Contrasting roles of NADPH oxidase isoforms in pressure-overload versus angiotensin II-induced cardiac hypertrophy

Increased production of reactive oxygen species (ROS) is implicated in the development of left ventricular hypertrophy (LVH). Phagocyte-type NADPH oxidases are major cardiovascular sources of ROS, and recent data indicate a pivotal role of a gp91phox-containing NADPH oxidase in angiotensin II (Ang II)-induced LVH. We investigated the role of this oxidase in pressure-overload LVH. gp91phox-/- mice and matched controls underwent chronic Ang II infusion or aortic constriction. Ang II-induced increases in NADPH oxidase activity, atrial natriuretic factor (ANF) expression, and cardiac mass were inhibited in gp91phox-/- mice, whereas aortic constriction-induced increases in cardiac mass and ANF expression were not inhibited. However, aortic constriction increased cardiac NADPH oxidase activity in both gp91phox-/- and wild-type mice. Myocardial expression of an alternative gp91phox isoform, Nox4, was upregulated after aortic constriction in gp91phox-/- mice. The antioxidant, N-acetyl-cysteine, inhibited pressure-overload-induced LVH in both gp91phox-/- and wild-type mice. These data suggest a differential response of the cardiac Nox isoforms, gp91phox and Nox4, to Ang II versus pressure overload.     

Platelet Indices and Their Kinetics Predict Mortality in Patients of Sepsis

Platelet indices are inexpensive, easily accessible parameters and potentially useful prognostic indicators in sepsis. In this study we explore the differences in platelet indices and their kinetics between sepsis survivors and non-survivors. A retrospective cohort-study of 97 cases of culture-positive sepsis at a tertiary-care center in North India. Demographics, clinical and laboratory parameters at admission were assessed. Platelet count (PLT), mean-platelet-volume (MPV), platelet-distribution-width (PDW) and plateletcrit (PCT) on admission, and third, fifth and last days of hospitalization were analyzed. Fractional change in platelet indices (ΔMPV_72h, ΔPDW_72h, ΔPCT_72h, and ΔPLT_72h) by day-3 were calculated. Unpaired and paired t-tests were used to compare survivors with non-survivors, and to study the change in platelet indices with time. Logistic regression was used for multivariate analysis. ROC-curves and optimum cut-offs to predict mortality were obtained. There were 64 survivors. Non-survivors had significantly higher ΔMPV_72h, ΔPDW_72h, day-1 MPV and PDW, and lower ΔPLT_72h. MPV and PDW increased, and PLT decreased with time among non-survivors. Trends were reversed in survivors. Only MPV and PDW showed significant change by day-3. Both were independent predictors of mortality on multivariate analysis, alongside ΔMPV_72h and ΔPLT_72h. On ROC analysis, MPV, PDW, ΔMPV_72h, ΔPDW_72h and ΔPLT_72h effectively predicted mortality. Cut-off for MPV was 10.25 fL (sensitivity = 93.9%, specificity = 60.9%), and PDW, 12.6% (sensitivity = 84.8%, specificity = 51.6%). A rise in MPV and a fall in PLT was associated with mortality in this study. MPV and PDW values at admission are effective predictors of mortality and may be used in conjunction with traditional parameters.     

Impact of catheter ablation versus medical therapy on cognitive function in atrial fibrillation: a systematic review

Journal of Interventional Cardiac Electrophysiology - Atrial fibrillation is associated with an increased risk of cognitive impairment. It is unclear whether the restoration of sinus rhythm with...     

Transcatheter closure of aortopulmonary window

Aortopulmonary window is an uncommon congenital cardiac defect. Most infants presenting with aortopulmonary window will require conventional surgical repair. Experience with transcatheter closure of aortopulmonary window is limited. We report the case of a 9-year-old girl with aortopulmonary window, in whom transcatheter closure was performed successfully using Amplatzer ductal occluder device.     

Frequent occurrence of hypogonadotropic hypogonadism in type 2 diabetes

Type 2 diabetes is associated with lower total testosterone (T) levels in cross-sectional studies. However, it is not known whether the defect is primary or secondary. We investigated the prevalence of hypogonadism in type 2 diabetes by measuring serum total T, free T (FT), SHBG, LH, FSH, and prolactin (PRL) in 103 type 2 diabetes patients. FT was measured by equilibrium dialysis. FT was also calculated by using T and SHBG (cFT). Hypogonadism was defined as low FT or cFT. The mean age was 54.7 +/- 1.1 yr, mean body mass index (BMI) was 33.4 +/- 0.8 kg/m(2), and mean HbA1c was 8.4 +/- 0.2%. The mean T was 12.19 +/- 0.50 nmol/liter (351.7 +/- 14.4 ng/dl), SHBG was 27.89 +/- 1.65 nmol/liter, and FT was 0.250 +/- 0.014 nmol/liter. Thirty-three percent of patients were hypogonadal. LH and FSH levels were significantly lower in the hypogonadal group compared with patients with normal FT levels (3.15 +/- 0.26 vs. 3.91 +/- 0.24 mIU/ml for LH and 4.25 +/- 0.45 vs. 5.53 +/- 0.40 mIU/ml for FSH; P < 0.05). There was a significant inverse correlation of BMI with FT (r = -0.382; P < 0.01) and T (r = -0.327; P < 0.01). SHBG correlated inversely with BMI (r = -0.267; P < 0.05) but positively with age (r = 0.538; P < 0.001) and T (r = 0.574; P < 0.001). FT correlated strongly with cFT (r = 0.919; P < 0.001) but not with SHBG. LH levels correlated positively with FT (r = 0.287; P < 0.05). We conclude that hypogonadotropic hypogonadism occurs commonly in type 2 diabetes.     

BMS-747158-02: a novel PET myocardial perfusion imaging agent.

BACKGROUND: BMS-747158-02 is a fluorine 18-labeled pyridaben derivative designed as a new myocardial perfusion imaging agent for use with positron emission tomography (PET). This study evaluated BMS-747158-02 in animal models of cardiac perfusion and compared it with established single photon emission computed tomography agents. METHODS AND RESULTS: In a rat biodistribution study, BMS-747158-02 (15 microCi) had substantially higher myocardial uptake than technetium 99m sestamibi (100 microCi) at 15 minutes (3.5% +/- 0.3% %ID/g vs 1.9% +/- 0.1% %ID/g) and 120 minutes (3.2% +/- 0.4% of injected dose per gram vs 1.8% +/- 0.0% of injected dose per gram) after intravenous administration. Uptake ratios of heart to lung and liver at 60 minutes were also higher for BMS-747158-02 (12.7 +/- 1.4 and 3.7 +/- 0.2, respectively) than Tc-99m sestamibi (5.9 +/- 0.5 and 2.4 +/- 0.4, respectively). In an isolated rabbit heart model at flow rates of 1.66 to 5.06 mL x min(-1).g(-1) wet left ventricular weight, the net BMS-747158-02 heart uptake increased proportionally (0.93 +/- 0.15 to 2.44 +/- 0.40 mL.min(-1) x g(-1)) and to a greater extent than that of thallium 201 (0.76 +/- 0.02 to 1.11 +/- 0.02 mL x min(-1) x g(-1)) or Tc-99m sestamibi (0.49 +/- 0.03 to 0.77 +/- 0.08 mL x min(-1) x g(-1)). PET imaging with BMS-747158-02 showed a clear and sustained cardiac uptake in rats, rabbits, and nonhuman primates with minimal lung interference and rapid liver clearance. Myocardial perfusion deficit zones created by either permanent left coronary ligation or reperfusion after ligation in rats were both clearly identified on PET cardiac images of BMS-747158-02 and had good agreement with in vitro histology. CONCLUSIONS: BMS-747158-02 exhibited high and sustained cardiac uptake that was proportional to blood flow, and it represents a new class of PET myocardial perfusion imaging agent.