On The Mechanism Of Plasminogen Activator Release By Ddavp: Animal Studies

In pentobarbitone anaesthetised dogs, IV infusion of 1-desamino-8-D-arginine vasopressin (DDAVP) over 15 minutes produced a dramatic increase in plasma plasminogen activator (PA) levels, as measured by the euglobulin lysis time. However, 70 ug/Kg of DDAVP were required, compared with circa O.4 ug/Kg for a similar response in unanaesthetised human subjects. Factor VIII levels increased only slightly in dogs even at these relatively high doses.

Infusion of 7.0 ug/Kg DDAVP into the femoral artery of dogs had no discernible effects on the PA level of ipsilateral femoral venous blood - similar to findings previously reported for humans. In contrast, infusion of this dose into the carotid artery of dogs produced a marked rise of PA in jugular venous and systemic blood.

Fifty mls of jugular venous effluent were collected immediately after DDAVP infusion to carotid artery, the plasma separated, stored frozen, and subsequently infused intravenously to another dog. PA levels rose moderately.

It is suggested that DDAVP acts on some cephalic receptor - possibly in the hypothalmus - from which a humoral factor is released which in turn releases PA from a peripheral storage site. The high doses of DDAVP required in these studies, and the relative lack of fVIII response, suggests that barbitone anaesthesia may interfere with this mechanism.