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.

Arterial oxygenation and oxygen delivery after hemoglobin-based oxygen carrier infusion in canine hypovolemic shock: A dose-response study

“…It shares most properties with Hb glutamer-250 (bovine; Hemopure [formerly HBOC-201], Biopure) (7), which is currently in phase III clinical trials and approved for use in humans in South Africa. Previous studies with low doses of Hb-200 (8,9) and HBOC-201 (10) revealed an improvement of hemodynamic functions, yet a significantly smaller increase in arterial oxygen content and oxygen delivery after HBOC infusion than expected based on the amount of Hb administered. Therefore, in the present study, our primary goal was to analyze whether infusion of Hb-200 will dosedependently and to a greater extent than conventional plasma expanders increase systemic oxygen delivery and tissue oxygenation in dogs subject to isovolemic resuscitation after acute blood loss.…”

“…Methods were essentially as described and discussed in detail previously (8,9) with modifications mentioned below.…”

Artificial Oxygen Carriers: Hemoglobin-Based Oxygen Carriers – Current Status 2004

“…However, systemic vasoconstriction is not paralleled by a reduced regional organ blood flow or impaired microcirculation [22,23]. In contrast, animal studies have shown improved tissue oxygenation during blood exchange, restoration of the pancreatic microcirculation and tissue oxygen tensions, and reduced acidosis with better mucosal integrity of the intestine after resuscitation from hemorrhagic shock with different HBOC [16,24,25]. In experimental acute pancreatitis bovine HBOC-301 was able to significantly reduce histologic tissue damage in rats [26].…”

Hemoglobin-Glutamer 200 Reduces Reperfusion Injury of the Cold Preserved Rat Liver by Induction of Heme Oxygenase-1

“…Hemoglobin-glutamer (HbG) 200 (Oxyglobin; Biopure, Cambridge, MA) is a hemoglobin-based oxygen carrying (HBOC) solution capable of improving organ oxygenation by increasing plasma and total hemoglobin concentration and an increased oxygen unloading in the microcirculation, due to its low oxygen affinity [17]. It contains 13 g/dL polymerized hemoglobin of bovine origin in a modified lactated Ringer's solution, which circulates in plasma and immediately transports oxygen to tissues upon infusion.…”

“…The osmolality of the solution is 300 mOsm/kg. The terminal elimination half-life of the drug is estimated to range between 18 and 43 h for dosages of 10 to 13 mL/kg [17].…”