Effects of early administration of a novel anticholinergic drug on acute respiratory distress syndrome induced by sepsis.
BACKGROUND
Acute respiratory distress syndrome (ARDS) is the inflammatory disorder of the lung most commonly caused by sepsis. It was hypothesized that treating the lung with penehyclidine hydrochloride (PHC), a new type of hyoscyamus drug, early in the development of sepsis could diminish the lung dysfunction.


METHODS
Sprague-Dawley rats were divided into 4 groups: 1) a control group; 2) a sham-operated group; 3) a cecal ligation and puncture (CLP) group; 4) a PHC-treated group. One hour after CLP surgery, rats were either untreated or treated with PHC via intraperitoneal injection. Lung wet/dry weight ratio, bronchoalveolar lavage fluid (BALF), serum tumor necrosis factor (TNF-α), interleukin 6 (IL-6), interleukin 10 (IL-10), total nitrite/nitrate (NOx), superoxide dismutase (SOD), malondialdehyde (MDA) in lung tissues, and pulmonary functions were examined 24 hour after surgery. Another 60 rats were randomly assigned to 4 equal groups to observe survival status 96 hours after surgery.


RESULTS
Treatment of PHC markedly decreased TNF-α, IL-6, NOx, SOD, MDA content, protein concentration in BALF, and lung wet/dry weight ratio and enhanced SOD activity (p<0.05), which are indicative of PHC-induced suppression in the pathogenesis of ARDS caused by sepsis. In comparison to group CLP/saline, plasma IL-10 level markedly increased in group CLP/PHC. In PHC-treated groups, the administered PHC had a significant protective effect on the lung dysfunction induced by sepsis.


CONCLUSIONS
We conclude that administration of PHC at the time of a systemic insult can protect the lung from the damaging effects of sepsis.
Department of Hepatobiliary Surgery, Hunan Provincial People's Hospital, Changsha, China.
Hao
H
Li
Zhaoxin
Z
Qian
Jianmin
J
Li
Xiaotong
X
Han
Min
M
Liu
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D018680:Cholinergic Antagonists / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D007274:Injections, Intraperitoneal; D015850:Interleukin-6 / Q000097:blood; D008315:Malondialdehyde / Q000097:blood; D009566:Nitrates / Q000097:blood; D009573:Nitrites / Q000097:blood; D011812:Quinuclidines / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D012128:Respiratory Distress Syndrome / Q000188:drug therapy* / Q000209:etiology*; D018805:Sepsis / Q000150:complications*; D018709:Statistics, Nonparametric; D013482:Superoxide Dismutase / Q000097:blood; D016019:Survival Analysis; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D018680:Cholinergic Antagonists; D015850:Interleukin-6; D009566:Nitrates; D009573:Nitrites; D011812:Quinuclidines; D014409:Tumor Necrosis Factor-alpha; C486140:penehyclidine; D008315:Malondialdehyde; D013482:Superoxide Dismutase