Hipertensão pulmonar experimental em cães anestesiados : papel da endotelina-1 e do tromboxano A2, e reversão pelo oxido nitrico inalatorio

AUTOR(ES)
DATA DE PUBLICAÇÃO

2002

RESUMO

ln this study we investigated the pharmacological mechanisms underlying the pulmonary hypertension induced by the protamine-heparin complex in anaesthetized dogs. The animais were anaesthetized with pentobarbital sodium (Hypnoi, 30 mg/kg, i.v). Anaesthesia was maintained with a combination of fentanyl citrate (0.01 mg/kg/h, i.v) and diazepam (0.25 mg/kglh, i.v). The administration of heparin (500 Ul/kg) following protamine (10 mg/kg) lead to a marked increase in the pulmonary hypertension (280 %) accompanied by a significant increase in the transpulrnonary gradient. This phenomenon was observed within 1-3 mins after protamine administration.We also observed significant decreases of mean arterial blood pressure, systolic volume and cardiac output, and a significant tachycardia. The index of systemic vascular resistance was not significantly altered. Arterial blood gas analysis showed that pO2 and pCO2 were not changed. Dogs pre-treated with the cydooxygenase inhibitor indomethacin (10 mg/kg) showed a reduction of the pulmonary hypertension and increased the transpulmonary.gradient induced by the heparin-protamine complex. This treatment also attenuated the decrease of cardiac output and tachycardia. Similarly, pre-treatment of the animais with the thromboxane syntetase inhibitor dazoxiben (10 mg/kg) prevented the pulmonary hypertension and increased transpulmonary gradient. Moreover, this treatment was not able to affect the decrease of cardiac output and heart rate. The thromboxane Az levels were markedly increased after protamine (2 min) injection, and maintained elevated until the end of experiment protocol. lndomethacin pre-treatment abolished the thromboxane Az release. The mixed ETA/ETB endothelin receptor antagonist tezosentan (10 mg/kg bolus + 10 mg/kg/h infusion) decreased significantly the puimonary hypertension, cardiac output and heart rate. ln addition, NO inalation(3 ppm) reduced the pulmonarj hypertension and transpulmonary gradient. ln summary, our data showed that the heparinprotamine complex administration induces pulmonary hypertension mediated by both thromboxane. Az and endothelin -1 release.

ASSUNTO(S)

sistema cardiovascular debito cardiaco pulmões - doenças obstrutivas pressão arterial

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