Effects of Liposome‐Encapsulated Hemoglobin on Gastric Wound Healing in the Rat

Liposome‐encapsulated hemoglobin ( LEH ) may improve microcirculation and oxygen ( O 2 ) metabolism at a surgical wound to accelerate its healing. Ten mL/kg of LEH with high ( h ‐ LEH ) or low O 2 ‐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 O 2 supply, aerobic metabolism, and suppressed inflammation in the wound.