Cardiovascular effects of protamine sulfate are dependent on the presence and type of circulating heparin.

Man's response to clinical doses of protamine is highly variable. We investigated the influence of circulating heparin in nine swine (mean age 6 weeks, weight 10 kg). Through a sternotomy we implanted an electromagnetic flow probe around the pulmonary artery for cardiac output determination and catheters into the ascending aorta, pulmonary artery, right atrium, and left atrium for pressure monitoring. Each animal was allowed to recover and was studied awake on 3 consecutive days. Protamine, 3 mg/kg, beef lung heparin, 300 U/kg, and pork mucosal heparin, 300 U/kg, followed by protamine, were given in rotation by intravenous bolus. Protamine alone had no effect. Beef lung heparin followed by protamine induced a marked increase in pulmonary artery pressure (mean 38 +/- 3 to 51 +/- 5 mm Hg in 3 minutes). Pulmonary vascular resistance doubled (mean 0.12 +/- 0.01 to 0.23 +/- 0.04 R within 4 minutes), returning to normal within 15 minutes. Cardiac index and aortic pressure changed minimally. Pork mucosal heparin followed by protamine induced a similar but greater increase in mean pulmonary arterial pressure; however, cardiac index fell significantly (p less than 0.05, 207 +/- 16 to 117 +/- 16 ml/kg/min-1 at 1 minute) despite a regular rhythm and adequate left atrial filling pressure. Thus cardiac contractility was depressed. Systemic hypotension occurred in three of nine pigs. Both mean pulmonary vascular resistance and systemic vascular resistance increased (0.12 +/- 0.01 to 0.67 +/- 0.25 R and 0.40 +/- 0.04 to 1.09 +/- 0.25 R, respectively), significantly (p less than 0.05) more with pork than beef heparin. These data demonstrate that cardiovascular response to protamine neutralization varies significantly in regard to the type of heparin used. Furthermore, circulating heparin is required to produce those effects previously attributed to protamine alone.