Liposome-encapsulated hemoglobin reduces the size of cerebral infarction in rats: effect of oxygen affinity.
Liposome-encapsulated hemoglobin (LEH) with a low oxygen affinity (l-LEH, P(50) = 45 mm Hg) was found to be protective in the rodent and primate models of ischemic stroke. This study investigated the role of LEH with a high O(2) affinity (h-LEH, P(50) = 10 mm Hg) in its protective effect on brain ischemia. The extent of cerebral infarction was determined 24 h after photochemically induced thrombosis of the middle cerebral artery from the integrated area of infarction detected by triphenyltetrazolium chloride staining in rats receiving various doses of h-LEH as well as l-LEH. Both h-LEH and l-LEH significantly reduced the extent of cortical infarction. h-LEH remained protective at a lower concentration (minimal effective dose [MED]: 0.08 mL/kg) than l-LEH (MED: 2 mL/kg) in the cortex. h-LEH reduced the infarction extent in basal ganglia as well (MED: 0.4 mL/kg), whereas l-LEH provided no significant protection. h-LEH provided better protection than l-LEH. The protective effect of both high- and low-affinity LEH may suggest the importance of its small particle size (230 nm) as compared to red blood cells. The superiority of h-LEH over l-LEH supports an optimal O(2) delivery to the ischemic penumbra as the mechanism of action in protecting against brain ischemia and reperfusion.
Fukumoto
Dai
D
Hamamatsu Photonics K.K., Hamamatsu, Japan.
Kawaguchi
Akira T
AT
Haida
Munetaka
M
Yamano
Mariko
M
Ogata
Yoshitaka
Y
Tsukada
Hideo
H
D000818:Animals; D001802:Blood Substitutes / Q000008:administration & dosage* / Q000378:metabolism / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002544:Cerebral Infarction / Q000188:drug therapy* / Q000473:pathology; D004195:Disease Models, Animal; D006801:Humans; D008081:Liposomes; D008297:Male; D010100:Oxygen / Q000097:blood / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013927:Thrombosis / Q000139:chemically induced
D001802:Blood Substitutes; D008081:Liposomes; D010100:Oxygen