Early surgery increases mitochondrial DNA release and lung injury in a model of elderly hip fracture and chronic obstructive pulmonary disease.

Abstract

Hip fractures are one of the most common injuries in elderly individuals and are associated with a high incidence of complications and mortality. Clinical guidelines recommend early reparative surgery within 24-48 h from hospital admission; however, it is currently unknown whether this principle of early surgery is applicable for patients with hip fracture and chronic obstructive pulmonary disease (COPD). To investigate the systemic inflammatory response and lung injury as a result early surgery in elderly patients with hip fracture and COPD, a COPD model was created, by daily exposure to cigarette smoke, and evaluated. Rats (5 months of age) were exposed to cigarette smoking for 37 weeks to create a COPD group. Rats not exposed to cigarette smoke formed the control group. All rats experienced hip fracture, which was subsequently treated with surgery at 24 h (early fixation; EF) or 72 h (late fixation; LF) after fracture, respectively. Serum mitochondrial DNA (mtDNA), tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-10 were measured at 2 and 24 h after surgery. Cytokine and myeloperoxidase (MPO) activity in the lung tissue were measured and assessed via bronchoalveolar lavage. The serum mtDNA, IL-6 and IL-10 levels in the control group and in the COPD group increased rapidly at 2 h and peaked at 24 h, while TNF-α levels peaked at 2 h and subsequently decreased. Rats that received EF in the COPD group demonstrated a significant increase of TNF-α (P<0.001 at 2 h), IL-6 (P<0.001 at 2 and 24 h), IL-10 (P=0.010 at 2 h and P=0.001 at 24 h) and mtDNA (P<0.001 at 24 h) compared with the rats that received LF. LF in experimental rats also significantly reduced the severity of MPO activity (P<0.001 and P=0.001) and permeability (P=0.009 and P=0.018) in pulmonary samples at 2 or 24 h, respectively, compared with EF. However, LF in the control group did not demonstrate a significant advantage at reducing MPO and permeability in serum and pulmonary samples. The present study indicated that early surgery increased mtDNA and cytokine release in a model of elderly hip fracture with COPD, and LF may reduce the severity of the inflammatory response and degree of permeability in pulmonary tissues.