title: Effects of liposome-encapsulated hemoglobin on gastric wound healing in the rat.
abstract: Liposome-encapsulated hemoglobin (LEH) may improve microcirculation and oxygen (O2 ) metabolism at a surgical wound to accelerate its healing. Ten mL/kg of LEH with high (h-LEH) or low O2 -affinity (l-LEH), homologous red blood cells (RBC), empty liposome or saline as a control was infused before a 10-mm incision and interrupted suture closure of the gastric wall in a total of 110 rats. Two and 4 days later, the stomach was excised for bursting pressure determination and histological sampling. The dose-response relationship was examined in 70 additional rats receiving progressively reduced doses of h-LEH. Hypoxia-inducible factor-1α (HIF-1α) was stained immunohistochemically in 54 other rats to examine its accumulation at the anastomotic sites. Bursting pressure of the surgical wound was significantly higher 2 days after surgery only in the h-LEH-treated rats (P < 0.05), but not at 4 days after surgery, when other rats showed increased bursting pressure to a nonsignificant level. Histological examination revealed less granulocyte infiltration, better granulation, and more macrophage infiltration in h-LEH-treated rats at 2 days, but no longer at 4 days postsurgery. Dose-response study revealed that 0.4 mL/kg of h-LEH (hemoglobin 24 mg/kg) was effective for elevating bursting pressure at 2 days. h-LEH-treated rats had significantly suppressed HIF-1α accumulation in the wound 6, 24, and 48 h after surgery as compared with control animals treated with homologous RBC or saline. In conclusion, the results suggest that h-LEH, but not l-LEH or homologous transfusion, may accelerate wound healing early after gastric incision and anastomosis in the rat. The mechanism(s) appears to be related to improved O2 supply, aerobic metabolism, and suppressed inflammation in the wound.
authors.affiliation: Department of Cell Transplantation and Regenerative Medicine, Tokai University School of Medicine, Isehara, Kanagawa, Japan.
authors.forename: Akira T
authors.initials: AT
authors.lastname: Kawaguchi
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Okamoto
authors.forename: Yoshihumi
authors.initials: Y
authors.lastname: Kise
authors.forename: Susumu
authors.initials: S
authors.lastname: Takekoshi
authors.forename: Chieko
authors.initials: C
authors.lastname: Murayama
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Makuuchi
mesh_terms: D000818:Animals; D001802:Blood Substitutes / Q000494:pharmacology / Q000627:therapeutic use*; D016503:Drug Delivery Systems; D005753:Gastric Mucosa / Q000378:metabolism; D006454:Hemoglobins / Q000494:pharmacology / Q000627:therapeutic use*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D008081:Liposomes / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013270:Stomach / Q000187:drug effects / Q000601:surgery; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D001802:Blood Substitutes; D006454:Hemoglobins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008081:Liposomes; C057506:hemoglobin L
keywords: Aerobic metabolism; Artificial oxygen carriers; Hypoxia-inducible factor-1α; Ischemia and reperfusion; Liposome-encapsulated hemoglobin; Wound healing