L-arginine and physostigmine in hemorrhagic shock: Lack of evidence for synergism

Abstract

We have previously shown the protective effects of both Larginine and phystigmine in an experimental model of severe hemorrhagic shock, when these substances were used as monotherapy. It was of interest to investigate whether the combination of L-arginine (300 mg/kg, i.v. bolus) and physostigmine (0.07 mg/kg, i.v. bolus) could produce further beneficial cardiovascular and/or metabolic effects in anaesthetized hemorrhaged rabbits (intermittent bleeding; 40% of the estimated blood volume for 15 min). Selected cardiovascular and biochemical parameters were assessed before bleeding and at several points up to 60 min after the end of bleeding. Drugs were injected 1-2 min after the end of bleeding (Phy-group) or 10 min later (L-Arg+Phy-group). Control rabbits received the corresponding volumes of saline only (0.6-2.0 ml; S-group). Physostigmine (0.07 mg/kg) produced a rapid and sustained increase in mean arterial pressure, the effect being attenuated in L-argininepretreated rabbits (Phy- and L-Arg+Phy-group respectively). The beneficial effecs of L-arginine on heart rate and hemoglobin oxygen saturation in venous blood were not completely lost in rabbits of the LArg+ Phy group, and such a combination partially improved acid-base status (decrease in PaCO2 in arterial blood) and produced further hemodilution (decresase in hematocrit) 15-60 min after the end of bleeding. However, the combination of L-arginine and physostigmine does not offer any significant advantage over the monotherapy with these drugs in hemorrhagic shock