LEFT-VENTRICULAR OXYGEN AND SUBSTRATE UPTAKE IN CHRONICALLY HYPOXEMICLAMBS

Myocardial oxygen demand may be increased in chronically hypoxemic lam bs because of their increased heart rate. Therefore, we determined whe ther left ventricular (LV) oxygen supply, oxygen uptake and oxygen dem and were proportionally increased in 6-wk-old lambs, after 4 wk of hyp oxemia (n = 15), as compared with control lambs (n = 14). In addition, we determined whether LV glucose, pyruvate, lactate, FFA and ketoacid s uptake were altered in hypoxemic lambs, because of alterations in ar terial glucose, pyruvate and lactate concentrations, that may occur in hypoxemia. Hypoxemia was induced by the combination of an atrial sept al defect and pulmonary stenosis. Arterial oxygen saturation was decre ased in hypoxemic lambs (67 +/- 8 versus 91 +/- 3%, p < 0.001), Hb con centration was increased, so that arterial oxygen concentration was si milar in both groups of lambs. Myocardial mass (61 +/- 13 versus 44 +/ - 9 g, p < 0.001) and total myocardial blood flow (117 +/- 36 versus 6 2 +/- 27 mL . min-1, p < 0.001) were increased, mainly due to right ve ntricular hypertrophy. LV oxygen demand, estimated by the rate pressur e product (2072 +/- 465 versus 1467 +/- 358 kPa . beat . min-1, p < 0. 001), and oxygen uptake (723 +/- 223 versus 556 +/- 184 mumol . min-1 . 100 g-1, p < 0.05) were proportionally increased in hypoxemic lambs. LV oxygen supply increased linearly with oxygen uptake (r = 0.96) in all lambs, by adjustments in LV blood flow, which was increased in hyp oxemic lambs (168 +/- 41 versus 134 +/- 45 mL . min-1 . 100 g-1, p < 0 .05). The increase in 1,V oxygen uptake in hypoxemic lambs was proport ional to the increase in heart rate (166 +/- 33 versus 118 +/- 25 beat s. min-1, p < 0.001). Arterial lactate, pyruvate and beta-hydroxybutyr ate concentrations were slightly increased in hypoxemic lambs, but LV substrate uptake was practically unaltered as compared with control la mbs. FFA and beta-hydroxybutyrate contributed most to LV substrate upt ake, whereas the contribution of glucose, pyruvate and lactate was neg ligible. The total oxygen extraction ratios (0.45 +/- 0.43 versus 0.51 +/- 0.50) indicate that approximately 50% of the fuels for the LV wer e identified. We conclude that LV oxygen supply is matched to increase d oxygen demand in chronically hypoxemic lambs, by the increase in LV blood flow. LV substrate uptake is unaltered in hypoxemic lambs; gluco se, pyruvate and lactate uptake is negligible, despite an increased ar terial pyruvate and lactate concentration. FFA and ketoacid uptake are insufficient to fuel LV oxidative metabolism.