Progressive hypoxemia limits left ventricular oxygen consumption and contractility

Abstract

To study the cardiac effects of progressive hypoxemia, we measured the left ventricular end-systolic pressure-volume relation (ESPVR), myocardial oxygen consumption (ṀVO2), and myocardial oxygen delivery (ṀQO2) in eight thoracotomized dogs anesthetized with fentanyl and droperidol. We specifically looked for evidence of oxygen supply limitation of ṀVO2 and depressed contractility (altered ESPVR) during stepwise decreases in inspired oxygen fraction. We hypothesized that the reported relation between ṀVO2 and left ventricular pressure-volume area (PVA) may hold when inadequate ṀQO2 determines ṀVO2, which then may limit PVA, manifested partly as a change in the ESPVR. Initially, as arterial oxygen saturation was decreased from 95 ± 3% to 64 ± 14%, coronary blood flow increased so that ṀQO2 was maintained with no change in myocardial extraction ratio (ER(m) = ṀVO2/ṀQO2). During this first phase, lactate utilization, PVA, and ESPVR did not change. When oxygen saturation was further reduced, coronary blood flow rose no higher and ER(m) increased, but not enough to maintain ṀVO2. Lactate consumption decreased and ST segments rose, signaling a change from aerobic metabolism. ṀVO2 decrease was associated with a fall in PVA, which was due to a fall in blood pressure and a significant depression of the ESPVR. Specifically, the volume intercept of the ESPVR increased in all dogs (6.5-20.1 ml, p < 0.0001), accounting for two thirds of the increase in end-systolic volume. The slope of the ESPVR decreased during hypoxia (13.1-6.1 mm Hg/ml, p < 0.02), accounting for only one third of the observed increase in end-systolic volume. We believe that the evidence of anaerobic metabolism, the decrease in PVA, and the depression of the ESPVR demonstrates onset of oxygen supply limitation of ṀVO2. Our data are consistent with the hypothesis that limited ṀVO2 may limit PVA. The hypoxic volume intercept alteration of the ESPVR is different from changes in the slope of ESPVR seen with other interventions. This may be analogous to recent observations in isolated muscle that show hypoxic depression in contractility to be different from other interventions.