Endotoxin-induced pulmonary dysfunction is prevented by C1-esterase inhibitor.
In septic shock, hypotension, disseminated intravascular coagulation, and neutrophil activation are related to the activation of the blood coagulation contact system. This study evaluates in dogs the effect of the C1-esterase inhibitor (C1-INH), a main inhibitor of the blood coagulation contact system, on the cardiovascular and respiratory dysfunction associated with endotoxic shock. Two groups were included: controls, which received Escherichia coli endotoxin, and a C1-INH group in which C1-INH was infused before E. coli endotoxin administration. In both groups, endotoxin produced hypodynamic shock; however, the decrease in the systolic index and the ventricular systolic work indexes were greater in controls than the C1-INH group. In controls, the arterial O2 partial pressure decreased by 30% and the alveolo-arterial O2 difference increased by 625%, these parameters remained unchanged in the C1-INH group. Hypoxemia was associated with increased intrapulmonary shunt, decreased blood coagulation contact factors, and decreased C3c. In contrast, C1-INH administration prevented endotoxin-induced hypoxemia, the increase in intrapulmonary shunt, and the decrease in blood coagulation contact factors. This study shows that, in dogs with endotoxic shock, pulmonary dysfunction is associated with an activation of the blood coagulation contact phase system. An inhibition of this system by C1-INH prevented the hypoxemia induced by endotoxic shock.
Unidad de Investigación, Hospital Universitario Reina Sofía, Spain.
R
R
Guerrero
F
F
Velasco
M
M
Rodriguez
A
A
Lopez
R
R
Rojas
M A
MA
Alvarez
R
R
Villalba
V
V
Rubio
A
A
Torres
D
D
del Castillo
D000818:Animals; D003174:Complement C1 Inactivator Proteins / Q000494:pharmacology*; D015932:Complement C3c / Q000032:analysis; D004285:Dogs; D004731:Endotoxins / Q000494:pharmacology*; D005172:Factor XI / Q000032:analysis; D005174:Factor XII / Q000032:analysis; D006321:Heart / Q000503:physiopathology*; D006439:Hemodynamics; D006801:Humans; D000860:Hypoxia / Q000517:prevention & control; D007231:Infant, Newborn; D008168:Lung / Q000503:physiopathology*; D011288:Prekallikrein / Q000032:analysis; D012772:Shock, Septic / Q000188:drug therapy / Q000503:physiopathology*
D003174:Complement C1 Inactivator Proteins; D004731:Endotoxins; C044101:endotoxin, Escherichia coli; D015932:Complement C3c; D005174:Factor XII; D005172:Factor XI; D011288:Prekallikrein