Pretreatment with a deleted form of hepatocyte growth factor (dHGF) prevents the mortality of plasma-loss-induced hypovolemic shock in rats.

Severe trauma, infection, burn, pancreatitis and major surgery often induce circulatory collapse leading to multiple organ failure and death. It is hypothesized that therapy for the attenuation of circulatory collapse may improve the prognosis in these diseases. Previous work has documented that pretreatment with a deleted form of hepatocyte growth factor (dHGF) in normal rats increases the circulating plasma volume that reflects its accelerating action of hepatic protein synthesis. Therefore, the effects of pretreatment with dHGF on hypovolemic shock models were studied in rats. Rats were intravenously administered dHGF (1 mg/kg, twice daily for 5-6 days) or vehicle, and subjected to a 25% total body surface area full-thickness burn or a trypsin-induced acute pancreatitis. In rats that were receiving vehicle, survival rates on day 7 after injury induction were 12% in the burn model and 5% in the pancreatitis model, respectively. In both models, hematocrit values were apparently increased and circulating plasma volumes were decreased compared to sham-operated rats at 6 h after injury induction. The pretreatment of animals with dHGF increased the survival rates on day 7 to 40% in the burn model and 29% in the pancreatitis model. dHGF-treatment in normal rats decreased the hematocrit values and increased the circulating plasma volumes, and these changes of hematocrit value and circulating plasma volume were also maintained after injury induction. These findings suggest that dHGF pretreatment prevents the mortality in the severe burn and acute pancreatitis, and that its effect may contribute to ameliorating the progressing of plasma-loss-induced hypovolemia.