INTRODUCTION: Protamine reversal of heparin anticoagulation in patients often produces profound hypotension. The present study was aimed to investigate the effectiveness of pretreatment with a small dose (0.5 mg.kg (-1)) of protamine in attenuating protamine-induced systemic hypotension in heparinized dogs. METHODS: Forty mongrel dogs were pretreated with either intravenous saline (control group, n=19) or protamine 0.5 mg.kg (-1) (protamine group, n=11) 5 minutes after heparin (300 IU.kg (-1), iv) during 1.5% halothane anesthesia. All dogs were then given protamine 3 mg.kg (-1) over a period of 30 s through right atrium 10 minutes after the pretreatment. Mean arterial pressure (MAP), mean pulmonary arterial pressure (MPAP), left ventricular end-diastolic pressure (LVEDP), heart rate (HR), and cardiac output and left circumflex coronary flow (LCX flow) via Doppler flowmeter were continuously recorded in baseline conditions and up to 20 minutes. Calculated parameters included cardiac index (CI), systemic and pulmonary vascular resistance indices (SVRI and PVRI), and LV dp/dt. RESULTS: In the control group, protamine infusion caused immediate but transient decreases of MAP (-42%), CI (-58%), LVEDP (-53%) and dP/dt (-25%), and increases of MPAP (39%), SVRI (38%) and PVRI (4.0 fold). Protamine pretreatment significantly attenuated but not completely blocked the hemodynamic responses to protamine. LCX flow increased significantly (213~258%) immediately after protamine infusion in both groups. CONCLUSIONS: These results suggest that, in the heparinized dog, pretreatment with a small dose of protamine attenuates the degree of hypotension that may follow the rapid administration of protamine.