The new
opiate antagonist
Win 44,441-3 (-)-isomer was infused intravenously in cats at a rate of 2 mg . kg-1 . h-1 to determine its effect in
hemorrhagic shock. Hemorrhaged cats treated with
Win 44,441-3 maintained post reinfusion mean arterial blood pressure (MABP) at a higher value compared to cats receiving only the vehicle. Final MABP was 70 +/- 11 mm Hg for cats receiving vehicle compared to 103 +/- 7 mm Hg for cats receiving
Win 44,441-3. These values represent 60 +/- 9% and 85 +/- 6% of initial MABP for the vehicle- and Win 44,441-3-treated cats respectively.
Win 44,441-2 (+)-isomer, the inactive stereoisomer of
Win 44,441-3, was also infused at 2 mg . kg-1 . h-1 in cats subjected to
hemorrhagic shock. The final pressure in this group was 72 +/- 8 mm Hg which is 61 +/- 8% of the initial pressure for this group.
Win 44,441-3 and
Win 44,441-2 were both ineffective in moderating increases in circulating lysosomal
hydrolase activity in shocked cats. Neither isomer stabilized lysosomal membranes or retarded proteolysis in vitro. Plasma
myocardial depressant factor was significantly reduced by the
opiate antagonist,
Win 44,441-3 during
shock. Our results show that the systemic infusion of an
opiate antagonist improves the hemodynamic state of cats subjected to
hemorrhagic shock while the (+)-isomer which lacks
opiate antagonist activity produces no such improvement.