Determination of the kinetic and thermodynamic properties for bisulfite addition to: acetophenone, 2-chloroacetophenone and trans-cinnamaldehyde

The equilibrium constants for bisulfite addition to acetophenone, 2-choloroacetophenone and trans-cinnamaldehyde were determined using an ultraviolet spectrophotometric method. The absorbance of the carbonyl compound was monitored as aliquots of a bisulfite solution were added to the reaction cell. By plotting 1/A versus [HSO3-], and dividing the slope by the intercept, it was possible to determine Keq. All determinations were made at pH 4.66 and ionic strength 1.0. By determining Keq at various temperatures it was also possible to determine ΔH° and ΔS°. The equilibrium constants for bisulfite addition to: acetophenone, 2-choloracetophenone and trans-cinnamaldehyde, were determined to be: 5.8 M-1, 53 M-1, and 1030 M-1 respectively. The rate constants for bisulfite addition to trans-cinnamaldehyde were also determined using an ultraviolet spectrophotometric method. The change in absorbance, after the addition of bisulfite, was monitored at one second intervals for fifteen minutes. The forward and reverse rate constants for bisulfite addition to trans-cinnamaldehyde were determined to be, 24.3 M-1 s-1 and 2.4x10-2 s-1 respectively

Chronotropic incompetence predicts mortality in severe obstructive pulmonary disease

We evaluated the prevalence of chronotropic incompetence (CI), a marker of autonomic dysfunction, and its prognostic value in patients with chronic obstructive pulmonary disease (COPD). We performed a retrospective analysis of 449 patients with severe COPD who underwent a cardiopulmonary exercise test, after excluding patients with lung volume reduction surgery, left ventricular dysfunction and those not in sinus rhythm. CI was defined as percent predicted heart rate reserve (%HRR). Events were defined as death or lung transplant during a median follow-up of 68 months. Median age was 61 years; median percent predicted forced expiratory volume in one second (%FEV1) of 25% and median %HRR of 33%. The hazard ratio for an event in the lowest quartile of %HRR, taking the highest quartile as reference, was of 3.2 (95% confidence interval: 2.1-4.8; p < 0.001). In a multivariate regression model, %HRR was an independent predictor of events. In conclusion, Cl was an independent and powerful outcome predictor in patients with severe COPD. (C) 2013 Elsevier B.V. All rights reserved

Chronotropic incompetence predicts mortality in severe obstructive pulmonary disease

We evaluated the prevalence of chronotropic incompetence (CI), a marker of autonomic dysfunction, and its prognostic value in patients with chronic obstructive pulmonary disease (COPD). We performed a retrospective analysis of 449 patients with severe COPD who underwent a cardiopulmonary exercise test, after excluding patients with lung volume reduction surgery, left ventricular dysfunction and those not in sinus rhythm. CI was defined as percent predicted heart rate reserve (%HRR). Events were defined as death or lung transplant during a median follow-up of 68 months. Median age was 61 years; median percent predicted forced expiratory volume in one second (%FEV1) of 25% and median %HRR of 33%. The hazard ratio for an event in the lowest quartile of %HRR, taking the highest quartile as reference, was of 3.2 (95% confidence interval: 2.1-4.8; p < 0.001). In a multivariate regression model, %HRR was an independent predictor of events. In conclusion, Cl was an independent and powerful outcome predictor in patients with severe COPD. (C) 2013 Elsevier B.V. All rights reserved

Cardiac myosin activation with omecamtiv mecarbil in systolic heart failure

BACKGROUND The selective cardiac myosin activator omecamtiv mecarbil has been shown to improve cardiac function in patients with heart failure with a reduced ejection fraction. Its effect on cardiovascular outcomes is unknown. METHODS We randomly assigned 8256 patients (inpatients and outpatients) with symptomatic chronic heart failure and an ejection fraction of 35% or less to receive omecamtiv mecarbil (using pharmacokinetic-guided doses of 25 mg, 37.5 mg, or 50 mg twice daily) or placebo, in addition to standard heart-failure therapy. The primary outcome was a composite of a first heart-failure event (hospitalization or urgent visit for heart failure) or death from cardiovascular causes. RESULTS During a median of 21.8 months, a primary-outcome event occurred in 1523 of 4120 patients (37.0%) in the omecamtiv mecarbil group and in 1607 of 4112 patients (39.1%) in the placebo group (hazard ratio, 0.92; 95% confidence interval [CI], 0.86 to 0.99; P = 0.03). A total of 808 patients (19.6%) and 798 patients (19.4%), respectively, died from cardiovascular causes (hazard ratio, 1.01; 95% CI, 0.92 to 1.11). There was no significant difference between groups in the change from baseline on the Kansas City Cardiomyopathy Questionnaire total symptom score. At week 24, the change from baseline for the median N-terminal pro-B-type natriuretic peptide level was 10% lower in the omecamtiv mecarbil group than in the placebo group; the median cardiac troponin I level was 4 ng per liter higher. The frequency of cardiac ischemic and ventricular arrhythmia events was similar in the two groups. CONCLUSIONS Among patients with heart failure and a reduced ejection, those who received omecamtiv mecarbil had a lower incidence of a composite of a heart-failure event or death from cardiovascular causes than those who received placebo. (Funded by Amgen and others; GALACTIC-HF ClinicalTrials.gov number, NCT02929329; EudraCT number, 2016 -002299-28.)