Nebulized N-Acetyl Cysteine Protects the Pulmonary Graft Inside the Non–Heart-Beating Donor

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• 作者：Filip R. Rega ; Wim A. Wuyts ; Bart M. Vanaudenaerde ; Nicole C. Jannis ; Arne P. Neyrinck ; Geert M. Verleden ; Toni E. Lerut and Dirk E.M. Van Raemdonck
• 刊名：The Journal of Heart and Lung Transplantation
• 出版年：2005
• 期刊代码：161_10532498
• 类别：med
• 出版时间：2005
• 卷：24
• 期：9
• 页码：1369-1377
• 文件大小：161 K

摘要

Background

The use of lungs from non–heart-beating donors (NHBD) might significantly alleviate the organ shortage. The tolerable warm ischemic period after cardiac arrest, however, is limited to approximately 1 hour. If the lung could be safely protected inside the cadaver, this time period may be prolonged. This would help to obtain family consent and to organize organ retrieval.

Methods

Pigs (30.8 ± 0.6 kg) were killed, left untouched for 3 hours, and divided into 3 groups. Nebulized N-acetyl cysteine (NAC) (300 mg), a precursor of the antioxidant agent glutathione, was administered during 10 minutes before death in Group I (NAC-NHBD, n = 6) and 15 minutes after death in Group II (NHBD-NAC, n = 6). In the control group, no aerosol was administered (NHBD, n = 6). After a warm ischemic interval of 3 hours, both lungs in all groups were topically cooled for 1 hour. Thereafter, the left lung was prepared for evaluation in an isolated reperfusion circuit. Hemodynamic, aerodynamic, and oxygenation parameters were measured. Wet-to-dry weight ratio (W/D) was calculated after reperfusion. The right lung was used to measure reduced glutathione (GSH) and oxidized glutathione (GSSG) levels (μmol/g) in lung homogenates and total protein levels in bronchial lavage fluid.

Results

Pulmonary vascular resistance, mean airway pressure, and W/D were significantly decreased in NAC-NHBD (1930 ± 144 Dynes · sec · cm⁻⁵, 14.2 ± 0.5 cm H₂O, and 7.4 ± 0.4; p < 0.01, 0.01, and 0.05, respectively) and NHBD-NAC (1837 ± 180 Dynes · sec · cm⁻⁵, 13.3 ± 1.2 cm H₂O, and 7.3 ± 0.3; p < 0.01, 0.05, and 0.05, respectively) when compared with the control group (5051 ± 530 Dynes · sec · cm⁻⁵, 17 ± 0.4 cm H₂O, 8.5 ± 0.1, respectively). GSH/GSSG ratio was significantly higher and protein levels were significantly lower in NAC-NHBD (1.7 ± 0.1 and 1315 ± 60 μg/ml; p < 0.05 and 0.05, respectively) and NHBD-NAC (1.7 ± 0.2 and 1475 ± 159 μg/ml; p < 0.05 and 0.05, respectively) when compared with the control group (1.2 ± 0.1 and 2150 ± 200 μg/ml).

Conclusions

Nebulized NAC administered before or shortly after death attenuates early ischemia reperfusion injury via upregulation of glutathione. NAC might be a promising tool to protect the pulmonary graft from both controlled and uncontrolled NHBD.