Protamine induced arterial hypoxaemia: the relationship to hypoxic pulmonary vasoconstriction

Protamine administration may induce arterial hypoxaemia in dogs and humans. However, the responsible mechanism has not been established. Protamine, as it is a pulmonary vasoactive substance, may interfere with normal hypoxic pulmonary vasoconstriction (HPV) and cause arterial hypoxaemia. This possibility was tested in dogs utilizing a one lung hypoxic model. One lung hypoxic ventilation decreased pulmonary blood flow in the hypoxic lung from 1022 +/- 96 ml X min-1 (mean +/- SEM) to 846 +/- 39 ml X min-1 (p less than 0.05) while increasing blood flow from 833 +/- 85 ml X min-1 to 1109 +/- 101 ml X min-1 (p less than 0.05) in the normoxic lung, resulting in 24 per cent effective diversion of blood flow. Protamine infusion, after heparinization, markedly elevated pulmonary vascular resistance in both lungs but preferentially in the normoxic lung (102 +/- 27 per cent increase in normoxic lung, 60 +/- 6.4 per cent increase in hypoxic lung) and significantly reversed the pulmonary blood flow shift induced by one lung hypoxic ventilation (effective diversion of blood flow was reduced to four per cent). Concurrently, arterial PO2 further decreased. Our results demonstrate that protamine interferes with effectiveness of pre-existing HPV and suggest that this mechanism, at least in part, may be responsible for arterial hypoxaemia observed after protamine infusion. The marked generalized pulmonary vasoconstriction with protamine appears to be the direct force that interferes with pre-existing auto-regulatory HPV. In addition to the well known haemodynamic effects of protamine, protamine infusion may also cause arterial hypoxaemia in those patients in whom HPV plays a significant role in maintaining arterial oxygenation.