Limb ischemic preconditioning mitigates lung injury induced by haemorrhagic shock/resuscitation in rats

• Published in: Resuscitation 2011-06, Vol.82 (6), p.760-766
• Main Authors: Jan, Woan-Ching, Chen, Cay-Huyen, Tsai, Pei-Shan, Huang, Chun-Jen
• Format: Article
• Language: English
• Subjects: Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Biological and medical sciences; Emergency; Emergency and intensive cardiocirculatory care. Cardiogenic shock. Coronary intensive care; Heme oxygenase; Hindlimb - blood supply; IL-6; Intensive care medicine; Ischemia/reperfusion; Ischemic Preconditioning; Lung Injury - etiology; Lung Injury - prevention & control; Male; Medical sciences; MIP-2; Nitric oxide; Rats; Rats, Sprague-Dawley; Resuscitation - adverse effects; Shock, Hemorrhagic - complications
• ISSN: 0300-9572; 1873-1570
• DOI: 10.1016/j.resuscitation.2011.02.010

Abstract Aim of the study Haemorrhagic shock and subsequent resuscitation induce acute lung injury. We elucidated whether bilateral lower limb ischemic pre-conditioning (IP) could mitigate lung injury in haemorrhagic shock/resuscitation rats. The role of heme oxygenase-1 (HO-1) was also elucidated. Method Adult male rats were randomized to receive haemorrhagic shock/resuscitation (HS), HS plus IP, or HS plus IP plus the HO-1 inhibitor tin protoporphyrin (SnPP) ( n = 12 in each group). Sham groups were employed simultaneously. For pre-conditioning, 3 cycles of limb IP (10 min ischemia followed by 10 min reperfusion) were performed immediately before haemorrhagic shock. Haemorrhagic shock (mean arterial pressure: 40–45 mmHg) was induced by blood drawing and maintained for 120 min. SnPP was injected 5 min before resuscitation. Shed blood/saline mixtures were re-infused to achieve resuscitation. After monitoring for another 8 h, rats were sacrificed. Arterial blood gas and alveolar–arterial oxygen difference (lung function index), histology, polymorphonuclear leukocytes/alveoli ratio (leukocyte infiltration index), wet/dry weight ratio (water content index), inflammatory molecules (e.g., chemokine, cytokine, prostaglandin E2 ), and malondialdehyde (lipid peroxidation index) assays were preformed. Results Haemorrhagic shock/resuscitation induced significant lung function alterations and significant increases in leukocyte infiltration, water content, inflammation, and lipid peroxidation in lungs. Histological analysis confirmed that haemorrhagic shock/resuscitation caused marked lung injury. Limb IP significantly mitigated the adverse effects of haemorrhagic shock/resuscitation. Moreover, the protective effects of limb IP were reversed by SnPP. Conclusions Limb IP mitigates lung injury in haemorrhagic shock/resuscitation rats. The mechanisms may involve HO-1.