Immediate changes in cardiac autonomic tone and stroke volume during microgravity simulation using head-down tilt

Objectives: Gravity plays an important role in the day-to-day functioning of the cardiovascular system (CVS) in the human body. The absence of gravity severely affects CVS functioning. Out of existing simulation models of microgravity, the 6° head-down tilt (HDT) is frequently used analog to replicate the physiological effects of microgravity on earth. Materials and Methods: The present study has been designed to determine the specificity of 6° HDT usage as a microgravity simulation. The heart rate variability (HRV), blood pressure (BP), cardiac output (CO), and stroke volume (SV) responses to 5 min exposures were investigated for 4°, 6°, and 8° HDT. It was hypothesized that the graded HDT around 6° will demonstrate reversal of autonomic parameters. The study was conducted on 28 male subjects aged 20–30 years. Results: The study reveals that there was a significant rise in diastolic and mean BP at 6° and 8° HDT as compared to baseline. It was also observed that the high-frequency power in HRV was increased at 6° HDT (P = 0.026), with a concomitant reduction in the low-frequency power (P = 0.03) of HRV. The CO was increased at 6° and 8° HDT as compared to baseline (P = 0.037 and 0.021, respectively). There were no significant changes observed in any of the recorded parameters at 4° HDT. The cardiopulmonary volume receptors might have sensed the blood volume change in HDT as in microgravity simulation the blood passively shifts to cephalad. To overcome the low blood volume problem, the heart tried to pump extra blood through increased CO. At 8° HDT, it was observed that the cardiac sympathetic activity and CO were increased, which is not observed during microgravity exposures. Conclusion: The study suggests that 6° head-down-tilt is the best tilt level for producing microgravity on earth to study immediate cardiovascular parameters as it is a balanced compromise of increased vagal activity and CO without activation of cardiac sympathetic activity. Therefore, our data provide physiological evidence in support of 6° HDT microgravity simulation for the study of immediate cardiovascular responses.

Short-Term Fasting and Ingestion of Caloric Drinks Affect Heartbeat-Evoked Potentials and Autonomic Nervous System Activity in Males

Central nervous systems receive and process information from the internal and external environment to maintain homeostasis. This includes interoceptive awareness of the organism’s nutritional state. Whenever food supply is required, feelings of hunger initiate the search for and the consumption of appropriate amounts of nutrients. How this is physiologically regulated in humans has been subjected to research into interoceptive awareness of body states during fasting and food consumption. However, there is no research on the distinct effects of carbohydrate or protein intake on interoception. Therefore, we aimed to investigate the impact of fasting and consumption of standardized carbohydrate and protein shakes on interoception in a repeated-measures cross-over design in a sample of 37 healthy, normal weight males. As a physiological correlate of interoception, we measured heartbeat-evoked potentials (HEPs), which are suggested to reflect the cortical representation of cardiac signals, during eight-minutes resting state EEG-recordings. After a 16-hour fasting period, the HEP amplitudes were lower over right central and parietal electrodes and increased after ingestion of the nutritional shake. Exploratory analyses indicated that the difference between fasting and satiety was more prominent at carbohydrate compared protein testing days. Correlation analyses with heart rate variability (HRV) suggested that high cardiac sympathetic activity is related to lower HEP amplitudes. Furthermore, cardiac sympathetic activity and stress indices decreased from before to after the intervention, whereas HRV increased. Together, this study shows for the first time that fasting and the intake of a nutritional shake affects cardiac measures of autonomic nervous system functioning and the neural correlates of cardiac interoception. These findings could be relevant for diets and psychosomatic disorders, including eating disorders.

The prognostic significance of cardiac sympathetic activity and dyssynchrony in cardiac resynchronization therapy in ischemic and non-ischemic heart failure patients

Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Russian Foundation for Basic Research Introduction Impaired cardiac sympathetic activity and contractility are associated with poor prognosis in patients with heart failure after cardiac resynchronization therapy (CRT). There are few prognostic data of the cardiac sympathetic activity and dyssynchrony in patients with chronic heart failure of various etiologies. Purpose To examine the prognostic significance of scintigraphic cardiac sympathetic activity and contractility in predicting the response to CRT and to assess the differences between patients with ischemic (IHF) and non-ischemic (NIHF) heart failure. Methods This study included 38 heart failure patients (24 male; mean age of 56 ± 11 years; 16 patients with ischemic etiology), who were submitted to CRT. Before CRT all patients underwent 123I-metaiodobenzylguanidine (123I-MIBG) imaging for cardiac sympathetic activity evaluating: early and delay heart to mediastinum ratio (eH/M and dH/M), summed MIBG Score (eSMS and dSMS). Moreover all patients underwent gated SPECT with the assessments of left ventricle dyssynchrony indexes: standard deviation (SD) and histogram bandwidth (HBW). In addition, all patients underwent gated blood-pool SPECT (GBPS) to assessed ejection fraction (EF) and stroke volume (SV) of both ventricles. Results One year after CRT response defined as LV ESV decreased by≥15% and/or LV EF increase by≥5%. Baseline cardiac sympathetic activity parameters showed significant differences between responders and non-responders only in NIHF patients: eH/M: 2.27 (2.02–2.41) vs. 1.64 (1.32–2.16); dH/M: 2.18 (2.11–2.19) vs. 1.45 (1.23 – 1.61); eSMS: 7 (5-7) vs. 15.5 (10–28.5); dSMS: 10 (10–13) vs. 16.5 (15.5–29). Significant differences in baseline LV dyssynchrony indexes between responders and non-responders were in patients of both group: in NIHF patients - SD: 54.3 (43–58) degree vs. 65 (62–66) degree; HBW: 179.5 (140–198) degree vs. 211 (208-213) degree, p < 0.054 in IHF patients - HBW: 162 (115.2–180) degree vs. 115.2 (79.2–136.8) degree. Contractility of RV was significantly differed between responders and non-responders in IHF patients: RV EF: 54.5 (41-56) % vs. 44.5 (37–49.5) %; RV SV: 80 (69-101) ml vs. 55.5 (50–72.5) ml. According to univariate logistic regression analyses in IHF patients LV dyssynchrony indexes – SD (OR = 1.55; 95% CI 1.09-2.2; p < 0.5) and HBW (OR = 1.13; 95% CI 1.02-1.24; p < 0.5), as well as RV indexes – RV EF (OR = 1.11; 95% CI 1.001-1.23; p < 0.5), RV SV (OR = 1.07; 95% CI 1.003-1.138; p < 0.5) were predictors of CRT response. In the group of NIHF patients, dH/M (OR = 1.47; 95% CI 1.08-2; p < 0.5), SD (OR = 0.83; 95% CI 0.73-0.95; p < 0.5), HBW (OR = 0.96; 95% CI 0.93-0.99; p < 0.5) showed the predictive value in terms of CRT response. Conclusion Scintigraphic methods can be used to select patients for CRT. Cardiac 123I-MIBG scintigraphy and gated SPECT may be used for predicting CRT response in NIHF patients. Whereas in IHF patients ECG-gated SPECT and GBPS may be valuable for predicting the response to CRT.

Abstract 16277: Evaluation of Left Peri Atrial Cardiac Sympathetic Activity Using Mibg Scintigraphy Before and After Cryoballoon Ablation of Paroxysmal Atrial Fibrillation

Introduction: Accelerated cardiac sympathetic activity has been implicated in the development of atrial fibrillation. Ablation or excision of atrial epicardial ganglia for the treatment of atrial fibrillation has been reported. However, visualization of the atrial neural network is considered difficult. We attempted to image the sympathetic innervation with 123 I-metaiodobenzylguanidine (MIBG) using a novel solid-state whole-body scanner (VERITON). Methods: We performed pulmonary vein isolation using a cryoballoon in 10 patients with paroxysmal atrial fibrillation. MIBG images using specific processing were evaluated before and 3 months after ablation to evaluate the neural network of the left peri-atrial cardiac sympathetic activity and its response to ablation. Discrete epicardial accumulation of MIBG was identified using MIBG images fused with atrial computed tomography images. We quantitatively calculated the discrete MIBG accumulation in each pulmonary vein within 2 cm from its ostium, which may have been modified by balloon ablation. Results: Discrete MIBG accumulation was generally reproducible in the pre- and postoperative evaluations. The discrete MIBG accumulation value was 2.8 per case, with an average count of 4.15х10 5 PROPCNTS. Of the overall 28 accumulations, 15 had disappeared and three had changed in accumulation level and location after ablation. There was no specific pattern of sympathetic image modification. However, the group in which accumulation disappeared had a significantly smaller cross-sectional area of the pulmonary vein than the group in which it did not (17.2±3.4 mm vs 19.7±1.7 mm, p=0.0056). For reference, the average cryoballoon size was 28 mm. Conclusions: The sympathetic innervation of the left atrium was visualized using MIBG imaging, and the image was modified by cryoballoon ablation. The ability to image sympathetic nerve modification by catheter ablation will be clinically useful.

Age-dependent cardiac remodelling – role of sex hormones

Background While cardiovascular mortality in women has exceeded those in men, women continue to be underrepresented in cardiovascular clinical trials. Further, preclinical experiments are predominantly conducted in male animals, rendering sex-specific variables contributing to cardiovascular disease largely unknown. As age and menopause remain to be key risk factors for cardiovascular disease in women, the aim of this study was to identify key variables of cardiac remodelling in the aging female and male heart, as well as to assess effects of sex hormone deprivation on left ventricular (LV) morphology, LV function and cardiac sympathetic activity. Materials and methods Gonadectomized and sham-operated FVB/N mice of both sexes were subjected to positron emission tomography (PET) and cardiac magnetic resonance (CMR) imaging at the age of 4 (young cohort) and 20 (aged cohort) months (total n=123, 55% females). Following tail-vein injection of [11C]meta-hydroxynorephedrine ([11C]mHED), a widely used PET probe in preclinical and clinical assessment of cardiac sympathetic integrity, animals were scanned and cardiac sympathetic outflow was derived from myocardial [11C]mHED uptake. Cardiac parameters including LV volumes and left ventricular ejection fraction (LVEF) were obtained from electrocardiogram (ECG)-gated CMR imaging. Results and discussion A significant increase of LVEF was observed in aging females (p=0.012, Figure 1), but not in males. The latter was not associated with a higher cardiac output, and was a consequence of reduced LV end-systolic volumes (p=0.008), unveiling a substantial reduction of size in the aging female heart. As this age-dependent observation was not present in gonadectomized animals (p=0.414), the lack of growth-stimulating estrogen might account for reduction of cardiac size in aging females. Thus, despite a significantly heightened body weight, female heart size is reduced with age. Accordingly, sufficient cardiac output was maintained via increased heart rate (p=0.005) and cardiac sympathetic activity (p=0.040, Figure 1). Gonadectomy accelerated age-dependent changes in LV morphology and function in female mice. While sex hormone deprivation blunted cardiac sympathetic activity and norepinephrine levels in male mice, an opposite trend was observed in females. Conclusion Despite increasing body weight with age, aged female and male hearts maintain a stable circulatory blood supply, however, by distinct mechanisms. While the “shrinking” female heart requires an increased heart rate and cardiac sympathetic activity to compensate for smaller ventricular volumes, aging males maintain cardiac size. Importantly, sex hormone deprivation at a young age accelerates age-dependent changes in LV morphology and function in female mice, but not in male mice. The increased sympathetic activity reflects a higher stress level in aged females that might expose them to a higher cardiac vulnerability at postmenopausal age. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Swiss National Science Foundation; Swissheart Foundation

Prognostic significance of cardiac sympathetic innervation and contractility in heart failure patients submitted to cardiac resynchronization therapy

Introduction In chronic heart failure patients, cardiac resynchronization therapy (CRT) does not lead to the expected result in 30% of cases. There is a lack of prognostic data related to the cardiac sympathetic activity and contractility assessment in ischemic (IHF) and non-ischemic (CHF) heart failure patients. Purpose To assess the prognostic value of radionuclide cardiac sympathetic innervation and contractility assessment in IHF and NIHF patients submitted to CRT. Methods This study included 38 HF patients (24 male; mean age of 56±11 years), who were submitted to CRT: NYHA class II/III (n=10/28), mean QRS=159.3±17.9ms. The etiology of HF was ischemic in 16 patients and non-ischemic in 22 of them. Before CRT all patients underwent 123I-metaiodobenzylguanidine (123I-MIBG) imaging for cardiac sympathetic activity evaluating. The following indexes were estimated: early and delayed heart to mediastinum ratio (eH/M and dH/M), summed MIBG Score (eSMS and dSMS). Moreover all patients underwent gated myocardial perfusion scintigraphy with the assessments of LV dyssynchrony indexes: standard deviation (SD) and histogram bandwidth (HBW). In addition, all patients underwent gated blood-pool SPECT with both ventricles ejection fraction (EF) and stroke volume (SV) assessment. Results One year after CRT all patients were divided into two groups: responders (IHF group n=11; NIHF group n=15) and non-responders (IHF group n=5; NIHF group n=7). Among baseline scintigraphic parameters the following ones showed significant differences between responders vs. non-responders. In IHF patients - HBW: 162 (115.2–180) degree vs. 115.2 (79.2–136.8) degree, p<0.05; RV_EF: 54.5 (41–56)% vs. 44.5 (37–49.5)%, p<0.05; RV_SV: 80 (69–101)ml vs. 55.5 (50–72.5)ml, p<0.05. In group of NIHF patients responders and non-responders were significantly differed in the following preoperative parameters: eH/M: 2.27 (2.02–2.41) vs. 1.64 (1.32–2.16), p<0.05; dH/M: 2.18 (2.11–2.19) vs. 1.45 (1.23–1.61), p<0.05; eSMS: 7 (5–7) vs. 15.5 (10–28.5), p<0.05; dSMS: 10 (10–13) vs. 16.5 (15.5–29), p<0.05, SD: 54.3 (43–58) degree vs. 65 (62–66) degree, p<0.05; HBW: 179.5 (140–198) degree vs. 211 (208–213) degree, p<0.05. Univariate logistic regression in IHF patients showed that LV dyssynchrony indexes – SD (OR=1.55; 95% CI 1.09–2.2; p<0.5) and HBW (OR=1.13; 95% CI 1.02–1.24; p<0.5), as well as RV indexes – RV_EF (OR=1.11; 95% CI 1.001–1.23; p<0.5), RV_SV (OR=1.07; 95% CI 1.003–1.138; p<0.5) were predictors of CRT response. In the group of NIHF patients, dH/M (OR=1.47; 95% CI 1.08–2; p<0.5), SD (OR=0.83; 95% CI 0.73–0.95; p<0.5), HBW (OR=0.96; 95% CI 0.93–0.99; p<0.5) showed the predictive value in terms of CRT response. Conclusion(s) The positive response to CRT in IHF patients showed a link with LV dyssynchrony and preserved RV contractility. Whereas in NIHF patients the functional state of cardiac sympathetic activity, as well as LV dyssynchrony, were associated with CRT response. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Russian Foundation for Basic Research