Abnormalities in autonomic function in obese boys at-risk for insulin resistance and obstructive sleep apnea.

Study objectivesCurrent evidence in adults suggests that, independent of obesity, obstructive sleep apnea (OSA) can lead to autonomic dysfunction and impaired glucose metabolism, but these relationships are less clear in children. The purpose of this study was to investigate the associations among OSA, glucose metabolism, and daytime autonomic function in obese pediatric subjects.MethodsTwenty-three obese boys participated in: overnight polysomnography; a frequently sampled intravenous glucose tolerance test; and recordings of spontaneous cardiorespiratory data in both the supine (baseline) and standing (sympathetic stimulus) postures.ResultsBaseline systolic blood pressure and reactivity of low-frequency heart rate variability to postural stress correlated with insulin resistance, increased fasting glucose, and reduced beta-cell function, but not OSA severity. Baroreflex sensitivity reactivity was reduced with sleep fragmentation, but only for subjects with low insulin sensitivity and/or low first-phase insulin response to glucose.ConclusionsThese findings suggest that vascular sympathetic activity impairment is more strongly affected by metabolic dysfunction than by OSA severity, while blunted vagal autonomic function associated with sleep fragmentation in OSA is enhanced when metabolic dysfunction is also present

Antecedent Hypoglycemia Impairs Autonomic Cardiovascular Function: Implications for Rigorous Glycemic Control

OBJECTIVE— Glycemic control decreases the incidence and progression of diabetic complications but increases the incidence of hypoglycemia. Hypoglycemia can impair hormonal and autonomic responses to subsequent hypoglycemia. Intensive glycemic control may increase mortality in individuals with type 2 diabetes at high risk for cardiovascular complications. We tested the hypothesis that prior exposure to hypoglycemia leads to impaired cardiovascular autonomic function

Widespread depolarization during expiration: A source of respiratory drive?

Respiration influences various pacemakers and rhythms of the body during inspiration and expiration but the underlying mechanisms are relatively unknown. Understanding this phenomenon is important, as breathing disorders, breath holding, and hyperventilation can lead to significant medical conditions. We discuss the physiological modulation of heart rhythm, blood pressure, sympathetic nerve activity, EEG, and other changes observed during inspiration and expiration. We also correlate the intracellular mitochondrial respiratory metabolic processes with real-time breathing and correlate membrane potential changes with inspiration and expiration. We propose that widespread minor hyperpolarization occurs during inspiration and widespread minor depolarization occurs during expiration. This depolarization is likely a source of respiratory drive. Further knowledge of intracellular and extracellular ionic changes associated with respiration will enhance our understanding of respiration and its role as a modulator of cellular membrane potential. This could expand treatment options for a wide range of health conditions, such as breathing disorders, stress-related disorders, and further our understanding of the Hering–Breuer reflex and respiratory sinus arrhythmia

Reduced preabsorptive insulin response in aged rats:differential effects of amphetamine and arginine-vasopressin

The experiments presented here have been designed to investigate whether the age-related attenuation of the vagal reactivity to emotional stressors and its modulation by amphetamine (Amph) or arginine-vasopressin (AVP) can be generalized for other physiological response patterns. We therefore studied the vagal control of the endocrine pancreas during food intake. Young (3 months old) and aged (27 months old) male Wistar rats were provided with permanent cardiac catheters allowing free movement and repeated, stress-free blood sampling. The vagally mediated preabsorptive insulin response (PIR) in relation to food intake as seen in young rats was reduced in aged ones. Blood glucose increments were the same at both ages. Administration of Amph (0.5 mg/kg; s.c.) 30 min before, or AVP (10 µg/kg; s.c.) 60 min before presentation of a test meal led to an elevation of the magnitude of insulin secretion in young rats but reduced the response in aged rats. Moreover, the PIR was not reinstated in aged rats. Blood glucose increments were not influenced by the treatments. The results are interpreted in terms of age-related general reduction of parasympathetic reactivity. The differential effect of amphetamine and AVP treatment on the insulin response suggests that the central aminergic or peptidergic drive of vagal output to the endocrine pancreas is also age-related

Evidence for cardiovascular autonomic dysfunction in foetal programming of hypertension following a maternal high fat or high sucrose diet

Studies support the hypothesis that a maternal high fat (HFD) or high sucrose (HSU) diet during pregnancy is associated with hypertension in offspring due to mechanisms of fetal programming. In this study we tested the programming effect of a HFD and HSU diet on cardiovascular and autonomic responses at rest and in response to dehydration (DS) and air jet (AJ) stress. Pregnant rat dams were placed on a HFD (59% fat), HSU (10%w/v) or control (5% fat) diet. At 6 months the offspring were implanted with telemetry blood pressure transmitters. BP and derived spontaneous baroreflex sensitivity, heart rate variability and BP variability were measured at rest, during DS and during AJ. Offspring from a maternal HF diet show elevated BP at rest compared to controls. In response to AJ and DS, all animals showed an increase in cardiovascular variables, however, the magnitude of increase in cardiovascular variables were similar between groups in both male and female rats. We found limited evidence of altered autonomic function in the HFD rats, despite their higher blood pressure. Offspring from a maternal HSU diet showed no differences in cardiovascular or autonomic responses at rest or in response to either DS or AJ

Effects of Isometric Handgrip Training in Patients With Peripheral Artery Disease: A Randomized Controlled Trial

BackgroundMeta‐analyses have shown that isometric handgrip training (IHT) can reduce brachial systolic and diastolic blood pressure (BP) by >6/4 mm Hg, respectively. However, whether IHT promotes these effects among patients with peripheral artery disease, who exhibit severe impairment in cardiovascular function, is currently unknown. This study aimed to evaluate the effects of IHT on the cardiovascular function of patients with peripheral artery disease. Methods and ResultsA randomized controlled trial with peripheral artery disease patients assigned to either the IHT or control group was conducted. The IHT group performed 3 sessions per week, for 8 weeks, of unilateral handgrip exercises, consisting of 4 sets of isometric contractions for 2 minutes at 30% of maximum voluntary contraction and a 4‐minute interval between sets. The control group received a compression ball in order to minimize the placebo effects, representing sham training. The primary outcome was brachial BP. The secondary outcomes were central BP, arterial stiffness parameters, cardiac autonomic modulation, and vascular function. The IHT program reduced diastolic BP (75 [10] mm Hg preintervention versus 72 [11] mm Hg postintervention), with no change in the control group (74 [11] mm Hg preintervention versus 74 [11] mm Hg postintervention), with this between‐group difference being significant (P=0.04). Flow‐mediated dilation improved in the IHT group (6.0% [5.7] preintervention versus 9.7% [5.5] postintervention), with no change in the control group (7.6% [5.5] preintervention versus 7.4% [5.1] postintervention), with this between‐group difference being significant (P=0.04). There was no change in other measured variables over the intervention period. ConclusionsIHT reduced brachial diastolic BP and improved local vascular function in patients with peripheral artery disease

A preliminary study of brain macrovascular reactivity in impaired glucose tolerance and type-2 diabetes: Quantitative internal carotid artery blood flow using magnetic resonance phase contrast angiography.

OBJECTIVE: The aims of this study were (1) to examine cerebrovascular autoregulation in subjects with impaired glucose tolerance and type 2 diabetes and (2) to clarify whether cardiovascular autonomic nerve function is associated with abnormal cerebrovascular autoregulation. RESEARCH DESIGN AND METHODS: Totally, 46 subjects were recruited (12 = impaired glucose tolerance, 17 = type 2 diabetes and 17 = healthy volunteers). Arterial blood flow was assessed within the internal carotid artery at baseline and 20 min after intravenous pharmacological stress (1 g acetazolamide), using quantitative magnetic resonance phase-contrast angiography. Internal carotid artery vascular reactivity and pulsatility index was determined. All subjects underwent baroreceptor reflex sensitivity assessment. RESULTS: Subjects with impaired glucose tolerance and type 2 diabetes had significantly lower internal carotid artery vascular reactivity [40.2%(19.8) and 41.5%(18.7)], respectively, compared with healthy volunteers [57.0%(14.2); analysis of variance, p = 0.02]. There was no significant difference in internal carotid artery vascular reactivity between type 2 diabetes and impaired glucose tolerance groups (p = 0.84). There was a significant positive correlation between baroreceptor reflex sensitivity (low frequency:high frequency) with cardiac rhythm variability (ρ = 0.47, p = 0.04) and PI (ρ = 0.46, p = 0.04). CONCLUSION: We have demonstrated significant cerebrovascular haemodynamic abnormalities in subjects with type 2 diabetes and impaired glucose tolerance. This was associated with greater sympathovagal imbalance. This may provide an important mechanistic explanation for increased risk of cerebrovascular disease in diabetes. It also highlights that these abnormalities may already be present in prediabetes

Evidence for cardiovascular autonomic dysfunction in foetal programming of hypertension following a maternal high fat or high sucrose diet

Studies support the hypothesis that a maternal high fat (HFD) or high sucrose (HSU) diet during pregnancy is associated with hypertension in offspring due to mechanisms of fetal programming. In this study we tested the programming effect of a HFD and HSU diet on cardiovascular and autonomic responses at rest and in response to dehydration (DS) and air jet (AJ) stress. Pregnant rat dams were placed on a HFD (59% fat), HSU (10%w/v) or control (5% fat) diet. At 6 months the offspring were implanted with telemetry blood pressure transmitters. BP and derived spontaneous baroreflex sensitivity, heart rate variability and BP variability were measured at rest, during DS and during AJ. Offspring from a maternal HF diet show elevated BP at rest compared to controls. In response to AJ and DS, all animals showed an increase in cardiovascular variables, however, the magnitude of increase in cardiovascular variables were similar between groups in both male and female rats. We found limited evidence of altered autonomic function in the HFD rats, despite their higher blood pressure. Offspring from a maternal HSU diet showed no differences in cardiovascular or autonomic responses at rest or in response to either DS or AJ

Emotional orienting during interoceptive threat in orthostatic intolerance: dysautonomic contributions to psychological symptomatology in the postural tachycardia syndrome and vasovagal syncope

Cognitive and emotional processes are influenced by interoception (homeostatic somatic feedback), particularly when physiological arousal is unexpected and discrepancies between predicted and experienced interoceptive signals may engender anxiety. Due to the vulnerability for comorbid psychological symptoms in forms of orthostatic intolerance (OI), this study investigated psychophysiological contributions to emotional symptomatology in 20 healthy control participants (13 females, mean age 36 ± 8 years), 20 postural tachycardia syndrome (PoTS) patients (18 females, mean age 38 ± 13 years) and 20 vasovagal syncope (VVS) patients (15 females, mean age 39 ± 12 years). We investigated indices of emotional orienting responses (OR) to randomly presented neutral, pleasant and unpleasant images in the supine position and during the induced interoceptive threat of symptom provocation of head-up tilt (HUT). PoTS and VVS patients produced greater indices of emotional responsivity to unpleasant images and, to a lesser degree, pleasant images, during interoceptive threat. Our findings are consistent with biased deployment of response-focused emotion regulation (ER) while patients are symptomatic, providing a mechanistic underpinning of how pathological autonomic overexcitation predisposes to anxiogenic traits in PoTS and VVS patients. This hypothesis may improve our understanding of why orthostasis exacerbates cognitive symptoms despite apparently normal cerebral autoregulation, and offer novel therapeutic targets for behavioural interventions aimed at reducing comorbid cognitive-affective symptoms in PoTS and VVS