Repeated administration of protamine does not attenuate circulatory changes caused by protamine reversal of heparin...

To determine whether repeated administration of protamine attenuates circulatory changes caused by protamine reversal of heparin and to evaluate the significance of nitric oxide generation.

Prospective, randomized, controlled, animal study.

University research laboratory.

Twenty-seven adult mongrel dogs.

The animals were randomly assigned to 3 groups (n = 9 in each) according to the pretreatment. The control group was pretreated with normal saline, and the 2 other groups were given 2 different doses of protamine: protamine 0.1 (protamine, 0.1 mg/kg) and protamine 1.0 (protamine, 1.0 mg/kg). Under general anesthesia, all animals were anticoagulated with intravenous heparin, 200 IU/kg. Five minutes after heparin injection, preadministered saline (control) or protamine in saline was infused during 60 seconds. Five minutes after the pretreatment, protamine, 2.0 mg/kg in control, 1.9 mg/kg in protamine 0.1, or 1.0 mg/kg in protamine 1.0, was administered intravenously during 10 seconds.

Percent changes in mean arterial blood pressure among the 3 groups at each period were not significantly different except 60 minutes after protamine infusion. Mean pulmonary arterial pressure in the protamine 1.0 group at 5, 15, 20, and 60 minutes was higher than in the control group. Serum nitrate concentration was not significantly different among the 3 groups at baseline and 10 minutes after protamine injection.

Repeated administration of protamine does not attenuate circulatory changes caused by protamine reversal of heparin in dogs. Nitric oxide generation does not appear to be responsible for the phenomenon.