Early hydrogen peroxide-induced pulmonary endothelial cell dysfunction: Detection and prevention

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Abstract

Objectives:

To 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)-l,3propanediamine, which protects cells in culture against 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.

Intervention:

Continuous hydrogen peroxide infusion at increasing concentrations and infusion times, preceded or not by a N-(2-mercaptoethyl)-l,3-propanediamine infusion.

Measurements and Main Results:

Early pulmonary endothelial cell alterations, assessed by the lung extraction (% extraction) of 123Imetaiodobenzylguanidine. Permeability edema by % extraction of 125I-human serum albumin and the lung dry-to-wet weight ratio.

Measurements and Main Results:

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-123Imetaiodobenzylguanidine 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)-l,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.

Conclusions:

a) Hydrogen peroxide-induced lung endothelial cell dysfunction was detected at an early stage, before any permeability defect appeared; b) N-(2-mercaptoethyl)-l,3-propanediamine protected against such damage. (Crit Care Med 1994; 22:157-162)

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