Objective To investigate the effect of phenylephrine （an α-adrenergic agonist） on alveolar fluid clearance （AFC） in ventilator-induced lung injury and the possible mechanism involved. Methods A total of 170 mal...Objective To investigate the effect of phenylephrine （an α-adrenergic agonist） on alveolar fluid clearance （AFC） in ventilator-induced lung injury and the possible mechanism involved. Methods A total of 170 male Wistar rats were randomly allocated into 17 groups （n= 10） using ran- dom number tables. Short-term （40 minutes） mechanical ventilation with high tidal volume （HVT） was per- formed to induce lung injury, impair active Na＋ transport and lung liquid clearance in the rats. Unventilated rats served as controls. To demonstrate the effect of phenylephrine on AFC, phenylephrine at different con- centrations （1×10^-5, 1 ×10^-6, 1×10^-7, 1×10^-8, and 1×10^-9 mol/L） was injected into the alveolar space of the HVT ventilated rats. To identify the influence of adrenergic antagonists, Na＋ channel, and microtubular sys- tem on the effect of phenylephrine, phenylephrine at 1×10^-5mol/L combined with prazosin （an α1-adrener- gic antagonist, 1×10^-4 mol/L）, yohimbine （an α2-adrenergic antagonist, 1×10^-4 mol/L）, atenolol （a β1- adrenergic antagonist, 1×10^-5 mol/L）, ICI- 118551 （an β2-adrenergic antagonist, 1×10^-5 mol/L）, amiloride （a Na＋ channel blocker, 51×10^-4mol/L）, ouabain （a Na＋/K＋-ATPase blocker, 5~×10^-4mol/L）, colchicine （a mi- crotubular disrupting agent, 0.25 mg/100 g body weight）, or β-lumicolchicine （an isomer of colchicine, 0.25 mg/100 g body weight） were perfused into the alveolar space of the rats ventilated with HVT for 40 minutes. AFC and total lung water content were measured. Results Basal AFC in control rats was （17.47±2.56）%/hour, which decreased to （9.64± 1.32）%/hour in HVT ventilated rats （P=0.003）. The perfusion of phenylephrine at 1 ×10^-8, 1×10^-7, 1×10^-6, and 1×10^-5 mol/L significantly increased the AFC in HVT ventilated rats （all P〈0.05）. This effect of phenylephrine on AFC was suppressed by prazosin, atenolol, and ICI-118551 in HVT ventilated rats by 53%, 31%, and 37%, respectively （all P〈0.05）. The AFC-stimulating effect of phenylephrine was lowered by 33% and 42% with amiloride and ouabain, respectively （both P〈0.05）. Colchicine significantly inhibited the effect of phenylephrine （P=0.031）. Conclusion Phenylephrine could increase the AFC in HVT-ventilated rats and accelerate the ab- sorption of pulmonary edema.展开更多
基金Supported by the Natural Science Foundation of Liaoning Province (201202245)
文摘Objective To investigate the effect of phenylephrine （an α-adrenergic agonist） on alveolar fluid clearance （AFC） in ventilator-induced lung injury and the possible mechanism involved. Methods A total of 170 male Wistar rats were randomly allocated into 17 groups （n= 10） using ran- dom number tables. Short-term （40 minutes） mechanical ventilation with high tidal volume （HVT） was per- formed to induce lung injury, impair active Na＋ transport and lung liquid clearance in the rats. Unventilated rats served as controls. To demonstrate the effect of phenylephrine on AFC, phenylephrine at different con- centrations （1×10^-5, 1 ×10^-6, 1×10^-7, 1×10^-8, and 1×10^-9 mol/L） was injected into the alveolar space of the HVT ventilated rats. To identify the influence of adrenergic antagonists, Na＋ channel, and microtubular sys- tem on the effect of phenylephrine, phenylephrine at 1×10^-5mol/L combined with prazosin （an α1-adrener- gic antagonist, 1×10^-4 mol/L）, yohimbine （an α2-adrenergic antagonist, 1×10^-4 mol/L）, atenolol （a β1- adrenergic antagonist, 1×10^-5 mol/L）, ICI- 118551 （an β2-adrenergic antagonist, 1×10^-5 mol/L）, amiloride （a Na＋ channel blocker, 51×10^-4mol/L）, ouabain （a Na＋/K＋-ATPase blocker, 5~×10^-4mol/L）, colchicine （a mi- crotubular disrupting agent, 0.25 mg/100 g body weight）, or β-lumicolchicine （an isomer of colchicine, 0.25 mg/100 g body weight） were perfused into the alveolar space of the rats ventilated with HVT for 40 minutes. AFC and total lung water content were measured. Results Basal AFC in control rats was （17.47±2.56）%/hour, which decreased to （9.64± 1.32）%/hour in HVT ventilated rats （P=0.003）. The perfusion of phenylephrine at 1 ×10^-8, 1×10^-7, 1×10^-6, and 1×10^-5 mol/L significantly increased the AFC in HVT ventilated rats （all P〈0.05）. This effect of phenylephrine on AFC was suppressed by prazosin, atenolol, and ICI-118551 in HVT ventilated rats by 53%, 31%, and 37%, respectively （all P〈0.05）. The AFC-stimulating effect of phenylephrine was lowered by 33% and 42% with amiloride and ouabain, respectively （both P〈0.05）. Colchicine significantly inhibited the effect of phenylephrine （P=0.031）. Conclusion Phenylephrine could increase the AFC in HVT-ventilated rats and accelerate the ab- sorption of pulmonary edema.
