Intratracheal dopamine attenuates pulmonary edema and improves survival after ventilator-induced lung injury in rats

Abstract

Intoduction Clearance of alveolar oedema depends on active transport of sodium across the alveolar-epithelial barrier. β-Adrenergic agonists increase clearance of pulmonary oedema, but it has not been established whether β-agonist stimulation achieves sufficient oedema clearance to improve survival in animals. The objective of this study was to determine whether the increased pulmonary oedema clearance produced by intratracheal dopamine improves the survival of rats after mechanical ventilation with high tidal volume (HVT). MethodsThis was a randomized, controlled, experimental study. One hundred and thirty-two Wistar-Kyoto rats, weighing 250 to 300 g, were anaesthetized and cannulated via endotracheal tube. Pulmonary oedema was induced by endotracheal instillation of saline solution and mechanical ventilation with HVT. Two types of experiment were carried out. The first was an analysis of pulmonary oedema conducted in six groups of 10 rats ventilated with low (8 ml/kg) or high (25 ml/kg) tidal volume for 30 or 60 minutes with or without intratracheally instilled dopamine. At the end of the experiment the animals were exsanguinated and pulmonary oedema analysis performed. The second experiment was a survival analysis, which was conducted in two groups of 36 animals ventilated with HVT for 60 minutes with or without intratracheal dopamine; survival of the animals was monitored for up to 7 days after extubation. ResultsIn animals ventilated at HVT with or without intratracheal dopamine, oxygen saturation deteriorated over time and was significantly higher at 30 minutes than at 60 minutes. After 60 minutes, a lower wet weight/dry weight ratio was observed in rats ventilated with HVT and instilled with dopamine than in rats ventilated with HVT without dopamine (3.9 ± 0.27 versus 4.9 ± 0.29; P = 0.014). Survival was significantly (P = 0.013) higher in animals receiving intratracheal dopamine and ventilated with HVT, especially at 15 minutes after extubation, when 11 of the 36 animals in the HVT group had died as compared with only one out of the 36 animals in the HVT plus dopamine group. ConclusionIntratracheal dopamine instillation increased pulmonary oedema clearance in rats ventilated with HVT, and this greater clearance was associated with improved survival.

Conservative fluid management prevents age-associated ventilator induced mortality

“…These results support the general finding that age increases the incidence and severity of edema (5)(33). They also demonstrate our experimental model’s ability to induce ventilator-associated pulmonary edema with HVT mechanical ventilation and subsequently attenuate it through conservative fluid administration alone.…”

“…Pulmonary edema is a hallmark of VILI and the severity and susceptibility to pulmonary edema increases with age (25)(5)(21)(41). Some of the driving forces behind development and progression of pulmonary edema both in general and in VILI are increases in pulmonary intravascular pressure, decreased epithelial barrier integrity/increased permeability, and increased local and systemic inflammatory cytokine presence.…”

GABA receptor ameliorates ventilator-induced lung injury in rats by improving alveolar fluid clearance

“…However, it does not differentiate between interstitial and alveolar edema [1]. The wet-to-dry ratios in our study were similar to those in Sprague-Dawley rats [35,38,48], but higher than those reported in Wistar-Kyoto rats [49]. The increase in wet-to-dry ratio was evident as early as 30 minutes, but remained the same for up to 60 minutes.…”

Amiloride-Sensitive Sodium Channels and Pulmonary Edema

“…Consistent with the idea of β -agonists as potential therapeutic tools, β -adrenergic agonist treatment improved fluid clearance and edema resolution in experimental models of ALI/ARDS [68–71]. The activation of transepithelial Na + transport and alveolar fluid clearance by β -adrenergic agonists was also shown to reduce extravascular lung water in patients who were part of the so-called BALTI trial ( beta-agonist lung injury trial, BALTI ), a clinical trial that addressed the possibility of β -agonist treatment in ALI/ARDS [72].…”