Cardiopulmonary effects of vatinoxan in sevoflurane-anaesthetised sheep receiving dexmedetomidine

Abstract

The effects of pre-treatment with vatinoxan (MK-467) on dexmedetomidine-induced cardiopulmonary alterations were investigated in sheep. In a crossover study design with a 20-day washout, seven sheep were anaesthetised with sevoflurane in oxygen and air. The sheep were ventilated with the pressure-limited volume-controlled mode and a positive end-expiratory pressure of 5cmH2O. Peak inspiratory pressure (PIP) was set at 25cmH2O. The sheep received either 150μg/kg vatinoxan HCl (VAT+DEX) or saline intravenously (IV) 10min before IV dexmedetomidine HCl (3μg/kg, DEX). Cardiopulmonary variables were measured before treatments (baseline), 3min after vatinoxan or saline, and 5, 15 and 25min after dexmedetomidine. Computed tomography (CT) of lung parenchyma was performed at baseline, 2min before dexmedetomidine, and 10, 20 and 30min after DEX. Bronchoalveolar lavage (BAL) was performed after the last CT scan and shortly before sheep recovered from anaesthesia. After VAT, cardiac output significantly increased from baseline. DEX alone significantly decreased partial arterial oxygen tension, total dynamic compliance and tidal volume, whereas PIP was significantly increased. With VAT+DEX, these changes were minimal. No significant changes were detected in haemodynamics from baseline after DEX. With VAT+DEX, mean arterial pressure and systemic vascular resistance were significantly decreased from baseline, although hypotension was not detected. On CT, lung density was significantly increased with DEX as compared to baseline. No visual abnormalities were detected in bronchoscopy and no differences were detected in the BAL fluid after either treatment. The pre-administration of vatinoxan alleviates dexmedetomidine-induced bronchoconstriction, oedema and hypoxaemia in sevoflurane-anaesthetised sheep.