title: Beta-adrenergic stimulation restores oxygen extraction reserve during acute normovolemic hemodilution.
abstract: Compensatory increases in oxygen extraction (EO(2)) 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 beta-adrenergic agonist isoproterenol (ISOP) could augment cardiac output (CO) during ANH, it could reverse the increases in EO(2) 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 (DO(2)), oxygen consumption (OV0312;O(2)), and EO(2), as well as regional DO(2), were calculated. Measurements were obtained under the following conditions in each dog: 1) baseline-1, 2) ISOP (0.1 micro g. 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 DO(2), which, in the presence of an unchanged OV0312;O(2), reduced EO(2). 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 DO(2) declined; systemic OV0312;O(2) was maintained by an increase in EO(2). ANH-related increases in RBF maintained DO(2) in myocardium, brain, duodenum, and pancreas, whereas DO(2) declined in kidney and spleen. ISOP during ANH increased CO and systemic DO(2), which returned systemic EO(2) to baseline, and it increased RBF in myocardium, kidney, duodenum, and spleen. We conclude that 1) beta-adrenergic stimulation with ISOP restored the systemic EO(2) 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.
  
  
  CONCLUSIONS
  By restoring the oxygen extraction reserve, isoproterenol and other inotropic drugs can enhance the margin of safety and extend the limit to which hematocrit can be reduced safely during acute normovolemic hemodilution. The use of this approach will depend on the degree of hemodilution, the extent of mixed venous oxygen desaturation, and whether increases in cardiac output are possible or desirable.
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000758:Anesthesia; D000818:Animals; D002248:Carbon Monoxide / Q000097:blood; D004285:Dogs; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006438:Hemodilution; D007262:Infusions, Intravenous; D007545:Isoproterenol / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D008863:Microspheres; D009200:Myocardial Contraction / Q000187:drug effects; D010100:Oxygen / Q000097:blood*; D010101:Oxygen Consumption / Q000187:drug effects; D012039:Regional Blood Flow / Q000187:drug effects
chemical_list: D000318:Adrenergic beta-Agonists; D002248:Carbon Monoxide; D007545:Isoproterenol; D010100:Oxygen