Heparin-protamine reactions in pigs: role of oxygen-derived free radicals

We tested the hypothesis that pulmonary hypertension and thromboxane A2 release after heparin neutralization by protamine are mediated by oxygen free radicals. Forty-five pigs in five groups were studied during general anesthesia. Group I animals received 250 IU heparin followed by 100 mg protamine after 15 min. Group II and group III animals received dimethyl sulfoxide (DMSO) and dimethylthiourea (DMTU) 30 min before heparin infusion. Group IV animals were given superoxide dismutase (SOD) 5 min before protamine. Group V served for testing the pulmonary vascular reactivity in DMTU-treated animals to a thromboxane A2 analogue (U-46619). Generation of oxygen free radicals by polymorphonuclear granulocytes (PMNs) was measured in vitro by chemiluminescence. Severe pulmonary hypertension and thromboxane A2 release after protamine were not prevented by either DMSO or SOD. DMTU reduced pulmonary vasoconstriction to U-46619 and protamine but not to TxA2 release, indicating that DMTU had unspecific vascular effects in group III. Heparin-protamine released no oxygen free radicals from isolated PMNs. The results indicate that oxygen free radicals do not have a key role in mediating pulmonary vasoconstriction after protamine neutralization of heparin.