BACKGROUND: The warm ischemic period in non-heart-beating donor lungs may contribute to a higher degree of ischemia-reperfusion injury after lung transplantation. We investigated the impact and timing of administration of N-acetyl cysteine (NAC) on inflammatory parameters. METHODS: Ischemia (I) was induced by clamping the hilum of the left lung for 90 minutes, and some protocols were followed by reperfusion (R) for 4 hours. Mice were divided into nine groups (n = 6/group): three control groups ([sham] (thoracotomy only), [I] and [I+R]); two groups with saline instillation only ([saline+I] and [saline+I+R]); and four experimental groups with NAC (50 mg/kg), administered by instillation ([NAC+I], [NAC+I+R] and [I+NAC+R]) or by aerosol ([NACaero+I+R]). Cell counts and protein levels in bronchoalveolar lavage (BAL) were determined. RESULTS: NAC administered prior to hilar clamping led to a significant decrease in macrophages and lymphocytes and interleukin (IL)-1 beta levels after ischemia. NAC also resulted in significantly fewer macrophages, lymphocytes and neutrophils as well as IL-1 beta, keratinocyte cytokine (KC), monocyte chemoattractant protein (MCP)-1 and IL-6 levels in BAL taken after reperfusion. CONCLUSIONS: NAC treatment prior to warm ischemia attenuates inflammatory changes after both the ischemic and reperfusion periods.
BACKGROUND: The warm ischemic period in non-heart-beating donor lungs may contribute to a higher degree of ischemia-reperfusion injury after lung transplantation. We investigated the impact and timing of administration of N-acetyl cysteine (NAC) on inflammatory parameters. METHODS:Ischemia (I) was induced by clamping the hilum of the left lung for 90 minutes, and some protocols were followed by reperfusion (R) for 4 hours. Mice were divided into nine groups (n = 6/group): three control groups ([sham] (thoracotomy only), [I] and [I+R]); two groups with saline instillation only ([saline+I] and [saline+I+R]); and four experimental groups with NAC (50 mg/kg), administered by instillation ([NAC+I], [NAC+I+R] and [I+NAC+R]) or by aerosol ([NACaero+I+R]). Cell counts and protein levels in bronchoalveolar lavage (BAL) were determined. RESULTS:NAC administered prior to hilar clamping led to a significant decrease in macrophages and lymphocytes and interleukin (IL)-1 beta levels after ischemia. NAC also resulted in significantly fewer macrophages, lymphocytes and neutrophils as well as IL-1 beta, keratinocyte cytokine (KC), monocyte chemoattractant protein (MCP)-1 and IL-6 levels in BAL taken after reperfusion. CONCLUSIONS:NAC treatment prior to warm ischemia attenuates inflammatory changes after both the ischemic and reperfusion periods.
Authors: Mahzad Akbarpour; Emilia Lecuona; Stephen F Chiu; Qiang Wu; Melissa Querrey; Ramiro Fernandez; Félix L Núñez-Santana; Haiying Sun; Sowmya Ravi; Chitaru Kurihara; James M Walter; Nikita Joshi; Ziyou Ren; Scott C Roberts; Alan Hauser; Daniel Kreisel; Wenjun Li; Navdeep S Chandel; Alexander V Misharin; Thalachallour Mohanakumar; G R Scott Budinger; Ankit Bharat Journal: J Clin Invest Date: 2020-08-03 Impact factor: 14.808
Authors: Alexandra Sakelliou; Ioannis G Fatouros; Ioannis Athanailidis; Dimitrios Tsoukas; Athanasios Chatzinikolaou; Dimitris Draganidis; Athanasios Z Jamurtas; Christina Liacos; Ioannis Papassotiriou; Dimitrios Mandalidis; Kimon Stamatelopoulos; Meletios A Dimopoulos; Asimina Mitrakou Journal: Oxid Med Cell Longev Date: 2016-11-15 Impact factor: 6.543