Early hydrogen peroxide-induced pulmonary endothelial cell dysfunction: detection and prevention.
OBJECTIVE
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)-1,3-propanediamine, which protects cells in culture against hydrogen peroxide-mediated damage, can exert the same protection in this model.


METHODS
Intervention study; before-after trial.


METHODS
Research laboratory.


METHODS
Isolated, perfused, rat lung model.


METHODS
Continuous hydrogen peroxide infusion at increasing concentrations and infusion times, preceded or not by a N-(2-mercaptoethyl)-1,3-propanediamine infusion.


RESULTS
Early 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.


CONCLUSIONS
a) 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.
Jolliet
P
P
Medical ICU, Hôpital Cantonal Universitaire, Geneva, Switzerland.
Polla
B
B
Donath
A
A
Slosman
D
D
D004999:Amifostine / Q000627:therapeutic use; D000818:Animals; D004727:Endothelium / Q000187:drug effects; D006861:Hydrogen Peroxide / Q000633:toxicity*; D008171:Lung Diseases / Q000139:chemically induced* / Q000517:prevention & control; D008297:Male; D008624:Mercaptoethylamines / Q000627:therapeutic use; D010477:Perfusion; D011837:Radiation-Protective Agents / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley
D008624:Mercaptoethylamines; D011837:Radiation-Protective Agents; C020174:N-(2-mercaptoethyl)-1,3-diaminopropane; D006861:Hydrogen Peroxide; D004999:Amifostine