Effect of Phenylephrine on Alveolar Fluid Clearance in Ventilator-induced Lung Injury

Abstract

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. A total of 170 male Wistar rats were randomly allocated into 17 groups (n=10) using random number tables. Short-term (40 minutes) mechanical ventilation with high tidal volume (HVT) was performed 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 concentrations (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 system on the effect of phenylephrine, phenylephrine at 1×10(-5) mol/L combined with prazosin (an α1-adrenergic 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, 5×10(-4) mol/L), ouabain (a Na(+)/K(+)-ATPase blocker, 5×10(-4) mol/L), colchicine (a microtubular 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. 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). Phenylephrine could increase the AFC in HVT-ventilated rats and accelerate the absorption of pulmonary edema.