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(Circulation. 2001;104:2975.)
© 2001 American Heart Association, Inc.

Basic Science Reports

Antithrombin III Prevents Early Pulmonary Dysfunction After Lung Transplantation in the Dog

Angel Salvatierra, MD, PhD; Rafael Guerrero, MD, PhD; Mariano Rodriguez, MD, PhD; Antonio Alvarez, MD, PhD; Fuensanta Soriano, MD; Rosario Lopez-Pedrera, PhD; Rafael Ramirez, MD, PhD; Julia Carracedo, MD, PhD; Fernando Lopez-Rubio, MD; Javier Lopez-Pujol, MD, PhD; Francisco Velasco, MD, PhD

From Servicios de Cirugía Torácica (A.S., A.A., J.L.-P.), Cuidados Intensivos (R.G., F.S.), Hematología (F.V.), y Anatomía Patológica (F.L.-R.), Unidad de Investigación (M.R., R.L.-P., R.R., J.C.), Hospital Universitario Reina Sofía, Universidad de Córdoba, Spain.

Correspondence to Mariano Rodriguez, MD, Unidad de Investigación, Hospital Universitario Reina Sofia, Avda Menéndez Pidal s/n, 14004-Córdoba, Spain. E-mail mrodriguez{at}sofia.hrs.sas.cica.es

Background— Ischemia-reperfusion injury with the resulting inflammatory response is a devastating complication of lung transplantation; much of the tissue damage could be diminished by control of the inflammatory response. Recent studies have show that antithrombin III (AT III) has an anti-inflammatory effect in addition to its established role in the regulation of blood coagulation. Thus, we hypothesized that the administration of AT III might help to prevent ischemia-reperfusion injury after lung transplantation.

Methods and Results— The study was performed in a dog model of orthotopic lung transplantation. Dogs were randomly assigned to receive either vehicle (controls) or AT III. We observed that in control dogs, during the 180-minute period after lung transplantation, the arterial O₂ partial pressure decreased and both the alveolar-arterial O₂ difference and the pulmonary vascular resistance increased. By contrast, these parameters remained unchanged in the group of dogs receiving AT III. Dogs with transplants receiving AT III did not show an increase in cell adhesion molecules, and histological examination revealed almost an absence of inflammatory response. The administration of AT III produced a marked increase in serum prostacyclin (PGI₂) levels, whereas in control dogs, the PGI₂ levels did not change. The beneficial effect of AT III was not observed when dogs received indomethacin to prevent the stimulation of PGI₂ release by AT III.

Conclusions— Our results demonstrate that AT III prevents ischemia-reperfusion injury in a dog model of lung transplantation and that this effect is conditioned by an increase in PGI₂ production.

Key Words: ischemia • reperfusion • thrombin • lung • transplantation • coagulation

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