Catecholamine Clearance from Alveolar Spaces of Rat and Human Lungs
Thoracic Surgery, Kanazawa Medical University, Uchinada, Ishikawa, Japan. Respiration
(Impact Factor: 2.59).
03/2005; 72(2):189-96. DOI: 10.1159/000084051
Although aerosolized beta-adrenergic agonists have been used as a therapy for the resolution of pulmonary edema, the mechanisms of catecholamine clearance from the alveolar spaces of the lung are not well known.
To determine whether catecholamine clearance from the alveolar spaces is correlated with the fluid transport capacity of the lung.
Albumin solution containing epinephrine (10(-7)M) or norepinephrine (10(-7)M) was instilled into the alveolar spaces of isolated rat and human lungs. Alveolar fluid clearance rate was estimated by the progressive increase in the albumin concentration over 1 h. Catecholamine clearance rate was estimated by the changes in catecholamine concentration and alveolar fluid volume over 1 h.
The norepinephrine clearance rate was faster than the epinephrine clearance rate in the rat and human lungs. In the rat lungs, amiloride (a sodium channel blocker) caused a greater decrease in alveolar fluid clearance and epinephrine clearance rate than propranolol (a nonselective beta-adrenergic antagonist). Although propranolol and phentolamine (an alpha-adrenergic antagonist), and 5-(N-ethyl-N-isoprophyl)amiloride (a Na+/H+ antiport blocker) changed neither the alveolar fluid clearance nor the norepinephrine clearance rate, amiloride and benzamil (a sodium channel blocker) decreased both clearance rates. As in the rat lungs, amiloride decreased alveolar fluid and norepinephrine clearance rates in the human lungs.
These results indicate that the catecholamine clearance rate from the alveolar spaces is correlated with alveolar fluid clearance in rat and human lungs.
Available from: PubMed Central
- "In this setup, the rate of ex vivo AFC was significantly reduced in human lobes intratracheally administrated ketamine. Addition of amiloride to the instillate decreased AFC by about 50%, which is in accordance with previous studies [17, 18, 22, 24]. Previous studies showed that S-ketamine via iv at clinically relevant bolus concentrations does not affect AFC in rats , the difference might result from the many divergent properties of ENaC between different species. "
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ABSTRACT: Ketamine is a broadly used anaesthetic for analgosedation. Accumulating clinical evidence shows that ketamine causes pulmonary edema with unknown mechanisms. We measured the effects of ketamine on alveolar fluid clearance in human lung lobes ex vivo. Our results showed that intratracheal instillation of ketamine markedly decreased the reabsorption of 5% bovine serum albumin instillate. In the presence of amiloride (a specific ENaC blocker), fluid resolution was not further decreased, suggesting that ketamine could decrease amiloride-sensitive fraction of AFC associated with ENaC. Moreover, we measured the regulation of amiloride-sensitive currents by ketamine in A549 cells using whole-cell patch clamp mode. Our results suggested that ketamine decreased amiloride-sensitive Na+ currents (ENaC activity) in a dose-dependent fashion. These data demonstrate that reduction in lung ENaC activity and lung fluid clearance following administration of ketamine may be the crucial step of the pathogenesis of resultant pulmonary edema.
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