Alternations in the cardiovascular autonomic regulation and growth factors in autism

Autism spectrum disorder (ASD) represents a serious neurodevelopmental disorder associated with autonomic nervous system dysregulation. The aim was to study complex cardiovascular autonomic regulation using heart rate variability (HRV) and systolic blood pressure variability (SBPV) linear/non-linear analysis at rest and during orthostasis, and to assess plasma levels of epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF) in autistic children. Twenty-five ASD boys and 25 age and gender-matched children at the age 7 15 years were examined. After venous blood taking, continuous ECG and blood pressure biosignals were recorded at rest and during orthostasis. Evaluated parameters: RR intervals, high- and low-frequency band of HRV spectral analysis (HF-HRV, LF-HRV), symbolic dynamics parameters 0V %, 1V %, 2LV %, 2UV %, low- and high-frequency band of SBPV (LF-SBPV, HF-SBPV), systolic, diastolic, mean blood pressure, EGF, VEGF plasma levels. RR intervals were significantly shortened and the HF-HRV, LF-SBPV, HF-SBPV parameters were significantly lower at rest, the HF-HRV and LF-SBPV remained lower during orthostasis in autistic children compared to controls (p0.05). EGF plasma levels were significantly lower in ASD compared to controls (p=0.046). No significant differences were found in remaining parameters. Our study revealed tachycardia, cardiovagal underactivity, and blunted sympathetic vasomotor regulation at rest and during orthostasis in autistic children. Additionally, complex heart rate dynamics are similar in autistic children than controls. Furthermore, EGF was reduced in autistic children without significant correlations with any autonomic parameters. We suggest that the abnormal complex cardiovascular reflex control could contribute to understanding the pathway linking autonomic features and autism.

The autonomic cardiac nervous system and arrhythmogenesis: risk stratification in the foreseeable future

Both experimental and clinical studies have shown that the autonomic nervous system plays an important role in arrhythmogenesis. Many methods describing cardiovascular autonomic regulation have been developed and tested for use as predictors of arrhythmic and other cardiovascular events. The majority of studies have focused on patients with known cardiac disease, such as prior myocardial infarction or congestive heart failure. All-cause mortality, as well as non-sudden and sudden cardiac death have been used as main endpoints. Sudden cardiac death has often been considered to be equivalent to arrhythmic cardiac arrest. Despite promising results in this field, markers of the autonomic nervous system are still not routinely used in clinical practice, mainly due to the fact that measurement of these markers does not result in evidence-based therapeutic implications. There is still a lack of randomized trials using autonomic markers as pre-defined variables in selecting patients for the studies, which would have yielded results that an intervention reduces the arrhythmic or other endpoint in those with abnormal or impaired autonomic regulation. Hence, at present, the possible use of autonomic assessment in predicting life-threatening arrhythmias is restricted to individual cases at the borders of intervention guidelines.

Acknowledging Sex Differences in In vivo Experiments: Dilemma

The role of the Autonomic Nervous System (ANS) and its organ-specific functions are largely elucidated. Heart Rate Variability (HRV) analysis is a popular tool for the assessment of autonomic cardiac control. Heart rate and its changes are a sensitive indicator of ANS function, therefore cardiovascular autonomic regulation is considered to be the most reliable indicator of ANS activity and status. HRV refers to beat to beat variation in the heart rate that quantifies the interplay between sympathetic and parasympathetic activity of the ANS. Although patterns of HRV hold considerable promise for clarifying issues in clinical applications,

Role of Neuroendocrine, Immune, and Autonomic Nervous System in Anorexia Nervosa-Linked Cardiovascular Diseases

Anorexia nervosa represents a severe mental disorder associated with food avoidance and malnutrition. In patients suffering from anorexia nervosa, cardiovascular complications are the main reason leading to morbidity and mortality. However, the origin and pathological mechanisms leading to higher cardiovascular risk in anorexia nervosa are still unclear. In this aspect, the issue of exact pathological mechanisms as well as sensitive biomarkers for detection of anorexia nervosa-linked cardiovascular risk are discussed. Therefore, this review synthesised recent evidence of dysfunction in multiple neuroendocrine axes and alterations in the immune system that may represent anorexia nervosa-linked pathological mechanisms contributing to complex cardiovascular dysregulation. Further, this review is focused on identification of non-invasive biomarkers for the assessment of increased cardiovascular risk in anorexia nervosa that can be linked to a clinical application. Complex non-invasive assessment of cardiovascular autonomic regulation—cardiac vagal control (heart rate variability), sympathetic vascular activity (blood pressure variability), and cardiovascular reflex control (baroreflex sensitivity)—could represent a promising tool for early diagnosis, personalized therapy, and monitoring of therapeutic interventions in anorexia nervosa particularly at a vulnerable adolescent age.

Arterial stiffness and haemodynamic regulation in adolescent anorexia nervosa versus obesity

Cardiovascular complications contribute to higher morbidity and mortality in patients with anorexia nervosa. We aimed to study biomarkers of cardiovascular risk in anorexic, normal-weight, and obese adolescents with focus on complex cardiovascular autonomic regulation and early arteriosclerotic damage. We examined 20 adolescent girls with anorexia nervosa, 20 obese girls, and 20 healthy normal-weight controls. Collected data: body composition analysis, 5 min recordings of R–R intervals and beat-to-beat blood pressure (BP), and arterial stiffness evaluated using cardio-ankle vascular index (CAVI). Evaluated parameters: beat-to-beat heart rate and BP variability, haemodynamic parameters (total peripheral resistance (TPR) cardiac output), CAVI, and anthropometric indices, including novel body roundness index (BRI). Adolescents with anorexia nervosa had increased CAVI associated with lower arterial constriction indexed by low-frequency band of BP variability compared with normal-weight peers (p = 0.03, p = 0.04, respectively) and obese adolescents (p < 0.01, p = 0.01, respectively). After normalization of CAVI and TPR by BRI, the relationship between CAVI and TPR was significant for all groups with the highest slope in the anorexia nervosa group (R2 = 0.724, p < 0.01). This is the first study revealing early arteriosclerotic damage in anorexic girls with increased CAVI. Complex analysis of cardiovascular autonomic regulation, and early arteriosclerotic, hemodynamic, and anthropometric changes in spectrum anorexia nervosa, normal weight, and obesity could help to understand the mechanisms of increased cardiovascular risk in malnutrition. Novelty Girls with anorexia nervosa showed signs of early arteriosclerotic damage indexed by CAVI. Insufficient sympathetic cardiovascular control was found already in adolescents with anorexia nervosa. The effect of body composition on CAVI was best predicted by novel body roundness index.

Dynamics of the cardiovascular autonomic regulation during orthostatic challenge is more relaxed in women

Linear dynamic analysis of cardiovascular and respiratory time series was performed in healthy subjects with respect to gender by shifted short-term segments throughout a head-up tilt (HUT) test. Beat-to-beat intervals (BBI), systolic (SYS) and diastolic (DIA) blood pressure and respiratory interval (RESP) time series were acquired in 14 men and 15 women. In time domain (TD), the descending slope of the auto-correlation function (ACF) (BBI_a31cor) was more pronounced in women than in men (p<0.05) during the HUT test and considerably steeper (p<0.01) at the end of orthostatic phase (OP). The index SYS_meanNN was slightly but significantly lower (p<0.05) in women during the complete test, while higher respiratory frequency and variability (RESP_sdNN) were found in women (p<0.05), during 10–20 min after tilt-up. In frequency domain (FD), during baseline (BL), BBI-normalized low frequency (BBI_LFN) and BBI_LF/HF were slightly but significantly lower (p<0.05), while normalized high frequency (BBI_HFN) was significantly higher in women. These differences were highly significant from the first 5 min after tilt-up (p<0.01) and highly significant (p<0.001) during 10–14 min of OP. Findings revealed that men showed instantaneously a pronounced and sustained increase in sympathetic activity to compensate orthostatism. In women, sympathetic activity was just increased slightly with delayed onset without considerably affecting sympatho-vagal balance.

Increased receptor activity-modifying protein 1 in the nervous system is sufficient to protect against autonomic dysregulation and hypertension

Calcitonin gene-related peptide (CGRP) can cause migraines, yet it is also a potent vasodilator that protects against hypertension. Given the emerging role of CGRP-targeted antibodies for migraine prevention, an important question is whether the protective actions of CGRP are mediated by vascular or neural CGRP receptors. To address this, we have characterized the cardiovascular phenotype of transgenic nestin/hRAMP1 mice that have selective elevation of a CGRP receptor subunit in the nervous system, human receptor activity-modifying protein 1 (hRAMP1). Nestin/hRAMP1 mice had relatively little hRAMP1 RNA in blood vessels and intravenous injection of CGRP caused a similar blood pressure decrease in transgenic and control mice. At baseline, nestin/hRAMP1 mice exhibited similar mean arterial pressure, heart rate, baroreflex sensitivity, and sympathetic vasomotor tone as control mice. We previously reported that expression of hRAMP1 in all tissues favorably improved autonomic regulation and attenuated hypertension induced by angiotensin II (Ang II). Similarly, in nestin/hRAMP1 mice, hypertension caused by Ang II or phenylephrine was greatly attenuated, and associated autonomic dysregulation and increased sympathetic vasomotor tone were diminished or abolished. We conclude that increased expression of neuronal CGRP receptors is sufficient to induce a protective change in cardiovascular autonomic regulation with implications for migraine therapy.