Oxygen Regulation of Energy Metabolism in Isolated Pig Hearts: A Near-IR Spectroscopy Study

Intracellular pO2in cardiac muscle is determined by the balance between its diffusion from vascular (VS) to intracellular space (IS) and uptake by mitochondria. Cessation of mechanical work decreases O2demand and should reduce the O2gradient between VS and IS. In this work, the effects of arterial pO2(pO2a) on myoglobin (Mb) oxygenation, O2uptake and lactate formation rates [V(O2) and V(Lac),μmol/min/g wet weight, respectively] in beating and KCl-arrested pig hearts were compared. pO2awas decreased stepwise (five steps, 10 min/step) from 528±24 to 54±19 mmHg by changing the ratio of O2/CO2(95:5%) to N2/CO2(95:5%) in the gas mixture from 100/0 through 50/50, 25/75, 10/90 to 0/100. While recording mechanical function, visible/near-infrared (near-IR) spectra (400–2500 nm) were acquired from the left ventricular wall every 45 s (32 scans) using a fiber-optic light guide connected to an NIRSystems spectrometer. Relative MbO2in the epicardium + midmural layer and the epicardium was estimated from absorbance changes (second derivative) at 764 and 584 nm, respectively. In beating hearts, a decrease in pO2aresulted in a decrease in MbO2(similar in both layers) and V(O2) (from 1.26±0.15 to 0.22±0.10) and an increase in V(Lac) from 0 to 2.43±0.76. In arrested hearts an increase in V(Lac) (0.55±0.24) was observed only at the lowest pO2aand the Mb oxygenation curve was shifted towards lower vascular pO2[(pO2a+pO2v)/2] by 160 mmHg. Oxygen consumption (oxygen flux) correlated linearly with calculated values of the oxygen gradients between the vascular and cytoplasmic spaces in both beating and arrested hearts. However, the diffusion rate constant was 3.5 times lower in arrested hearts. Conclusions: (1) hypoxia in KCl-arrested hearts results in only moderate activation of anaerobic glycolysis; (2) oxygenation of the epicardial and midmural LV layers is similar; and (3) a large pO2gradient exists between VS and IS in beating and arrested crystalloid-perfused hearts.