Carbonic anhydrase inhibitor attenuates ischemia-reperfusion induced acute lung injury.

Chou-Chin Lan,Kun-Lun Huang,Shih-En Tang,Chung-Kan Peng,Chin-Pyng Wu,Nades Palaniyar

doi:10.1371/journal.pone.0179822

Abstract

Ischemia-reperfusion (IR)-induced acute lung injury (ALI) is implicated in several clinical conditions including lung transplantation, cardiopulmonary bypass surgery, re-expansion of collapsed lung from pneumothorax or pleural effusion and etc. IR-induced ALI remains a challenge in the current treatment. Carbonic anhydrase has important physiological function and influences on transport of CO2. Some investigators suggest that CO2 influences lung injury. Therefore, carbonic anhydrase should have the role in ALI. This study was undertaken to define the effect of a carbonic anhydrase inhibitor, acetazolamide (AZA), in IR-induced ALI, that was conducted in a rat model of isolated-perfused lung with 30 minutes of ischemia and 90 minutes of reperfusion. The animals were divided into six groups (n = 6 per group): sham, sham + AZA 200 mg/kg body weight (BW), IR, IR + AZA 100 mg/kg BW, IR + AZA 200 mg/kg BW and IR+ AZA 400 mg/kg BW. IR caused significant pulmonary micro-vascular hyper-permeability, pulmonary edema, pulmonary hypertension, neutrophilic sequestration, and an increase in the expression of pro-inflammatory cytokines. Increases in carbonic anhydrase expression and perfusate pCO2 levels were noted, while decreased Na-K-ATPase expression was noted after IR. Administration of 200mg/kg BW and 400mg/kg BW AZA significantly suppressed the expression of pro-inflammatory cytokines (TNF-α, IL-1, IL-6 and IL-17) and attenuated IR-induced lung injury, represented by decreases in pulmonary hyper-permeability, pulmonary edema, pulmonary hypertension and neutrophilic sequestration. AZA attenuated IR-induced lung injury, associated with decreases in carbonic anhydrase expression and pCO2 levels, as well as restoration of Na-K-ATPase expression.

Highlights

Exposure of the lungs to periods of ischemia and the initiation of reperfusion causes ischemiareperfusion (IR)-induced acute lung injury (ALI)[1]
IR-induced ALI is an important issue in lung transplantation[1], which provides a potential cure for patients with end-stage pulmonary diseases
And beyond of lung transplantation, IR-induced ALI affects treatment of cardiopulmonary bypass and re-expansion of collapsed lung associated with pneumothorax or pleural effusion[3,4,5] The mortality associated with IR-induced ALI remains high despite the availability of modern treatments

Summary

Introduction

Exposure of the lungs to periods of ischemia and the initiation of reperfusion causes ischemiareperfusion (IR)-induced acute lung injury (ALI)[1]. IR-induced ALI is an important issue in lung transplantation[1], which provides a potential cure for patients with end-stage pulmonary diseases. Despite advances in organ preservation and peri-operative care, IR-induced ALI remains a significant cause of post-transplantation mortality and morbidity[2]. It has been widely accepted that effective organ preservation is one of the keys to successful lung and heart-lung transplantation[2]. And beyond of lung transplantation, IR-induced ALI affects treatment of cardiopulmonary bypass and re-expansion of collapsed lung associated with pneumothorax or pleural effusion[3,4,5] The mortality associated with IR-induced ALI remains high despite the availability of modern treatments. There is a need for -more effective treatments for IR-induced ALI

Methods

Results

Discussion

Conclusion