Clearance of bile and trypsin in rat lungs following aspiration of human gastric fluid

Abstract

Purpose: In the clinical setting, there is no reliable tool for diagnosing gastric aspiration. A potential way of diagnosing gastric fluid aspiration entails bronchoalveolar lavage (BAL) with subsequent examination of the BAL fluid for gastric fluid components that are exogenous to the lungs. The objective of this study was to determine the longevity of the gastric fluid components bile and trypsin in the lung, in order to provide an estimate of the time frame in which assessment of these components in the BAL might effectively be used as a measure of aspiration.

Materials and methods: Human gastric fluid (0.5 mg/kg) was infused in the right lung of intubated male Fischer 344 rats (n = 30). Animals were sacrificed at specified times following the experimentally induced aspiration, and bronchoalveolar lavage fluid (BALF) was collected. Bile concentrations were analyzed by an enzyme-linked chromatogenic method, and the concentration of trypsin was quantified using an ELISA. Data were analyzed using non-linear regression and a one-phase decay equation.

Results: In this experimental model, the half-life of bile was 9.3 hours (r(2) = 0.81), and the half-life of trypsin was 9.0 hours (r(2) = 0.68).

Conclusions: The half-lives of bile and trypsin in the rodent aspiration model suggest that the ability to detect aspiration may be limited to a few days post-aspiration. If studies using rats are any indication, it may be most effective to collect BAL samples within the first 24 hours of suspected aspiration events in order to detect aspiration.

Keywords: aspirate; bile acid; lung; rat; trypsin.

Figure 1.

Concentration of bile in BALF at several time points after initial gastric fluid aspiration. After rats received aspiration with human gastric fluid containing a negligible initial bile concentration (0.12 μmol/L, n = 9) or a much more appreciable bile concentration (165.0 μmol/L, n = 9), BALF was collected at 3 hours, 24 hours, and 48 hours after aspiration. Each point represents the average of three animals, and the standard error is shown. The half-life was determined by non-linear regression as described in the Methods.

Figure 2.

Concentration of bile in BALF at several time points after initial gastric fluid aspiration. After rats (n = 18) received aspiration with human gastric fluid containing appreciable (165.0 μmol/L or 4866 μmol/L) initial bile concentrations, BALF was collected at 3, 6, 12, 18, 24, and 48 hours after aspiration. Each point represents the average of three animals, and the standard error is shown. The mean concentration of bile in the BALF as a percentage of the initial (calculated) concentration was 77.9% after 3 hours, 64.9% after 6 hours, 43.6% after 12 hours, 26.9% after 18 hours, 13.4% after 24 hours, and 2.1% after 48 hours. The half-life was determined by non-linear regression as described in the Methods.

Figure 3.

Concentration of trypsin in BALF at several time points after initial gastric fluid aspiration. Rats (n = 12) received aspiration with human gastric fluid containing an initial bile concentration of 4866 μmol/L and an initial trypsin concentration of 52.35 μg/mL. The concentration of trypsin was assayed by ELISA in BALF samples acquired at 0 hours, 6 hours, 12 hours, and 18 hours after aspiration. Each point represents the average of three animals, and the standard error is shown. The half-life was determined by nonlinear regression as described in the Methods.