title: Resuscitation with diaspirin crosslinked hemoglobin increases cerebral and renal blood perfusion in hemorrhaged rats.
abstract: Diaspirin crosslinked hemoglobin (DCLHb Baxter Healthcare Corp., Round Lake, IL, USA), a hemoglobin-based blood substitute has been found to be an effective resuscitative agent following hemorrhage in animals. The present study was undertaken to determine the effect of DCLHb on microvascular perfusion in the brain and kidney following hemorrhage in anaesthetized, male Sprague Dawley rats using laser Doppler flowmetry. Hemorrhage was induced by withdrawal of arterial blood at a rate of 0.5 to 1.0 ml/min until blood pressure of 35-40 mmHg was achieved. This was maintained for up to 30 min. The arterial blood pH, pO2, pCO2 and total hemoglobin (THb) were monitored. Hemorrhage significantly decreased pH, pCO2 and THb and increased pO. Hemorrhage significantly decreased (26%) brain blood perfusion due to a decrease (17%) in the concentration of moving red blood cells (CMBC). In the kidney there was a greater decrease (65%) in blood perfusion due to a significant decrease in both CMBC (28%) and red blood cell velocity (49%). Resuscitation with vehicle (Ringer's lactate, 4 ml/kg, i.v.) did not produce any improvement in cerebral and renal blood perfusion. Resuscitation with DCLHb (400 mg/kg, i.v.) improved perfusion in the brain (112%) due to an increase in the CMBC (69%) and the velocity of red blood cells (33%). Similarly, in the kidney, DCLHb increased perfusion (178%) by increasing CMBC (55%) and red blood cell velocity (89%) of hemorrhaged rats. The increase in renal blood perfusion was more marked (p < 0.001) than the changes in cerebral blood perfusion following resuscitation with DCLHb in hemorrhaged rats. It is concluded that DCLHb can significantly increase cerebral and renal blood perfusion of hemorrhaged rats and this effect may contribute to its efficacy as a resuscitative solution.
authors.affiliation: Department of Pharmaceutics & Pharmacodynamics, University of Illinois at Chicago 60612, USA.
authors.forename: A
authors.initials: A
authors.lastname: Kumar
authors.forename: A P
authors.initials: AP
authors.lastname: Sen
authors.forename: P R
authors.initials: PR
authors.lastname: Saxena
authors.forename: A
authors.initials: A
authors.lastname: Gulati
mesh_terms: D000136:Acid-Base Equilibrium; D000818:Animals; D001241:Aspirin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D001784:Blood Gas Analysis; D001794:Blood Pressure; D001802:Blood Substitutes / Q000737:chemistry / Q000494:pharmacology; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology*; D003432:Cross-Linking Reagents / Q000737:chemistry / Q000494:pharmacology; D006339:Heart Rate; D006454:Hemoglobins / Q000737:chemistry / Q000494:pharmacology*; D006470:Hemorrhage / Q000188:drug therapy* / Q000503:physiopathology; D017078:Laser-Doppler Flowmetry; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology; D010092:Oximetry; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology*; D012151:Resuscitation
chemical_list: D001802:Blood Substitutes; D003432:Cross-Linking Reagents; D006454:Hemoglobins; C083478:diaspirin-cross-linked hemoglobin; D001241:Aspirin