Mirabegron Ameliorated Atherosclerosis of ApoE-/- Mice in Chronic Intermittent Hypoxia but Not in Normoxia.

PURPOSE: It has been established that obstructive sleep apnea (OSA) is an independent risk factor for atherosclerosis. Chronic intermittent hypoxia (CIH) activates sympathoadrenal system and upregulates ß3 adrenergic receptor (ß3 AR). However, the effect of selective ß3 AR agonist mirabegron in CIH-induced atherosclerosis remains unknown. METHODS: We generated a CIH-induced atherosclerosis model through exposing ApoE-/- mice to CIH (8 h per day, cyclic inspiratory oxygen fraction 5-21%, 60-s cycle) for 6 weeks after 4-week high-fat dieting and investigated the effects of mirabegron, a selective ß3 AR agonist, on CIH-induced atherosclerosis. The coronary endarterectomy (CE) specimens from coronary artery disease patients with OSA and without OSA were collected. RESULTS: The expression of ß3 AR was significantly elevated in CIH-induced atherosclerosis model. Furthermore, treatment with mirabegron (10mg/kg per day by oral administration for 6 weeks) ameliorated atherosclerosis in ApoE-/- mice in CIH but not in normoxia. Mechanistically, mirabegron activated ß3 AR and ameliorated intraplaque oxidative stress by suppressing p22phox expression and reactive oxygen species (ROS) level. In addition, in human CE specimens, ß3 AR was also upregulated associated with increased p22phox expression and ROS level both in the lumen and in the plaque of coronary artery in OSA subjects. CONCLUSION: This study first demonstrated that mirabegron impeded the progression of CIH-induced atherosclerosis, at least in part, via ß3 AR-mediated oxidative stress, suggesting a promising therapeutic strategy for protecting against atherosclerosis induced by CIH.

[Distribution and antibiotics resistance related to nosocomial pathogenic bacteria infection in patients after cardiac surgery].

OBJECTIVE: To investigate the clinical distribution and antibiotics resistance of nosocomial infection caused pathogenic bacteria in patients after cardiac surgery. METHODS: Clinical data from 612 patients after cardiac surgery under microbiologically documented nosocomial infection was retrospectively analyzed from January 2007 to December 2012. Identification on related bacterial was performed in an automatic ATB Expression system while antimicrobial susceptibility was tested by Kirby-Bauer method. RESULTS: were analyzed by WHONET5.4. RESULTS: There were 697 strains of clinical pathogenic bacilli isolates identified and 421 (60.4%) of them were isolated from sputum while 185 (26.5%) were from blood. Acinetobacter spp. (124 strains, 17.8%), Pseudomonas aeruginosa (85 strains, 12.2%) and Klebsiella pneumoniae (50 strains, 7.2%) were the predominant Gram-negative bacilli while S. epidermidis (75 strains, 10.8%) was the predominant Gram-positive cocci. The predominant eumycete was Candida albicans (43 strains, 6.2%). RESULTS: from the susceptibility test showed that carbapenems, cefoperazone/sulbactam and piperacillin/tazobactam were the most active antibiotics. The detection of meticillin-resistant Staphylococcus (MRS) were 82.9% in S aureus and 95.9% in coagulase negative Staphylococcus. There was no Staphylococcus strains resistant to vancomycin found. CONCLUSION: Non-fermenting Gram-negative bacilli and Staphylococcus appeared the important pathogens in patients after cardiac surgery. Drug resistance to antibiotics was quite common. Prevention on nosocomial infection and rational use of antibiotics remained very important in reducing the amount of drug resistant strains.