A pulmonary mock circulation model for a better understanding of protamine reversal of heparin

Neutralization of heparin by protamine is a common procedure following extracorporeal circulation (cardiopulmonary bypass) of blood. Protamine administration has been shown to cause serious hemodynamic derangement in some patients. Obstruction of the pulmonary vascular bed following protamine administration has been suggested to be the primary cause of hemodynamic changes. The present study was undertaken to test the hypothesis that macromolecular complexes formed between cationic protamine with anionic heparin or other plasma components cause the obstruction of the vascular bed. An in vitro mock circulation model was designed to examine the formation of such complexes. In this model, blood or plasma was passed through a glass bead column at a constant flow rate while the pressure between the syringe pump and the column was closely monitored. No increase in pressure was noted when blood, plasma or saline alone or with added heparin were passed through the column. Addition of protamine to either blood or plasma resulted in a significant increase in the pressure; this increase was even greater when heparin was also present in the test medium. That the increase in pressure was due to the obstruction of the column was confirmed by using 1251-protamine and documenting that complexes formed between protamine and plasma proteins/heparin were retained in the column. These observations suggested that protamine formed large insoluble complexes with plasma proteins. Heparin appeared to help consolidate these complexes thus causing a rapid increase in the pressure. This may explain why the hemodynamic changes following protamine administration are more pronounced in patients with circulating heparin.