EARLY HYDROGEN PEROXIDE-INDUCED PULMONARY ENDOTHELIAL-CELL DYSFUNCTION - DETECTION AND PREVENTION

Objectives: To determine a) whether hydrogen peroxide-induced, early l ung endothelial cell dysfunction can be detected in an isolated, perfu sed, rat lung model; and b) whether the organic phosphothioate N-(2-me rcaptoethyl)-1,3-propanediamine, which protects cells in culture again st hydrogen peroxide-mediated damage, can exert the same protection in this model. Design: Intervention study; before-after trial. Setting: Research laboratory. Model: Isolated, perfused, rat lung model. Interv ention: Continuous hydrogen peroxide infusion at increasing concentrat ions and infusion times; preceded or not by a N-(2-mercaptoethyl)-1,3- propanediamine infusion. Measurements and Main Results: Early pulmonar y endothelial cell alterations, assessed by the lung extraction (% ext raction) of I-123-metaiodobenzylguanidine. Permeability edema by % ext raction of I-125-human serum albumin and the lung dry-to-wet weight ra tio. Control experiments: % extraction-I-123-metaiodobenzylguanidine: 21.7 +/- 3.8% (n = 7). With increasing concentrations of hydrogen pero xide (0.025, 0.125, 0.5, and 2 mmol), % extraction-I-123-metaiodobenzy lguanidine was progressively depressed (n = 28, ANOVA, p <.05), signif icantly decreased from controls at 2 mmol (10.2 +/- 5.0%, n = 7, p <.0 5). When the 2-mmol hydrogen peroxide infusion was preceded by the N-( 2-mercaptoethyl)-1,3-propanediamine (2 mmol) infusion, % extraction-I- 123-metaiodobenzylguanidine (19.9 +/- 2.9%, n = 5) was not significant ly different from controls (n = 7) and was significantly greater than after the 2-mmol hydrogen peroxide infusion alone (8.7 +/- 7.4%, p <.0 5, n = 8). In all experiments, % extraction of human serum albumin rat io and dry-to-wet weight ratio were not significantly different from t hat of controls. Conclusions: a) Hydrogen peroxide-induced lung endoth elial cell dysfunction was detected at an early stage, before any perm eability defect appeared; b) N-(2-mercaptoethyl) -1,3-propanediamine p rotected against such damage.