The effect of physostigmine on the haemorrhagic hypovolemia in anaesthetized rabbits

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

“…bolus injection of physostigmine (0.07 mg/kg) in hemorrhaged rabbits pretreated with L-NAME (30 mg/kg) immediately after the end of bleeding, resulted in severe bradycardia, metabolic acidosis and high mortality during the first 15 min of the after-bleeding period (unpublished results from our laboratory). On the other hand, we have previously indicated that physostigmine and L-arginine might produce a sinergistic action in this model of shock (Savi} et al, 1991(Savi} et al, , 1992@uni} et al, 1995).…”

“…Physostigmine-induced a raise of the mean arterial pressure (MAP) in rabbits subjected to severe hypovolemia (approx. 40% of the estimated blood volume for 15 min) ( Table 1) could be explained by several mechanisms Savi} et al, 1991Savi} et al, , 1992@uni} et al, 1995;Prostran et al, 1994Prostran et al, , 1996Prostran et al, , 1997. First, its central cholinergically-mediated stimulation of the peripheral sympathetic tonus and the release of vasopressin could contribute to defence mechanisms in shock.…”

“…However, the beneficial effects of physostigmine (0.07 mg/kg, i.v. bolus) on arterial pressure and survival in hemorrhaged rats and rabbits could not be attributed only to the increased peripheral vasoconstriction, and several other hypothesis have arisen (Savi} et al, 1991(Savi} et al, , 1992@uni} et al, 1995). The presumed anti-shock effects of physostigmine have been explained by the stimulation of adrenaline release from the adrenal medulla since (a) nicotinic, but not muscarinic antagonists abolished the protective effects of physostigmine in hemorrhaged rabbits (Guarini et al, 1989), and (b) nicotinic agonist dimethylphenylpiperazinium (DMPP) (0.5 mg/kg) produced a rapid and sustained reversal of hemorrhagic shock in rats via stimulation of adrenaline release from the adrenal medulla (Bazzani et al, 1996).…”

“…Physostigmine has been extensively used in various models of hemorrhagic shock with remarkable success (Guarini et al, 1989;Savi} et al, 1991Savi} et al, , 1992@uni} et al, 1995;Todorovi} et al, 1996Todorovi} et al, , 1997. As a lipid-soluble anticholinestrase, it is distributed in the central nervous system and may increase blood pressure via central cholinergically mediated activation of the peripheral adrenergic system (Varagi}, 1955;Prostran et al, 1994Prostran et al, , 1996Prostran et al, , 1997.…”

“…The presumed anti-shock effects of physostigmine have been explained by the stimulation of adrenaline release from the adrenal medulla since (a) nicotinic, but not muscarinic antagonists abolished the protective effects of physostigmine in hemorrhaged rabbits (Guarini et al, 1989), and (b) nicotinic agonist dimethylphenylpiperazinium (DMPP) (0.5 mg/kg) produced a rapid and sustained reversal of hemorrhagic shock in rats via stimulation of adrenaline release from the adrenal medulla (Bazzani et al, 1996). Also, physostigmine caused a significant hemodilution in hemorrhaged rabbits (Savi} et al, 1991(Savi} et al, , 1992. In addition, the same authors surmised that this anticholinesterase may antagonize the action of endogenous substances (e.g.…”