Results, meta-analysis and a first evaluation of UNOxR, the urinary nitrate-to-nitrite molar ratio, as a measure of nitrite reabsorption in experimental and clinical settings

Diabetes mellitus: pathophysiological changes and therap

Effect of normobaric hypoxic exercise on blood pressure in old individuals

Purpose: To test the hypothesis that the combination of endurance training and hypoxia leads to greater improvements in resting and exercise blood pressure in old sedentary individuals compared to endurance training only. Methods: We randomly assigned 29 old overweight participants (age: 62 ± 6 years, body mass index (BMI): 28.5 ± 0.5 kg/m2, 52% men) to single blind 8-week bicycle exercise in hypoxia (fraction of inspired oxygen (FIO2) = 0.15) or normoxia (FIO2 = 0.21). Brachial blood pressure was measured at rest, during maximal incremental exercise testing, and during a 30 min constant work rate test, at baseline and after the training period. Results: Work rate, heart rate and perceived exertion during training were similar in both groups, with lower oxygen saturation for participants exercising under hypoxia (88.7 ± 1.5 vs. 96.2 ± 1.2%, t(27) = - 13.04, p < 0.001, |g|= 4.85). Office blood pressure and blood pressure during incremental exercise tests did not change significantly in either group after the training program. Systolic blood pressure during the constant work rate test was reduced after training in hypoxia (160 ± 18 vs. 151 ± 14 mmHg, t(13) = 2.44 p < 0.05, |d|= 0.55) but not normoxia (154 ± 22 vs. 150 ± 16 mmHg, t(14) = 0.75, p = 0.46, |d|= 0.18) with no difference between groups over time (F = 0.08, p = 0.77, η2 = 0.01). Conclusion: In old individuals hypoxia in addition to exercise does not have superior effects on office or exercise blood pressure compared to training in normoxia

Cardiac pacemaker channel (HCN4) inhibition and atrial arrhythmogenesis after releasing cardiac sympathetic activation

Clinical trials and studies with ivabradine implicate cardiac pacemaker channels (HCN4) in the pathogenesis of atrial arrhythmias. Because acute changes in cardiac autonomic tone predispose to atrial arrhythmias, we studied humans in whom profound cardiac sympathetic activation was rapidly relieved to test infuences of HCN4 inhibition with ivabradine on atrial arrhythmias. We tested 19 healthy participants with ivabradine, metoprolol, or placebo in a double blind, randomized, cross-over fashion on top of selective norepinephrine reuptake inhibition with reboxetine. Subjects underwent combined head up tilt plus lower body negative pressure testing followed by rapid return to the supine position. In the current secondary analysis with predefned endpoints before data unblinding, continuous fnger blood pressure and ECG recordings were analyzed by two experienced cardiac electrophysiologists and a physician, blinded for treatment assignment. The total atrial premature activity (referred to as atrial events) at baseline did not difer between treatments. After backwards tilting, atrial events were signifcantly higher with ivabradine compared with metoprolol or with placebo. Unlike beta-adrenoreceptor blockade, HCN4 inhibition while lowering heart rate does not protect from atrial arrhythmias under conditions of experimental cardiac sympathetic activation. The model in addition to providing insight in the role of HCN4 in human atrial arrhythmogenesis may have utility in gauging potential atrial pro-arrhythmic drug properties