title: Hemodilution with liposome-encapsulated low-oxygen-affinity hemoglobin does not attenuate hypothermic cerebral ischemia in rats.
abstract: Hypothermia decreases cerebral metabolism and increases hemoglobin oxygen affinity. A hypothesis that the reversal of increased oxygen affinity would further attenuate hypothermic cerebral ischemia was tested by evaluating the effects of liposome-encapsulated hemoglobin (LipoHb) with low oxygen affinity (P50 = 40-50 mmHg) on hypothermic incomplete cerebral ischemia. Wistar rats were randomly assigned to one of the following two groups: (A) exchange transfusion with LipoHb solution (Hb = 6 g/dl) (LipoHb, n = 5), (B) no exchange transfusion (control, n = 5). After surface cooling to 22 degrees C, forebrain ischemia was induced for 15 min by bilateral carotid artery occlusion combined with a decrease in the mean arterial pressure (MAP) to 40 mmHg. (31)P-magnetic resonance spectroscopy was performed during ischemia and 45 min of reperfusion. After reperfusion, MAP was significantly higher in the control group than in the LipoHb group (P < 0.01), although there were no significant differences during ischemia. Intracellular pH and phosphocreatine (PCr) levels decreased during ischemia and returned to the preischemic level in both groups following reperfusion. The LipoHb group had a significantly larger decrease and smaller recovery in PCr than the control group (P < 0.0001). Althouth beta-adenosine triphosphate decreased during ischemia in the LipoHb group, it increased in the control group (P < 0.0001). Inorganic phosphate (Pi) increased during ischemia and decreased to the normal value after reperfusion. The LipoHb group experienced a significantly larger production of Pi than the control group (P = 0.02). Hemodilution with high-P50 LipoHb does not reduce ischemic energy depletion induced by hypothermic incomplete forebrain ischemia in rats.
authors.affiliation: Department of Cardiovascular Surgery, Hamamatsu Rosai Hospital, Hamamatsu 430-8525, Japan. toda-ind@umin.ac.jp
authors.forename: Teiji
authors.initials: T
authors.lastname: Oda
authors.forename: Tetsuhiro
authors.initials: T
authors.lastname: Kimura
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Ogata
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Fujise
mesh_terms: D000345:Affinity Labels; D000818:Animals; D002545:Brain Ischemia / Q000175:diagnosis / Q000209:etiology / Q000628:therapy*; D004195:Disease Models, Animal; D006438:Hemodilution / Q000379:methods*; D006454:Hemoglobins / Q000008:administration & dosage*; D007036:Hypothermia, Induced / Q000009:adverse effects; D008081:Liposomes; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051381:Rats; D016896:Treatment Outcome
chemical_list: D000345:Affinity Labels; D006454:Hemoglobins; D008081:Liposomes