Intra-abdominal surgery causes plasma extravasation which, in the rat, is prevented by combined histaminergic H1 and H2 blockade. We evaluated the relative importance of H1 and H2 blockade in this situation. Cloralose-anaesthetized Wistar rats were subjected to a standardized abdominal trauma. Mean arterial pressure (MAP), heart rate (HR) and haematocrit (Hct) were monitored and plasma volume (PV) was determined before and 1 h after the trauma. Compared to non-traumatized rats (n = 8), the trauma decreased PV and increased Hct (n = 8). MAP decreased during the actual trauma, whereas HR remained stable throughout. In animals given cimetidine 25 mg kg-1 i.v. just prior to the trauma (n = 8), PV, Hct and MAP changed, as in the non-blocked rats. In contrast, pyrilamine, 10 mg kg-1, completely prevented the decrease in PV and the increase in Hct (n = 7), but not the decrease in MAP. The findings suggest that a histaminergic H1 mechanism is of importance for the plasma loss elicited by intra-abdominal trauma.
Tumor cells are dependent on glutamine metabolism and acivicin, which is a selective glutamine antagonist, has been shown to effectively retard tumor growth in several malignancies. However, systemic treatment with acivicin is associated with significant side effects. The purpose of the present study was to examine whether use of an in vivo isolated liver perfusion model may allow administration of lethal doses of acivicin and compare it to regional infusion of acivicin in the hepatic artery. Five days after tumor inoculation, acivicin was administered by an isolated liver perfusion model or by regional infusion via the hepatic artery. It was found that regional infusion of acivicin (5 and 10 mg/kg) via the hepatic artery caused systemic illness and diarrhea, and all animals in this group died within 3 days. In contrast, we observed no signs of systemic illness, diarrhea or hepatocellular injury in rats receiving isolated liver perfusion with or without acivicin (10 mg/kg) administration. Noteworthy, we found that isolated perfusion with acivicin reduced the glutamine content in liver tumors by 39% compared to perfusion with control medium. In line with this, it was found that isolated perfusion with acivicin (10 mg/kg) inhibited tumor growth in the liver. Taken together, this study suggests that application of the isolated liver perfusion model avoids the toxic and lethal effects of high doses of chemotherapy, herein acivicin, and may provide a useful approach to treat liver tumors in vivo.
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