1.
Preserved Autonomic Cardiovascular Regulation With Cardiac Pacemaker Inhibition: A Crossover Trial Using High-Fidelity Cardiovascular Phenotyping.
Heusser, K, Tank, J, Brinkmann, J, Schroeder, C, May, M, Großhennig, A, Wenzel, D, Diedrich, A, Sweep, FC, Mehling, H, et al
Journal of the American Heart Association. 2016;(1)
Abstract
BACKGROUND Sympathetic and parasympathetic influences on heart rate (HR), which are governed by baroreflex mechanisms, are integrated at the cardiac sinus node through hyperpolarization-activated cyclic nucleotide-gated channels (HCN4). We hypothesized that HCN4 blockade with ivabradine selectively attenuates HR and baroreflex HR regulation, leaving baroreflex control of muscle sympathetic nerve activity intact. METHODS AND RESULTS We treated 21 healthy men with 2×7.5 mg ivabradine or placebo in a randomized crossover fashion. We recorded electrocardiogram, blood pressure, and muscle sympathetic nerve activity at rest and during pharmacological baroreflex testing. Ivabradine reduced normalized HR from 65.9±8.1 to 58.4±6.2 beats per minute (P<0.001) with unaffected blood pressure and muscle sympathetic nerve activity. On ivabradine, cardiac and sympathetic baroreflex gains and blood pressure responses to vasoactive drugs were unchanged. Ivabradine aggravated bradycardia during baroreflex loading. CONCLUSIONS HCN4 blockade with ivabradine reduced HR, leaving physiological regulation of HR and muscle sympathetic nerve activity as well as baroreflex blood pressure buffering intact. Ivabradine could aggravate bradycardia during parasympathetic activation. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00865917.
2.
Exercise training improves baroreflex sensitivity in type 2 diabetes.
Loimaala, A, Huikuri, HV, Kööbi, T, Rinne, M, Nenonen, A, Vuori, I
Diabetes. 2003;(7):1837-42
Abstract
Type 2 diabetes is a strong risk factor for coronary heart disease and sudden cardiac death. It is associated with reduced baroreflex sensitivity (BRS) and heart rate variability (HRV), which are indicators of increased risk for mortality and morbidity in various patient populations. This study was designed to assess the effects of exercise training on BRS, HRV, and hemodynamics in patients with type 2 diabetes. Subjects (50 men, mean age 53.3 +/- 5.1 years) with type 2 diabetes were randomized into either a control group, in which they received conventional treatment only, or an exercise group, in which they received conventional treatment together with heart rate-controlled endurance training twice a week and supervised muscle strength training twice a week for 12 months. Measurements taken at baseline and follow-up included VO(2max), standard time and frequency domain measures of HRV during 24-h recording, and BRS by the phenylephrine method. Cardiac index, systemic vascular resistance index, stroke index, and pulse wave velocity were measured by whole-body impedance cardiography. Significant improvements in VO(2max) (exercise group: +2.3 ml x kg(-1) x min(-1); P < 0.005 vs. control group), muscle strength, and glycemic control (exercise group: HbA(1c) -0.9%; P < 0.001 vs. control group) were observed in the exercise group. BRS increased in the exercise group, from 6.8 to 8.6 ms/mmHg, and decreased in the control group, from 7.5 to 6.4 ms/mmHg (95% CI for the difference between 0.05 and 4.36 ms/mmHg; P < 0.05). No significant changes in the time or frequency domain measures of HRV or in systemic hemodynamics were observed. We concluded that exercise training improves BRS sensitivity in type 2 diabetes subjects in addition to increasing the exercise capacity and muscle strength and improving glucose control. These beneficial effects in reflectory autonomic regulation and glucose control caused by exercise may be associated with improved prognosis of type 2 diabetes patients.