Increase In Rate-pressure Product Research Articles

Changes in rate-pressure product associated with pregnancy

In nonpregnant individuals, the rate-pressure product, the product of heart rate and systolic blood pressure, is used as a noninvasive surrogate of myocardial O2 consumption during cardiac stress testing. Pregnancy is considered a physiological cardiovascular stress test. Evidence describing the impact of pregnancy on myocardial O2 demand, as assessed by the rate-pressure product, is limited. This study aimed to describe changes in the rate-pressure product for each pregnancy trimester, during labor and delivery, and the postpartum period among low-risk pregnancies. This was a retrospective cohort study that assessed uncomplicated pregnancies delivered vaginally at term. We collected rate-pressure product (heart rate × systolic blood pressure) values preconception, during pregnancy for each trimester (at ≤13 weeks + 6/7 days, at 14 weeks + 0/7 days through 27 weeks + 6/7 days, and at ≥28 weeks + 0/7 days), during the labor and delivery encounter (hospital admission until complete cervical dilation, complete cervical dilation until placental delivery, and after placental delivery until hospital discharge), and during the outpatient postpartum visit at 2 to 6 weeks after delivery. We calculated the percentage change at each time point from the preconception rate-pressure product (delta rate-pressure product). We used a mixed-linear model to analyze differences in the mean delta rate-pressure product over time and the influence of prepregnancy age, prepregnancy body mass index, and neuraxial anesthesia status during labor and delivery on these estimates. Our cohort comprised 316 patients. The mean rate-pressure product increased significantly from preconception starting at the third trimester of pregnancy and during labor and delivery (P≤.05). The mean delta rate-pressure product peaked at 12% and 38% in the third trimester and during labor and delivery, respectively. Prepregnancy body mass index was inversely correlated with the mean delta rate-pressure product changes (estimate, -0.308; 95% confidence interval, -0.536 to -0.80; P=.008). In contrast, neither the prepregnancy age, nor neuraxial anesthesia status during labor had a significant influence on this parameter. This study validates the transient but significant increase in the rate-pressure product, a clinical estimate of myocardial O2 demand, during uncomplicated pregnancies delivered vaginally at term. Pregnant individuals with lower prepregnancy body mass index experienced a sharper increase in this parameter. Patients who receive neuraxial anesthesia during labor and delivery experience similar changes in the rate-pressure product as those who did not.

Noninvasive evaluation of dynamic microvascular dysfunction in ischemia and no obstructive coronary artery disease patients with suspected vasospasm.

In patients with ischemia and no obstructive coronary artery disease (INOCA), a dynamic coronary microvascular dysfunction (CMD) is frequent but difficult to capture by noninvasive means.The aim of our study was to assess dynamic CMD in INOCA patients with stress echocardiography after vasoconstrictive and vasodilator stimuli. In this prospective single-center study, we have enrolled 40 INOCA patients (age 56.3 ± 13 years, 32 women). All participants underwent stress echocardiography with hyperventilation (HYP), followed by supine bicycle exercise (HYP+EXE) and adenosine (ADO). Stress echocardiography included an assessment of regional wall motion abnormality (RWMA) and coronary flow velocity (CFV) in the distal left anterior descending (LAD) coronary artery. HYP induced a 30% increase in rate pressure product (rest = 10 244 ± 2353 vs. HYP = 13 214 ± 3266 mmHg x bpm, P < 0.001) accompanied by a paradoxical reduction in CFV (HYP< rest) in 21 patients (52%). HYP alone was less effective than HYP+EXE in inducing anginal pain (6/40, 15% vs. 10/40, 25%, P = 0.046), ST segment changes (6/40, 15% vs. 24/40, 60%, P < 0.001), and RWMA (6/40, 15% vs. 13/40, 32.5%, P = 0.008). ADO-induced vasodilation was preserved (≥2.0) in all patients. In patients with INOCA, a coronary vasoconstriction after HYP is common, in absence of structural CMD detectable with ADO. HYP+EXE test represents a more powerful ischemia inducer than HYP alone. Stress echocardiography with LAD-CFV may allow the noninvasive assessment of dynamic and structural coronary microcirculation during stress.

Abstract 15515: SGLT2 Inhibitor Empagliflozin Increases Fatty Acid Oxidation, Coupling Between Glycolysis and Glucose Oxidation, and Decreases Left Ventricular Hypertrophy in Mice With Hypertrophic Cardiomyopathy Due to Myosin R403Q Mutation

Background: A metabolic switch from fatty acid oxidation (FAO) to glycolysis associates with LV hypertrophy (LVH). Glucagon signaling increases FAO in the heart and sodium-glucose co-transporter 2 inhibitors (SGLT2i) raise glucagon/insulin ratio (GIR) in patients. We have shown that SGLT2i reprogram cardiac metabolic genes favoring FAO, yet the mechanism is unknown. Hypothesis: SGLT2i increases GIR, thereby increasing FAO and glycolysis/glucose oxidation coupling (GGC), which in turn attenuates LVH and fibrosis in a murine model of HCM (R403Q myosin mutation). Methods: Mice 9 weeks of age were treated ± SGLT2i empagliflozin (EMPA, 0.15 mg/g chow). After 2 weeks, prior to LVH onset, myocardial transcriptomic analysis was performed. After 16 weeks, echocardiography, proteomics, fasted GIR, and histology were obtained. Glucose fluxes, energetics and 13 C substrate oxidation were measured in isolated beating hearts by 31 P and 13 C NMR spectroscopy. Results: R403Q mice had ↓GIR which was normalized by EMPA. Transcriptomics (2 weeks) and proteomics (16 weeks) confirmed downregulation of electron transport and FAO pathways, and upregulation of LVH and fibrosis pathways. At 16 weeks, R403Q hearts exhibited LVH, fibrosis, ↓diastolic function and ↓contractile reserve (rate pressure product increase between low and high workload). Metabolically, R403Q had ↑glucose uptake and ↓GGC with ↑lactate production; ↓FAO and impaired energetics (↓free energy of ATP hydrolysis, ΔG ~ATP , at both workloads). The HCM phenotype and all measures of metabolic dysfunction were partially or completely prevented by EMPA. Conclusion: R403Q hearts display marked metabolic reprogramming that appears early in the disease process and leads to energetic dysfunction. SGLT2i corrects GIR, attenuates metabolic reprogramming and the energetic, structural and functional features of HCM. SGLT2i and possibly other measures to modulate glucagon signaling hold therapeutic potential in HCM.

S-23-2: CLINICAL SIGNIFICANCE OF WORK STRESS INDUCED INCREASE IN BLOOD PRESSURE IN HYPERTENSION MANAGEMENT

We usually spend about one third time of a day for working. So it is critically important for our health if the working condition is comfortable or stressful. In many developed countries including Japan, retirement age tended to be delayed due to several reasons. This means that we must spend more time for work in our life. Elderly people are vulnerable to brain and heart diseases. So the establishment of less stressful work condition and risk management is increasingly important to prevent work-related cardiovascular events or Karoshi. Among 203 Karoshi cases received worker compensation in Japan, 60 % died of stroke while remaining cardiovascular diseases. For occupational factor, long working has been considered as a risk of Karoshi. Meta-analysis has also shown that long working hours are associated with increased risk of cardiovascular diseases, especially for stroke. In Karoshi cases, most prevalent risk factor was hypertension (40%). However, the review of literature has shown that the relationship between long working hours and blood pressure increase or hypertension is inconsistent. Interestingly, some data showed that long working hours are associated with lower risk of hypertension, suggesting that the relationship between working long hours and blood pressure increase is confounded by other factors like qualitative work stress. Karoshi unexpectedly occur. Therefore in a real world, we need to obtain an individual information on blood pressure response during work to adequately manage work-related hypertension. Ambulatory blood pressure monitoring is an ideal method to monitor blood pressure behavior during work but is not practical to perform repeatedly with short duration. Self-measurement of blood pressure may replace ambulatory monitoring to examine work-related blood pressure variation. We studied 207 treated hypertensive subjects working for 29 Rosai hospitals. Blood pressures and heart rate were measured by themselves with an automated device at standardized conditions 4 times a day: after waking, 10:00 h, 16:00 h, and before sleep on three days (Monday, Friday, and Saturday or Sunday). We could observe clear daily and weekly variation of rate pressure product (systolic blood pressure × heart rate). The increase in rate pressure product on Monday morning was significantly correlated with urinary albumin excretion and job strain index in women. Our data showed the feasibility of self-monitoring of blood pressure and heart rate at workplace. This method would be useful to monitor work-stress related hypertension in several overwork situation.

Body mass index associated differences in cardiac stress energetics in type 2 diabetes

Abstract Background Patients with T2D and heart disease have normal body mass index (BMI), suggesting that diabetes and obesity mediate cardiovascular change by different mechanisms. Changes in cardiac energy metabolism in lean diabetic patients during exercise stress have not been previously reported. Objectives We aimed to assess if there are BMI-associated differences in cardiac stress metabolism in patients with T2D. Methods Twenty-five overweight T2D patients (O-T2D) and eleven lean T2D patients (LnT2D), age- and ethnicity-matched and with no other comorbidities were studied. Patients were on oral hypoglycaemics only and were free of diabetes complications. Participants underwent rest and dobutamine stress phosphorus magnetic resonance spectroscopy (31P-MRS) and cardiovascular magnetic resonance (CMR) at 3T for the assessment of myocardial phosphocreatine to ATP ratio (PCr/ATP) as a measure of myocardial energetics, biventricular volumes, rest and stress left ventricular (LV) ejection fraction, global longitudinal shortening, and mitral in-flow E/A ratio for assessment of diastolic function and perfusion. Intravenous Dobutamine was administered at a dose of 10μg/kg/min, increasing at 90 second intervals up to a maximum of 40 μg/kg/min to achieve a target heart rate of 65% of the age-predicted maximal heart rate. Mean rate pressure product (RPP) was recorded at rest and stress. Heart rate was maintained at target for the duration of the 31P-MRS and stress CMR cine, mitral in-flow and perfusion acquisitions. Results The cardiac volumes, systolic or diastolic function and LV mass were similar between LnT2D and O-T2D. Although the O-T2D patients had a numerically lower rest and stress PCr/ATP ratio, this did not reach statistical significance. Resting PCr/ATP was reduced in LnT2D and O-T2D patients similarly. However, LnT2D showed a greater reduction in PCr/ATP (stress PCr/ATP LnT2D 1.51±0.2 vs O-T2D 1.41±0.25, p=0.02) despite similar increases in RPP. Stress myocardial blood flow (MBF) was also significantly lower in the O-T2D patients. There were significant correlations of BMI with LV mass (r=0.35, p=0.03); stress LVEF (r=−0.34, p=0.04); stress MBF stress (r=−0.53, p=0.001) and stress E/A (r=0.46, p=0.01) (figure 1). Conclusions Despite their better stress perfusion and similar glycaemic control, LnT2D show worse metabolic reserve characterised by more significant decrements in energetics in response to hemodynamic stress compared to overweight patients with T2D. Higher BMI correlates inversely with stress myocardial blood flow and with stress left ventricular ejection fraction. The presence of these subtle alterations in measures of stress metabolism and perfusion might signify a distinct metabolic phenotype of “lean diabetic cardiomyopathy”. Future studies are needed to further delineate alterations in cardiac energy metabolism in lean and overweight/obese type 2 diabetes patients, and their role in the development of cardiac dysfunction. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Wellcome TrustBHF

Cardiometabolic determinants of cardiorespiratory fitness at rest, during exercise and post-exercise periods

We aimed to assess the relationship between cardiorepiratory fitness (CRF) and cardiometabolic parameters among young Nigerian adults. 100 young adults (50 males, 50 females) aged 20-30 years, selected from College of Health Sciences, Nnamdi Azikiwe University, Nigeria, participated in the study. Subjects’ demographic data and medical information were obtained through the use of structured pre-exercise health and lifestyle screening questionnaire, physical examination and morphometric measurements. Exercise test was carried out using a mechanically braked magnetic ergometer bicycle at an incremental workload of 30 W every 2 min until the subject reached a volitional exhaustion. Blood pressure (BP) and heart rate (HR) were measured at rest, during exercise and at post-exercise periods. Data indicated a significantly (Ρ&lt;0.05) lower resting HR and rate pressure product (RPP), but higher targeted HR reserve, %RPP increase, peak oxygen pulse, cardiac output, exercise duration and work rate compared with the intermediate and unfit groups in both sexes. Age and BMI adjusted correlation test also indicated significant associations between peak oxygen consumption (VO2) and resting HR, resting RPP, targeted HR reserve, oxygen pulse, cardiac output, % RPP increase, actual HR reserve, exercise duration, and work rate. In contrast, resting BP, resting pulse pressure, peak systolic blood pressure (SBP), peak HR, percentage maximum HR, SBP recovery and HR recovery did not correlate with peak VO2. The present findings suggest that a multiple approach involving both metabolic and cardiovascular interventions might be appropriate when implementing strategies to enhance CRF and improve general well-being.

Analysis Of Physiological Determinants During A Single Bout Of German Volume Training

While resistance training (RT) has been proposed as a useful adjunct in a primary prevention setting and rehabilitation context, the exact application of training intensity and volume for maximal therapeutic effects is still unclear. In this regard, German Volume Training (GVT), or the 10 sets method, has been utilized by athletes for decades and may prove a safe and effective method in improving strength and cardiorespiratory endurance, and modifying coronary risk factors. PURPOSE: To determine the physiological determinants during a single bout of German Volume Training. METHODS: Using a within-group design, untrained healthy males (n = 19; mean age: 22 ± 1 years) served as their own inactive controls prior to engaging in a single one-hour bout of GVT consisting of leg press, chest press, latissimus dorsi pull-downs and shoulder press for 10 sets of 10 repetitions each with a 60-second rest between sets and a three-minute rest period between exercises. Differences from pre- to post-test were examined using t-tests with alpha levels set at p ≤ 0.05. RESULTS: An acute bout of GVT significantly (p ≤ 0.05) decreased systolic blood pressure (SPB) (from 119 ± 9 mmHg to 110 ± 9 mmHg; p = 0.042), diastolic BP (DBP) (from 77 ± 10 mmHg to 68 ± 10 mmHg; p = 0.037) and mean arterial pressure (MAP) (from 91 ± 9 mmHg to 82 ± 8 mmHg; p = 0.028), but increased rate pressure product (RPP) (from 8370 ± 826 to 12332 ± 1602; p = 0.008). Increases were observed in carbon dioxide production (VCO2) (from 0.34 ± 0.09 L.min-1 to 0.65 ± 0.32 L.min-1; p = 0.021). No changes were found in any of the measured spirometry parameters. CONCLUSION: This study suggests that GVT is of sufficient safety and provides the appropriate intensity to be included in general primary prevention and rehabilitation settings.

Abstract 9199: A Novel Small Molecule Troponin Activator Increases Cardiac Contractile Function Without Negative Impact on Energetics or Diastolic Function

Background: Current heart failure (HF) therapies improve cardiac energy balance and prolong survival by unloading the failing heart without targeting the underlying problem of reduced cardiac contractility. Traditional inotropic medications, also termed calcitropes, stimulate contractility via energetically costly augmentation of calcium cycling and worsen patient survival. Myotropes are a new class of agents that activate the sarcomere directly, independent of cAMP and calcium. We hypothesize that a novel myotrope, troponin activator (TA1), increases contractility without the deleterious myocardial energetic impact of calcitrope dobutamine (DOB). Methods: We determined the pharmacodynamics of TA1 ex vivo and in vivo in anesthetized normal rats. Isolated rat hearts were perfused with incremental concentrations of TA1 or DOB to compare their effect on cardiac contractility and high-energy phosphate concentrations using 31 P NMR spectroscopy. Results: A dose dependent increase in contractility was observed in vivo by echocardiography after acute administration of TA1. In isolated hearts, increasing concentrations of TA1 and DOB similarly increased rate pressure product (RPP), which is a product of developed pressure (DevP) and heart rate (HR). At equivalent doses (DOB 120 nM, TA1 60 nM), TA1 increased DevP more and HR less compared to DOB. DOB decreased phosphocreatine (PCr) to ATP ratio and free energy of ATP hydrolysis (ΔG ~ATP ) and elevated left ventricular end-diastolic pressure (LVEDP). In contrast, the TA1 increased RPP without any effect on HR, LVEDP, PCr/ATP ratio or ΔG ~ATP . Conclusions: Here we describe a novel myotrope, TA1, that increased myocardial contractility by sensitizing the sarcomere to calcium without impairing diastolic function or depleting the cardiac energy reserve. Since energetic depletion negatively correlates with long term survival, TA1 may represent a superior alternative to traditional inotropes in HF management.

Myocardial blood flow during passive heat exposure in healthy young adults

INTRODUCTION Extreme heat events, such as heatwaves, are associated with a greater risk of cardiovascular mortality. However, the pathophysiology that links extreme heat and cardiovascular mortality remains unknown. Upon exposure to a hot environment, cardiac contractility and heart rate increase thereby presumably increasing myocardial metabolism. Although greater oxygen extraction contributes, an increase in myocardial metabolism is primarily met by greater myocardial blood flow. It is therefore conceivable that the required myocardial blood flow during heat exposure exceeds the capacity for myocardial blood flow to increase in vulnerable individuals. However, the extent to which myocardial blood flow increases during heat exposure is unknown. The purpose of this study is to test the hypothesis that passive heat exposure increases myocardial blood flow. METHODS Five healthy adults (31 ± 3 years, 2 women/3 men) participated in 1 experimental visit during which myocardial blood flow was measured by positron emission computed/tomography. Measurements were performed at baseline and during passive heat stress (water-perfused suit with water at 50°C) at an increase in core (rectal) temperature of 0.5°C, 1.0°C, and 1.5°C. Heart rate and rhythm (ECG) and blood pressure (automated auscultation) were also measured. RESULTS Relative to baseline, rate pressure product was greater at an increase in rectal temperature of 0.5°C (+4165 ± 623 bpm × mmHg, p=0.01), 1.0°C (+5015 ± 519 bpm × mm Hg, p<0.01) and 1.5°C (+7516 ± 261 bpm × mm Hg, p<0.01). The increase in rate pressure product was primarily due to an increase in heart rate (p<0.01), as systolic blood pressure was not affected by heat exposure (p=0.12). Relative to baseline values, myocardial blood flow increased at an increase in rectal temperature of 0.5°C (+0.45 ± 0.09 mL/min/g, p=0.03), 1.0°C (+0.61 ± 0.06 mL/min/g, p<0.01) and 1.5°C (+1.10 ± 0.22 mL/min/g, p=0.02). Overall, myocardial blood flow increased 2.7 ± 1.0-fold relative to baseline at an increase in rectal temperature of 1.5°C. The change in myocardial blood flow during heat exposure correlated with the change in rate pressure product (r=0.78, p<0.01). CONCLUSION These results suggest that passive heat exposure increases myocardial blood flow in proportion with the increase in rate pressure product in young healthy adults.

Safety and feasibility of dopamine-atropine stress echocardiography.

Dobutamine-atropine stress echocardiography (DSE) has lower sensitivity in patients with advanced liver disease (ALD) due to vasodilation. Dopamine-atropine stress echocardiography (DopSE) may be an alternative to DSE in ALD patients by improving the blood pressure response to stress. The safety and tolerability of DSE and DopSE were compared in 10 volunteers. The safety, adverse effects, and efficacy of DopSE were then assessed in 105 patients, 98 of whom had ALD. Dopamine was infused in stepwise fashion from 5µg/kg/min to a peak dose of 40µg/kg/min. Atropine was given before and in early stages of dopamine infusion up to cumulative dose of 1.5mg. The hemodynamic responses of 98 ALD patients were compared with 102 patients with ALD who underwent standard DSE. In normal volunteers, systolic BP increased more with DopSE compared to DSE (61±19mmHg vs 39±15mmHg, P=.008). In 105 patients who underwent DopSE, none had adverse effects that required early stress termination. In the groups with ALD, the systolic BP increase (38±28mmHg vs 12±27mmHg, P<.001) and peak rate pressure product (RPP) (22861±5289 vs 17211±3848, P=<.001) were both higher in those undergoing DopSE versus DSE. The sensitivity and specificity of DopSE were 45% and 88%, respectively for coronary disease (≥70% stenosis) in 37 patients who had angiography. Dopamine-atropine stress echocardiography appears to be a safe stress modality and provides greater increases in RPP in patients with ALD compared to DSE.

Effect of banana leaf bath on blood pressure, pulse rate, and its related variables in healthy individuals

Introduction: Sunbath (heliotherapy) is a popular treatment modality being used since ancient times in many parts of the world. Banana leaf bath (BLB), a type of sunbath, is commonly employed in the treatment of various diseases in India. This study was conducted to evaluate the effect of BLB on blood pressure (BP) in healthy individuals. Materials and Methods: A single group pretest and posttest study design was adopted. Twenty (9 males, 11 females) healthy individuals aged 23.80 ± 3.93 years were recruited. All the subjects underwent a 30-min session of BLB. Assessments such as systolic-BP (SBP), diastolic-BP (DBP), and pulse rate (PR) were measured using an automatic BP monitor before and after the intervention, while pulse pressure (PP), mean arterial pressure (MAP), rate pressure product (RPP), and double product (Do-P) were derived using standard formula. Statistical analysis was performed using Statistical Package for the Social Sciences version-16. Results: Results of this study showed a significant increase in SBP, PP, and MAP with a significant reduction in PR and no significant difference in DBP, RPP, and Do-P in the posttest assessment compared with baseline assessment. However, subgroups (male group and female group) analysis showed the presence of a significant increase in RPP in male participants unlike in female participants. Conclusion: Results of this study suggest that 30 min of BLB might increases SBP, PP, and MAP and reduces PR with and without affecting cardiac workload in males and females, respectively.

Sex-Specific Associations Between Cardiac Workload, Peripheral Vascular Calcification, and Bone Mineral Density: The Gambian Bone and Muscle Aging Study.

Noncommunicable diseases (NCD) are rapidly rising in Africa, with multimorbidity increasing the burden on health and social care. Osteoporosis and cardiovascular disease (CVD) share common risk factors; both often remain undiagnosed until a major life-threatening event occurs. We investigated the associations between cardiac workload, peripheral vascular calcification (PVC), and bone parameters in Gambian adults. The Gambian Bone and Muscle Aging Study (GamBAS) recruited 249 women and 239 men aged 40 to 75+ years. Body composition and areal bone mineral density (aBMD) were measured using dual-energy X-ray absorptiometry; peripheral quantitative computed tomography (pQCT) scans were performed at the radius and tibia. Supine blood pressure and heart rate were measured and used to calculate rate pressure product and pulse pressure. Presence of PVC was determined from tibia pQCT scans. Sex interactions were tested (denoted as p-int); adjustments were made for residuals of appendicular lean mass (ALM) and fat mass (FM). There were negative associations between rate pressure product and aBMD in women only, all p-int < .05; after adjustment for ALM residuals, for every 10% increase in rate pressure product, aBMD was lower at the whole body (-0.6% [-1.2, -0.1]), femoral neck (-0.9% [-1.8, -0.05]), L1 to L4 (-0.6% [-1.7, 0.5]), and radius (-1.9% [-2.8, -0.9]); there were similar associations when adjusted for FM residuals. Similar negative associations were found between pulse pressure and aBMD in women only. PVC were found in 26.6% men and 22.5% women; women but not men with calcification had poorer cardiac health and negative associations with aBMD (all sites p-int < .001). There were consistent associations with cardiac parameters and pQCT outcomes at the radius and tibia in women only. Multiple markers of cardiac health are associated with poorer bone health in Gambian women. In the context of epidemiological transition and changing NCD burden, there is a need to identify preventative strategies to slow/prevent the rising burden in CVD and osteoporosis in Sub-Saharan Africa. © 2020 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Does the combination of resistance training and stretching increase cardiac overload?

OBJECTIVES:To compare the effects of combinations of resistance training (RT) and static stretching (SS) on heart rate (HR), systolic pressure (SBP), diastolic pressure (DBP), rate pressure product (RPP), oxygen saturation (SpO2), rating of perceived effort (RPE), and heart rate variability (HRV) in men.METHODS:Twelve normotensive healthy men participated in four protocols: a) SS+RT, b) RT+SS, c) RT, and d) SS. Variables were measured before, immediately after, and 15, 30, and 45 min after the sessions.RESULTS:The combination of SS and RT increased (p<0.001) HR when compared to the effects of the noncombined protocols (from 2.38 to 11.02%), and this result indicated metabolic compensation. Regarding DBP, there were differences (p<0.001) between the RT and SS groups (53.93±8.59 vs. 67.00±7.01 mmHg). SS has been shown to be able to reduce (p<0.001) SpO2 (4.67%) due to the occlusion caused by a reduction in the caliber of the blood vessels during SS compared to during rest. The increase in RPP (6.88% between RT and SS+RT) along with the HR results indicated higher metabolic stress than that reflected by the RPE (combined protocols increased RPE from 21.63 to 43.25%). The HRV analysis confirmed these results, showing increases (p<0.01) in the LF index between the combined and noncombined protocols. Compared to the effect of RT, the combination of SS and RT promoted a vagal suppression root mean square of the successive differences (RMSSD) index (from 9.51 to 21.52%) between the RT and SS+RT groups (p<0.01) and between the RT and RT+SS groups (p<0.001).CONCLUSION:Static stretching increases cardiac overload and RPE, reducing oxygen supply, especially when performed in combination with RT.

A study on rate pressure product in south Indian pregnant women with anaemia

Background: Anaemia is a cause of serious concern and contributes to a significantly higher maternal mortality. Rate Pressure Product (RPP) is a major determinant of myocardial oxygen consumption and blood flow. There is an increase in oxygen demand in anemia. Thus, in the present study, we have compared the difference in RPP between a normal pregnant women and pregnant women with anemia.Methods: A total of 180 pregnant women (normal pregnant woman - 90 and pregnant woman with anaemia - 90) belonging to different trimesters of pregnancy were included in the study. Age, height, and weight were recorded, and their body mass index was calculated. The systolic blood pressure, diastolic blood pressure, heart rate was recorded and RPP was calculated.Results: There was a significant increase in RPP in pregnant woman with anaemia in all three trimesters of pregnancy, but the significant increase was more in the third trimester.Conclusions: The present study shows that there is an increase in RPP in pregnant woman with anaemia and they are more prone to hemodynamic stress and cardiovascular risks, especially in their third trimester of pregnancy. This hemodynamic change may be taken into account to prevent the cardiovascular complications associated with anemia in pregnancy. Thus, RPP can be used as a sensitive non-invasive simple marker for early diagnosis of cardiovascular disease in pregnant woman.

Leptin Modifies the Rat Heart Performance Associated with Mitochondrial Dysfunction Independently of Its Prohypertrophic Effects.

Background Functional receptors for leptin were described on the surface of cardiomyocytes, and there was a prohypertrophic effect with high concentrations of the cytokine. Therefore, leptin could be a link between obesity and the prevalence of cardiovascular diseases. On the other hand, a deleterious effect of leptin on mitochondrial performance was described, which was also associated with the evolution of cardiac hypertrophy to heart failure. The goal of our study was to analyze the effect of the exposure of rat hearts to a high concentration of leptin on cardiac and mitochondrial function. Methods Rat hearts were perfused continuously with or without 3.1 nM leptin for 1, 2, 3, or 4 hours. Homogenates and mitochondria were prepared by centrifugation and analyzed for cardiac actin, STAT3, and pSTAT3 by Western blotting, as well as for mitochondrial oxidative phosphorylation, membrane potential, swelling, calcium transport, and content of oxidized lipids. Results In our results, leptin induced an increased rate-pressure product as a result of increased heart rate and contraction force, as well oxidative stress. In addition, mitochondrial dysfunction expressed as a loss of membrane potential, decreased ability for calcium transport and retention, faster swelling, and less respiratory control was observed. Conclusions Our results support the role of leptin as a deleterious factor for cardiac function and indicates that mitochondrial dysfunction could be a trigger for cardiac hypertrophy and failure.

Physiological Responses to Daily Use of Beta-Three Adrenergic Receptor Agonist, Mirabegron

Background: Brown Adipose Tissue (BAT) in adult humans has become increasingly recognized to contribute to energy consumption and modulate metabolism. To date, BAT stimulation has predominately relied on cold exposure. However, long-term cold exposure is impractical as a treatment option for obesity and diabetes. Thus, we investigated if a chronic pharmacotherapeutic approach could stimulate BAT and contribute to metabolic health. Methods: In an ongoing study, 6 healthy female volunteers received 4 weeks of daily mirabegron (Myrbetriq, Astellas Pharma) 100 mg, a β3 adrenergic receptor (AR) agonist. Acute responses were determined by comparing effects before and then five hours after dosing. Chronic changes were assessed after 4 weeks of treatment. The primary endpoint was the change in BAT metabolic activity measured by 18F-FDG PET/CT. Secondary endpoints included resting energy expenditure (REE), insulin and glucose sensitivity, liver steatosis, and cardiovascular stimulation. Results: Acute effects of mirabegron included consistent increases in rate pressure product (RPP), REE, and serum non-esterified fatty acids (NEFA) (p&amp;lt;0.05, p=0.06, p&amp;lt;.05). After 4 weeks, there was a wide range of changes in BAT volume (41 ± 223 mL, p=0.86). Body weight was unchanged (0.3 ± 0.62 kg). Several physiological responses after chronic treatment were blunted, including smaller mirabegron-induced increases in RPP, NEFA, and REE. Yet, there were significant increases in sleeping EE (72 ± 23 kcal/d, p=0.03), insulin sensitivity (1.5 ± .6 (mU/L*min, p=0.05), and liver steatosis (30 ± 10 dB/m, p = 0.04) after 4 weeks. Conclusions: Acute treatment with mirabegron in women successfully activates BAT thermogenesis. Preliminary data show chronic treatment resulted in a blunting of several responses, consistent with physiological attenuation of β-AR signaling. The increases in sleeping EE and improved insulin sensitivity suggest chronic mirabegron treatment may help alleviate metabolic disease. Disclosure A. O'Mara: None. A. Cypess: None. C. Cero: None. J.W. Johnson: None. J.D. Linderman: None. B. Leitner: None. L. Fletcher: None. R. Brychta: None. D. Kapuria: None. S. McGehee: None. Y. Rotman: None.

Increased rate pressure product is linked to sympathovagal imbalance in Indian obese postmenopausal women

Increased rate pressure product is linked to sympathovagal imbalance in Indian obese postmenopausal women

Chronic activation of hypothalamic oxytocin neurons improves cardiac function during left ventricular hypertrophy-induced heart failure

A distinctive hallmark of heart failure (HF) is autonomic imbalance, consisting of increased sympathetic activity, and decreased parasympathetic tone. Recent work suggests that activation of hypothalamic oxytocin (OXT) neurons could improve autonomic balance during HF. We hypothesized that a novel method of chronic selective activation of hypothalamic OXT neurons will improve cardiac function and reduce inflammation and fibrosis in a rat model of HF. Two groups of male Sprague-Dawley rats underwent trans-ascending aortic constriction (TAC) to induce left ventricular (LV) hypertrophy that progresses to HF. In one TAC group, OXT neurons in the paraventricular nucleus of the hypothalamus were chronically activated by selective expression and activation of excitatory DREADDs receptors with daily injections of clozapine N-oxide (CNO) (TAC + OXT). Two additional age-matched groups received either saline injections (Control) or CNO injections for excitatory DREADDs activation (OXT NORM). Heart rate (HR), LV developed pressure (LVDP), and coronary flow rate were measured in isolated heart experiments. Isoproterenol (0.01 nM-1.0 µM) was administered to evaluate β-adrenergic sensitivity. We found that increases in cellular hypertrophy and myocardial collagen density in TAC were blunted in TAC + OXT animals. Inflammatory cytokine IL-1β expression was more than twice higher in TAC than all other hearts. LVDP, rate pressure product (RPP), contractility, and relaxation were depressed in TAC compared with all other groups. The response of TAC and TAC + OXT hearts to isoproterenol was blunted, with no significant increase in RPP, contractility, or relaxation. However, HR in TAC + OXT animals increased to match Control at higher doses of isoproterenol. Activation of hypothalamic OXT neurons to elevate parasympathetic tone reduced cellular hypertrophy, levels of IL-1β, and fibrosis during TAC-induced HF in rats. Cardiac contractility parameters were significantly higher in TAC + OXT compared with TAC animals. HR sensitivity, but not contractile sensitivity, to β-adrenergic stimulation was improved in TAC + OXT hearts.

Inhibition of sarcolemmal FAT/CD36 by sulfo-N-succinimidyl oleate rapidly corrects metabolism and restores function in the diabetic heart following hypoxia/reoxygenation.

AimsThe type 2 diabetic heart oxidizes more fat and less glucose, which can impair metabolic flexibility and function. Increased sarcolemmal fatty acid translocase (FAT/CD36) imports more fatty acid into the diabetic myocardium, feeding increased fatty acid oxidation and elevated lipid deposition. Unlike other metabolic modulators that target mitochondrial fatty acid oxidation, we proposed that pharmacologically inhibiting fatty acid uptake, as the primary step in the pathway, would provide an alternative mechanism to rebalance metabolism and prevent lipid accumulation following hypoxic stress.Methods and resultsHearts from type 2 diabetic and control male Wistar rats were perfused in normoxia, hypoxia and reoxygenation, with the FAT/CD36 inhibitor sulfo-N-succinimidyl oleate (SSO) infused 4 min before hypoxia. SSO infusion into diabetic hearts decreased the fatty acid oxidation rate by 29% and myocardial triglyceride concentration by 48% compared with untreated diabetic hearts, restoring fatty acid metabolism to control levels following hypoxia-reoxygenation. SSO infusion increased the glycolytic rate by 46% in diabetic hearts during hypoxia, increased pyruvate dehydrogenase activity by 53% and decreased lactate efflux rate by 56% compared with untreated diabetic hearts during reoxygenation. In addition, SSO treatment of diabetic hearts increased intermediates within the second span of the Krebs cycle, namely fumarate, oxaloacetate, and the FAD total pool. The cardiac dysfunction in diabetic hearts following decreased oxygen availability was prevented by SSO-infusion prior to the hypoxic stress. Infusing SSO into diabetic hearts increased rate pressure product by 60% during hypoxia and by 32% following reoxygenation, restoring function to control levels.ConclusionsDiabetic hearts have limited metabolic flexibility and cardiac dysfunction when stressed, which can be rapidly rectified by reducing fatty acid uptake with the FAT/CD36 inhibitor, SSO. This novel therapeutic approach not only reduces fat oxidation but also lipotoxicity, by targeting the primary step in the fatty acid metabolism pathway.

Cardiovascular Responses to Unilateral, Bilateral, and Alternating Limb Resistance Exercise Performed Using Different Body Segments.

Moreira, OC, Faraci, LL, de Matos, DG, Mazini Filho, ML, da Silva, SF, Aidar, FJ, Hickner, RC, and de Oliveira, CEP. Cardiovascular responses to unilateral, bilateral and alternating limb resistance exercise performed using different body segments. J Strength Cond Res 31(3): 644-652, 2017-The aim of this study was to verify and compare the cardiovascular responses to unilateral, bilateral, and alternating limb resistance exercise (RE) performed using different body segments. Fifteen men experienced in RE were studied during biceps curls, barbell rows, and knee extension exercises when performed bilaterally, unilaterally, and using alternating limbs. The protocol consisted of 3 sets of 10 repetitions at 80% of 10 repetition maximum with 2-minute rest between sets. Heart rate (HR) and blood pressure (BP) were measured after the last repetition. There was a statistically significant increase in HR, systolic blood pressure (SBP), and rate pressure product (RPP), from rest to postexercise. The RPP was higher in the third set of all exercises and in all 3 forms of execution, when compared with the first set. Bilateral biceps curls caused a greater increase in RPP (first and second sets) and HR, compared with the same exercise performed unilaterally. Furthermore, the performance of bilateral biceps curls induced greater HR and RPP, in all sets, compared with bilateral knee extension and barbell rows. There was also a significantly higher SBP for the alternating second and third sets and also for the bilateral third set of the knee extensions as compared with the barbell rows. It was concluded from the data of this study that the cardiovascular response was increased from rest to postexercise in all forms of exercise, especially immediately after the third set of RE. For exercises performed bilaterally with the upper body (biceps curls), there was a greater cardiovascular response when compared with the same exercise performed unilaterally or with lower-body exercise performed bilaterally.