Effect of Propranolol, Barbiturate Anesthesia and Splenectomy on Factor VIII: C and Plasminogen Activator Release Induced by DDAVP

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Abstract
After the injection of DDAVP in 39 non-anaesthezised dogs (0.4 μg/kg) factor VIII: C activity rose to 145% of baseline values (p <0.0001) and the fibrinolytic potential of euglobulin precipitate rose to 196% (p <0.0001). The injection of DDAVP was repeated three times in each dog of a group of good responder animals at weekly intervals, but after: A) Pentobarbital anesthesia (30 mg/kg) - the increase of factor VIII: C was reduced from 164% to 116% (n = 11; p <0.0005) and the increase in fibrinolytic activity was reduced from 270% to 192% (n = 11; p <0.05). B) Injection of propranolol (1 mg/kg) - the increase of factor VIII :C was reduced from 167% to 110% (n = 13; p <0.0005) and there was no significant decrease of fibrinolytic activity (n = 13; n.s.). C) Splenectomy - the increase of factor VIII: C was reduced from 166% to 122% (n = 10; p <0.0005) and fibrinolytic activity was not significantly changed from 196% to 256% (n = 9; n.s.). There were no statistically significant differences in the increases of factor VIII :C and fibrinolytic potential of euglobulin precipitate after repeating only the injection of DDAVP three times in the same animal at weekly intervals (n = 5; n.s.). We conclude that the increases in factor VIII: C and fibrinolytic activities observed after DDAVP infusion in the dog are due to different mechanisms of action. Pentobarbital anesthesia reduced the increase of factor VIII: C and fibrinolytic activity, but on the other hand, beta-blockade and splenectomy influenced differently the behaviour of both biological activities. Injection of the synthetic analogue of vasopressin 1-deamino-8-d-arginine vasopressin (DDAVP) increases the plasma levels of factor VIII procoagulant activity (factor VIII: C) and plasminogen activator both in man and dog (1, 2, 3, 4). The mechanism of action of DDAVP in determining these responses is not well known. In this work, after having confirmed that DDAVP increases factor VIII: C and fibrinolytic activity in the blood of the unanaesthezised dog, and in order to clarify the mechanisms involved in these pharmacological effects, we repeated the DDAVP injection in animals previously submitted to propranolol, pentobarbital anesthesia and splenectomy.