• P Jolliet, B Polla, A Donath, and D Slosman.
• Medical ICU, Hôpital Cantonal Universitaire, Geneva, Switzerland.
• Crit. Care Med. 1994 Jan 1; 22 (1): 157-62.

ObjectivesTo determine a) whether hydrogen peroxide-induced, early lung endothelial cell dysfunction can be detected in an isolated, perfused, rat lung model; and b) whether the organic phosphothioate N-(2-mercaptoethyl)-1,3-propanediamine, which protects cells in culture against hydrogen peroxide-mediated damage, can exert the same protection in this model.DesignIntervention study; before-after trial.SettingResearch laboratory.ModelIsolated, perfused, rat lung model.InterventionContinuous hydrogen peroxide infusion at increasing concentrations and infusion times, preceded or not by a N-(2-mercaptoethyl)-1,3-propanediamine infusion.Measurements And Main ResultsEarly pulmonary endothelial cell alterations, assessed by the lung extraction (% extraction) of 123I-metaiodobenzylguanidine. Permeability edema by % extraction of 125I-human serum albumin and the lung dry-to-wet weight ratio. Control experiments: % extraction-123I-metaiodobenzylguanidine: 21.7 +/- 3.8% (n = 7). With increasing concentrations of hydrogen peroxide (0.025, 0.125, 0.5, and 2 mmol), % extraction-123I-metaiodobenzylguanidine was progressively depressed (n = 28, ANOVA, p < .05), significantly decreased from controls at 2 mmol (10.2 +/- 5.0%, n = 7, p < .05). When the 2-mmol hydrogen peroxide infusion was preceded by the N-(2-mercaptoethyl)-1,3-propanediamine (2 mmol) infusion, % extraction-123I-metaiodobenzylguanidine (19.9 +/- 2.9%, n = 5) was not significantly different from controls (n = 7) and was significantly greater than after the 2-mmol hydrogen peroxide infusion alone (8.7 +/- 7.4%, p < .05, n = 8). In all experiments, % extraction of human serum albumin ratio and dry-to-wet weight ratio were not significantly different from that of controls.Conclusionsa) Hydrogen peroxide-induced lung endothelial cell dysfunction was detected at an early stage, before any permeability defect appeared; b) N-(2-mercaptoethyl)-1,3-propanediamine protected against such damage.

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