Significant Changes In Heart Rate Research Articles

Heart rate, oxygen uptake, and energy expenditure response of an SL3 class parabadminton athlete to a progressive test and simulated training session: a case study.

This investigation demonstrated a routine of evaluation and training of an athlete of the SL3 class of parabadminton for 2 days continuously monitored by a metabolic analyzer with measurements of oxygen consumption (V̇O2), carbon dioxide production, and heart rate (HR). The results showed HR and V̇O2 responses varying between 50% and 99.54% of HRmax (mean HR 80.92bpm), and 6% and 104% (mean V̇O2 35.25mL/kg/min) of V̇O2max, during the simulated game. The exercise test and the simulated training session showed significant changes in HR and V̇O2, reinforcing the need for considerable energy input to training and assessment.

Mindfulness-Based Group Medical Visits in Primary Care for Stress and Anxiety: An Observational Study

Background: The prevalence of anxiety disorders in primary care is 20%, with 41% of these patients reporting no current treatment. Patients with anxiety are also more likely to have comorbidities with other medical and/or psychiatric conditions, increasing medical costs. Integrating mindfulness-based interventions (MBIs) into a group medical visit (GMV) format has been successfully used to manage pain, but limited literature is available on the effectiveness of these visit formats for patients with stress and anxiety. Methods: Ninety-two adult patients with self-reported stress and/or anxiety were recruited from three university outpatient primary care clinics between 2016 and 2019. Participants attended at least 4 of 6 weekly GMVs focused on MBIs. Change in heart rate, blood pressure, Generalized Anxiety Disorder-7 (GAD-7) score, and 9 item Patient Health Questionnaire (PHQ-9) score from the first to last visit were evaluated using mixed effect linear regression models. Results: Both GAD-7 (estimated change: -5.1; 95% confidence interval [CI]: -6.4 to -3.7) and PHQ-9 (estimated change: -3.3; 95% CI: -4.3 to -2.2) scores significantly decreased from the first to last visit. These reductions were independent of age, sex, and number of visits attended. No significant changes in heart rate or blood pressure were found. Conclusions: Significant reductions in anxiety and depression in primary care patients were observed after a 6-week standardized mindfulness based GMV. Intergroup variability was not significant indicating that the intervention is reproducible over time and across providers. Future randomized controlled trials with appropriate controls will better evaluate which components of the intervention account for findings.

Short-term anthracyclines-induced cardiotoxicity in breast cancer patients.

e18703 Background: Anthracycline-containing regimens are effective treatment of early breast cancer; however, they can induce irreversible myocardial damage, leading to significant morbidity and mortality. The main aim of this study was to describe and evaluate early anthracycline cardiotoxicity. Methods: This was a prospective study including breast cancer patients who where candidates for adjuvant anthracycline-based chemotherapy. Patients were assessed at baseline with history, physical exam, standard 12-lead electrocardiography (ECG) and 2D echocardiography, and then shortly after completion of anthracycline-based chemotherapy. We reported the ECG parameters, LVEF calculated using Simpson's biplane method and global longitudinal strain (GLS). Cardiotoxicity was defined as a decline ≥ 5% in LVEF accompanied or not by clinical manifestations of heart failure, or a decline ≥ 10% in GLS. Statistical analysis was performed using SPSS version 26. For comparisons, we used two-tailed Student's t-test. Associations between risk factors and cardiotoxicity were assessed using linear and logistic regression; a p value < 0.05 was considered significant. Results: 171 patients with stage I (10.3%), stage II (81%) or stage III (8.7%) invasive ductal breast carcinoma, with a mean age of 48,1 ± 10 years. Obesity was found in 59 patients and 92 were overweight. Among comorbidities, hypertension was present in 11.7%, diabetes mellitus in 5.2%, and dyslipidemia in 4.6%. The most common concomitant medications were β-blockers in 6.4%, followed by angiotensin II receptor blockers in 5.2%, Statins in 4.6%, biguanides in 5.2%. Cardiac function was assessed 12 ± 7 days before and 19 ± 8 days post chemotherapy. 94 patients received Doxorubicin with a cumulative dose of 240 mg/m2, and 77 received Epirubicin with a cumulative dose of 300 mg/m2. Subclinical Cardiotoxicity was observed in 9 patients (5.2%), defined as a decline ≥ 5% in LVEF and in one patient (0.5%) defined by GLS decline ≥ 10%. This patient had the lowest post-therapy LVEF (40.2%) of the cohort. LVEF and GLS although reduced significantly after treatment, remained within the normal range. (LVEF: 62.8 ± 3% vs. 58 ± 6%, p = 0.03), (GLS: -19.0 ± 2.4% vs. -17.1 ± 1.0%, p = 0.01). Patients receiving Doxorubicin had lower LVEF compared to Epirubicin after therapy (57.1 ± 2% vs. 61.4 ± 2%, p = 0.03). Additionally, we found significant ECG changes in Heart Rate (72.6 ± 11,6 vs. 85.2 ± 14.4 bpm, p = 0.013) and QTc (410.1 ± 24.9 vs. 427.7 ± 26.5 ms, p = 0.032). Cardiotoxicity was not associated with any cardiovascular risk factors. Doxorubicin use was the only risk factor, confirmed on multivariate analysis (p = 0,02). Conclusions: Anthracycline-based chemotherapy has detrimental subclinical effect on electrical activity and left ventricle systolic function in the short term after adjuvant chemotherapy. We did not observe any significant effect of risk factors, it is therefore important to monitor all patients.

Microbeam Irradiation of the Beating Rodent Heart: An Ex Vivo Study of Acute and Subacute Effects on Cardiac Function

Microbeam radiation therapy (MRT) has shown several advantages compared with conventional broad-beam radiation therapy in small animal models, including a better preservation of normal tissue function and improved drug delivery based on a rapidly increased vascular permeability in the target region. Normal tissue tolerance is the limiting factor in clinical radiation therapy. Knowledge of the normal tissue tolerance of organs at risk is therefore a prerequisite in evaluating any new radiation therapy approach. With an irradiation target in the thoracic cavity, the heart would be the most important organ at risk. We used the ex vivo beating rodent heart in the Langendorff perfusion system at the synchrotron to administer microbeam irradiation (MBI) with a peak dose of 40 or 400 Gy. By continuously recording the electrocardiogram, the left ventricular pressure, and the aortic pressure before, during and after MBI, we were able to assess acute and subacute effects of MBI on electrophysiological and mechanical cardiac function. In addition, we analyzed histologic and ultrastructural sequelae caused by MBI. There were no significant changes in heart rate, heart rate variability, systolic increase of left ventricular pressure or aortic pressure. Moreover, the changes of heart rate, left ventricular pressure and aortic pressure by adding 10-5 mol/L norepinephrine to the perfusate, were also not significant between MBI and sham experiments. However, the rate-pressure product as a surrogate marker for maximum workload after MBI was significantly lower compared with sham-irradiated controls. On the structural level, no severe membranous, sarcomeric, mitochondrial or nuclear changes caused by MBI were detected by desmin immunohistochemistry and electron microscopy. With respect to acute and subacute toxicity, an MBI peak dose up to 400Gy did not result in severe changes in cardiac electrophysiology or mechanics.

Central Nucleus of Amygdala Mediate Pressor Response Elicited by Microinjection of Angiotensin II into the Parvocellular Paraventricular Nucleus in Rats.

Background: The Paraventricular Hypothalamic Nucleus (PVN) coordinates autonomic and neuroendocrine systems to maintain homeostasis. Microinjection of angiotensin II (AngII) into the PVN has been previously shown to produce pressor and bradycardia responses. Anatomical evidence has indicated that a substantial proportion of PVN neurons is connected with the neurons in the central amygdala (CeA). The present study aimed to examine the possible contribution of the CeA in cardiovascular responses evoked by microinjection of AngII into the parvocellular portion of PVN (PVNp) before and after microinjection of cobalt chloride (CoCl2) into the CeA.Methods: The experiments were conducted at the Department of Physiology of Shiraz University of Medical Sciences, from April 2019 to November 2019. There were two groups of 21 eight-week-old urethane anesthetized male rats, namely saline (n=9 rats) and AngII (n=12 rats) groups. Drugs (100 nL) were microinjected via a single-glass micropipette into the PVNp and CeA. Their blood pressure (BP) and heart rate (HR) were recorded throughout the experiments. The mean arterial pressure (MAP) and heart rate (HR) were compared to the pre-injection values using paired t test, and to those of the saline group using independent t test.Results: Microinjection of AngII into the PVNp produced pressor response (P<0.0001) with no significant changes in HR (P=0.70). Blockade of CeA with CoCl2 attenuated the pressor response to microinjection of AngII into the PVNp (P<0.001).Conclusion: In the PVNp, Ang II increased the rats’ blood pressure. This response was in part mediated by the CeA. Our study suggested that these two nuclei cooperate to perform their cardiovascular functions.

Heart rate variability during different phases of menstrual cycle

The purpose of the present study was to determine whether there is a menstrual cycle effect on heart rate variability. Ten healthy regularly cycling females (age 19‐23 years) were studied during the follicular phase (FP) and luteal phase (LP) of menstrual cycle over two month. We found significant changes in heart rate (65,35±0,68 beats/min in FP vs 73,18±0,92 beats/min in LP, p&lt;0,0005), AMo and stress index during the menstrual cycle with a minimum in the follicular phase (36,81±1,14 % and 76,86±5,74 p.d.u. respectively) and maximum in the luteal phase (42,05±1,27 % and 107,70±7,77 p.d.u. respectively, p&lt;0,003). The HF and LF components decreased more during the luteal phase (655,56±46,64 ms2 and 981,85±66,64 ms2 respectively) than during the follicular phase (997,42±83,36 ms2 and 1524,66±145,17 ms2 respectively, p&lt;0,05). In the follicular phase SDNN, pNN50, MxDMn were significantly higher (0,057±0,002 s, 41,49±1,79 % and 0,333±0,012 s respectively) than in the luteal phase (0,051±0,002 s, 29,73±1,88 % and 0,303±0,012 s respectively, p&lt;0,05). Furthermore, the VIK was higher in the luteal phase compared to the follicular phase (p=0,003). These findings indicate that sympathetic nervous activity in the luteal phase is greater than in the follicular phase, whereas parasympathetic nervous activity is predominant in the follicular phase. A difference of the balance of ovarian hormones may be responsible for these changes of autonomic functions during the menstrual cycle.

Evaluation of lung ventilation distribution using electrical impedance tomography in standing sedated horses with capnoperitoneum

ObjectiveTo determine changes in distribution of lung ventilation with increasing intra-abdominal pressure (IAP) from carbon dioxide (CO2) insufflation in standing sedated horses. Study designProspective experimental study. AnimalsA group of six healthy adult horses. MethodsEach horse was sedated with acepromazine, detomidine and butorphanol and sedation maintained with a detomidine infusion. The horse was restrained in a stocks system and a 32 electrode electrical impedance tomography (EIT) belt was wrapped around the thorax at the fifth–sixth intercostal space. EIT images and arterial blood samples for PaO2 and PaCO2, pH and lactate concentration were obtained during capnoperitoneum at 0 (baseline A), 5, 8 and 12 mmHg as IAP increased and at 8, 5, 0 (baseline B) mmHg as IAP decreased. At each IAP, after a 2 minute stabilization period, EIT images were recorded for ≥ 2 minutes to obtain five consecutive breaths. Statistical analysis was performed using anova for repeated measures with Geisser-Greenhouse correction and a Tukey’s multiple comparison test for parametric data. The relationship between PaO2 and the center of ventilation in the ventral-dorsal (CoV-VD) and right-left (CoV-RL) directions or total impedance change as a surrogate for tidal volume (ΔZVT) were tested using linear regression analysis. Significance was assumed when p ≤ 0.05. ResultsThere were no significant changes in CoV-VD, CoV-RL, PaO2, PaCO2, lactate concentration, pH, heart rate and respiratory rate with targeted IAP. There was a significant decrease in ΔZVT compared with baseline A at 5 mmHg IAP as IAP was increased. Conclusions and clinical relevanceCapnoperitoneum causes a significant decrease in ΔZVT in standing sedated horses with increasing IAP.

Cardiovascular effects of hyoscine butylbromide in patients under general anaesthesia.

Cardiovascular effects for drugs such as hyoscine butylbromide are poorly documented in the literature, unlike atropine, which is considered the antimuscarinic of choice in the presence of intraoperative bradycardia. The aim of the study was to describe the dose-related cardiovascular effect of hyoscine butylbromide in patients between 18 and 65 years of age, with low perioperative risk undergoing elective surgery under general anaesthesia on an outpatient basis or hospitalised at our institution between 1 January and 31 May 2019. Descriptive, cross-sectional, retrospective study; 28 patients with low perioperative risk who underwent general anaesthesia were selected. Changes in heart rate and blood pressure were analysed during the first 6 minutes after the administration of hyoscine butylbromide. The data obtained was recorded in a Microsoft Excel database and analysed using the Excel analysis tool and IBM SPSS. The average dose of 0.15mg/kg of hyoscine butylbromide achieved an increase in heart rate and mean arterial pressure in 96% and 92.8%, respectively, in the first 6 minutes after the administration. Significant changes in heart rate and blood pressure were obtained during the first 6 minutes at doses between 0.05mg/kg and 0.15mg/kg. Hyoscine butylbromide generates positive effects on the heart rate and blood pressure of patients under general anaesthesia, representing a possible alternative in the management of intraoperative bradycardia.

The effect of norepinephrine on clinical and hemodynamic parameters in neonates with shock: a retrospective cohort study.

changes in mean blood pressure (MBP) at 6, 12, and 24h post-initiation of NE. Changes in (i) diastolic BP, systolic BP, and vasoactive inotrope score (VIS) at 6, 12, and 24h, (ii) urine output after initiation of NE ii) pH, lactate, fraction of inspired oxygen (FiO2) after initiation of NE, and (iv) adverse outcomes. Fifty infants received NE with mean (SD) gestational age of 34.3 (4.3) weeks and a mean birth weight of 2215 (911) g. Treatment began at a median age of 36 (IQR: 15.2, 67.2) hours of life and lasted 30.5 (IQR: 12.7, 58) hours. MBP improved from 34.4mm Hg (SD: 6.6) at baseline to 39.4mm Hg (SD: 10.5, p < 0.001) at 6h, to 39.6mm Hg (SD: 12.1, p = 0.002) at 12h and to 40.4mm Hg (SD: 15.5, p = 0.004) at 24h after NE initiation. Vasoactive inotrope score declined from 30 (20, 32) to 10 (4, 30; p < 0.001) at 24h. Urine output improved within 24h [1.5ml/kg/h (0.5, 2.3) at baseline to 3 (1.9, 4.3) at 24h; p = 0.04]. Oxygen requirement decreased after NE initiation. The use of NE appears to be effective and safe for treating systemic hypotension in neonates. Being a retrospective study, trial registration was not considered. •Dopamine has traditionally been used as the initial agent for treatment of neonatal hypotension. •Norepinephrine has recently been recommended as the first-choice vasopressor agent to correct hypotension in adults and pediatric patients, with insufficient data on the cardiovascular effects of NE in neonates What is new: •Mean blood pressure improved significantly at 6, 12, and 24h with reduction in vasoactive infusion score at 12 and 24h after norepinephrine infusion. •No significant change in heart rate or abnormal abdominal adverse effects noted in this study.

The impact of treatment of periodic limb movements in sleep on blood pressure in patients with and without sleep apnea

Improving sleep quality in patients with obstructive sleep apnea (OSA) by positive airway pressure therapy is associated with a decrease of blood pressure (BP). It remains elusive, whether treatment of sleep disturbances due to restless legs syndrome with symptomatic periodic limb movements in sleep (PLMS) affects BP as well. The present study provides first data on this issue. Retrospective study on patients undergoing polysomnography in a German University Hospital. Inclusion criteria were first diagnosis of restless legs syndrome with PLMS (PLM index ≥ 15/h and PLM arousal index ≥ 5/h) with subsequent initiation of levodopa/benserazide or dopamine agonists. Exclusion criterion was an initiation or change of preexisting positive airway pressure therapy between baseline and follow-up. BP and Epworth sleepiness scale were assessed at two consecutive polysomnographies. After screening of 953 PLMS data sets, 114 patients (mean age 62.1 ± 12.1 years) were included. 100 patients (87.7%) were started on levodopa/benserazide, 14 patients (12.2%) on dopamine agonists. Treatment was associated with significant reductions of PLM index (81.2 ± 65.0 vs. 39.8 ± 51.2, p < 0.001) and ESS (6 [interquartile range, IQR, 3–10.5] vs. 5 [IQR 3–10], p = 0.013). Systolic BP decreased from 132.9 ± 17.1 to 128.0 ± 15.8 mmHg (p = 0.006), whereas there was no significant change of diastolic BP (76.7 ± 10.9 vs. 75.1 ± 9.2 mmHg, p = 0.15) and heart rate (71.5 ± 11.9 vs. 71.3 ± 12.7, p = 0.84). The number of antihypertensive drugs remained unchanged with a median of 2 (IQR 1–3, p = 0.27). Dopaminergic treatment of PLMS is associated with an improvement of sleep quality and a decrease of systolic BP comparable to treatment OSA.

Hemodynamic variations in arterial wave reflection associated with the application of increasing levels of PEEP in healthy subjects

Positive end-expiratory pressure (PEEP) may affect arterial wave propagation and reflection, thus influencing ventricular loading conditions. The aim of the study was to investigate the hemodynamic variations in arterial wave reflection (i.e., wave reflection time, augmentation index, left ventricular ejection time, diastolic time, SEVR) associated with the application of increasing levels of PEEP in healthy subjects. We conducted a prospective observational study. Study population was selected from students and staff. Pulse contour wave analysis was performed from the right carotid artery during stepwise increase in PEEP levels (from 0 cmH2O, 5 cmH20, 10 cmH2O) with applanation tonometry. Sixty-two healthy volunteers were recruited. There were no significant changes in heart rate, augmentation index (AIx), left ventricular ejection time, Diastolic time (DT) among all of the different steps. A significant increase of time to the inflection point (Ti) was observed during all steps of the study. Diastolic area under the curve (AUC) divided by systolic-AUC (SEVR) increased from baseline to PEEP = 5 cmH2O, and from baseline to PEEP = 10 cmH2O. AIx and Ti were significantly correlated (directly) at the baseline and during PEEP = 10 cmH2O. Ti and DT were significantly correlated at the baseline and during PEEP = 5 cmH2O. In our preliminary results, low levels of PEEP played a role in the interaction between the heart and the vascular system, apparently mediated by a prolongation of the diastolic phase and a reduction in the systolic work of the heart.Clinical trials registration number: NCT03294928, 19/09/2017.

Evaluation of the Effect of Left Nostril Breathing on Cardiorespiratory Parameters and Reaction Time in Young Healthy Individuals

Background: Pranayama, a yogic breathing practice, produces several physiological responses in healthy individuals. Hypertension is a critical and booming public health challenge all over the world. Yoga is one of the effective methods to reduce blood pressure (BP) and pulse rate (PR).Objective: To evaluate the effect of left nostril breathing (LNB) exercise on cardiorespiratory parameters and reaction time (RT) in young healthy individuals.Materials and methods: In this study, 106 young healthy individuals between 18 and 25 years of age were included. The systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse rate (PR), respiratory rate (RR), vital capacity (VC), peak expiratory flow rate (PEFR), and reaction time (RT) of volunteers were recorded at baseline (before exercise) and after two weeks of left nostril breathing exercise performed 45 minutes daily.Results: There was a significant reduction in SBP (126.64 ± 15.51 mmHg versus 116.29 ± 11.91 mmHg; Cohen’s d (effect size): 0.87; p < 0.0001)), DBP (76.57 ± 14.87 mmHg versus 71.07 ± 11.39 mmHg; Cohen’s d: 0.48; p < 0.0001), PR (85.32 ± 15.44/minute versus 81.77 ± 13.02/minute; Cohen’s d: 0.27; p < 0.0001), and RR (14.26 ± 2.15/minute to 13.17 ± 2.03/minute; Cohen’s d: 0.54; p < 0.0001). A significant increase was observed in VC (3.42 ± 0.62 versus 3.67 ± 0.65; Cohen’s d: 0.39; p < 0.0001) and PEFR (467.81 ± 46.66 versus 498.29 ± 51.50; Cohen’s d: 0.59; p < 0.0001). There was a significant decrement in auditory reaction time (ART) (164.36 ± 27.20 ms versus 143.84 ± 20.32 ms; Cohen’s d: 0.85; p < 0.0001) and visual reaction time (VRT) (190.25 ± 31.48 ms versus 163.75 ± 21.72 ms; Cohen’s d: 0.98; p < 0.0001). There was no significant change in maximum heart rate (MHR) after cardiorespiratory activity (CRA) (p > 0.434).Conclusion: Left nostril breathing is associated with a decrease in cardiovascular parameters and an increase in VC and PEFR. This technique may be useful for putting up a fight against the stress and strain of daily life. This simple exercise may also be a beneficial adjuvant to pharmacological therapy in hypertensive patients.

DOP45 Long-term cardiac safety of ozanimod in phase 3 clinical program of Ulcerative Colitis and relapsing multiple sclerosis

Abstract Background Sphingosine-1-phosphate (S1P) receptor modulators may be associated with bradycardia and atrioventricular conduction delays. A previous analysis demonstrated first-dose ozanimod had minimal effects on cardiac function, including in patients (pts) with a known history of cardiovascular disease. This analysis evaluated long-term cardiac safety following continuous ozanimod treatment from the phase 3 ulcerative colitis (UC) True North trial and multiple sclerosis (MS) 12-mo SUNBEAM and 24-mo RADIANCE trials. Methods Ozanimod 0.92 mg (equivalent to ozanimod HCl 1 mg)–treated pts from True North and pooled SUNBEAM/RADIANCE trials were included. In True North, pts in Cohort 1 received double-blind ozanimod or placebo and pts in Cohort 2 received open-label ozanimod in the induction period; in the maintenance period, pts with clinical response to ozanimod at 10 weeks were rerandomized to double-blind ozanimod or placebo. In True North, ECGs were monitored at screening, day 1, wk-10, and wk-52; heart rate (HR) was monitored at every visit. In the MS trials, ECGs were monitored at screening, baseline, day 15, and end of treatment (EOT); HR was monitored similarly at the beginning, then every 3 mo until EOT. Cardiac-related treatment-emergent AEs (TEAEs) were reported. Results In the UC trial, continuous ozanimod treatment was not associated with any clinically significant changes in HR or ECG. The incidence of cardiac-related TEAEs with ozanimod during induction in Cohorts 1 and 2 was low (Table). In maintenance, cardiac-related TEAEs were reported in 1.3% (3/230) of pts in the continuous ozanimod group (Table); incidence was numerically higher in ozanimod pts with (2 of 57 pts [3.5%]) versus without (1 of 173 pts [0.6%]) prior history of cardiovascular disease. Cardiac-related serious AEs (SAEs) were uncommon (angina pectoris, coronary artery stenosis, pericarditis in 1 patient each). In the pooled MS studies, no clinically significant HR or ECG changes were associated with chronic treatment up to mo 24. The incidence of cardiac-related TEAEs was low with ozanimod (Table); incidence was similar among pts with (6 of 171 pts [3.5%]) versus without (24 of 711 pts [3.4%]) prior history of cardiovascular disease. Two of 882 patients experienced cardiac-related SAEs resulting in hospitalization with ozanimod in the MS studies (asymptomatic sinus bradycardia [HR 44 bpm] and symptomatic supraventricular tachycardia). Conclusion Ozanimod had a manageable long-term cardiac safety profile with a low incidence of bradycardia and few serious long-term cardiac safety findings in the phase 3 UC and MS ozanimod trials.

Effects of continuous goal-directed analgesia on fluid resuscitation of massive burn patients during shock

Effects of continuous goal-directed analgesia on fluid resuscitation of massive burn patients during shock

3-Hydroxyphenylacetic Acid: A Blood Pressure-Reducing Flavonoid Metabolite.

Regular intake of polyphenol-rich food has been associated with a wide variety of beneficial health effects, including the prevention of cardiovascular diseases. However, the parent flavonoids have mostly low bioavailability and, hence, their metabolites have been hypothesized to be bioactive. One of these metabolites, 3-hydroxyphenylacetic acid (3-HPAA), formed by the gut microbiota, was previously reported to exert vasorelaxant effects ex vivo. The aim of this study was to shed more light on this effect in vivo, and to elucidate the mechanism of action. 3-HPAA gave rise to a dose-dependent decrease in arterial blood pressure when administered i.v. both as a bolus and infusion to spontaneously hypertensive rats. In contrast, no significant changes in heart rate were observed. In ex vivo experiments, where porcine hearts from a slaughterhouse were used to decrease the need for laboratory animals, 3-HPAA relaxed precontracted porcine coronary artery segments via a mechanism partially dependent on endothelium integrity. This relaxation was significantly impaired after endothelial nitric oxide synthase inhibition. In contrast, the blockade of SKCa or IKCa channels, or muscarinic receptors, did not affect 3-HPAA relaxation. Similarly, no effects of 3-HPAA on cyclooxygenase nor L-type calcium channels were observed. Thus, 3-HPAA decreases blood pressure in vivo via vessel relaxation, and this mechanism might be based on the release of nitric oxide by the endothelial layer.

Evaluation of change in heart rate variability due to different soundscapes

Abstract Soundscapes affect the health and quality of life of humans. Noisy soundscapes have a negative impact on humans causing annoyance, sleep disturbance and cardiovascular issues. This paper analyses the change in heart rate variability (HRV) due to exposure of different soundscape stimuli. A total of 40 soundscape stimuli were collected from New Delhi India, which were grouped into three clusters, ‘Loud’, ‘Active’ and ‘Silent’, based on psychoacoustic indicators. Listening experiments were conducted with 25 healthy participants, during which electro-cardiography responses were collected as response variable. HRV analysis was performed to analyse the change in time domain (Heart rate, SDNN, NN50, pNN50) and frequency domain (VLF, LF, HF, LF/LF ratio) parameters. A significant change in heart rate is observed with an increase in loudness of stimuli. The change in HRV is analysed by considering noise sensitivity level of participants. A significant decrease in SDNN is noted for participants with high noise sensitivity. Frequency domain parameters of HRV did not exhibit a significant change due to noise exposure. A significant decrease in SDNN suggests imbalanced autonomic nervous system activation, which increases the risk of cardiovascular diseases, particularly for people with high noise sensitivity.

1099. Evaluation of the Safety and Pharmacokinetics (PK) following Administration of Single and Multiple Doses of Anti-Staphylococcal Lysin, LSVT-1701, in Healthy Adult Subjects

BackgroundLSVT-1701 is an anti-staphylococcal phage lysin being developed for treatment of MRSA infections in combination with SoC antibiotics. The safety and PK of single ascending doses of LSVT-1701 0.1 to 10 mg/kg in healthy adult volunteers were previously described (Jun, et.al, AAC 2017;61:e02629-16). We further evaluated the safety and PK of multiple ascending doses of LSVT-1701 in healthy adult subjects.MethodsStudy ITB-101-1b was a Phase 1, randomized, double-blind, placebo-controlled, multiple ascending dose study. 8 subjects were randomized 3:1 to active:placebo in each cohort. LSVT-1701 was administered as a 6 mg/kg single dose and twice daily (BID) doses of 1.5, 3.0, and 4.5 mg/kg for 4 days (24h between Doses 1-2, 12h between Doses 2-6). Study drugs were administered as a 1-hour IV infusion. Serial serum samples were collected over 24 hours following the first and last doses for measurement of LSVT-1701 concentrations by a validated ELISA method. PK analysis of LSVT-1701 concentration-time data was done using noncompartmental methods. Safety was assessed by AEs, clinical labs, vital signs, and ECG.Results30/32 (94%) subjects completed the study. No subjects withdrew due to AEs, and there were no severe AEs, no serious AEs, and no deaths. AEs were of mild (97%) to moderate (3%) intensity and were reported by all subjects in the LSVT-1701 6 mg/kg single dose group and 1-3 (17-50%) of subjects receiving 1.5 to 4.5 mg/kg BID or placebo. The most common AEs of headache, chills, rigors, and fever generally lasted for ≤2 days with or without acetaminophen treatment, and no clinically significant changes in blood pressure, heart rate, ECG, or clinical labs (other than transient increases in CRP) were observed. Infusion site reactions (erythema, pain, induration, warmth) were observed with BID administration of LSVT-1701, but not with the single 6 mg/kg dose or placebo. LSVT-1701 exposure increased greater than in proportion to dose and t1/2 was concentration-dependent, increasing with higher doses. No accumulation in LSVT-1701 exposure was observed.Summary of LSVT-1701 PK Parameters Summary of LSVT-1701 PK ParametersConclusionThe safety and PK profile of LSVT-1701 is favorable for evaluation in patients with S. aureus infections, including bacteremia and infective endocarditis, for which new treatments are needed.Disclosures Mary Beth Wire, Pharm#, Lysovant (Consultant) Soo youn Jun, PhD, iNtRON Biotechnology (Consultant) In-Jin Jany, PhD, iNtRON (Consultant) Jun Gi Hwang, PhD, Lysovant (Consultant) David Huang, MD, PhD, Lysovant (Consultant)

The effect of spinal manipulative therapy and home stretching exercises on heart rate variability in patients with persistent or recurrent neck pain: a randomized controlled trial

BackgroundPersistent or recurrent neck pain is, together with other chronic conditions, suggested to be associated with disturbances of the Autonomic Nervous System. Acute effects on the Autonomic Nervous System, commonly measured using Heart Rate Variability, have been observed with manual therapy. This study aimed to investigate the effect on Heart Rate Variability in (1) a combination of home stretching exercises and spinal manipulative therapy versus (2) home stretching exercises alone over 2 weeks in participants with persistent or recurrent neck pain.MethodsA randomized controlled clinical trial was carried out in five multidisciplinary primary care clinics in Stockholm from January 2019 to April 2020. The study sample consisted of 131 participants with a history of persistent or recurrent neck. All participants performed home stretching exercises daily for 2 weeks and were scheduled for four treatments during this period, with the intervention group receiving spinal manipulative therapy in addition to the home exercises. Heart Rate Variability at rest was measured at baseline, after 1 week, and after 2 weeks, with RMSSD (Root mean square of successive RR interval differences) as the primary outcome. Both groups were blinded to the other group intervention. Thus, they were aware of the purpose of the trial but not the details of the “other” intervention. The researchers collecting data were blinded to treatment allocation, as was the statistician performing data analyses. The clinicians provided treatment for participants in both groups and could not be blinded. A linear mixed-effects model with continuous variables and person-specific random intercept was used to investigate the group-time interaction using an intention to treat analysis.ResultsSixty-six participants were randomized to the intervention group and sixty-five to the control group. For RMSSD, a B coefficient of 0.4 (p value: 0.9) was found, indicating a non-significant difference in the regression slope for each time point with the control group as reference. No statistically significant differences were found between groups for any of the Heart Rate Variability indices.ConclusionAdding four treatments of spinal manipulation therapy to a 2-week program of daily stretching exercises gave no significant change in Heart Rate Variability.Trial Registration: The trial was registered 03/07/2018 at ClinicalTrials.gov, registration number: NCT03576846. (https://pubmed.ncbi.nlm.nih.gov/31606042/)

In vivo toxicity of bioreactor-grown biomass and exopolysaccharides from Malaysian tiger milk mushroom mycelium for potential future health applications

Natural mycelial biomass (MB) and exopolysaccharides (EPS) of Malaysian tiger milk mushroom Lignosus rhinocerus are considered high-end components due to their high commercial potential value in drug discovery. This study aims to evaluate the toxicity of the mushroom extracts’ generated in a bioreactor using the zebrafish embryo toxicity (ZFET) model assay as a new therapy for treating asthma. Both MB and EPS extracts, at concentrations 0.16–10 mg/mL, were tested for ZFET and early development effects on Zebrafish Embryos (ZE) during 24–120 h post-fertilisation (HPF). Findings revealed that MB was deemed safe with an LC50 of 0.77 mg/mL; the EPS were non-toxic (LC50 of 0.41 mg/mL). Neither MB nor EPS delayed hatching nor teratogenic defects in the treated ZE at a 2.5 mg/mL dose. There were no significant changes in the ZE heart rate after treatments with MB (130 beats/min) and EPS (140 beats/min), compared to that of normal ZE (120–180 beats/min). Mixing both natural compounds MB and EPS did not affect toxicity using ZFET testing; thus, intimating their safe future use as therapeutic interventions. This represents the first study to have used the ZFET assay on MB and EPS extracts of L. rhinocerus for future health applications.

Feasibility and First Results of Heart Failure Monitoring Using the Wearable Cardioverter-Defibrillator in Newly Diagnosed Heart Failure with Reduced Ejection Fraction.

The wearable cardioverter–defibrillator (WCD) is used in patients with newly diagnosed heart failure and reduced ejection fraction (HFrEF). In addition to arrhythmic events, the WCD provides near-continuous telemetric heart failure monitoring. The purpose of this study was to evaluate the clinical relevance of additionally recorded parameters, such as heart rate or step count. We included patients with newly diagnosed HFrEF prescribed with a WCD. Via the WCD, step count and heart rate were acquired, and an approximate for heart rate variability (HRV5) was calculated. Multivariate analysis was performed to analyze predictors for an improvement in left ventricular ejection fraction (LVEF). Two hundred and seventy-six patients (31.9% female) were included. Mean LVEF was 25.3 ± 8.5%. Between the first and last seven days of usage, median heart rate fell significantly (p < 0.001), while median step count and HRV5 significantly increased (p < 0.001). In a multivariate analysis, a delta of HRV5 > 23 ms was an independent predictor for LVEF improvement of ≥10% between prescription and 3-month follow-up. Patients with newly diagnosed HFrEF showed significant changes in heart rate, step count, and HRV5 between the beginning and end of WCD prescription time. HRV5 was an independent predictor for LVEF improvement and could serve as an early indicator of treatment response.