Adiponectin Ameliorated Pancreatic Islet Injury Induced by Chronic Intermittent Hypoxia through Inhibiting the Imbalance in Mitochondrial Fusion and Division.

Objective This study aimed to assess the protective value of adiponectin (APN) in pancreatic islet injury induced by chronic intermittent hypoxia (CIH). Methods Sixty rats were randomly divided into three groups: normal control (NC) group, CIH group, and CIH with APN supplement (CIH+APN) group. After 5 weeks of CIH exposure, we conducted oral glucose tolerance tests (OGTT) and insulin released test (IRT), examined and compared the adenosine triphosphate (ATP) levels, mitochondrial membrane potential (MMP) levels, reactive oxygen species (ROS) levels, enzymes gene expression levels of Ant1, Cs, Hmox1, and Cox4i1 which represented mitochondrial tricarboxylic acid cycle function, the protein and gene expression levels of DRP1, FIS1, MFN1, and OPA1 which represented mitochondrial fusion and division, and the protein expression levels of BAX, BCL-2, cleaved Caspase-3, and cleaved PARP which represented mitochondrial associated apoptosis pathway of pancreatic islet. Results OGTT and IRT showed blood glucose and insulin levels had no differences among the NC, CIH and CIH+APN groups (both P>0.05) at 0 min, 20 min, 30 min, 60 min, 120 min. However, we found that compared to NC group, CIH increased the ROS level, reduced ATP level and MMP level. The islets of CIH exposed rats showed reduced gene expression levels of Ant1, Cs, Hmox1, and Cox4i1, decreased protein and gene expression levels of MFN1 and OPA1, increased protein and gene expression levels of DRP1 and FIS1, increased protein expression levels of cleaved Caspase-3 and cleaved PARP, with lower ratio of BCL-2/BAX at protein expression level. All the differences among three groups were statistically significant. APN treated CIH rats showed mitigated changes in the above measurements associated with islet injuries. Conclusion APN may ameliorate the pancreatic islet injury induced by CIH via inhibiting the imbalance in mitochondrial fusion and division.

Obstructive Sleep Apnea Increases the Perioperative Risk of Cardiac Valve Replacement Surgery: A Prospective Single-Center Study.

STUDY OBJECTIVES: Sleep apnea is common in patients referred for cardiac valve replacement (CVR). We aimed to determine the association of obstructive sleep apnea (OSA) and central sleep apnea (CSA) with perioperative events in CVR surgery in patients with rheumatic valvular heart disease (RVHD). METHODS: Between April 2010 and April 2014, 290 patients with RVHD undergoing CVR were screened for sleep apnea 1 to 7 days before CVR. Baseline medications, cardiac function, sleep parameters, perioperative events, and related risk factors were evaluated. RESULTS: OSA patients had longer duration of intensive care unit (ICU) stay and mechanical ventilation compared with no sleep-disordered breathing and CSA patients. Patients with CSA had a higher rate of pacemaker use and higher first dose of dobutamine in ICU. NYHA Class and the presence of OSA were independently associated with overall worsening of postoperative recovery (ICU stay ≥ 25 h). Age, NYHA class, and the presence of OSA were independently associated with postoperative respiratory insufficiency (mechanical ventilation ≥ 20 h). Preoperative atrial fibrillation, pulmonary hypertension, and OSA were independently associated with postoperative pacemaker use. CONCLUSIONS: RVHD patients with OSA have an increased incidence of perioperative adverse events. OSA was independently associated with overall postoperative recovery, respiratory insufficiency, and higher rate of postoperative pacemaker use, while CSA was not associated with postoperative events.

Adiponectin protects rat heart from left ventricular remodeling induced by chronic intermittent hypoxia via inhibition of TGF-ß/smad2/3 pathway.

OBJECTIVE: Obstructive sleep apnea syndrome (OSAS) is associated with many cardiovascular disorders. Chronic intermittent hypoxia (CIH) is the primary player in OSAS of the many associated factors. This study was in order to investigate the effects of the Adiponectin (Ad) on left ventricular remodeling induced by CIH. METHODS: Forty-five rats were randomly divided into three groups: normal control (NC) group, CIH group and CIH plus Ad supplemented (CIH + Ad) group. After 35 days' CIH exposure, masson analysis was used to detect the left ventricular fibrosis and western blot was used to measure the protein expression of collagen I, collagen III and TGF-ß/smad2/3 pathway. Gene analysis by RT-PCR was used to study the MMP2 and TIMP2. RESULTS: After CIH exposure, the fibrosis of left ventricular in CIH group was significantly remarkable than that in both NC and CIH + Ad groups (P<0.05), although statistical difference existed between NC and CIH + Ad groups (P<0.05). In addition, the protein expression of collagen I as well as collagen III and the ratio of mRNA levels of MMP2/TIMP2 were the highest in CIH group but the lowest in NC group, with CIH + Ad group in between. There was a significant difference among three groups (all P<0.05). The TGF-ß/smad2/3 pathway was activated obviously in CIH group, but less noticeably in CIH + Ad group (P<0.05) with a significant difference in the two groups. CONCLUSIONS: The present study showed that Ad could ameliorate the left ventricular remodeling induced by CIH via inhibition of the expression of TGF-ß/smad2/3 pathway.

Overnight fluid shifts in subjects with and without obstructive sleep apnea.

OBJECTIVE: To investigate the characteristics of baseline body fluid content and overnight fluid shifts between non-obstructive sleep apnea (non-OSA) and obstructive sleep apnea (OSA) subjects. METHODS: A case-controlled study was performed between February 2013 and January 2014, with 36 (18 OSA and 18 non-OSA) outpatients enrolled in this study. Polysomnographic parameters and results of body fluid were compared between the two groups. RESULTS: There were no differences in age, weight, and body mass index (BMI) between groups. Compared with the non-OSA group, OSA group had significantly higher neck circumference (NC) and fluid volume shift in the legs. OSA patients had higher left and right leg fluid indices than non-OSA subjects. There were significant correlations between apnoea-hypopnoea index and baseline fluid indices in both legs as well as the reduction in overnight change in both legs fluid volume. The increase in NC was also significantly correlated with the reduction in overnight change in both legs fluid volume, but not with the change in head and neck fluid volume. There were significant correlations between change in NC and increased fluid shifts in head and neck volume. CONCLUSIONS: OSA patients had a higher baseline fluid content in both legs as compared with non-OSA subjects, which may be the basic factor with regards to fluid shifts in OSA patients. The increase in head and neck fluid shift volume did not directly correlate with the severity of OSA.

Adiponectin alleviates contractile dysfunction of genioglossus in rats exposed to chronic intermittent hypoxia.

BACKGROUND: Genioglossal dysfuntion takes an important role in pathogenesis of obstructive sleep apnea hypopnea syndrome (OSAHS) in which chronic intermittent hypoxia (CIH) is the major pathological origin. Recent studies have suggested genioglossal injury induced by CIH might be improved by adiponectin. The aim of this study was to investigate the effects of adiponectin on genioglossus contractile properties in rats exposed to CIH. METHODS: Thirty-nine healthy male Wistar rats were randomly divided into three groups: normal control (NC), CIH and adiponectin supplement (CIH+Ad) with 13 rats in each. Rats in NC were kept breathing normal air, while rats in CIH and CIH+Ad experienced the same CIH environment eight hours per day for 35 successive days. Rats in CIH+Ad were given intravenous adiponectin of 10 µg twice a week for 30 successive days. Rats in the NC and CIH were injected with normal saline as a control. After 35 days' CIH exposure, the levels of serum adiponectin and genioglossus contractile properties were compared. RESULTS: Serum adiponectin level was significantly lower in CIH than in NC (1210 ng/ml vs. 2236 ng/ml). Serum adiponectin level in CIH+Ad (1844 ng/ml) was significantly higher than CIH but lower than NC. Twitch tension, time to peak tension, half relaxation time and tetanic tension were significantly lower in CIH than NC and improved in CIH+Ad. All mean tetanic fatigue indices decreased more rapidly in the first 20 seconds than during the subsequent 100 seconds. Tetanic fatigue indices in NC and CIH+Ad were significantly higher compared to CIH. CONCLUSIONS: CIH could lead to hypoadiponectinaemia, impaired genioglossus contractile properties and decreased fatigue resistance in rats. Such changes could be partially offset by supplementation of adiponectin.

Adiponectin protects the genioglossus of rats against chronic intermittent hypoxia-induced injury via inhibition of endoplasmic reticulum stress.

BACKGROUND: Obstructive sleep apnea hypopnea syndrome, characterized by chronic intermittent hypoxia (CIH), is closely correlated with genioglossus dysfunction. CIH has been identified to mediate mitochondrial damage in genioglossus. It has been reported that endoplasmic reticulum stress (ERS) could be induced by mitochondrial dysfunction. This study aimed to investigate the role of ERS in CIH-induced genioglossus injury, as well as the possible intervention effect of adiponectin (Ad) supplement in rats. METHODS: Forty-five male Wistar rats were randomly divided into three groups and submitted to room air (group A, n=15) as a control or CIH (groups B and C, n=15, respectively). Throughout the exposure period, intravenous Ad was given in group C; while intravenous normal saline was simultaneously given in groups A and B. After 35-day exposure, genioglossus samples were obtained from the pentobarbital-anaesthetized rats via surgical dissection, following blood sampling. Western blotting was applied to detect expressions of ERS signals and associated apoptotic pathways in genioglossus. Serum adiponectin levels were assessed via enzyme-linked immunosorbent assay (ELISA). RESULTS: Significant hypoadiponectinemia was revealed in group B only (P < 0.05). Compared to those in groups A and C, expressions of markers involved in ERS, such as glucose regulated protein 78 (GRP78), p-PERK, phosphorylated eukaryotic initiation factor 2a (p-eIF2a), phosphorylated inositol-requiring transmembrane kinase/endoribonuclease 1a (p-IRE1a), spliced X-Box binding protein 1 (XBP1s) and activating transcription factor 6 (ATF6), were significantly enhanced in group B (all P < 0.01); while no significant difference was shown between groups A and C (all P > 0.05). ERSassociated apoptotic pathways were remarkably activated in group B. The involved markers detected as the expression of CCAAT/enhancer binding protein homologous protein (CHOP), B-cell lymphoma/leukemia associatied X protein (BAX) and caspase-12 were significantly elevated (all P < 0.01). Transvenous adiponectin supplement improved the above CIHinduced pathological changes in group C. CONCLUSION: Beyond hypoadiponectinemia, CIH could enhance ERS and induce activation of ERS-associated apoptotic pathways in genioglossus, which could be significantly improved by adiponectin supplement.