Salvage of nonischemic control lung from injury by unilateral ischemic lung with apocynin, a nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor, in isolated perfused rat lung

Ischemia reperfusion (I/R) injury of the lung affects the function of the nonischemic lung. Our objective is to determine how apocynin, which is a nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor, protects the nonischemic control right lung (RL) from injury by the unilateral ischemic left lung (LL). In isolated ventilated (by air containing 5% CO₂) rat lungs, in which differential perfusion of the RL or LL was feasible, the LL was selectively made ischemic (60 min) and reperfused (30 min) in a nonrecirculating or recirculating manner with buffer (Krebs-Henseleit) solution, or in a recirculating manner with buffer that contained apocynin (10 mmol/L) or apocynin + TACEI (tumor necrosis factor)-α converting enzyme inhibitor; 10 μg/mL) (each group: n = 12) or with buffer that contained SOD (superoxide dismutase, 3000 U before ischemia and at reperfusion) or SOD + TACEI (each group: n = 5). The permeability of pulmonary endothelium/epithelium (wet/dry ratio and protein content of bronchoalveolar lavage fluid of each lung), perfusion pressure, and cytokine messenger RNA (mRNA) expression was increased not only in the LL (compared with nonischemic control RL, P < 0.01 with paired-samples T) but also in the RL in recirculating groups (compared with RL in the nonrecirculating group). Apocynin + TACEI as well as SOD + TACEI prevented those permeability increases in the RL by the ischemic LL. However, apocynin with or without TACEI as well as SOD with or without TACEI could only partially ameliorate I/R injury in the LL (P < 0.01 by 1-way analysis of variance [ANOVA]). TNF-α and possibly reactive oxygen species produced and released from the ischemic lung may synergistically induce control RL (remote organ) damage.

Abbreviations: ANOVA, analysis of variance, BAL, bronchoalveolar lavage, DPI, diphenyleneiodonium, GAPDH, glyceraldehyde-3-phosphate dehydrogenase, IL, interleukin, i.p., intraperitoneal, I/R, ischemia reperfusion, LA, left atrium, LL, left lung, mRNA, messenger RNA, NADPH, nicotinamide adenine dinucleotide phosphate, NF-κB, nuclear factor-κB, PA, pulmonary artery, PEEP, positive end-expiratory pressure, RL, right lung, ROS, reactive oxygen species, RT-PCR, reverse transcriptase polymerase chain reaction, SOD, superoxide dismutase, TACEI, tumor necrosis factor-α converting enzyme inhibitor, TNF-α, tumor necrosis factor-α