β-Adrenergic Stimulation Restores Oxygen Extraction Reserve During Acute Normovolemic Hemodilution

Compensatory increases in oxygen extraction (Eo2) during acute normovolemic hemodilution (ANH) have the effect of decreasing tissue oxygen tension values, thus increasing the threat of tissue hypoxia. We hypothesized that if the β-adrenergic agonist isoproterenol (ISOP) could augment cardiac output (CO) during ANH, it could reverse the increases in Eo2 and restore the margin of safety for tissue oxygenation. Studies were performed in seven anesthetized (isoflurane) dogs. CO was measured by using thermodilution, and regional blood flow (RBF) was measured by using radioactive microspheres. Systemic oxygen delivery (Do2), oxygen consumption (V̇o2), and Eo2, as well as regional Do2, were calculated. Measurements were obtained under the following conditions in each dog: 1) baseline-1, 2) ISOP (0.1 μg · kg−1 · min−1 IV), 3) baseline-2, 4) ANH, and 5) ISOP during ANH. Hematocrit was 45% ± 3% under baseline conditions and 18% ± 3% during ANH. Before ANH, ISOP caused parallel increases in CO and systemic Do2, which, in the presence of an unchanged V̇o2, reduced Eo2. RBF increased in myocardium and spleen, decreased in pancreas, and did not change in brain, spinal cord, or other tissues. ANH caused increases in CO, which were insufficient to offset the decrease in arterial oxygen content, and thus systemic Do2 declined; systemic V̇o2 was maintained by an increase in Eo2. ANH-related increases in RBF maintained Do2 in myocardium, brain, duodenum, and pancreas, whereas Do2 declined in kidney and spleen. ISOP during ANH increased CO and systemic Do2, which returned systemic Eo2 to baseline, and it increased RBF in myocardium, kidney, duodenum, and spleen. We conclude that 1) β-adrenergic stimulation with ISOP restored the systemic Eo2 reserve during ANH, without apparent adverse effects in the individual body tissues, and that 2) the use of inotropic drugs, such as ISOP, may extend the limit to which hematocrit can be reduced safely during ANH.