Am. J. Respir. Crit. Care Med., Vol 155, No. 3, Mar 1997, 1147-1154.
C1-esterase inhibitor prevents early pulmonary dysfunction after lung transplantation in the dog
A Salvatierra, F Velasco, M Rodriguez, A Alvarez, R Lopez-Pedrera, R Ramirez, J Carracedo, F Lopez-Rubio, A Lopez-Pujol and R Guerrero
Servicio de Cirugia Toracica, Hospital Universitario Reina Sofia, Universidad de Cordoba, Spain.
The success of lung transplantation to a large extent depends on effective
protection of the graft from ischemic injury after reperfusion. Although
mechanisms have not been clarified, the pathologic findings of ischemic
injury after reperfusion are similar to adult respiratory distress
syndrome, a condition in which the blood coagulation contact system is
activated. This study evaluates the effect of C1-esterase inhibitor
(C1-INH), the main inhibitor of the blood coagulation contact system, on
short-term lung function in a dog model of orthotopic lung transplantation.
Twelve lung transplantations were performed after 24 h of ischemic time.
Dogs were randomly assigned to receive either vehicle (Control) or C1-INH.
After the lung transplantation in the control group, Pao2 decreased by 84%
and both the AaPO2 and the Qs/Qt% increased (340 and 530%, respectively, p
< 0.01); these parameters remained unchanged in the C1-INH group. The
hypoxemia observed in control animals was associated with decreased blood
coagulation contact factors, complement consumption, increased expression
of adhesion glycoproteins in leukocytes, and extensive intraalveolar and
interstitial neutrophil infiltration. In contrast, C1- INH administration
prevented hypoxemia, the decrease in blood coagulation contact factors, the
activation of the complement system, the increase in expression of
leukocyte adhesion molecules, and inflammatory cell infiltrate. This study
has demonstrated that in a dog model of lung transplantation, the
administration of C1-INH prevents early pulmonary dysfunction, and it
suggests that activation of blood coagulation contact system and complement
are important mechanisms causing ischemic injury after reperfusion.
