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Survival and graft function in a large animal lung transplant model after 30 h preservation and substitution of the nitric oxide pathway


Hillinger, Sven; Sandera, Peter; Carboni, Giovanni L; Stammberger, Uz; Zalunardo, Marco; Schoedon, Gabriele; Schmid, Ralph A (2001). Survival and graft function in a large animal lung transplant model after 30 h preservation and substitution of the nitric oxide pathway. European Journal of Cardio-Thoracic Surgery, 20(3):508-513.

Abstract

Objective: Substitution of the nitric oxide- (NO-) pathway improves early graft function following lung transplantation. We previously demonstrated that 8-Br-cGMP (second messenger of NO) to the flush solution and tetrahydrobiopterin (BH4, coenzyme of NO synthase) given as additive during reperfusion improve post-transplant graft function. In the present study, the combined treatment with 8-Br-cGMP and BH4 was evaluated. Methods: Unilateral left lung transplantation was performed in weight matched outbred pigs (24-31kg). In group I, grafts were preserved for 30h (n=5). 8-Br-cGMP (1mg/kg) was added to the flush solution (Perfadex™, 1.5l, 1°C) and BH4 (10mg/kg/h) was given to the recipient for 5h after reperfusion. In group II, lungs were transplanted after a preservation time of 30h (n=3) and prostaglandin E1 (250g) was given into the pulmonary artery (PA) prior to flush. In all recipients 1h after reperfusion the contralateral right PA and bronchus were ligated to assess graft function only. Survival time after reperfusion, extravascular lung water index (EVLWI), hemodynamic variables, and gas exchange (PaO2) were assessed during a 12h observation period. Results: All recipients in group I survived the 12h assessment, whereas none of the group II animals survived more than 4h after reperfusion with a rapid increase of EVLWI up to 24.8±6.7ml/kg. In contrast, in group I EVLWI reached up to 8.9±1.5ml/kg and returned to nearly normal levels at 12h (6.1±0.8ml/kg). In two animals of group I the gas exchange deteriorated slightly. The other three animals showed normal arterial oxygenation over the entire observation time. Conclusion: Our data indicate that the combined substitution of the NO pathway during preservation and reperfusion reduces ischemia/reperfusion injury substantially and that this treatment even allows lung transplantation after 30h preservation in this model

Abstract

Objective: Substitution of the nitric oxide- (NO-) pathway improves early graft function following lung transplantation. We previously demonstrated that 8-Br-cGMP (second messenger of NO) to the flush solution and tetrahydrobiopterin (BH4, coenzyme of NO synthase) given as additive during reperfusion improve post-transplant graft function. In the present study, the combined treatment with 8-Br-cGMP and BH4 was evaluated. Methods: Unilateral left lung transplantation was performed in weight matched outbred pigs (24-31kg). In group I, grafts were preserved for 30h (n=5). 8-Br-cGMP (1mg/kg) was added to the flush solution (Perfadex™, 1.5l, 1°C) and BH4 (10mg/kg/h) was given to the recipient for 5h after reperfusion. In group II, lungs were transplanted after a preservation time of 30h (n=3) and prostaglandin E1 (250g) was given into the pulmonary artery (PA) prior to flush. In all recipients 1h after reperfusion the contralateral right PA and bronchus were ligated to assess graft function only. Survival time after reperfusion, extravascular lung water index (EVLWI), hemodynamic variables, and gas exchange (PaO2) were assessed during a 12h observation period. Results: All recipients in group I survived the 12h assessment, whereas none of the group II animals survived more than 4h after reperfusion with a rapid increase of EVLWI up to 24.8±6.7ml/kg. In contrast, in group I EVLWI reached up to 8.9±1.5ml/kg and returned to nearly normal levels at 12h (6.1±0.8ml/kg). In two animals of group I the gas exchange deteriorated slightly. The other three animals showed normal arterial oxygenation over the entire observation time. Conclusion: Our data indicate that the combined substitution of the NO pathway during preservation and reperfusion reduces ischemia/reperfusion injury substantially and that this treatment even allows lung transplantation after 30h preservation in this model

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Item Type:Journal Article, refereed, original work
Communities & Collections:National licences > 142-005
Dewey Decimal Classification:610 Medicine & health
Scopus Subject Areas:Health Sciences > Surgery
Health Sciences > Pulmonary and Respiratory Medicine
Health Sciences > Cardiology and Cardiovascular Medicine
Language:English
Date:1 September 2001
Deposited On:25 Sep 2018 13:12
Last Modified:15 Apr 2021 14:49
Publisher:Oxford University Press
ISSN:1010-7940
OA Status:Hybrid
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1016/s1010-7940(01)00820-x

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