Myocardial Energy Response to Glyceryl Trinitrate: Physiology Revisited

Objective: Although intravenous nitrates are commonly used in clinical medicine, they have been shown to increase myocardial oxygen consumption and inhibit complex IV of the electron transport chain. As such we sought to measure whether myocardial energetics were impaired during glyceryl trinitrate (GTN) infusion.Methods: 10 healthy volunteers underwent cardiac magnetic resonance imaging to assess cardiac function and 31phosphorus magnetic resonance spectroscopy to measure Phosphocreatine/ATP (PCr/ATP) ratio and creatine kinase forward rate constant (CK kf) before and during an intravenous infusion of GTN.Results: During GTN infusion, mean arterial pressure (78 ± 7 vs. 65 ± 6 mmHg, p < 0.001), left ventricular (LV) stroke work (7,708 ± 2,782 vs. 6,071 ± 2,660 ml mmHg, p < 0.001), and rate pressure product (7,214 ± 1,051 vs. 6,929 ± 976 mmHg bpm, p = 0.06) all fell. LV ejection fraction increased (61 ± 3 vs. 66 ± 4%, p < 0.001), with cardiac output remaining constant (6.2 ± 1.5 vs. 6.5 ± 1.4 l/min, p = 0.37). Myocardial PCr/ATP fell during GTN infusion (2.17 ± 0.2 vs. 1.99 ± 0.22, p = 0.03) with an increase in both CK kf (0.16 ± 0.07 vs. 0.25 ± 0.1 s−1, p = 0.006) and CK flux (1.8 ± 0.8 vs. 2.6 ± 1.1 μmol/g/s, p = 0.03).Conclusion: During GTN infusion, despite reduced LV stroke work and maintained cardiac output, there was a 44% increase in myocardial ATP delivery through CK. As PCr/ATP fell, this increase in ATP demand coincided with GTN-induced impairment of mitochondrial oxidative phosphorylation. Overall, this suggests that while GTN reduces cardiac work, it does so at the expense of increasing ATP demand beyond the capacity to increase ATP production.

Spleen Perfusion as an Index of Gender Impact on Sympathetic Nervous System Response to Exercise

Objective: Sympathetic nervous system (SNS) reaction to exercise is gender dependent. Nevertheless, clinically applicable methods to identify this difference are still missing. An organ largely sensitive to SNS is the spleen whose response to exercise can be easily evaluated, being included in the field of view of myocardial perfusion imaging (MPI). Here, we aimed to verify whether gender interferes with the spleen perfusion and its response to exercise.Methods: For this purpose, we evaluated 286 original scans of consecutive patients submitted to MPI in the course of 2019. Our standard procedure implies a single-day stress-rest sequence with a gap of ≥2 h between the administrations of 180 and 500 MBq of 99mTc-Sestamibi, respectively. Imaging is performed 30 min after radiotracer administration, with scan duration set at 25 and 35 s per view, respectively. Non-gated scans were reconstructed with the filtered back-projection method. A volume of interest was drawn on the spleen and heart to estimate the dose-normalized average counting rate that was expressed in normalized counts per seconds (NCPS).Results: In all subjects submitted to exercise MPI (n = 228), NCPS were higher during stress than at rest (3.52 ± 2.03 vs. 2.78 ± 2.07, respectively; p < 0.01). This effect was not detected in the 58 patients submitted to dipyridamole-stress. The response to exercise selectively involved the spleen, since NCPS in heart were unchanged irrespective of the used stressor. This same response was dependent upon gender, indeed spleen NCPS during stress were significantly higher in the 75 women than in the 153 men (3.86 ± 1.8 vs. 3.23 ± 1.6, respectively, p < 0.01). Again, this variance was not reproduced by heart. Finally, spleen NCPS were lower in the 173 patients with myocardial reversible perfusion defects (summed difference score ≥3) than in the remaining 55, despite similar values of rate pressure product at tracer injection.Conclusion: Thus, exercise interference on spleen perfusion can be detected during MPI. This effect is dependent upon gender and ischemia confirming the high sensitivity of this organ to SNS activation.

A Novel Small Molecule Troponin Activator Increases Cardiac Contractile Function Without Negative Impact on Energetics

Background: Current heart failure (HF) therapies unload the failing heart without targeting the underlying problem of reduced cardiac contractility. Traditional inotropes (i.e. calcitropes) stimulate contractility via energetically costly augmentation of calcium cycling and worsen patient survival. A new class of agents - myotropes - activate the sarcomere directly, independent of calcium. We hypothesize that a novel myotrope TA1 increases contractility without the deleterious myocardial energetic impact of a calcitrope dobutamine. Methods: We determined the effect of TA1 in bovine cardiac myofibrils and human cardiac microtissues, ex vivo in mouse cardiac fibers and in vivo in anesthetized normal rats. Effects of increasing concentrations of TA1 or dobutamine on contractile function, phosphocreatine (PCr) and ATP concentrations and ATP production were assessed by 31 P NMR spectroscopy on isolated perfused rat hearts. Results: TA1 increased the rate of myosin ATPase activity in isolated bovine myofibrils and calcium sensitivity in intact mouse papillary fibers. Contractility increased dose dependently in human cardiac microtissues and in vivo in rats as assessed by echocardiography. In isolated rat hearts, TA1 and dobutamine similarly increased rate pressure product (RPP). Dobutamine increased both developed pressure (DevP) and heart rate (HR) accompanied by decreased PCr to ATP ratio and decreased free energy of ATP hydrolysis (ΔG~ ATP ) and elevated left ventricular end-diastolic pressure (LVEDP). In contrast, the TA1 increased DevP without any effect on HR, LVEDP, PCr/ATP ratio or ΔG~ ATP . Conclusions: Novel myotrope, TA1, 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, myotropes may represent a superior alternative to traditional inotropes in heart failure management.

Impact of Lipid Profile, Cardiac Biomarkers, Serum Angiotensin-Converting Enzyme Activity, Oxidative Stress and Antioxidant on Blood Pressure Status

The hemodynamic determinants of myocardial oxygen demand measured were heart rate (HR), systolic blood pressure (BP), and rate pressure product (RPP). This study aimed to evaluate the impact of lipid profile, cardiac biomarkers, and serum angiotensin-converting enzyme (ACE) activity, oxidative stress (plasma malondialdehyde, MDA; conjugated diene, DC), and antioxidant status (glutathione peroxidase, GPx) on BP. Three hundred and six non-ST-elevated myocardial infarction (NSTEMI) patients compared to 410 healthy controls. The diastolic and systolic BP was correlated positively with serum ACE activity. The rate pressure product (RPP) was correlated negatively with Fasting glucose (r= -0.144; p = 0.012), HbA1c (r= -0.117; p = 0.041) and GPx activity (r= -0.148; p = 0.009), and positively with smoking (r = 0,197; p = 0.001), BMI (r = 0,219; p = 0.001), peak cTnI (r = 0.131; p = 0.022), serum ACE activity (r = 0,190; p = 0.001) and DC level (r = 0.189; p = 0.001) in NSTEMI patients. Regarding healthy controls, no correlation was found between the diastolic or systolic BP with serum ACE activity, peak cTnI, MDA, DC level, GPx activity, and lipid parameters. The existence of a specific correlation between the rate pressure product, diastolic and systolic BP and, lipid profile, serum ACE activity and, cardiac biomarkers, oxidative stress, and antioxidant status increase the NSTEMI risk on patients.

Blood pressure, heart rate, and rate pressure product behavior during interval and continuous aerobic exercise (Comportamiento de la presión arterial, frecuencia cardíaca y doble producto durante el ejercicio aeróbico a intervalos y continuo)

The purpose of the present study was to compare the blood pressure, heart rate, and rate pressure product behavior during interval and continuous aerobic exercise in physically active women. Eight physically active women with prior indoor cycling experience were recruited for the present study. Participants visited the laboratory for three sessions, the first visit was used for familiarization and the remaining two visits were to perform the experimental protocols in a randomized order: 1) Twenty-one minutes of continuous indoor cycling at 70% of maximum heart rate (CONT), and 2) Twenty-one minutes of interval indoor cycling, alternating one minute at 90% and two minutes at 60% of maximum heart rate (INT). To assess the hemodynamic behavior, blood pressure, heart rate, and rate pressure product were also measuring at 6-minute (During-6), 12-minute (During-12), 18-minute (During-18), and 21-minute (During-21) intervals. Both protocols (continuous and interval) showed significant increases in blood pressure, heart rate, and rate pressure product in three out of four moments (During-6, During-12, and During-21), with the interval protocol showing higher values compared to the continuous protocol. The results of this study have practical implications for both prescription and cardiac rehabilitation and may be used in an athletic and non-athletic population, since a hypotension effect and lower cardiac workload is advantageous to one’s fitness. Resumen. El propósito del presente estudio fue comparar lo comportamiento de la presión arterial, la frecuencia cardíaca y doble producto durante el ejercicio aeróbico continuo y a intervalos en mujeres físicamente activas. Para el presente estudio se reclutaron ocho mujeres físicamente activas con experiencia previa en ciclismo indoor. Los participantes visitaron el laboratorio durante tres sesiones, la primera visita se utilizó para familiarizarse y les das visitas restantes fueron para realizar los protocolos experimentales en un orden aleatorio: 1) Veintiún minutos de ciclismo indoor continuo al 70% de la frecuencia cardíaca máxima (CONT), y 2) Veintiún minutos de ciclismo indoor a intervalos, alternando un minuto al 90% y dos minutos al 60% de la frecuencia cardíaca máxima (INT). Para evaluar el comportamiento de la presión arterial, la frecuencia cardíaca y doble producto también se midieron a los 6 minutos (Durante-6), 12 minutos (Durante-12), 18 minutos (Durante-18) y 21 minutos (durante-21) durante la actividad. Ambos los protocolos (CONT y INT) mostraron aumentos significativos en la presión arterial, la frecuencia cardíaca, y el doble producto en tres de cuatro momentos (Durante-6, Durante-12 y durante-21), con el protocolo INT que muestra los valores más altos en comparación al protocolo CONT. Los resultados de este estudio tienen implicaciones prácticas tanto para la prescripción médica como para la rehabilitación cardíaca y pueden usarse en una población atlética y no atlética, ya que un efecto de hipotensión y una menor carga de trabajo cardíaco son ventajosos para la aptitud física.

Effect of yoga on cardiovascular functions and psychological aspects of people on public service-related work: an exploratory study

Objectives Yoga is increasingly being introduced in workplace settings to improve health and well-being. However, there is a lack of studies reporting the effect of yoga in people on public service-related work, who are at high risk for various health-related problems. Thus, the objective of this study was to find the effect of yoga on cardiovascular functions and psychological (stress, anxiety, and depression) aspects of people on public service-related work. Methods A single-group pre-test and post-test experimental study design was adopted. Eighty-two participants aged 41.52 ± 7.44 years who are working in the Tamil Nadu Public Service Commission were undergone 1-h of yoga (under the supervision of a yoga & naturopathy doctor) a day, 5-days a week for a period of 1-month at their office. Cardiovascular functions such as systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse rate (PR) were measured using an automatic BP monitor. Psychological variables such as stress, anxiety, and depression were measured using Depression Anxiety and Stress Scales (DASS) before and after the intervention. Results Results of this study showed a significant reduction in body mass index, SBP, DBP, PR, mean arterial pressure, rate pressure product, and double product. Though results showed insignificant (just missed the statistical significance [p=0.056]) reduction in anxiety, it showed clinical improvement (i.e. the mean anxiety score has reduced from moderate category to mild category). However, there is neither statistically significant nor clinical difference in stress and depression. None of the participants reported any untoward events during the study period. Conclusions Results suggest that yoga might improve the cardiovascular functions and anxiety of people in public service-related work. However, no such significant improvement was noted in their stress and depression levels. However, a randomized controlled trial is required to warrant the results of this study.

Effect of yoga therapy on cardiovascular parameters in patients with psoriasis: A randomized control trial — pilot study

This study was done at the Centre for Yoga Therapy, Education and Research (CYTER) of Sri Balaji Vidyapeeth (SBV) to determine cardiovascular (CV) parameters in patients with psoriasis.Data of 20 patients (12 female, 8 male) with a mean age of 44.40 ± 15.2ywho were referred by Dept. of Dermatology and attended yoga therapy sessions at CYTER was used for analysis. Supervised yoga training was given to the participants who were randomized into the yoga group. Heart rate (HR), systolic and diastolic pressure (SP and DP) was recorded using non-invasive blood pressure (NIBP) apparatus before and after the study period of 12 weeks. CV indices such as Pulse pressure (PP), mean pressure (MP), rate-pressure product (RPP), and double product (DoP) were derived using appropriate formulae.The inter-group comparison showed significant change (p<0.05) in SP. The derived CV indices such as PP, RPP & DoP also showed significant changes. (p<0.05) after 12 weeks of Yoga training. The intragroup comparison in the control group showed a significant increase in SP and DP (p<0.05). There is a healthy reduction in SP and derived CV indices following 12 weeks of yoga training. The magnitude of this reduction depends on the pre-existing medical condition and intensity of the disease in each individual. These changes may be attributed to enhanced harmony of cardiac autonomic function as a result of coordinated breath-body work and mind-body relaxation due to yoga resulting in a significant reduction in the perceived stress.

Blood Biomarkers Predict Cardiac Workload Using Machine Learning

Introduction. Rate pressure product (the product of heart rate and systolic blood pressure) is a measure of cardiac workload. Resting rate pressure product (rRPP) varies from one individual to the next, but its biochemical/cellular phenotype remains unknown. This study determined the degree to which an individual’s biochemical/cellular profile as characterized by a standard blood panel is predictive of rRPP, as well the importance of each blood biomarker in this prediction. Methods. We included data from 55,730 participants in this study with complete rRPP measurements and concurrently collected blood panel information from the Health Management Centre at the Affiliated Hospital of Hangzhou Normal University. We used the XGBoost machine learning algorithm to train a tree-based model and then assessed its accuracy on an independent portion of the dataset and then compared its performance against a standard linear regression technique. We further determined the predictive importance of each feature in the blood panel. Results. We found a fair positive correlation (Pearson r ) of 0.377 (95% CI: 0.375-0.378) between observed rRPP and rRPP predicted from blood biomarkers. By comparison, the performance for standard linear regression was 0.352 (95% CI: 0.351-0.354). The top three predictors in this model were glucose concentration, total protein concentration, and neutrophil count. Discussion/Conclusion. Blood biomarkers predict resting RPP when modeled in combination with one another; such models are valuable for studying the complex interrelations between resting cardiac workload and one’s biochemical/cellular phenotype.

Abstract P218: The Association Of Mid-life Cumulative Exposure To Systolic Blood Pressure, Myocardial Oxygen Demand, And Hypertension With Later-life Central Arterial Stiffness And Its 5-year Change: The Atherosclerosis Risk In Communities Study - Neurocognitive Study (ARIC-NCS)

Background: Greater central artery stiffness predicts cardiovascular disease and all-cause mortality, thus understanding arterial stiffness determinants has prevention implications. Reports of the temporal association of blood pressure with arterial stiffness are conflicting and the association with myocardial oxygen demand has not been evaluated. Objective: Characterize the association of mid- to later-life cumulative exposure to systolic blood pressure (SBP), myocardial oxygen demand, and hypertension (HTN) with arterial stiffness and its 5-year change in older adults. Methods: We included 1,975 adults (1151 women; 359 Black; visit 5 mean age 74 years) examined in visits 5 (2011-13) and 6 or 7 (2016-19) of the population-based ARIC-NCS with measures of arterial stiffness (carotid-femoral pulse wave velocity (cfPWV)). Higher cfPWV indicates greater arterial stiffness. We calculated cumulative exposures as the sum of averages from four consecutive visits from 1987-89 to 1996-98 divided by total time. Myocardial oxygen demand was calculated as the rate pressure product (RPP): (SBP x heart rate)/1,000. We derived HTN duration as the time since first HTN detection. Associations of cumulative exposures with visit 5 cfPWV and the 5-year cfPWV change were evaluated by multivariable linear regression adjusted for demographics and cardiometabolic factors. Results: Over the mean 5.7 years between visits 5 and 6 or 7, cfPWV increased by 144.9 cm/s (SD: 276.0; range -680.0, 961.5 cm/s). HTN at any visit, duration, and the time-weighted cumulative measures were associated with higher visit 5 cfPWV (Table). Prevalent HTN was inversely associated with cfPWV change. No statistically significant associations were observed for the other exposures and cfPWV change. Conclusion: Cumulative exposure to SBP, RPP, and HTN are modifiable traits associated with higher cfPWV at later-life, but not with rate of cfPWV change in older adulthood. HTN at visit 5 was associated with lower cfPWV change, albeit the change is of small magnitude.