosphate levels and myoglobin desaturation, respectively, in eight normal dogs and nine dogs with LVH produced by ascending aortic banding. The mean LV weight/body weight ratio was approximately twice normal in the LVH group. Infusion of dobutamine (15 and 30 μg/kg/min), and dobutamine+dopamine (each 20 μg/kg/min) caused progressive similar increases in the heart rate X systolic LV pressure product to a maximum of 57.4±3.3·103 in normal and 63.9±2.7·103 in LVH animals, while myocardial oxygen consumption increased from 0.09±0.01 to 0.24±0.04 in normals and from 0.10±0.02 to 0.25±0.03 ml/min/g in LVH. PCr/ATP ratios during basal conditions were lower in LVH hearts (1.73±0.10, 1.61±0.09 and 1.51±0.09 in subepicardium, midwall and subendocardium, respectively) as compared with normals (2.24±0.09, 2.01±0.08 and 1.89±0.07; each p<0.01 normal vs. LVH). Catecholamine infusions caused dose- related decreases in PCr/ATP and appearance of Pi which was more marked in LVH than in normal hearts. 1H-NMR spectroscopy did not detect deoxymyoglobin in either normal or LVH hearts even during the highest workloads. In contrast, occlusion of the anterior descending coronary artery resulted in a large deoxymyoglobin signal. Conclusions: Increases of cardiac work produced by catecholamine stimulation resulted in greater decreases of PCr and greater increases of Pi in hypertrophied than in normal hearts. These abnormalities were not the result of inadequate intracellular oxygen availability and consequently cannot be ascribed to demand ischemia.

Original languageEnglish (US)
Pages (from-to)616-626
Number of pages11
JournalCardiovascular Research
Volume42
Issue number3
DOIs
StatePublished - Jun 1 1999

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Keywords

  • Deoxymyoglobin
  • Dog
  • High energy phosphates
  • Nuclear magnetic resonance
  • Phosphocreatine

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