Use of Hemoglobin Vesicles During Cardiopulmonary Bypass Priming Prevents Neurocognitive Decline in Rats

Abstract

Background— Homologous blood use is considered to be the gold standard for cardiopulmonary bypass (CPB) priming in infants despite exposure of the patient to potential cellular and humoral antigens. However, the use of hemoglobin vesicles (HbVs), artificial oxygen carriers that encapsulate a concentrated hemoglobin solution within phospholipid bilayer membranes, for CPB priming may prevent neurocognitive decline in infants. The goal of this study was to determine whether HbV use offsets hemodilution caused by patient/priming volume-mismatched CPB and thereby prevents the development of postoperative neurocognitive deficits. Methods and Results— CPB was established in 28 male Sprague-Dawley rats (age, 14 to 16 weeks; weight, 450 grams) after cannulation of the tail artery and right atrium. The animals were randomly assigned to 1 of 3 groups: sham surgery (n=9), HbV (−) prime (n=10), or HbV (+) prime (n=9). CPB was conducted for 90 minutes at 200 mL/kg per minute. The hematocrit during CPB was 10.0±1.2% in the HbV (+) prime group and 9.9±1.3% in the HbV (−) prime group ( P =not significant). Learning and memory function were evaluated using 2 different maze tests (Maze-1 and Maze-2, in which the arrival times to the target were measured on the first, third, fifth, and seventh postoperative days). Learning and memory function were significantly better in the HbV (+) prime group than in the HbV (−) prime group (Maze-1, P =0.012; Maze-2, P =0.042); there was no difference between the HbV (+) prime and the sham surgery group. Conclusions— The use of HbV for CPB priming may serve as a substitute for homologous blood to prevent the unacceptable hemodilution and contribute to maintenance of intact neurocognitive function.

Hemoglobin-vesicles for a Transfusion Alternative and Targeted Oxygen Delivery

“…Addition of a plasma substitute solution such as recombinant albumin is effective to regulate colloid osmotic pressure Sakai et al, 2004;. We confirmed sufficient O 2 -transport comparable with RBC in the animal experiments of extreme hemodilution up to 90% blood exchange and resuscitation from hemorrhagic shock, and priming solution for cardiopulmonary bypass (ECMO) (Yamazaki et al, 2006).…”

Intestinal ischemia/reperfusion enhances microglial activation and induces cerebral injury and memory dysfunction in rats*

“…Previous reports (11,30) indicated that neurocognitive dysfunction could be produced by cardiopulmonary bypass which also involves II/R. In addition, the survivors who suffered from critical diseases involving systemic inflammatory response were commonly left with long-term cognitive dysfunction and impairment of life quality (31).…”

Acute 40% exchange-transfusion with hemoglobin-vesicles in a mouse pneumonectomy model

“…Pharmacodynamic, serologic, or metabolic analysis of the reticuloendothelial system has also been performed, [10–12] as have preclinical studies of the long-term survival of dogs after exchange transfusion of HbV. [13] While HbVs have been used to prime the fluid of heart-lung machines,[14] their perioperative effects have not been evaluated. In this study, we examined the performance of HbVs in a mouse model of pneumonectomy by monitoring postoperative survival and recovery.…”