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J Thorac Cardiovasc Surg 2003;126:1867-1874
© 2003 The American Association for Thoracic Surgery

Cardiopulmonary support and physiology

Exhaled carbon monoxide and inducible heme oxygenase expression in a rat model of postperfusion acute lung injury

^a Laboratoire d'Etudes des Greffes et Prothèses Cardiaques, Hôpital Broussais, Paris, France
^b Hôpital Européen Georges Pompidou, Paris, France
^c Hôpital Marie-Lannelongue, Le Plessis-Robinson, France

Received for publication May 10, 2002; revisions received May 15, 2003; accepted for publication June 18, 2003.

^* Address for reprints: Dr Rachid Zegdi, Hôpital Européen Georges Pompidou, Service de Chirurgie Cardiovasculaire, 20, rue Leblanc 75908 Paris France
rzegdi{at}hotmail.com

OBJECTIVE: Expression of inducible heme oxygenase has been shown to be increased in various visceral inflammatory disorders, which may confer a protective role. The purpose of our study was to determine whether the expression of inducible heme oxygenase was up-regulated within lungs in a rat model of extracorporeal circulation.

METHODS: Wistar rats underwent either a partial femoro-femoral extracorporeal circulation in normothermia for 3 hours (n = 5) or a sham procedure (n = 5). Exhaled carbon monoxide concentration was monitored with an infrared analyzer. After the rats were killed, lungs were harvested for determination of heme oxygenase activity and inducible heme oxygenase expression (by Western blot and immunohistochemistry). Lung injury was also assessed by arterial blood gas analysis and microscopic study.

RESULTS: Extracorporeal circulation was responsible for a lung injury characterized by decreased arterial blood oxygen saturation and typical morphologic findings (marked alveolar neutrophil infiltration; interstitial edema). Exhaled carbon monoxide concentration remained stable throughout the experiment in all sham rats, whereas it increased after extracorporeal circulation (from 0.16 ± 0.05 ppm at baseline to 0.7 ± 0.2 ppm at end of experiment; P = .0001). Pulmonary heme oxygenase activity and inducible heme oxygenase content (assessed by Western blot) were increased within lungs of rats that underwent extracorporeal circulation. Immunohistochemistry revealed that the expression of inducible heme oxygenase was mainly localized to inflammatory cells.

CONCLUSIONS: Post–extracorporeal circulation acute lung injury in rats was associated with an increased expression of inducible heme oxygenase, the functional significance of which remains to be determined.

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