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(Circulation. 2006;114:I-220 – I-225.)
© 2006 American Heart Association, Inc.

Myocardial Protection and Vascular Biology

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

Masataka Yamazaki, MD; Ryo Aeba, MD; Ryohei Yozu, MD; Koichi Kobayashi, MD

From Divisions of Cardiovascular Surgery (M.Y., R.A., R.Y.) and General Thoracic Surgery (K.K.), Keio University, Tokyo, Japan.

Correspondence to Ryo Aeba, Division of Cardiovascular Surgery, Keio University, 35 Shinanomachi, Shinjuku, Tokyo, 160-8582, Japan. E-mail aeba{at}sc.itc.keio.ac.jp

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.

Key Words: cardiopulmonary bypass • hemoglobin • nervous system • pediatrics