Assessment of nucleus accumbens impairment in a rat model of postoperative cognitive dysfunction using diffusion tensor imaging.

BACKGROUND: Postoperative cognitive dysfunction (POCD) often occurs in elderly patients, causing depression and other symptoms. Nucleus accumbens (NAc) is involved in depression. We investigate the diffusion tensor imaging (DTI) parameters of NAc in a POCD model of depression. METHODS: Twenty-month-old male Sprague-Dawley (SD) rats were randomly divided into the POCD and Sham groups. The POCD group underwent exploratory laparotomy to establish a POCD depression model, while the Sham group underwent a sham operation. The fractional anisotropy (FA) and mean diffusivity (MD) values of the bilateral NAc, behavioural changes of forced swimming test and sucrose preference rate, and pathological changes of glial fibrillary acidic protein (GFAP) fluorescent intensity were observed at 15 days (D15 ) and 30 days (D30 ) after the operation. RESULTS: The FA value of the bilateral NAc area in the POCD group was lower than that in the Sham group at the two time periods after the operation (P < 0.05). However, the MD value at D30 was higher in the POCD group than in the Sham group (P < 0.05). The FA value in the POCD group was lower at D30 than at D15 (P < 0.05). The floating time was prolonged while the sucrose preference rate was decreased in the POCD group compared with the Sham group (P < 0.05). The floating time in the POCD group was longer at D30 than at D15 . However, the sucrose preference rate in the POCD was lower at D30 than at D15 . The GFAP fluorescent intensity in the bilateral NAc region in the POCD group was higher than in the Sham group (P < 0.05). CONCLUSION: Microstructural changes of the NAc area are associated with POCD related depression. In addition, FA and MD were demonstrated to be effective in diagnosing and monitoring postoperative depression and its severity.

Abdominal surgery plus sevoflurane exposure induces abnormal emotional changes and cognitive dysfunction in aged rats.

BACKGROUND: Cognitive impairment, which includes perioperative psychological distress and cognitive dysfunction, can be determined by preoperative and post-operative neuropsychological tests. Several mechanisms have been proposed regarding the two-way communication between the immune system and the brain after surgery. We aimed to understand the mechanisms underlying perioperative neurocognitive disorders (PND) in elderly rats using an experimental abdominal surgery model. METHODS: 24-month-old SD rats were exposed to the abdominal surgery model (AEL) under 3% anesthesia. On day 15 and day 30 post-surgery, fractional anisotropy (FA) using diffusion kurtosis imaging (DKI) was measured. From day 25 to day 30 post-surgery, behavioral tests, including open field test (OFT), Morris water maze (MWM), novel object recognition (NOR), force swimming test (FST), and elevated plus maze (EPM), were performed. Then, the rats were euthanized to perform pathological analysis and western blot measurement. RESULTS: The rats exposed to AEL surgical treatment demonstrated significantly decreased time crossing the platform in the MWM, decreased recognition index in the NOR, reduced time in the open arm in the EPM, increased immobility time in the FST, and increased number of crossings in the OFT. Aged rats, after AEL exposure, further demonstrated decreased FA in the mPFC, nucleus accumbens (NAc), and hippocampus, together with reduced MAP2 intensity, attenuation of GAD65, VGlut2, CHAT, and phosphorylated P38MAPK expression, and increased reactive astrocytes and microglia. CONCLUSIONS: In this study, the aged rats exposed to abdominal surgery demonstrated both emotional changes and cognitive dysfunction, which may be associated with neuronal degeneration and reduced phosphorylated P38MAPK.

Clinical Efficacy and Safety of Combination Therapy with Amlodipine and Olmesartan or an Olmesartan/Hydrochlorothiazide Compound for Hypertension: A Prospective, Open-Label, and Multicenter Clinical Trial in China.

BACKGROUND: Amlodipine (AML) is the initial therapy most commonly prescribed for patients with hypertension in China. However, AML monotherapy is often less effective in achieving blood pressure (BP) control than other agents. OBJECTIVE: We performed a clinical study to evaluate efficacy and safety of a combination therapy with AML, olmesartan (OLM), or an OLM/hydrochlorothiazide (HCTZ) compound for Chinese patients with mild-to-moderate hypertension. METHODS: In the clinical trial, patients were initially treated with OLM 20 mg/d combined with AML 5 mg/d. Then OLM was uptitrated to 40 mg/d or changed to an OLM/HCTZ (20/12.5 mg/d) compound if the patients did not reach the target of seated diastolic BP <90 mm Hg (<80 mm Hg in patients with diabetes) after 8 weeks. RESULTS: The overall response rate of the combination therapy was 59.2% (95% CI, 54.23%-63.97%) at Week 2 and gradually increased to 97.1% (95% CI, 94.93%-98.47%) at the end of the study (Week 16). CONCLUSIONS: The combination therapy with OLM or OLM/HCTZ was well tolerated. The total incidence of adverse events was 42.9% (n = 176). Most of the adverse events were mild in severity (39.5%; n = 162) and not associated with the drugs (33.2%). In conclusion, combination therapy with AML, OLM, or OLM/HCTZ can significantly lower BP safely and achieve a high BP control rate in patients with mild-to-moderate hypertension in China. ClinicalTrial.org identifier: ChiCTR-ONC-12001963.

Intratracheal administration of isosorbide dinitrate improves pulmonary artery pressure and ventricular remodeling in a rat model of heart failure following myocardial infarction.

Pulmonary hypertension due to left heart disease is associated with poor outcomes. This study investigated the beneficial effects of isosorbide dinitrate (ISDN) inhalation on pulmonary pressure and ventricular remodeling in a rat model of heart failure (HF) following myocardial infarction (MI). To assess the effect of ISDN on pulmonary pressure, 20 male Sprague-Dawley (SD) rats were randomized to four groups: Normal saline (NS) 1 ml/kg, ISDN 1 mg/kg, NS 3 ml/kg or ISDN 3 mg/kg following coronary ligation. Assessments included pulmonary and systemic artery pressure alterations, lung weight/body weight and plasma nitric oxide (NO) concentration. To assess the effect of ISDN on ventricular remodeling, 30 SD rats were randomized to three groups: Sham surgery, MI-NS (intratracheal NS 3 ml/kg for 13 days following coronary ligation), and MI-ISDN (intratracheal ISDN 3 mg/kg for 13 days following coronary ligation). On day 15, all rats underwent echocardiogram and hemodynamic assessments. The area affected by MI was evaluated using microscopy and vascular endothelial growth factor (VEGF) expression was examined using immunohistochemistry. Plasma epinephrine, norepinephrine and brain natriuretic peptide (BNP) levels were assessed by ELISA. Intratracheal ISDN reduced pulmonary and systematic artery pressure without pulmonary edema when compared with NS. The reduction was associated with increased plasma NO levels. ISDN inhalation for 14 days reduced MI size and alleviated left and right ventricular remodeling following MI. These hemodynamic and morphological improvements were associated with decreased plasma epinephrine, norepinephrine and BNP levels, and an increased VEGF positive area at the border of MI region. In conclusion, intratracheal administration of ISDN was effective in improving ventricular remodeling and cardiac function in a rat model of HF following MI.

Atorvastatin antagonizes the visfatin-induced expression of inflammatory mediators via the upregulation of NF-κB activation in HCAECs.

The present study investigated whether atorvastatin antagonizes the visfatin-induced expression of inflammatory mediators in human coronary artery endothelial cells (HCAECs). Several analysis methods, such as reverse transcription-quantitative polymerase chain reaction, western blot analysis and H2DCFDA incubation, were used in the present study. The data showed that atorvastatin decreased the visfatin-induced expression of interleukin (IL)-6 and IL-8 in HCAECs. In addition, atorvastatin inhibited the visfatin-induced expression of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in HCAECs. In addition, the present study found that atorvastatin inhibited the visfatin-activated nuclear factor-κB (NF-κB) signal pathway by preventing extracellular signal-regulated kinase phosphorylation in HCAECs. Atorvastatin significantly inhibited visfatin-induced NF-κB activity via the upregulation of reactive oxygen species production. Atorvastatin, a visfatin antagonist (FK866) and an NF-κB inhibitor (BAY11-7082) decreased the visfatin-induced expression of inflammatory mediators via the upregulation of NF-κB activation in HCAECs. These results suggest that atorvastatin may inhibit the visfatin-induced upregulation of inflammatory mediators through blocking the NF-κB signal pathway. The findings of the present study provide a potential use for atorvastatin and visfatin in the pathogenesis of HCAEC dysfunction. This knowledge may contribute to the development of novel therapies for atherosclerosis.

Diagnosis of Dissection of the Coronary Artery Dissection by Multidetector Computed Tomography: A Comparative Study With Coronary Angiology.

OBJECTIVES: This study was to assess the diagnostic performance of multidetector computed tomography (MDCT) angiographic protocol for dissection of the coronary artery (DCA) detection compared with coronary angiology (CAG). METHODS: Intravascular ultrasound was used as the gold standard for DCA diagnosis. Thirty-six DCA patients and 34 non-DCA (control) participants were retrospectively reviewed. The CAG and MDCT angiography images were separately reviewed by 4 independent observers, and a 5-point grading scale was used for DCA diagnosis. Diagnostic performance was compared using receiver operating characteristic analysis. Sensitivity, specificity, and negative predictive values were calculated. RESULTS: The MDCT performed significantly better than that of CAG (AZ = 0.9943 ± 0.0034 vs AZ = 0.8411 ± 0.0274, respectively) for DCA detection. The sensitivity (98.6%), specificity (89.7%), and negative predictive value (98.4%) of MDCT for DCA were higher than those of CAG (77.8%, 79.4%, and 77.1%, respectively). CONCLUSIONS: Multidetector computed tomography angiography was a more sensitive and specific technique for the diagnosis of DCA compared with CAG.

Microelectrode array measurement of potassium ion channel remodeling on the field action potential duration in rapid atrial pacing rabbits model.

BACKGROUND: Atrial fibrillation (AF) arises from abnormalities in atrial structure and electrical activity. Microelectrode arrays (MEA) is a real-time, nondestructive measurement of the resting and action potential signal, from myocardial cells, to the peripheral circuit of electrophysiological activity. This study examined the field action potential duration (fAPD) of the right atrial appendage (RAA) by MEA in rapid atrial pacing (RAP) in the right atrium of rabbits. In addition, this study also investigated the effect of potassium ion channel blockers on fAPD. METHODS: 40 New Zealand white rabbits of either sex were randomly divided into 3 groups: 1) the control, 2) potassium ion channel blocker (TEA, 4-Ap and BaCl2), and 3) amiodarone groups. The hearts were quickly removed and right atrial appendage sectioned (slice thickness 500 µm). Each slice was perfused with Tyrode's solution and continuously stimulated for 30 minutes. Sections from the control group were superfused with Tyrode's solution for 10 minutes, while the blocker groups and amiodarone were both treated with their respective compounds for 10 minutes each. The fAPD of RAA and action field action potential morphology were measured using MEA. RESULTS: In non-pace (control) groups, fAPD was 188.33 ± 18.29 ms after Tyrode's solution superfusion, and 173.91 ± 6.83 ms after RAP. In pace/potassium ion channel groups, TEA and BaCl2 superfusion prolonged atrial field action potential (fAPD) (control vs blocker: 176.67 ± 8.66 ms vs 196.11 ± 10.76 ms, 182.22 ± 12.87 ms vs 191.11 ± 13.09 ms with TEA and BaCl2 superfusion, respectively, P < 0.05). 4-AP superfusion significantly prolonged FAPD. In pace/amiodarone groups, 4-Ap superfusion extended fAPD. CONCLUSIONS: MEA was a sensitive and stable reporter for the measurement of the tissue action potential in animal heart slices. After superfusing potassium ion channel blockers, fAPD was prolonged. These results suggest that Ito, IKur and IK1 remodel and mediate RAP-induced atrial electrical remodeling. Amiodarone alter potassium ion channel activity (Ito, IKur, IK1 and IKs), shortening fAPD.

Effects of vagus nerve stimulation via cholinergic anti-inflammatory pathway activation on myocardial ischemia/reperfusion injury in canine.

BACKGROUND: Acute myocardial infarction (AMI) was a type of disease with high mortality rate and high disability rate. And about 50% of the final area of myocardial infarction after AMI was led by ischemia/reperfusion (I/R) injury. The I/R injury was a kind of systemic inflammatory response, in which the main performance laid in the release of the large quantity of inflammatory cytokines. The basic experiments, clinical studies and the large scaled epidemiology investigations found that the low functions of vagus nerves had close relevance with the occurrence, development and prognosis of the cardiovascular diseases. This study investigate the effects of cholinergic anti-inflammatory pathway with with vagus never stimulation I/R injury in canine. METHODS: 18 adult mongrel dogs were randomly divided into 3 groups (n = 6): sham operation group (sham Group), ischemia/reperfusion group (I/R group), right vagus nerve stimulation and ischemia/reperfusion group (STM group). The hemodynamic indexes were measured after reperfusion 120 min. Through internal jugular venous blood, serum acetylcholine (Ach), tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) concentrations were detected by ELISA. Alpha 7 subunit Ach acetylcholine receptor (α7nAchR) expression level was detected with immunohistochemical method. HE staining was used to observe the degree of neutrophil infiltration. RESULTS: After ischemia/reperfusion 120 min, compared with sham group, TNF-α and IL-6 were significantly decreased, Ach content increased, the expression of α7nAchR protein was significantly reduced in I/R group (P < 0.05). Expression of α7nAchR protein, Ach content, TNF-α and IL-6 level had no significant difference in STM group (P < 0.05). Compared with I/R group, the expression of Ach and α7nAchR protein significantly increased the TNF- and IL-6 levels decreased in STM group (P < 0.05). Compared with the baseline, TNF-α and IL-6 levels significantly increased Ach content decreased in I/R group after ischemia /reperfusion 120 min (P < 0.05). Ach, TNF-α and IL-6 levels had no significant change in sham group and STM group of (P < 0.05). TNF-α and IL-6 were negatively correlated with Ach in I/R group (P < 0.05), and TNF-α, IL-6 were negatively correlated with Ach in group STM (P < 0.05). Massive infiltration of neutrophils were detected in myocardial tissue of I/R group, and a small number of neutrophils infiltration were detected in STM group. CONCLUSION: Right vagus nerve stimulation could activate anti-inflammatory pathway and inhibit the systemic and local inflammatory reaction to relieve myocardial I/R injury.

Pulsed electromagnetic field improves cardiac function in response to myocardial infarction.

Extracorporeal pulsed electromagnetic field (PEMF) has been shown the ability to improve regeneration in various ischemic episodes. Here, we examined whether PEMF therapy facilitate cardiac recovery in rat myocardial infarction (MI), and the cellular/molecular mechanisms underlying PEMF-related therapy was further investigated. The MI rats were exposed to active PEMF for 4 cycles per day (8 minutes/cycle, 30 ± 3 Hz, 5 mT) after MI induction. The data demonstrated that PEMF treatment significantly inhibited cardiac apoptosis and improved cardiac systolic function. Moreover, PEMF treatment increased capillary density, the levels of vascular endothelial growth factor (VEGF) and hypoxic inducible factor-1α in infarct border zone. Furthermore, the number and function of circulating endothelial progenitor cells were advanced in PEMF treating rats. In vitro, PEMF induced the degree of human umbilical venous endothelial cells tubulization and increased soluble pro-angiogenic factor secretion (VEGF and nitric oxide). In conclusion, PEMF therapy preserves cardiac systolic function, inhibits apoptosis and trigger postnatal neovascularization in ischemic myocardium.

Pulmonary antrum radial-linear ablation for paroxysmal atrial fibrillation: interim analysis of a multicenter trial.

BACKGROUND: Substrate abnormality in pulmonary vein (PV) antrum plays a critical role in mechanism of atrial fibrillation (AF). The present study compares the strategy of PV antrum radial-linear (PAR) ablation to encircling PV isolation for paroxysmal AF. METHODS AND RESULTS: A total of 86 patients with paroxysmal AF were randomly assigned to PAR ablation group or PV isolation group. The average procedure time was 161±21 minutes in PAR ablation group and 199±39 minutes in PV isolation group (P<0.01). The average fluoroscopy time was 25±5 minutes in PAR ablation group and 32±9 minutes in PV isolation group (P<0.001). At 14 (15-12) months of follow-up after single procedure, 31 of 42 (74%) patients in PAR ablation group and 22 of 44 patients (50%) in PV isolation group had no recurrence of AF off antiarrhythmic drug (P=0.0249); and 36 of 42 patients (86%) in PAR ablation group and 26 of 44 patients (59%) in PV isolation group had no recurrence of AF with antiarrhythmic drug (P=0.006). In addition, PAR ablation resulted in greater reduction of left atrial diameter than encircling PV isolation. Multivariable Cox regression analysis showed that only ablation strategy was independently associated with AF recurrence (hazard ratio, 0.31; 95% confidence interval, 0.12-0.78; P=0.013). No major adverse event related to the procedures occurred. CONCLUSIONS: This study suggests that PAR ablation is a potentially effective strategy for treatment of paroxysmal AF warranting further investigation. CLINICAL TRIAL REGISTRATION: URL: http://www.chictr.org; Unique identifier: ChiCTR-TRC-11001191.

Biomarkers, age, and coronary artery remodeling in patients with acute coronary syndrome.

To investigate the relationship between age and coronary artery remodeling in patients with acute coronary syndrome (ACS), 56 patients with ACS were identified by intravascular ultrasound (IVUS). Remodeling index (RI) (37 cases of RI > or =1 vs 19 cases of RI <1) and dimidiate age groups (27 patients younger than 60 years vs 29 patients 60 years or older) were compared, and the relationships among biomarkers, age, and arterial remodeling were analyzed. There was a significant difference in age between positive and negative remodeling groups (55+/-13 vs 62+/-10 years; P=.038); RI and triglyceride level showed a statistical correlation (r=0.32; P=.02) and a significant inverse correlation between age and RI (r=-0.47; P<.001). The multivariable linear regression analysis demonstrated that age was an independent predictor of RI (Bate -0.37; 95% confidence interval, 0.93-1.08; P=.04). Age may be an important factor of arterial remodeling. Low-density lipoprotein or triglyceride level may be associated with attenuated coronary vascular remodeling with aging.

Elevated expression of urotensin II and its receptor in diabetic cardiomyopathy.

OBJECTIVE: Urotensin II (UII) is a somatostatin-like peptide recently identified to have several cardiovascular effects, including potent vasoactive, cardiac inotropic and chronotropic properties. Our aim was to determine the degree of expression of UII and UII receptor (UT) in the myocardium of rats with streptozotocin (STZ)-induced diabetes. METHODS: Real-time polymerase chain reaction, Western blot, and immunohistochemistry were used to determine the degree of expression and location of UII and UT in the myocardium of STZ-induced diabetic rats. RESULTS: UII and UT expression were significantly enhanced in the myocardium of rats with diabetes compared with healthy controls on both messenger RNA and protein levels. Both UII and UT protein expression were mainly concentrated in the cardiomyocytes, endothelial cells, cardiac fibroblasts, and smooth muscle cells of diabetic cardiomyopathy (DCM). CONCLUSIONS: Our results suggest a possible role for the UII/UT system in the pathophysiology of DCM.

[Relationship between serum vasoactive factors and plaque morphology in patients with acute coronary syndrome].

OBJECTIVE: To investigate the relationship between vasoactive factors and plaque morphology in patients with acute coronary syndrome (ACS). METHODS: Intravascular ultrasound (IVUS) were performed and 7 serum vasoactive factors (sPE, tPA, MCP-1, IL-8, IL-6, sVCAM-1 and sCD40L) were measured through cytometric bead array, serum hs-CRP, HCY, glucose and lipid level were also determined in consecutively enrolled 56 patients with ACS. The changes of bio-factors were compared between vulnerable plaque and non-vulnerable plaque groups, AMI and UA patients, and patients with or without plaque rupture. RESULTS: Biomarkers were similar between patients with unstable angina pectoris and AMI. hs-CRP [(18.9 +/- 4.9) mg/l vs. (5.8 +/- 3.6) mg/L)] and IL-6 [19.5 pg/ml (9.2 - 44.6 pg/ml) vs. 5.3 pg/ml (2.3 - 13.4 pg/ml)] were significantly higher in the group of vulnerable plaque (P < 0.05) compared to non-vulnerable plaques group. sCD40L [(474 +/- 126) pg/ml vs. (238 +/- 35) pg/ml], sPE [(107.2 +/- 39.9) microg/ml vs. (49.1 +/- 5.6) microg/ml] and MCP-1 [(132 +/- 18) pg/ml vs. (127 +/- 13) pg/ml] were significantly increased in the plaque rupture group than that in non-plaque rupture group (all P < 0.05). Increasing of sCD40L, MCP-1, sPE and TC were independent risk factors for plaque rupture. CONCLUSIONS: IL-6 and hs-CRP are biomarkers for vulnerable plaques and diagnosis of acute myocardial infarction. sCD40L, MCP-1 and sPE may serve as the potential markers predicting plaque rupture in patients with ACS.