Indomethacin Exacerbates Oleic Acid-Induced Acute Respiratory Distress Syndrome in Adult Rats.

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2016-01
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Acute respiratory distress syndrome (ARDS) is an acute fulminant condition associated with acute lung injury and inflammation leading to hypoxemia, pulmonary edema and respiratory failure. Even though prostaglandins are inflammatory mediators, the role of prostaglandins in ARDS is still not clear. Therefore, we examined the involvement of prostaglandin in experimentally induced ARDS by using prostaglandin synthesis inhibitor, indomethacin. Experiments were conducted on anesthetized adult rats (total n=15). Cannulation of trachea, jugular vein and carotid artery was done in these rats. Recording of respiratory excursions (for respiratory frequency; RF), ECG (for heart rate; HR) and blood pressure, before and after lethal dose of oleic acid (75 µL i.v.) was done for 120 min or till death of the animals. Arterial blood sample was collected 15 min after oleic acid injection to determine PaO2/FiO2 ratio. Lungs were excised at the end of experiment for estimation of pulmonary water content. Administration of oleic acid produced progressive increase in the RF up to 45 min followed by decrease. Subsequently, the respiration stopped and all the animals died by 75 min (mean survival time = 64±8.2 min). HR and mean arterial pressure (MAP) exhibited an immediate decrease followed by an increase up to 45 min. Thereafter, the HR and MAP progressively decreased. PaO2/FiO2 ratio in this group was 182±2.6 mm Hg and pulmonary water content was significantly greater than saline control group. However in indomethacin pretreated rats, injection of oleic acid produced instantaneous decrease in RF and all the animals died within 10 min (mean survival time = 6.6±1.07 min). HR and MAP followed the same pattern as seen with RF. Pulmonary water content in indomethacin pretreated animals was also significantly greater than control group. These observations indicate that indomethacin exacerbates the OA-induced ARDS. Thus, prostaglandins play an important role in the pathophysiology of OA-induced ARDS.
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Parul Sharma, Ratna Pandey and Shripad B. Deshpande. Indomethacin Exacerbates Oleic Acid-Induced Acute Respiratory Distress Syndrome in Adult Rats. Indian Journal of Physiology and Pharmacology. 2016 Jan-Mar; 60(1): 82-89.