Effect of a neutrophil elastase inhibitor on acute lung injury after cardiopulmonary bypass

Abstract

Cardiopulmonary bypass (CPB) has been implicated as a cause of acute lung injury (ALI) in cardiac surgical patients. We used a bronchoscopic microsampling (BMS) probe to examine alveolar biochemical constituents and evaluated the effect of sivelestat sodium hydrate, a novel synthesized polymorphonuclear (PMN) neutrophil elastase inhibitor, on ALI induced by CPB. Twelve patients undergoing aortic valve replacement were treated with either sivelestat 0.2 mg/kg/h (sivelestat group, n=6) or 0.9% saline (control group, n=6) from the start of surgery. Samples were collected by the BMS probe at three time points: after tracheal intubation, 1 h after CPB introduction, and 3 h after CPB termination. Pulmonary function was assessed perioperatively. There were no differences in baseline characteristics. The concentration of PMN elastase was significantly suppressed in the sivelestat group, compared with the control group (P=0.001). The sivelestat group also had lower levels of interleukin-6 and interleukin-8. Alveolar-arterial oxygen difference markedly increased, and a worsening of the PaO(2)/FiO(2) ratio indicated severe impairment after CPB. However, sivelestat attenuated the pattern of physiological deterioration of gas exchange. Sivelestat may attenuate neutrophil elastase or proinflammatory cytokines, and improve pulmonary dysfunction in patients undergoing CPB.

Impact of Presurgical Mild Acute Respiratory Distress Syndrome on Surgical Mortality After Surgical Repair of Acute Type A Aortic Dissection

“…[1][2][3][4] Although it is recognized that activation of the inflammatory system caused by aortic injury due to acute aortic dissection may play a crucial role in the occurrence and development of acute lung injury, 1,5,6) the specific mechanism is still unclear. Acute lung injury or even severe ARDS is considered to be systemic complications of acute aortic dissection rather than a simple pulmonary disease.…”

Neutrophil Elastase Inhibitor Sivelestat Attenuates Perioperative Inflammatory Response in Pediatric Heart Surgery With Cardiopulmonary Bypass

“…4) This drug has been used clinically to treat acute lung injury associated with systemic inflammatory response syndrome. 5,6) Matsuzaki, et al reported that sivelestat reduced neutrophil elastase and IL-8 levels in a simulated extracorporeal circulation. 7) Ryugo, et al also reported that sivelestat suppressed neutrophil elastase and IL-8 levels in adult cardiovascular surgery with CPB.…”

Prevention of Pulmonary Edema after Minimally Invasive Cardiac Surgery with Mini-Thoracotomy Using Neutrophil Elastase Inhibitor

“…11,22) The beneficial effects of neutrophil elastase inhibitor on post-perfusion lung and ischemia-reperfusion and endothelial cell injuries have been demonstrated in several experiments. 17) We experienced two mild RPE cases after MICS. Fortunately, they recovered after using sivelestat and were extubated on POD3.…”

“…Although some organs can be involved, the lung is often the first organ damaged, making this a major complication of CPB. 17) It has been reported that activated neutrophils that accumulate in the lung and release chemical mediators, such as neutrophil elastase, play an important role in post-pump syndrome. Eguchi et al 18) described that neutrophil plays a key role in lung re-expansion capillaries injury.…”