Objective: To investigate in a rat model of ventilation-induced lung injury whether metabolic changes in the lung are reflected by an increased purine concentration (adenosine, inosine, hypoxanthine, xanthine, and urate; an index of adenosine-triphosphate breakdown) of the bronchoalveolar lavage fluid and whether purine can, thus, indirectly serve as a marker of ventilation-induced lung injury. Design: Prospective, randomized, controlled trial. Setting: Research laboratory. Subjects: Forty-two male Sprague-Dawley rats. Interventions: Five groups of Sprague-Dawley rats were subjected to 6 mins of mechanical ventilation. One group was ventilated at a peak inspiratory pressure of 7 cm H2O and a positive end-expiratory pressure of 0 cm H2O. A second group was ventilated at a peak inspiratory pressure of 45 cm H2O and a positive end-expiratory pressure of 10 cm H2O. Three groups of Sprague-Dawley rats were ventilated at a peak inspiratory pressure of 45 Cm H2O without positive end-expiratory pressure. Before mechanical ventilation, two of these groups received intratracheal administration of saline or exogenous surfactant at a dose of 100 mg/kg and one group received no intratracheal administration. A sixth group served as the nonventilated controls. Measurements and Main Results: Bronchoalveolar lavage fluid was collected in which both purine concentration (μM; mean ± SD) and protein concentration (mg/mL; mean ± SD) were determined. Statistical differences were analyzed using the one-way analysis of variance (ANOVA) with a Student- Newman-Keul's post hoc test. Purine and protein concentrations were different between groups (ANOVA p value for purine and protein, <.0001). Both purine and protein concentrations in bronchoalveolar lavage fluid were increased in Group 45/0 (3.2 ± 1.9 and 4.2 ± 1.6, respectively) compared with Group 7/0 (0.4 ± 0.1 [p < .05] and 0.4 ± 0.2 [p < .001]) and controls (0.2 ± 0.2 [p < .01] and 0.2 ± 0.1 [p < .001]) and in Group 45/Na (5.8 ± 2.5 and 4.2 ± 0.5) compared with Group 7/0 (purine and protein, p < .001) and the controls (purine and protein, p < .001). Positive end-expiratory pressure prevented an increase in purine and protein concentrations in bronchoalveolar lavage fluid (0.4 ± 0.3 and 0.4 ± 0.2, respectively) compared with Group 45/0 (purine, p < .01; protein, p < .001) and Group 45/Na (purine and protein, p < .001). Surfactant instillation preceding lung overinflation reduced purine and protein concentration in bronchoalveolar lavage fluid (2.1 ± 1.6 and 2.7 ± 1.0) compared with Group 45/Na (purine, p < .001; protein (p < .01). Surfactant instillation reduced protein concentration compared with Group 45/0 (p < .01). Conclusions: This study shows that metabolic changes in the lung as a result of ventilation-induced lung injury are reflected by an increased level of purine in the bronchoalveolar lavage fluid and that purine may, thus, serve as an early marker for ventilation-induced lung injury. Moreover, the study shows that both exogenous surfactant and positive end- expiratory pressure reduce protein infiltration and that positive end- expiratory pressure decreases the purine level in bronchoalveolar lavage fluid after lung overinflation.

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doi.org/10.1097/00003246-199904000-00035, hdl.handle.net/1765/67744
Critical Care Medicine
Department of Anesthesiology

Verbrugge, S.J.C, de Jong, J.W, Keijzer, E, Vazquez de Anda, G.F, & Lachmann, B.F. (1999). Purine in bronchoalveolar lavage fluid as a marker of ventilation- induced lung injury. Critical Care Medicine, 27(4), 779–783. doi:10.1097/00003246-199904000-00035