ALTERATIONS OF ENERGY METABOLISM IN HYPERTROPHIED HEARTS DURING ANOXIA: A P-31 NUCLEAR MAGNETIC RESONANCE STUDY

Abstract

The metabolic effect of anoxia on hypertrophied myocardium was investigated using P-31 NMR spectroscopy. Hearts from 18 mo. SHR (hypertrophied, n=7) and age-matched WKY (control, n=6) rats were mounted on a modified Langendorff apparatus, paced at 240/min and perfused with 36°C phosphate-free, glucose-containing buffer bubbled with oxygen or nitrogen (anoxia). Left ventricular pressure (LVP), LV dP/dt and perfusion pressure were continuously recorded while consecutive 3-min spectra were collected. This allowed temporal assessment of myocardial phosphate levels [incl. inorganic phosphate (P_i), creatine phosphate (CP) and ATP] during baseline conditions, anoxia and recovery. Anoxia was maintained until a 70% fall in LVP occured. Compared to the WKY, SHR rats had higher in vivo BP (163 vs 104; p<.001) and cardiac hypertrophy (heart/ body weight = 5.3 vs 3.5 mg/g; p<.001). During baseline perfusion, SHR hearts had higher resistance (9.8 vs 5.9 mmHg/cc/min/g; p=.003) but no significant difference in LVP or dP/dt. SHR hearts demonstrated a faster fall in high-energy phosphates and LVP during anoxia (SHR fell to 30% baseline LVP in 8.5 vs 13.0 mins; p=.018). Throughout the protocol SHR hearts had lower CP (3.8 vs 5.6 umoles/g; p=.008), ATP (3.2 vs 3.9 umoles/g; p=.047) and CP/P_i ratio (1.5 vs 2.5; p=.043). We conclude that chronically hypertrophied hearts have: (1) less ATP/g and CP/g than age-matched controls, and (2) a faster decline in mechanical and metabolic function during anoxia.

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