N-Acetyl Cysteine Attenuates the Inflammatory Response in Warm Ischemic Pig Lungs

Background

Lungs donated after cardiac death (DCD) may significantly reduce current organ shortage. However, the warm ischemic period following circulatory arrest may enhance ischemia-reperfusion injury (IRI). We investigated the possible therapeutic effect of N-acetyl cysteine (NAC), a potent anti-oxidative agent on IRI in a porcine ex vivo lung reperfusion model.

Materials and methods

NAC (50 mg/kg) was nebulized to pigs (n = 6/group) prior to sacrifice (NAC-DCD). In DCD-NAC, animals received NAC 15 min after death. Control animals did not receive an aerosol (DCD). Interleukin (IL)-1β, tumor necrosis factor-alpha, IL-8, lactate dehydrogenase activity and thiobarbituric acid reactive substances were measured and cells were counted in broncho-alveolar lavage from the right lung after a 3-h warm plus 1-h cold ischemic interval.

Results

There were no differences in cells between groups, however cell death was lower in NAC-DCD (10.3 ± 1.5%) and DCD-NAC (7.83 ± 1.8%) compared to DCD (18.0 ± 3.8%). IL-1β levels (111.5 ± 28.8 pg/mL and 92.2 ± 51.0 pg/mL versus 250.3 ± 56.6 pg/mL) and lactate dehydrogenase activity (1258.0 ± 440.9 U/L and 1606.0 ± 289.0 U/L versus 2848.0 ± 760.9 U/L) were significantly lower in NAC-DCD and DCD-NAC compared with DCD, respectively. These postischemic inflammatory markers correlated with functional parameters upon reperfusion of the left lung, reported in a previous study.

Conclusions

Administration of NAC prior to or shortly after circulatory arrest results in a marked reduction of inflammation during the warm ischemic phase.

Key Words: lung transplantation, donation after cardiac death, N-acetyl cysteine, pig