Small Increase In Heart Rate Research Articles

Alleviation of physiological stress response by apple aroma

ABSTRACT Objective The study evaluated the potential of apple aroma to alleviate physiological stress response induced by a short-term cognitive stressor. It investigated the effects of apple aroma on cardiac and peripheral autonomic nervous system activity under stressful conditions. Methods Within-subject experiments were conducted with 25 healthy male university students with a 30-minute calculation task under three conditions: Apple, Chamomile (CHA), and Di propylene glycol (DPG) (scentless air). The aroma administration was precisely controlled and counterbalanced. Cardiac activity on electrocardiograms and nose tip temperature were recorded throughout the experiment. A visual analog scale and a scent questionnaire were subjective measures. Results Apple aroma demonstrated a significantly smaller increase in heart rate (t [24] = 3.36, p = 0.008 vs. DPG, t [24] = 4.06, p = 0.001 vs. CHA), and a decrease in the high-frequency component of heart rate variability (t [24] = 2.81, p = 0.029 vs. DPG, t [24] = 3.48, p = 0.006 vs. CHA) compared to the other conditions, representing a smaller enhancement of cardiac sympathetic nervous system activity and smaller suppression of cardiac parasympathetic nervous system activity respectively. Conclusion Apple aroma showed efficacy in alleviating the physiological stress response in terms of cardiac activity. Apple was also considered significantly preferable and comfortable compared to the other conditions, which would be beneficial in the context of aromatherapy.

Abstract 66: Early-Life Sodium Restriction Programs Salt-Sensitivity of Autonomics and Blood Pressure in Adult C57BL/6J Mice

Extremely premature birth is a risk factor for sodium (Na) depletion due to renal immaturity and urine Na losses. We have proposed that Na depletion in preterm infants mechanistically contributes to their increased risk for cardiovascular and metabolic disease observed in adulthood, potentially due to changes during hypothalamic development. In humans, the hypothalamus matures between 20-25 weeks of gestation; in mice, this developmental window occurs between postnatal day (PD) 21 and PD42. Previously, we demonstrated in mice that dietary Na restriction from PD21 to PD42 induced long-lasting increases in energy expenditure via exaggerated autonomic activity. Therefore, we hypothesized that restricting dietary Na from PD21 to PD42 would similarly induce programmed changes in cardiovascular control via changes in autonomic and neurohypophyseal functions. Male C57BL/6J mice were provided a customized low (0.04%, n=7) or supplemented (0.30%, n=8) Na version of the soy protein-free Teklad 2920x diet from PD21 to PD42, after which they were returned to the standard (0.15% Na) 2920x diet. Radiotelemetric blood pressure (BP) transducers were implanted at 7-8 weeks of age. At 10 weeks of age, no differences in BP or heart rate (HR) were noted between groups. All animals were switched to a high (1%) Na diet at 12 weeks of age. At 16 weeks of age, systolic BP was not altered in the 0.30% Na group but significantly increased in the 0.04% Na group compared to the week 10 baseline (24h avg: +6±2 mmHg, p<0.05). Ganglionic block with chlorisondamine or β-adrenergic block with propranolol reduced heart rate (HR) to a greater extent (each p<0.05) in the 0.04% group. Conversely, muscarinic block with atropine resulted in a smaller increase in HR in this group (p<0.05). Urine elimination rates of aldosterone (0.30%: 1.96±0.44 vs 0.04%: 2.92±0.064 ng/d) and copeptin (0.30%: 0.16±0.03 vs. 0.04%: 0.14±0.02 ng/d) were similar between groups. Finally, at 18 weeks of age, all mice received the angiotensin AT 1 R antagonist losartan in drinking water. This caused a greater BP reduction in the 0.04% group at 20 weeks (24h avg: -12±2 vs -19±2 mmHg, p<0.05). Together, these data indicate that dietary Na restriction during hypothalamic development programs increased salt sensitivity of BP via a mechanism involving AT 1 R and characterized by increased sympathetic yet decreased parasympathetic activity.

Changes in standard of care (SOC) medication during long-term mavacamten treatment for obstructive hypertrophic cardiomyopathy (HCM): results from the EXPLORER cohort of MAVA-Long-Term Extension (LTE)

Abstract Introduction Mavacamten is efficacious and well tolerated in patients with obstructive HCM in the ongoing MAVA-LTE study (NCT03723655) as shown in previous interim analyses. Here, we present exploratory data from the EXPLORER cohort of MAVA-LTE investigating the effect of changes in SOC treatment on the efficacy and safety of mavacamten. Methods Patients who completed EXPLORER-HCM (NCT03470545) could enroll in MAVA-LTE and comprised the EXPLORER cohort. All patients in the EXPLORER cohort received mavacamten. Patients could receive beta blockers or nondihydropyridine calcium channel blockers (verapamil/diltiazem) as SOC treatment. After 24 weeks on study, SOC treatment could be adjusted. A cumulative interim analysis (data cut-off: May 31, 2022) was performed on patients who: received no SOC, discontinued SOC, had any reduction in SOC and had ≥50% reduction in SOC from baseline to data cut-off. Results In total, 231 patients (mean age, 60 years; 39% female) comprised the EXPLORER-LTE cohort (median time on study: 101 weeks at data cut-off). At baseline, 176 patients (76.2%) received beta blockers and 38 (16.5%) received nondihydropyridine calcium channel blockers. At data cut-off, 12 (5.2%) patients had received no SOC treatment from baseline, 11 (4.8%) patients had discontinued SOC, 27 (11.7%) patients had any dose reduction in SOC, 18 (7.8%) patients had a ≥50% reduction in SOC and 14 (6.1%) patients had an increase in SOC. In the no SOC subgroup, mavacamten treatment was associated with improvements from baseline to last visit in resting and Valsalva left ventricular outflow tract (LVOT) gradients, left atrial volume index (LAVI), and N-terminal pro B-type natriuretic peptide (NT-proBNP) levels (Table 1). Improvements in these parameters were also observed in the SOC discontinuation and SOC dose reduction subgroups (Table 1). In the SOC discontinuation subgroup, improvements in resting and Valsalva LVOT gradients, LAVI, and NT-proBNP levels from baseline were maintained after SOC discontinuation (Table 1). SOC medications were discontinued or reduced over a mean (range) period of 63 (9–96) and 62 (3–133) weeks, respectively. At data cut-off, left ventricular ejection fraction remained within the normal range for all patients regardless of the SOC subgroup. Patients who reduced SOC medication had small increases in heart rate (within normal range) from baseline to last visit (Table 2). Overall, blood pressure remained stable across subgroups throughout the observation period (Table 2). No patients experienced worsening of NYHA class from baseline to last visit or from withdrawal to last visit. Conclusions Beneficial and sustained effects on LVOT obstruction, NT-proBNP levels and symptoms in patients with symptomatic obstructive HCM were observed with long-term mavacamten treatment alone or after SOC discontinuation or dose reduction.

PDE4D mediates impaired β-adrenergic receptor signalling in the sinoatrial node in mice with hypertensive heart disease.

The sympathetic nervous system increases HR by activating β-adrenergic receptors (β-ARs) and increasing cAMP in sinoatrial node (SAN) myocytes while phosphodiesterases (PDEs) degrade cAMP. Chronotropic incompetence, the inability to regulate heart rate (HR) in response to sympathetic nervous system activation, is common in hypertensive heart disease; however, the basis for this is poorly understood. The objective of this study was to determine the mechanisms leading to chronotropic incompetence in mice with angiotensin II (AngII)-induced hypertensive heart disease. C57BL/6 mice were infused with saline or AngII (2.5 mg/kg/day for 3 weeks) to induce hypertensive heart disease. HR and SAN function in response to the β-AR agonist isoproterenol (ISO) were studied in vivo using telemetry and electrocardiography, in isolated atrial preparations using optical mapping, in isolated SAN myocytes using patch-clamping, and using molecular biology. AngII-infused mice had smaller increases in HR in response to physical activity and during acute ISO injection. Optical mapping of the SAN in AngII-infused mice demonstrated impaired increases in conduction velocity and altered conduction patterns in response to ISO. Spontaneous AP firing responses to ISO in isolated SAN myocytes from AngII-infused mice were impaired due to smaller increases in diastolic depolarization (DD) slope, hyperpolarization-activated current (If), and L-type Ca2+ current (ICa,L). These changes were due to increased localization of PDE4D surrounding β1- and β2-ARs in the SAN, increased SAN PDE4 activity, and reduced cAMP generation in response to ISO. Knockdown of PDE4D using a virus-delivered shRNA or inhibition of PDE4 with rolipram normalized SAN sensitivity to β-AR stimulation in AngII-infused mice. AngII-induced hypertensive heart disease results in impaired HR responses to β-AR stimulation due to up-regulation of PDE4D and reduced effects of cAMP on spontaneous AP firing in SAN myocytes.

Management of severe hypotension in a dog undergoing transvenous pacemaker implantation following acepromazine and subsequent terbutaline administration

AbstractThis case report describes events that occurred under general anaesthesia of a dog undergoing transvenous pacemaker implantation for third‐degree atrioventricular block. Following premedication with acepromazine and buprenorphine, general anaesthesia was induced with alfaxalone, and maintained with isoflurane in oxygen. The dog developed severe hypotension during the procedure with concurrent bradycardia before commencement of pacing. In order to increase the heart rate, terbutaline was administered intravenously. This was followed by a worsening of the hypotension, with only a small increase in heart rate. Blood pressure improved following noradrenaline infusion. The animal recovered uneventfully in intensive care, and was sedated due to its anxious temperament to avoid dislodgement of the pacemaker device in the postoperative period.

Differential regulation of sympathetic neural burst frequency and amplitude throughout normal pregnancy: a longitudinal study.

Sympathetic activation is a hallmark of pregnancy. However, longitudinal assessments of muscle sympathetic nerve activity (MSNA) in pregnancy are scarce and have primarily focused on burst occurrence (frequency) at rest, despite burst strength (amplitude) representing distinct characteristics of sympathetic outflow. Thus, we assessed MSNA burst amplitude distributions in healthy women to determine the impact of normal pregnancy on neural discharge patterns in response to orthostatic stress. Twenty-six women were studied longitudinally during pre-, early- (4-8 wk of gestation), and late (32-36 wk) pregnancy, as well as postpartum (6-10 wk after delivery). MSNA, blood pressure (BP), and heart rate (HR) were measured in the supine posture and during graded head-up tilt (30° and 60° HUT). Mean and median MSNA burst amplitudes were used to characterize burst amplitude distribution. In late pregnancy, women demonstrated smaller increases in HR (P < 0.001) during 60° HUT and larger increases in systolic BP (P = 0.043) throughout orthostasis, compared with prepregnancy. The increase in MSNA burst frequency during late- relative to prepregnancy (Late: Δ14[10] vs. Pre: Δ21[9] bursts/min; P = 0.001) was smaller during 60° HUT, whereas increases in burst incidence were smaller in late- relative to prepregnancy throughout orthostasis (P = 0.009). Nonetheless, median burst amplitude was smaller throughout orthostasis in late compared with prepregnancy (P = 0.038). Thus, while supine MSNA burst frequency was greater in late pregnancy, increases in burst frequency and strength during orthostasis were attenuated. These smaller, orthostatically induced MSNA increases may reflect natural adaptions of pregnancy serving to prevent sympathetic hyper-reactivity that is common in pathological states.

Sympathoexcitatory Responses to Isometric Handgrip Exercise Are Associated With White Matter Hyperintensities in Middle-Aged and Older Adults.

Vascular dysfunction may occur prior to declines in cognitive function and accumulation of neuropathology. White matter hyperintensities (WMH) develop due to cerebral ischemia and elevated blood pressure in midlife. The purpose of this study was to evaluate associations between cardiovascular and cerebrovascular responses to sympathoexcitatory stimuli and WMH burden in cognitively unimpaired middle-aged and older adults. Sixty-eight adults (age = 63 ± 4y, men = 20, women = 48) participated in this study. Participants completed isometric handgrip exercise (IHG) exercise at 40% of maximal voluntary contraction until fatigue followed by a 90s period of post-exercise ischemia. Heart rate (HR), mean arterial pressure (MAP), middle cerebral artery blood velocity (MCAv), and end-tidal CO2 were continuously measured throughout the protocol. Cerebrovascular resistance index (CVRi) was calculated as MAP/MCAv. WMH lesion volume and intracranial volume (ICV) were measured using a FLAIR and T1 scan on a 3T MRI scanner, respectively. WMH fraction was calculated as (WMH lesion volume/ICV)*100 and cubic root transformed. Multiple linear regressions were used to determine the association between cardiovascular and cerebrovascular responses to IHG exercise and post-exercise ischemia and WMH fraction. Multiple linear regression models were adjusted for age, sex, apolipoprotein ε4 status, and total work performed during IHG exercise. During IHG exercise, there were significant increases from baseline in HR (25 ± 12%), MAP (27 ± 11%), MCAv (5 ± 10%), and CVRi (22 ± 17%; P < 0.001 for all). During post-exercise ischemia, HR (8 ± 7%), MAP (22 ± 9%), and CVRi (23 ± 16%) remained elevated (P < 0.001) while MCAv (0 ± 10%) was not different compared to baseline. There was an inverse association between the percent change in HR (r = −0.42, P = 0.002), MAP (r = −0.41, P = 0.002), and CVRi (r = −0.31, P = 0.045), but not MCAv (r = 0.19, P = 0.971) in response to IHG exercise and WMH fraction. There were no associations between responses to post-exercise ischemia and WMH fraction. Lower sympathoexcitatory responses to IHG exercise are associated with greater WMH burden in middle-aged to older adults. These findings suggest that individuals who demonstrate smaller increases in HR, MAP, and CVRi in response to sympathoexcitatory stress have greater WMH burden.

Hypoglycaemia combined with mild hypokalaemia reduces the heart rate and causes abnormal pacemaker activity in a computational model of a human sinoatrial cell.

Low blood glucose, hypoglycaemia, has been implicated as a possible contributing factor to sudden cardiac death (SCD) in people with diabetes but it is challenging to investigate in clinical studies. We hypothesized the effects of hypoglycaemia on the sinoatrial node (SAN) in the heart to be a candidate mechanism and adapted a computational model of the human SAN action potential developed by Fabbri et al., to investigate the effects of hypoglycaemia on the pacemaker rate. Using Latin hypercube sampling, we combined the effects of low glucose (LG) on the human ether-a-go-go-related gene channel with reduced blood potassium, hypokalaemia, and added sympathetic and parasympathetic stimulus. We showed that hypoglycaemia on its own causes a small decrease in heart rate but there was also a marked decrease in heart rate when combined with hypokalaemia. The effect of the sympathetic stimulus was diminished, causing a smaller increase in heart rate, with LG and hypokalaemia compared to normoglycaemia. By contrast, the effect of the parasympathetic stimulus was enhanced, causing a greater decrease in heart rate. We therefore demonstrate a potential mechanistic explanation for hypoglycaemia-induced bradycardia and show that sinus arrest is a plausible mechanism for SCD in people with diabetes.

Cardiovascular Risk in Users of Mirabegron Compared with Users of Antimuscarinic Treatments for Overactive Bladder: Findings from a Non-Interventional, Multinational, Cohort Study.

IntroductionDuring clinical trials, mirabegron, a β3-adrenoreceptor agonist, was associated with increased vital signs vs placebo in patients with overactive bladder.ObjectiveThe purpose of this study was to compare incidence rates of adverse cardiovascular (CV) outcomes following mirabegron or antimuscarinic use.MethodsWe conducted an observational post-marketing safety study utilising real-world data. The study population was identified within five sources: Danish and Swedish National Registers, Clinical Practice Research Datalink (UK), Optum (USA) and Humana (USA). Episodes of time when patients were new users of mirabegron or antimuscarinics (October 2012–December 2018) were sourced from prescriptions and matched on propensity scores. Occurrences of major adverse cardiovascular events (MACE), acute myocardial infarction (AMI), stroke, CV mortality and all-cause mortality were identified. Outcome incidence rates and hazard ratios from Cox models were estimated.ResultsOverall, 152,026 mirabegron and 152,026 antimuscarinic episodes were matched. The population consisted of 63.1% women and 72.6% were ≥ 65 years old. There were no appreciable differences in the incidence rates of MACE, AMI or stroke between users of mirabegron and antimuscarinics. Incidence rates of CV mortality (hazard ratio 0.83, 95% confidence interval 0.73–0.95) and all-cause mortality (hazard ratio 0.80, 95% confidence interval 0.76–0.84) were no higher with mirabegron vs antimuscarinics. Results restricted to episodes at high risk for CV events or stratified by age (< 65 years, ≥ 65 years) or prior overactive bladder medication use were consistent with overall findings.ConclusionsThis large, multinational study found no higher risk of MACE, AMI, stroke, CV mortality or all-cause mortality among users of mirabegron relative to users of antimuscarinics.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40264-021-01095-7.

Determinants and consequences of heart rate and stroke volume response to exercise in patients with heart failure and preserved ejection fraction

A hallmark of heart failure with preserved ejection fraction (HFpEF) is impaired exercise capacity of varying severity. The main determinant of exercise capacity is cardiac output (CO), however little information is available about the relation between the constituents of CO-heart rate and stroke volume-and exercise capacity in HFpEF. We sought to determine if a heterogeneity in heart rate and stroke volume response to exercise exists in patients with HFpEF and describe possible clinical phenotypes associated with differences in these responses. Data from two prospective trials of HFpEF (n=108) and a study of healthy participants (n=42) with invasive haemodynamic measurements during exercise were utilized. Differences in central haemodynamic responses were analysed with regression models. Chronotropic incompetence was present in 39-56% of patients with HFpEF and 3-56% of healthy participants depending on the definition used, but some (n=47, 44%) had an increase in heart rate similar to that of healthy controls. Patients with HFpEF had a smaller increase in their stroke volume index (SVI) (HFpEF: +4 ± 10 mL/m2 , healthy participants: +24 ± 12 mL/m2 , P < 0.0001), indeed, SVI fell in 28% of patients at peak exercise. Higher body mass index and lower SVI at rest were associated with smaller increases in heart rate during exercise, whereas higher resting heart rate, and angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker use were associated with a greater increase in SVI in patients with HFpEF. The haemodynamic response to exercise was very heterogeneous among patients with HFpEF, with chronotropic incompetence observed in up to 56%, and 28% had impaired increase in SVI. This suggests that haemodynamic exercise testing may be useful to identify which HFpEF patients may benefit from interventions targeting stroke volume and chronotropic response.

PHYSIOLOGICAL AND ANXIETY RESPONSES TO SOCIALLY PRESCRIBED PERFECTIONISM FOR GYMNASTIC COMPETITION: CASE STUDY

The purpose of this study was to analyze the psychophysiological responses (anxiety, cortisol, heart rate, skin conductance) to acute psychological stress during a visualization of competition, under the influence of pressure for perfection exerted by parents, and pressure for perfection exercised by the coach. Artistic gymnasts (3 men and 3 women) with an age range of 13 to 15 years participated, who were present in four sessions for data collection that included salivary cortisol, heart rate and skin conductance. The first session was the baseline, where we apply a booklet of questionnaires that inquire about competitive anxiety and pressure for perfection. The remaining three sessions included guided viewing; session two to create mental images and live the gymnastic competition; the third highlights the pressure for perfection created by the coach (PPE); and the fourth highlights the pressure for perfection created by parents (PPP). The results showed that the visualization of competitive situation causes stress and anxiety, although the increase in salivary cortisol was within the normal daytime level. The physiological changes were greater in those gymnasts who perceived high PPE and PPP. However, for some gymnasts the situation was considered threatening (decrease in skin conductance, and small increases in heart rate), and for others was challenging (increase in skin conductance and heart rate). In conclusion, the pressure for perfection integrates a link for the different physiological responses in competition.

Virtual reality exposure therapy for adolescents with fear of public speaking: a non-randomized feasibility and pilot study

BackgroundPublic Speaking Anxiety (PSA) is a common anxiety with onset in adolescence and early adulthood. With the advent of consumer virtual reality (VR) technology, VR-delivered exposure therapy is now a scalable and practical treatment option and has previously been shown to be efficacious with adults. In this non-randomized feasibility and pilot trial, we explore the effect of one-session (90 min) VR-delivered exposure therapy for adolescents (aged 13–16) with PSA.MethodsA total of 27 adolescents were recruited from Norwegian high schools and completed self-report measures of PSA twice prior to treatment, 1 week after treatment, and at 1 and 3 month follow-up. Heart rate was recorded during the treatment session. A low-cost head-mounted VR display with a custom-built VR stimuli material depicting a cultural and age appropriate classroom and audience were used when a series of speech (exposure exercises) were performed.ResultsLinear mixed effects model revealed a significant decrease in PSA symptoms (Cohen’s d = 1.53) pre-post treatment, and improvements were maintained at follow-ups. Physiological data revealed a small increase in heart rate during exposure tasks. Based on feedback from the adolescents, the feasibility of the intervention was increased during the trial.ConclusionsThe results show that low-cost, consumer VR hardware can be used to deliver efficacious treatment for PSA in adolescents, in a feasible one-session format.

Efficacy of atropine sulfate/obidoxime chloride co-formulation against sarin exposure in guinea pigs

The efficacy and pharmacokinetics of the aqueous co-formulation contents of the Trobigard™ (atropine sulfate, obidoxime chloride) auto-injector were evaluated in a sarin exposed guinea pig model. Two subcutaneous (sc) sarin challenge doses were evaluated in guinea pigs instrumented with brain and heart electrodes for electroencephalogram (EEG) and electrocardiogram (ECG). Sarin challenge doses were chosen to reflect exposure subclasses with sublethal (moderate to severe clinical signs) and lethal consequences. The level of protection of intramuscular human equivalent doses of the co-formulation was defined by (1) the mitigation of signs and symptoms at a sublethal level and (2) the increase of survival time at the supralethal sarin dose levels.Pharmacokinetics of both atropine sulfate and obidoxime were proportional at 1 and 3 human equivalent doses, and only a small increase in heart rate was observed briefly as a side effect.At both sarin challenge doses, 54 μg/kg and 84 μg/kg, the co-formulation treatment was effective against sarin-induced effects. Survival rates were improved at both sarin challenge levels, whereas clinical signs and changes in EEG activity could not in all cases be effectively mitigated, in particular at the supralethal sarin challenge dose level. Reactivation of sarin inhibited cholinesterase was observed in blood, and higher brain cholinesterase activity levels were associated with a better clinical condition of the co-formulation treated animals.Although the results cannot be directly extrapolated to the human situation, pharmacokinetics and the effects over time related to plasma levels of therapeutics in a freely moving guinea pig could aid translational models and possibly improve prediction of efficacy in humans.

Abstract P393: Orthostatic Heart Rate-Blood Pressure Relationship Identifies Neurogenic Orthostatic Hypotension

Background: Neurogenic orthostatic hypotension (nOH) is a chronic disabling condition associated with significant morbidity and mortality. Currently, the diagnosis of nOH relies on impaired autonomic reflexes as determined by testing available only in specialized centers. Our objective was to test the hypothesis that a blunted heart rate (HR) increase in response to a given systolic blood pressure (SBP) fall will correctly diagnose nOH. Methods: We performed a retrospective study of nOH patients (studied in an inpatient environment off medications that can interfere with autonomic function) and control subjects. nOH was diagnosed on the basis of SBP fall ≥20 mmHg on standing associated with a decrease in SBP≥ 20 mmHg during phase 2 of the Valsalva maneuver and absence of phase 4 SBP overshoot. Controls had any SBP fall on standing but intact autonomic reflexes. Receiver operator characteristic curve (ROC) analysis was performed on the ratio of the changes from supine to 3 min standing in HR and SBP (ΔHR/ΔSBP). Results: We studied 171 nOH patients (66±1 years, males 61%, multiple system atrophy 42%, Parkinson disease 14%, pure autonomic failure 32% and undetermined 12%) and 53 controls (51±3 years, males 28%). nOH patients had a greater drop in standing SBP (-63±2 vs. -16±4 mmHg in controls; p&lt;0.01) but a smaller increase in HR (13±1 vs. 18±1 bpm in controls; p&lt;0.01). The ROC analysis at 95% Confidence Interval showed that a ΔHR/ΔSBP ratio &lt;0.445 had a 81% specificity and 79% sensitivity in identifying nOH (AUC=0.86, p&lt;0.01. Figure). Conclusions: Our study suggests that a simple ratio of ΔSBP/ΔHR &lt;0.445 during a posture test in clinic can reliably identify patients with nOH.

Pharmacology: Cardiovascular effects of mirabegron.

In clinical studies, mirabegron has been shown to cause a small increase in heart rate with a slight increase in QTc interval, as indicated on electrocardiograms. The mechanisms of these effects are unclear. The findings of a recent study might provide some new clues, although, the relevance of these new observations to the treatment of patients with overactive bladder syndrome have yet to be established.

Autonomic reactivity and vulnerability to depression: A multi-wave study.

The ability of the autonomic nervous system to flexibly adapt to environmental changes is thought to indicate efficient use of self-regulatory resources. Deficits in autonomic reactivity appear to characterize current depression; however, whether autonomic reactivity confers vulnerability to future depression when individuals encounter environmental stressors is unknown. Fluctuations in respiratory sinus arrhythmia (RSA) and heart rate (HR) were evaluated in response to emotion-eliciting films among 134 undergraduates. Negative events and depressive symptoms were assessed 5 times across 12 weeks. Multilevel modeling demonstrated that smaller decreases in RSA in response to sadness, greater increases in HR following sadness, and smaller increases in HR to amusement were prospectively associated with greater depressive symptoms when individuals encountered high levels of idiographically assessed negative events. These results demonstrate that the lack of contextually appropriate autonomic reactivity may confer vulnerability to depression under conditions of environmental stress, perhaps due to attenuated capacity for effective self-regulation. (PsycINFO Database Record

Impact of the Universal Adoption of Ring Block Anesthesia Pre-Circumcision in a Tertiary Care Center [26I

INTRODUCTION: Neonatal circumcision causes behavioral and physiologic changes consistent with the perception of pain. Ring block anesthesia pre-circumcision leads to a smaller increase in heart rate and respiratory rate. They demonstrated less arousal during each operative interval, less crying and a smaller decrease in oxygen saturation compared to infants not receiving anesthesia. A Joint commission site visit to our institution in March 2014 prompted the adoption of pre-circumcision anesthesia preferably ring block in April 2014 with the mindset of providing our pediatric patients with the same high quality care during a painful procedure. METHODS: A descriptive analysis of circumcision related data pertaining to the use of ring block anesthesia during circumcisions performed at Erlanger tertiary care facilities from March 2013 through March 2015. RESULTS: The use of ring block anesthesia application increased to 94.1% (n= 1394) out of 1482 post adoption compared to the prior 41.1% (n=727) out of 1770). Of note is the reduction in the total number of circumcision done in the hospital from n=1770 between March 2013 and 2014 to n=1394 between April 2014 and March 2015 of the study period. CONCLUSION: The near perfect implementation of ring block anesthesia pre-neonatal circumcision does illustrate the importance of hospital encouraged compliance in improving the quality of medical practice.

GLP-1 Receptor Agonists: Practical Considerations for Clinical Practice.

Type 2 diabetes (T2D) imparts an increased risk of adverse health outcomes in patients unable to achieve glycemic control. Patient education and individualization of treatment are important for effective management of T2D. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are a class of injectable glucose-lowering agents that lower A1C with added benefits of weight loss and improved cardiovascular risk markers. This review discusses the role of GLP-1RAs currently approved in the United States (exenatide, liraglutide, albiglutide, dulaglutide) for T2D management and characterizes the efficacy and safety profiles of individual GLP-1RAs. GLP-1RAs are recommended as a preferred add-on agent to existing metformin monotherapy, as first-line therapy if metformin is contraindicated or poorly tolerated, and for use in combination with other oral glucose-lowering agents or basal insulin. Shorter-acting GLP-1RAs (exenatide and liraglutide) offer improved coverage of postprandial hyperglycemia, while longer-acting GLP-1RA formulations (exenatide extended-release, dulaglutide, and albiglutide) further improve fasting plasma glucose, which can result in additional A1C lowering. Reductions in body weight and blood pressure appear similar among individual agents, and small increases in heart rate are of unknown clinical relevance. Gastrointestinal adverse events abate over time with continued treatment and are less frequent with longer-acting GLP-1RAs. Hypoglycemia incidence is low but increased when GLP-1RAs are used with insulin secretagogues or insulin. GLP-1RAs target multiple pathophysiologic mechanisms in patients with T2D and improve glycemic control, although there are some differences within this drug class that may be relevant in clinical practice. Therefore, selection of the most appropriate treatment for individual patients is important.

Post-Exercise Hypotension and Its Mechanisms Differ after Morning and Evening Exercise: A Randomized Crossover Study.

Post-exercise hypotension (PEH), calculated by the difference between post and pre-exercise values, it is greater after exercise performed in the evening than the morning. However, the hypotensive effect of morning exercise may be masked by the morning circadian increase in blood pressure. This study investigated PEH and its hemodynamic and autonomic mechanisms after sessions of aerobic exercise performed in the morning and evening, controlling for responses observed after control sessions performed at the same times of day. Sixteen pre-hypertensive men underwent four sessions (random order): two conducted in the morning (7:30am) and two in the evening (5pm). At each time of day, subjects underwent an exercise (cycling, 45 min, 50%VO2peak) and a control (sitting rest) session. Measurements were taken pre- and post-interventions in all the sessions. The net effects of exercise were calculated for each time of day by [(post-pre exercise)-(post-pre control)] and were compared by paired t-test (P<0.05). Exercise hypotensive net effects (e.g., decreasing systolic, diastolic and mean blood pressure) occurred at both times of day, but systolic blood pressure reductions were greater after morning exercise (-7±3 vs. -3±4 mmHg, P<0.05). Exercise decreased cardiac output only in the morning (-460±771 ml/min, P<0.05), while it decreased stroke volume similarly at both times of day and increased heart rate less in the morning than in the evening (+7±5 vs. +10±5 bpm, P<0.05). Only evening exercise increased sympathovagal balance (+1.5±1.6, P<0.05) and calf blood flow responses to reactive hyperemia (+120±179 vs. -70±188 U, P<0.05). In conclusion, PEH occurs after exercise conducted at both times of day, but the systolic hypotensive effect is greater after morning exercise when circadian variations are considered. This greater effect is accompanied by a reduction of cardiac output due to a smaller increase in heart rate and cardiac sympathovagal balance.

The efficacy and safety of the naltrexone/bupropion combination for the treatment of obesity: an update.

The combination of 32 mg naltrexone and 360 mg bupropion prolonged release (NB32) was recently approved by both the food and drug administration (FDA) and the European medicines agency (EMA) as an adjunct to a comprehensive lifestyle intervention to achieve weight loss. Randomized controlled trials with naltrexone/bupropion prolonged release were selected through a search based on PubMed listings using the terms "bupropion AND naltrexone". NB32 treatment resulted in 5.0-9.3% weight loss, while the placebo-subtracted weight loss was 3.2-5.2% during 56 weeks of treatment. The proportion of treated patients with ≥ 5% weight loss was 45-66%, while the placebo-subtracted proportion was 23-34%. NB32 was associated with a decrease in waist circumference, serum triglycerides and insulin resistance and an increase in high-density lipoprotein-cholesterol (HDL-C). Blood pressure mainly remained stable but there was a small increase in heart rate. The most common side effects were nausea, constipation, headache and vomiting. Serious adverse effects, which were very rare, included suicidal thoughts and seizures. In the majority of patients NB32 treatment was well tolerated. Naltrexone/bupropion combination appears to be an effective adjunct to a comprehensive lifestyle intervention in order to achieve weight loss and treat obesity-related comorbidities.