The hemodynamic effects of intra-aortic versus intravenous administration of protamine for reversal of heparin in pigs

Abstract

The hemodynamic effects of intra-aortic (IA) versus intravenous (IV) administration of protamine for reversal of heparin were studied in pigs. The animals were anesthetized with sodium thiopental, nitrous oxide, oxygen, and halothane. Twenty minutes after heparinization (3 mg/kg) the following hemodynamic parameters were measured: heart rate, arterial pressure, pulmonary artery pressure (PAP), left ventricular end-diastolic pressure, and cardiac output. Protamine sulfate (3 mg/kg) was injected over 30 seconds IV in Group I (five pigs) and into the ascending aorta (IA) in Group II (five pigs). After injection, the above measurements were repeated at 1.0, 2.5, 5, and 15 minutes. The hemodynamic effects of intravenous protamine (3 mg/kg) without prior heparinization were studied in Group III (four pigs). Groups I and II experienced a decrease in cardiac output (Group I, 14%; Group II, 29%) and a marked increase in PAP (Group I, 78%; Group II, 79%) and pulmonary vascular resistance (PVR) (Group I, 174%; Group II, 559%) which peaked at 1 minute after protamine injection (p less than 0.05). Cardiac output, PAP, and PVR returned to baseline within 15 minutes. Heart rate, arterial pressure, left ventricular end-diastolic pressure, and systemic vascular resistance (SVR) were unchanged. No hemodynamic abnormalities occurred in animals injected with protamine alone (Group III). It is concluded that IV or IA administration of protamine causes marked hemodynamic changes in heparinized pigs. This does not confirm a recent clinical study reporting stable hemodynamics after IA administration of protamine. The lack of circulatory effects of protamine in unheparinized pigs suggests that a protamine-heparin interaction may be involved.