title: Effects of haemoglobin-based oxygen carrier hemoglobin glutamer-200 (bovine) on intestinal perfusion and oxygenation in a canine hypovolaemia model.
abstract: The objective of this investigation was to study the effects of the first marketed haemoglobin-based oxygen carrier, Hemoglobin glutamer-200 (bovine) (Hb-200) (Oxyglobin) on splanchnic perfusion and oxygenation in a canine model of acute hypovolaemia. Twelve anaesthetized dogs [mean weight 30.8 (S.D. 1.4) kg] were instrumented for recordings of heart rate (HR), mean arterial pressure (MAP), central venous pressure (CVP), cardiac output and cranial mesenteric arterial (CMA) and venous blood flows (CMV). Total and plasma haemoglobin (Hb), oxygen content and saturation, lactate concentration, pH and blood gases were analysed in arterial, mixed venous and mesenteric venous blood samples. Measurements were made before (baseline) and after 1 h of haemorrhage, after which animals were resuscitated with either shed blood (controls) or Hb-200 until HR, MAP and CVP returned to prehaemorrhage levels. Recordings were repeated immediately and 3 h after termination of fluid resuscitation, after which organ specimens were obtained for microscopic examination. Haemorrhage (average 32 ml kg(-1)) reduced MAP to 50 mm Hg, increased HR and systemic vascular resistance (SVR), and was accompanied in both the systemic and the splanchnic circulation by significant decreases in blood flow, Hb content and oxygen delivery (DO2), and lactic acidosis. In controls, all variables recovered to baseline after isovolaemic resuscitation with shed blood. In dogs resuscitated with a small volume of Hb-200 (10 ml kg(-1)), HR, MAP, CVP and CMA and CMV blood flows returned to baseline. However, cardiac output, total Hb, oxygen content and systemic and mesenteric DO2 remained depressed while SVR increased further. Mesenteric and systemic acid-base status recovered in both groups, and there was no difference in microscopic tissue damage between groups. Thus, Hb-200 reconstituted splanchnic perfusion and oxidative metabolism in spite of pronounced systemic vasoconstriction and insufficient restoration of CO and DO2; it may improve diffusive oxygen transport in the microvasculature by virtue of haemodilution and its high efficiency in the uptake and release of oxygen.
authors.affiliation: Department of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Kennett Square 19348, USA.
authors.forename: B
authors.initials: B
authors.lastname: Driessen
authors.forename: J S
authors.initials: JS
authors.lastname: Jahr
authors.forename: F
authors.initials: F
authors.lastname: Lurie
authors.forename: S M
authors.initials: SM
authors.lastname: Griffey
authors.forename: R A
authors.initials: RA
authors.lastname: Gunther
mesh_terms: D000136:Acid-Base Equilibrium / Q000187:drug effects; D000818:Animals; D001802:Blood Substitutes / Q000494:pharmacology*; D002417:Cattle; D004195:Disease Models, Animal; D004285:Dogs; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006454:Hemoglobins; D020896:Hypovolemia / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D010100:Oxygen / Q000097:blood; D010101:Oxygen Consumption / Q000187:drug effects*; D013152:Splanchnic Circulation / Q000187:drug effects*
chemical_list: D001802:Blood Substitutes; D006454:Hemoglobins; C402601:hemoglobin glutamer-200; D010100:Oxygen