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Sample records for cardiac autonomic regulation

  1. Auditory stimulation and cardiac autonomic regulation

    PubMed Central

    Valenti, Vitor E.; Guida, Heraldo L.; Frizzo, Ana C. F.; Cardoso, Ana C. V.; Vanderlei, Luiz Carlos M.; de Abreu, Luiz Carlos

    2012-01-01

    Previous studies have already demonstrated that auditory stimulation with music influences the cardiovascular system. In this study, we described the relationship between musical auditory stimulation and heart rate variability. Searches were performed with the Medline, SciELO, Lilacs and Cochrane databases using the following keywords: “auditory stimulation”, “autonomic nervous system”, “music” and “heart rate variability”. The selected studies indicated that there is a strong correlation between noise intensity and vagal-sympathetic balance. Additionally, it was reported that music therapy improved heart rate variability in anthracycline-treated breast cancer patients. It was hypothesized that dopamine release in the striatal system induced by pleasurable songs is involved in cardiac autonomic regulation. Musical auditory stimulation influences heart rate variability through a neural mechanism that is not well understood. Further studies are necessary to develop new therapies to treat cardiovascular disorders. PMID:22948465

  2. Association between central auditory processing mechanism and cardiac autonomic regulation

    PubMed Central

    2014-01-01

    Background This study was conducted to describe the association between central auditory processing mechanism and the cardiac autonomic regulation. Methods It was researched papers on the topic addressed in this study considering the following data bases: Medline, Pubmed, Lilacs, Scopus and Cochrane. The key words were: “auditory stimulation, heart rate, autonomic nervous system and P300”. Results The findings in the literature demonstrated that auditory stimulation influences the autonomic nervous system and has been used in conjunction with other methods. It is considered a promising step in the investigation of therapeutic procedures for rehabilitation and quality of life of several pathologies. Conclusion The association between auditory stimulation and the level of the cardiac autonomic nervous system has received significant contributions in relation to musical stimuli. PMID:24834128

  3. Cardiac autonomic regulation and anger coping in adolescents.

    PubMed

    Vögele, Claus; Sorg, Sonja; Studtmann, Markus; Weber, Hannelore

    2010-12-01

    The current study investigated spontaneous anger coping, cardiac autonomic regulation and phasic heart rate responses to anger provocation. Forty-five adolescents (27 female, mean age 14.7 years) attended the single experimental session, which included monitoring of continuous heart rate and blood pressure responses to anger provocation (receiving an unfair offer) using a modified version of the Ultimatum Game (UG). Vagal activation was operationalized as high frequency component of heart rate variability during rest periods, and spontaneous baroreflex-sensitivity (SBR) during the UG. Adolescents employing cognitive reappraisal showed higher vagal activity under resting conditions and attenuated heart rate deceleration after receiving the unfair offer compared with participants who tended to ruminate about their anger and experienced injustice. Results from SBR suggested vagal withdrawal in anger ruminators during contemplation of the unfair offer. These results provide further support for the specificity and sensitivity of vagal responses to higher cortical functions such as emotion regulation.

  4. Spirituality and Autonomic Cardiac Control

    PubMed Central

    Berntson, Gary G.; Norman, Greg J.; Hawkley, Louise C.; Cacioppo, John T.

    2009-01-01

    Background Spirituality has been suggested to be associated with positive health, but potential biological mediators have not been well characterized. Purpose and Methods The present study examined, in a population based sample of middle-aged and older adults, the potential relationship between spirituality and patterns of cardiac autonomic control, which may have health significance. Measures of parasympathetic (high-frequency heart rate variability) and sympathetic (pre-ejection period) cardiac control were obtained from a representative sample of 229 participants. Participants completed questionnaires to assess spirituality (closeness to and satisfactory relation with God). Personality, demographic, anthropometric, health behavior, and health status information was also obtained. A series of multivariate regression models was used to examine the relations between spirituality, the autonomic measures, and two derived indexes-- cardiac autonomic balance (CAB, reflecting parasympathetic to sympathetic balance) and cardiac autonomic regulation (CAR, reflecting total autonomic control). Results Spirituality, net of demographics or other variables, was found to be associated with enhanced parasympathetic as well as sympathetic cardiac control (yielding a higher CAR); but was not associated with CAB. Although the number of cases was small (N=11), both spirituality and CAR were significant negative predictors of the prior occurrence of a myocardial infarction. Conclusions In a population based sample, spirituality appears to be associated with a specific pattern of cardiac autonomic regulation, characterized by a high level of cardiac autonomic control, irrespective of the relative contribution of the two autonomic branches. This pattern of autonomic control may have health significance. PMID:18357497

  5. Self-reported dieting success is associated with cardiac autonomic regulation in current dieters.

    PubMed

    Meule, Adrian; Lutz, Annika; Vögele, Claus; Kübler, Andrea

    2012-10-01

    Restrained eating, eating disorders and obesity have been associated with cardiac autonomic dysregulation. The current study investigated cardiac autonomic regulation in current dieters. Female students (N=50) indicated if they were currently trying to control their weight and completed the Perceived Self-Regulatory Success in Dieting Scale (PSRS). Heart beat intervals were recorded during two 10 min relaxation periods from which parameters of vagal-cardiac control (high frequency power in normalized units, HF n.u.) and sympathovagal balance (ratio of low and high frequency power, LF/HF) were calculated. In current dieters, self-reported dieting success was positively associated with HF and negatively associated with LF/HF. These associations were independent of current body-mass and food deprivation (i.e. hours since the last meal). We conclude that vagal-cardiac control reflects self-regulatory strength, rather than nutritional status, in current dieters.

  6. Effects of Emotion Regulation Difficulties on the Tonic and Phasic Cardiac Autonomic Response

    PubMed Central

    Berna, Guillaume; Ott, Laurent; Nandrino, Jean-Louis

    2014-01-01

    Background Emotion regulation theory aims to explain the interactions between individuals and the environment. In this context, Emotion Regulation Difficulties (ERD) disrupt the physiological component of emotions through the autonomic nervous system and are involved in several psychopathological states. Objective We were interested in comparing the influence of a film-elicited emotion procedure on the autonomic nervous system activity of two groups with different levels of emotion regulation difficulties. Methods A total of 63 women (undergraduate students) ranging from 18 to 27 (20.7±1.99) years old were included. Using the upper and lower quartile of a questionnaire assessing the daily difficulties in regulating emotions, two groups, one with low (LERD) and one with high (HERD) levels of emotion regulation difficulties, were constituted and studied during a film-elicited emotion procedure. Cardiac vagal activity (HF-HRV) was analyzed during three periods: baseline, film-elicited emotion, and recovery. Results The cardiovascular results showed a decrease in HF-HRV from baseline to elicitation for both groups. Then, from elicitation to recovery, HF-HRV increased for the LERD group, whereas a low HF-HRV level persisted for the HERD group. Conclusions The HERD group exhibited inappropriate cardiac vagal recovery after a negative emotion elicitation had ended. Cardiac vagal tone took longer to return to its initial state in the HERD group than in the LERD group. Prolonged cardiac vagal suppression might constitute an early marker of emotion regulation difficulties leading to lower cardiac vagal tone. PMID:25054913

  7. Effects of Effortful Swallow on Cardiac Autonomic Regulation.

    PubMed

    Gomes, Lívia M S; Silva, Roberta G; Melo, Monique; Silva, Nayra N; Vanderlei, Franciele M; Garner, David M; de Abreu, Luiz Carlos; Valenti, Vitor E

    2016-04-01

    Swallowing-induced changes in heart rate have been recently reported. However, it is not apparent the responses of heart rate variability (HRV) elicited by effortful swallow maneuver. We investigated the acute effects of effortful swallowing maneuver on HRV. This study was performed on 34 healthy women between 18 and 35 years old. We assessed heart rate variability in the time (SDNN, RMSSD, and pNN50) and frequency (HF, LF, and LF/HF ratio) domains and, visual analysis through the Poincaré plot. The subjects remained at rest for 5 min during spontaneous swallowing and then performed effortful swallowing for 5 min. HRV was analyzed during spontaneous and effortful swallowing. We found no significant differences for SDNN, pNN50, RMSSD, HF in absolute units (ms(2)). There is a trend for increase of LF in absolute (p = 0.05) and normalized (p = 0.08) units during effortful swallowing. HF in normalized units reduced (p = 0.02) during effortful swallowing and LF/HF ratio (p = 0.03) increased during effortful swallowing. In conclusion effortful swallow maneuver in healthy women increased sympathetic cardiac modulation, indicating a cardiac overload.

  8. Factors influencing the role of cardiac autonomic regulation in the service of cognitive control.

    PubMed

    Capuana, Lesley J; Dywan, Jane; Tays, William J; Elmers, Jamie L; Witherspoon, Richelle; Segalowitz, Sidney J

    2014-10-01

    Working from a model of neurovisceral integration, we examined whether adding response contingencies and motivational involvement would increase the need for cardiac autonomic regulation in maintaining effective cognitive control. Respiratory sinus arrhythmia (RSA) was recorded during variants of the Stroop color-word task. The Basic task involved "accepting" congruent items and "rejecting" words printed in incongruent colors (BLUE in red font); an added contingency involved rejecting a particular congruent word (e.g., RED in red font), or a congruent word repeated on an immediately subsequent trial. Motivation was increased by adding a financial incentive phase. Results indicate that pre-task RSA predicted accuracy best when response contingencies required the maintenance of a specific item in memory or on the Basic Stroop task when errors resulted in financial loss. Overall, RSA appeared to be most relevant to performance when the task encouraged a more proactive style of cognitive control, a control strategy thought to be more metabolically costly, and hence, more reliant on flexible cardiac autonomic regulation.

  9. Cardiac autonomic regulation is disturbed in children with euthyroid Hashimoto thyroiditis.

    PubMed

    Kilic, Ayhan; Gulgun, Mustafa; Tascilar, Mehmet Emre; Sari, Erkan; Yokusoglu, Mehmet

    2012-01-01

    Hashimoto thyroiditis (chronic autoimmune thyroiditis) is the most common form of thyroiditis in childhood. Previous studies have found autonomic dysfunction of varying magnitude in patients with autoimmune diseases, which is considered a cardiovascular risk factor. We aimed to evaluate the heart rate variability (HRV), a measure of cardiac autonomic modulation, in children with euthyroid Hashimoto thyroiditis (eHT). The study included 32 patients with eHT (27 girls and 5 boys; mean age 11 ± 4.1 years, range 8-16; body mass index 0.47 ± 0.69 kg/m(2)), as judged by normal or minimally elevated serum TSH levels (normal range: 0.34-5.6 mIU/l) and normal levels of free thyroid hormones (FT4 and FT3) and 38 euthyroid age-matched controls. Patients with eHT and control subjects underwent physical examination and 24-hour ambulatory ECG monitoring. Time-domain parameters of HRV were evaluated for cardiac autonomic functions. Children with eHT displayed significantly lower values of time-domain parameters of SDANN (standard deviation of the averages of NN intervals), RMSSD (square root of the mean of the sum of the squares of differences between adjacent NN intervals), NN50 counts (number of pairs of adjacent NN intervals differing by more than 50 ms) and PNN50 (NN50 count divided by the total number of all NN intervals) for each 5-min interval, compared to healthy controls (p < 0.05 for each), indicating the decreased beat-to-beat variation of heart rate. In conclusion, eHT is associated with disturbed autonomic regulation of heart rate. Hence, the children with eHT are at higher risk for developing cardiovascular diseases.

  10. Autonomic cardiac innervation: development and adult plasticity.

    PubMed

    Hasan, Wohaib

    2013-01-01

    Autonomic cardiac neurons have a common origin in the neural crest but undergo distinct developmental differentiation as they mature toward their adult phenotype. Progenitor cells respond to repulsive cues during migration, followed by differentiation cues from paracrine sources that promote neurochemistry and differentiation. When autonomic axons start to innervate cardiac tissue, neurotrophic factors from vascular tissue are essential for maintenance of neurons before they reach their targets, upon which target-derived trophic factors take over final maturation, synaptic strength and postnatal survival. Although target-derived neurotrophins have a central role to play in development, alternative sources of neurotrophins may also modulate innervation. Both developing and adult sympathetic neurons express proNGF, and adult parasympathetic cardiac ganglion neurons also synthesize and release NGF. The physiological function of these "non-classical" cardiac sources of neurotrophins remains to be determined, especially in relation to autocrine/paracrine sustenance during development.   Cardiac autonomic nerves are closely spatially associated in cardiac plexuses, ganglia and pacemaker regions and so are sensitive to release of neurotransmitter, neuropeptides and trophic factors from adjacent nerves. As such, in many cardiac pathologies, it is an imbalance within the two arms of the autonomic system that is critical for disease progression. Although this crosstalk between sympathetic and parasympathetic nerves has been well established for adult nerves, it is unclear whether a degree of paracrine regulation occurs across the autonomic limbs during development. Aberrant nerve remodeling is a common occurrence in many adult cardiovascular pathologies, and the mechanisms regulating outgrowth or denervation are disparate. However, autonomic neurons display considerable plasticity in this regard with neurotrophins and inflammatory cytokines having a central regulatory

  11. The effects of different styles of musical auditory stimulation on cardiac autonomic regulation in healthy women.

    PubMed

    Roque, Adriano L; Valenti, Vitor E; Guida, Heraldo L; Campos, Mônica F; Knap, André; Vanderlei, Luiz Carlos M; Ferreira, Celso; de Abreu, Luiz Carlos

    2013-01-01

    The literature investigated the effects of chronic baroque music auditory stimulation on the cardiovascular system. However, it lacks in the literature the acute effects of different styles of music on cardiac autonomic regulation. To evaluate the acute effects of baroque and heavy metal music on heart rate variability (HRV) in women. The study was performed in 21 healthy women between 18 and 30 years old. We excluded persons with previous experience with music instrument and those who had affinity with the song styles. All procedures were performed in the same sound-proof room. We analyzed HRV in the time (standard deviation of normal-to-normal respiratory rate (RR) intervals, root-mean square of differences between adjacent normal RR intervals in a time interval, and the percentage of adjacent RR intervals with a difference of duration greater than 50 ms) and frequency (low frequency [LF], high frequency [HF], and LF/HF ratio) domains. HRV was recorded at rest for 10 min. Subsequently they were exposed to baroque or heavy metal music for 5 min through an earphone. After the first music exposure they remained at rest for more 5 min and them they were exposed again to baroque or heavy metal music. The sequence of songs was randomized for each individual. The power analysis provided a minimal number of 18 subjects. Shapiro-Wilk to verify normality of data and analysis of variance for repeated measures followed by the Bonferroni test for parametric variables and Friedman's followed by the Dunn's post-test for non-parametric distributions. During the analysis of the time-domain indices were not changed. In the frequency-domain analysis, the LF in absolute units was reduced during the heavy metal music stimulation compared to control. Acute exposure to heavy metal music affected the sympathetic activity in healthy women.

  12. Acute Auditory Stimulation with Different Styles of Music Influences Cardiac Autonomic Regulation in Men

    PubMed Central

    da Silva, Sheila Ap. F.; Guida, Heraldo L.; dos Santos Antonio, Ana Marcia; de Abreu, Luiz Carlos; Monteiro, Carlos B. M.; Ferreira, Celso; Ribeiro, Vivian F.; Barnabe, Viviani; Silva, Sidney B.; Fonseca, Fernando L. A.; Adami, Fernando; Petenusso, Marcio; Raimundo, Rodrigo D.; Valenti, Vitor E.

    2014-01-01

    Background: No clear evidence is available in the literature regarding the acute effect of different styles of music on cardiac autonomic control. Objectives: The present study aimed to evaluate the acute effects of classical baroque and heavy metal musical auditory stimulation on Heart Rate Variability (HRV) in healthy men. Patients and Methods: In this study, HRV was analyzed regarding time (SDNN, RMSSD, NN50, and pNN50) and frequency domain (LF, HF, and LF / HF) in 12 healthy men. HRV was recorded at seated rest for 10 minutes. Subsequently, the participants were exposed to classical baroque or heavy metal music for five minutes through an earphone at seated rest. After exposure to the first song, they remained at rest for five minutes and they were again exposed to classical baroque or heavy metal music. The music sequence was random for each individual. Standard statistical methods were used for calculation of means and standard deviations. Besides, ANOVA and Friedman test were used for parametric and non-parametric distributions, respectively. Results: While listening to heavy metal music, SDNN was reduced compared to the baseline (P = 0.023). In addition, the LF index (ms2 and nu) was reduced during exposure to both heavy metal and classical baroque musical auditory stimulation compared to the control condition (P = 0.010 and P = 0.048, respectively). However, the HF index (ms2) was reduced only during auditory stimulation with music heavy metal (P = 0.01). The LF/HF ratio on the other hand decreased during auditory stimulation with classical baroque music (P = 0.019). Conclusions: Acute auditory stimulation with the selected heavy metal musical auditory stimulation decreased the sympathetic and parasympathetic modulation on the heart, while exposure to a selected classical baroque music reduced sympathetic regulation on the heart. PMID:25177673

  13. Regulation of Cardiac Autonomic Nervous System Control across Frailty Status: A Systematic Review

    PubMed Central

    Parvaneh, Saman; Howe, Carol L.; Toosizadeh, Nima; Honarvar, Bahareh; Slepian, Marvin J.; Fain, Mindy; Mohler, Jane; Najafi, Bijan

    2016-01-01

    Background Frailty is a geriatric syndrome that leads to impairment in interrelated physiological systems and progressive homeostatic dysregulation in physiological systems. Objective The focus of the present systematic review was to study the association between the activity of the cardiac autonomic nervous system (ANS) and frailty. Methods A systematic literature search was conducted in multiple databases: PubMed/MEDLINE, Embase, Cochrane Library, Web of Science, CINAHL and ClinicalTrials.gov; the last search was performed in March 2015. Inclusion criteria included: 1) the studied population was classified for frailty according to a standard definition, such as the Fried’s criteria; 2) had a non-frail control group; 3) heart rate (HR) and/or heart rate variability (HRV) were parameters of interest in the study. Results Of the 1544 articles screened, 54 were selected for full text review and six studies met inclusion criteria. Assessment of HRV using different standard time-domain, frequency-domain, and non-linear domain approaches confirmed the presence of an impaired cardiac ANS function in frail compared to non-frail participants. Furthermore, HR changes while performing a clinical test (e.g., seated step and lying to standing tests) were decreased in the frail group compared to the non-frail group. Conclusions The current systematic review provides evidence that the cardiac ANS is impaired in frail, compared to non-frail, older adults as indicated by a reduction in the complexity of HR dynamics, reduced HRV, and reduced HR changes in response to daily activities. Four out of six included articles recruited only female participants and in the other two articles the effect of gender on impairment of cardiac ANS was insufficiently investigated. Therefore, further studies are required to study the association between cardiac ANS impairments and frailty in males. Furthermore, HRV was studied only during static postures such as sitting, or without considering the

  14. [Significance of adreno- and cholino-inhibitors in cardiac rhythm autonomic regulation during different weather types].

    PubMed

    Denefil', O V

    2011-01-01

    In the experiments of 4.5-5 months old rats, we studied the influences of adrenal and cholinoblockators on the autonomic balance of cardiac rhythm during the I, II and III types of weather. Blockade of beta-adrenoreceptors and M-cholinoreceptors was evoked by anapriline (1.5 mg/kg) and atropine sulfate (1.0 mg/kg), respectively. Electrocardiograms for further analysis were registered in control and 30 minutes after injections of the blockers. It was shown that male rats have the highest activity of sympathetic nervous system under weather type I. High reactivity of beta-adrenoreceptors was determined under all weather types in males and females. In males, atropine blocks the autonomic M-cholinoreceptors under weather types II and III, while in females this effect is detected under all weather types. Furthermore, in males we detected a compensatory increase of sympathetic nervous system during all weather types, while in females such an increase was detected during weather types I and II. Collectively, we determined sex differences in adaptation to weather type changes which are connected to different reactivity of adreno- and cholinoreceptors.

  15. Cardiac Autonomic Regulation in Autism and Fragile X Syndrome: A Review

    PubMed Central

    Klusek, Jessica; Roberts, Jane E.; Losh, Molly

    2014-01-01

    Despite the significance of efforts to understand the biological basis of autism, progress in this area has been hindered, in part, by the considerable heterogeneity in the disorder. Fragile X syndrome (FXS), a monogenic condition associated with high risk for autism, may pave the way for the dissection of biological heterogeneity within idiopathic autism. This paper adopts a cross-syndrome biomarker approach to evaluate potentially overlapping profiles of cardiac arousal dysregulation (and broader autonomic dysfunction) in autism and FXS. Approaches such as this, aimed at delineating shared mechanisms across genetic syndromes, hold great potential for improving diagnostic precision, promoting earlier identification, and uncovering key systems that can be targeted in pharmaceutical/behavioral interventions. Biomarker approaches may be vital to deconstructing complex psychiatric disorders, and are currently promoted as such by major research initiatives such as the NIMH Research Domain Criteria (RDoC). Evidence reviewed here supports physiological dysregulation in a subset of individuals with autism, as evidenced by patterns of hyperarousal and dampened parasympathetic vagal tone, which overlap with the well-documented physiological profile of FXS. Moreover, there is growing support for a link between aberrant cardiac activity and core deficits associated with autism, such as communication and social impairment. The delineation of physiological mechanisms common to autism and FXS could lend insight into relationships between genetic etiology and behavioral endstates, highlighting FMR1 as a potential candidate gene. Research gaps and potential pitfalls are discussed to inform timely, well-controlled biomarker research that will ultimately promote better diagnosis and treatment of autism and associated conditions. PMID:25420222

  16. Cardiac autonomic nerve distribution and arrhythmia☆

    PubMed Central

    Liu, Quan; Chen, Dongmei; Wang, Yonggang; Zhao, Xin; Zheng, Yang

    2012-01-01

    OBJECTIVE: To analyze the distribution characteristics of cardiac autonomic nerves and to explore the correlation between cardiac autonomic nerve distribution and arrhythmia. DATA RETRIEVAL: A computer-based retrieval was performed for papers examining the distribution of cardiac autonomic nerves, using heart, autonomic nerve, sympathetic nerve, vagus nerve, nerve distribution, rhythm and atrial fibrillation as the key words. SELECTION CRITERIA: A total of 165 studies examining the distribution of cardiac autonomic nerve were screened, and 46 of them were eventually included. MAIN OUTCOME MEASURES: The distribution and characteristics of cardiac autonomic nerves were observed, and immunohistochemical staining was applied to determine the levels of tyrosine hydroxylase and acetylcholine transferase (main markers of cardiac autonomic nerve distribution). In addition, the correlation between cardiac autonomic nerve distribution and cardiac arrhythmia was investigated. RESULTS: Cardiac autonomic nerves were reported to exhibit a disordered distribution in different sites, mainly at the surface of the cardiac atrium and pulmonary vein, forming a ganglia plexus. The distribution of the pulmonary vein autonomic nerve was prominent at the proximal end rather than the distal end, at the upper left rather than the lower right, at the epicardial membrane rather than the endocardial membrane, at the left atrium rather than the right atrium, and at the posterior wall rather than the anterior wall. The main markers used for cardiac autonomic nerves were tyrosine hydroxylase and acetylcholine transferase. Protein gene product 9.5 was used to label the immunoreactive nerve distribution, and the distribution density of autonomic nerves was determined using a computer-aided morphometric analysis system. CONCLUSION: The uneven distribution of the cardiac autonomic nerves is the leading cause of the occurrence of arrhythmia, and the cardiac autonomic nerves play an important role in

  17. Cardiac coherence, self-regulation, autonomic stability, and psychosocial well-being

    PubMed Central

    McCraty, Rollin; Zayas, Maria A.

    2014-01-01

    The ability to alter one’s emotional responses is central to overall well-being and to effectively meeting the demands of life. One of the chief symptoms of events such as trauma, that overwhelm our capacities to successfully handle and adapt to them, is a shift in our internal baseline reference such that there ensues a repetitive activation of the traumatic event. This can result in high vigilance and over-sensitivity to environmental signals which are reflected in inappropriate emotional responses and autonomic nervous system dynamics. In this article we discuss the perspective that one’s ability to self-regulate the quality of feeling and emotion of one’s moment-to-moment experience is intimately tied to our physiology, and the reciprocal interactions among physiological, cognitive, and emotional systems. These interactions form the basis of information processing networks in which communication between systems occurs through the generation and transmission of rhythms and patterns of activity. Our discussion emphasizes the communication pathways between the heart and brain, as well as how these are related to cognitive and emotional function and self-regulatory capacity. We discuss the hypothesis that self-induced positive emotions increase the coherence in bodily processes, which is reflected in the pattern of the heart’s rhythm. This shift in the heart rhythm in turn plays an important role in facilitating higher cognitive functions, creating emotional stability and facilitating states of calm. Over time, this establishes a new inner-baseline reference, a type of implicit memory that organizes perception, feelings, and behavior. Without establishing a new baseline reference, people are at risk of getting “stuck” in familiar, yet unhealthy emotional and behavioral patterns and living their lives through the automatic filters of past familiar or traumatic experience. PMID:25324802

  18. Linking an Anxiety-Related Personality Trait to Cardiac Autonomic Regulation in Well-Defined Healthy Adults: Harm Avoidance and Resting Heart Rate Variability

    PubMed Central

    Kao, Lien-Cheng; Liu, Yu-Wen; Tzeng, Nian-Sheng; Kuo, Terry B. J.; Huang, San-Yuan

    2016-01-01

    Objective Anxiety trait, anxiety and depression states have all been reported to increase risks for cardiovascular disease (CVD), possibly through altering cardiac autonomic regulation. Our aim was to investigate whether the relationship between harm avoidance (HA, an anxiety-related personality trait) and cardiac autonomic regulation is independent of anxiety and depression states in healthy adults. Methods We recruited 535 physically and mentally healthy volunteers. Participants completed the Beck Anxiety Inventory (BAI), Beck Depression Inventory (BDI) and Tri-dimensional Personality Questionnaire. Participants were divided into high or low HA groups as discriminated by the quartile value. Cardiac autonomic function was evaluated by measuring heart rate variability (HRV). We obtained the time and frequency-domain indices of HRV including variance (total HRV), the low-frequency power (LF; 0.05–0.15 Hz), which may reflect baroreflex function, the high-frequency power (HF; 0.15–0.40 Hz), which reflects cardiac parasympathetic activity, as well as the LF/HF ratio. Results The BDI and HA scores showed associations with HRV parameters. After adjustment for the BDI scores and other control variables, HA is still associated with reduced variance, LF and HF power. Compared with the participants with low HA, those with high HA displayed significant reductions in variance, LF and HF power and a significant increase in their LF/HF ratio. Conclusion This study highlights the independent role of HA in contributing to decreased autonomic cardiac regulation in healthy adults and provides a potential underlying mechanism for anxiety trait to confer increased risk for CVD. PMID:27482240

  19. Cardiac autonomic dysfunction in anabolic steroid users.

    PubMed

    Maior, A S; Carvalho, A R; Marques-Neto, S R; Menezes, P; Soares, P P; Nascimento, J H M

    2013-10-01

    This study aimed to evaluate if androgenic-anabolic steroids (AAS) abuse may induce cardiac autonomic dysfunction in recreational trained subjects. Twenty-two men were volunteered for the study. The AAS group (n = 11) utilized AAS at mean dosage of 410 ± 78.6 mg/week. All of them were submitted to submaximal exercise testing using an Astrand-Rhyming protocol. Electrocardiogram (ECG) and respired gas analysis were monitored at rest, during, and post-effort. Mean values of VO2 , VCO2 , and VE were higher in AAS group only at rest. The heart rate variability variables were calculated from ECG using MATLAB-based algorithms. At rest, AAS group showed lower values of the standard deviation of R-R intervals, the proportion of adjacent R-R intervals differing by more than 50 ms (pNN50), the root mean square of successive differences (RMSSD), and the total, the low-frequency (LF) and the high-frequency (HF) spectral power, as compared to Control group. After submaximal exercise testing, pNN50, RMSSD, and HF were lower, and the LF/HF ratio was higher in AAS group when compared to control group. Thus, the use of supraphysiological doses of AAS seems to induce dysfunction in tonic cardiac autonomic regulation in recreational trained subjects.

  20. Cardiac autonomic nervous system activity in obesity.

    PubMed

    Liatis, Stavros; Tentolouris, Nikolaos; Katsilambros, Nikolaos

    2004-08-01

    The development of obesity is caused by a disturbance of energy balance, with energy intake exceeding energy expenditure. As the autonomic nervous system (ANS) has a role in the regulation of both these variables, it has become a major focus of investigation in the fields of obesity pathogenesis. The enhanced cardiac sympathetic drive shown in most of the studies in obese persons might be due to an increase in their levels of circulating insulin. The role of leptin needs further investigation with studies in humans. There is a blunted response of the cardiac sympathetic nervous system (SNS) activity in obese subjects after consumption of a carbohydrate-rich meal as well as after insulin administration. This might be due to insulin resistance. It is speculated that increased SNS activity in obesity may contribute to the development of hypertension in genetically susceptible individuals. It is also speculated that the increase in cardiac SNS activity under fasting conditions in obesity may be associated with high cardiovascular morbidity and mortality.

  1. Low-level Pb and Cardiovascular Responses to Acute Stress in Children: The Role of Cardiac Autonomic Regulation

    PubMed Central

    Gump, Brooks B.; MacKenzie, James A.; Bendinskas, Kestutis; Morgan, Robert; Dumas, Amy K.; Palmer, Christopher D.; Parsons, Patrick J.

    2010-01-01

    Objective A number of studies suggest that Pb exposure increases cardiovascular disease risk in humans. As a potential mechanism for this effect, we recently reported a significant association between early childhood Pb levels and cardiovascular response to acute stress. The current study considers the association between current Pb levels and the autonomic nervous system activation pattern underlying the cardiovascular response to stress in a new cohort of children. Methods We assessed blood Pb levels as well as cardiovascular responses to acute stress in 9–11 year old children (N = 140). Sympathetic activation (measured with pre-ejection period) and parasympathetic activation (measured with high frequency heart rate variability) were also assessed. Results In a sample with very low levels of blood Pb (M = 1.01 μg/dL), we found that increasing blood Pb was associated with coinhibition of sympathetic and parasympathetic activation in response to acute stress. In addition, increasing Pb levels were associated with the hemodynamic stress response pattern typical of coinhibition – significantly greater vascular resistance and reduced stroke volume and cardiac output. Conclusions Blood Pb levels were associated with significant autonomic and cardiovascular dysregulation in response to acute psychological stress in children. Moreover, these effects were significant at Pb levels considered to be very low and notably well below the 10 μg/dL the Centers for Disease Control and Prevention definition of an elevated blood Pb level. The potential for autonomic dysregulation at levels of Pb typical for many US children would suggest potentially broad public health ramifications. PMID:20934510

  2. Altered cardiac autonomic nervous function in depression

    PubMed Central

    2013-01-01

    Background Depression is an independent risk factor for coronary artery disease. Autonomic instability may play a mediating or moderating role in this relationship; however this is not well understood. The objective of this study was to explore cardiac autonomic function and cardiac arrhythmia in depression, the correlation between depression severity and Heart Rate Variability (HRV) related indices, and the prevalence of arrhythmia. Methods Individuals (n = 53) with major depression as assessed by the Diagnostic and Statistical Manual of Mental Disorders, who had a Hamilton Rating Scale for Depression (HAMD) score ≥20 and a Zung Self-Rating Depression Scale score > 53 were compared to 53 healthy individuals, matched for age and gender. Multichannel Electrocardiograph ECG-92C data were collected over 24 hours. Long-term changes in HRV were used to assess the following vagally mediated changes in autonomic tone, expressed as time domain indices: Standard deviation of the NN intervals (SDNN), standard deviation of 5 min averaged NN intervals (SDANN), Root Mean Square of the Successive Differences (RMSSD) and percentage of NN intervals > 50 ms different from preceding interval (pNN50). Pearson’s correlations were conducted to explore the strength of the association between depression severity (using the SDS and HRV related indices, specifically SDNN and low frequency domain / high frequency domain (LF/HF)). Results The values of SDNN, SDANN, RMSSD, PNN50 and HF were lower in the depression group compared to the control group (P<.05). The mean value of the LF in the depression group was higher than the in control group (P<.05). Furthermore the ratio of LF/HF was higher among the depression group than the control group (P<.05). A linear relationship was shown to exist between the severity of the depression and HRV indices. In the depression group, the prevalence of arrhythmia was significantly higher than in the control group (P<.05), particularly

  3. Measuring cardiac autonomic nervous system (ANS) activity in children.

    PubMed

    van Dijk, Aimée E; van Lien, René; van Eijsden, Manon; Gemke, Reinoud J B J; Vrijkotte, Tanja G M; de Geus, Eco J

    2013-04-29

    The autonomic nervous system (ANS) controls mainly automatic bodily functions that are engaged in homeostasis, like heart rate, digestion, respiratory rate, salivation, perspiration and renal function. The ANS has two main branches: the sympathetic nervous system, preparing the human body for action in times of danger and stress, and the parasympathetic nervous system, which regulates the resting state of the body. ANS activity can be measured invasively, for instance by radiotracer techniques or microelectrode recording from superficial nerves, or it can be measured non-invasively by using changes in an organ's response as a proxy for changes in ANS activity, for instance of the sweat glands or the heart. Invasive measurements have the highest validity but are very poorly feasible in large scale samples where non-invasive measures are the preferred approach. Autonomic effects on the heart can be reliably quantified by the recording of the electrocardiogram (ECG) in combination with the impedance cardiogram (ICG), which reflects the changes in thorax impedance in response to respiration and the ejection of blood from the ventricle into the aorta. From the respiration and ECG signals, respiratory sinus arrhythmia can be extracted as a measure of cardiac parasympathetic control. From the ECG and the left ventricular ejection signals, the preejection period can be extracted as a measure of cardiac sympathetic control. ECG and ICG recording is mostly done in laboratory settings. However, having the subjects report to a laboratory greatly reduces ecological validity, is not always doable in large scale epidemiological studies, and can be intimidating for young children. An ambulatory device for ECG and ICG simultaneously resolves these three problems. Here, we present a study design for a minimally invasive and rapid assessment of cardiac autonomic control in children, using a validated ambulatory device (1-5), the VU University Ambulatory Monitoring System (VU

  4. Cardiac Autonomic Control in Individuals With Down Syndrome

    ERIC Educational Resources Information Center

    Goulopoulou, Styliani; Baynard, Tracy; Collier, Scott; Giannopoulou, Ifigenia; Figueroa, Arturo; Beets, Michael; Pitetti, Kenneth; Fernhall, Bo

    2006-01-01

    Our goal in this study was to compare cardiac autonomic control at rest between 50 individuals with Down syndrome and 24 control participants without disabilities. Resting autonomic function was assessed using analysis of heart rate variability. Participants with Down syndrome had reduced total heart rate variability, which indicates possible…

  5. Alterations in cardiac autonomic control in spinal cord injury.

    PubMed

    Biering-Sørensen, Fin; Biering-Sørensen, Tor; Liu, Nan; Malmqvist, Lasse; Wecht, Jill Maria; Krassioukov, Andrei

    2017-02-15

    A spinal cord injury (SCI) interferes with the autonomic nervous system (ANS). The effect on the cardiovascular system will depend on the extent of damage to the spinal/central component of ANS. The cardiac changes are caused by loss of supraspinal sympathetic control and relatively increased parasympathetic cardiac control. Decreases in sympathetic activity result in heart rate and the arterial blood pressure changes, and may cause arrhythmias, in particular bradycardia, with the risk of cardiac arrest in those with cervical or high thoracic injuries. The objective of this review is to give an update of the current knowledge related to the alterations in cardiac autonomic control following SCI. With this purpose the review includes the following subheadings: 2. Neuro-anatomical plasticity and cardiac control 2.1 Autonomic nervous system and the heart 2.2 Alteration in autonomic control of the heart following spinal cord injury 3. Spinal shock and neurogenic shock 3.1 Pathophysiology of spinal shock 3.2 Pathophysiology of neurogenic shock 4. Autonomic dysreflexia 4.1 Pathophysiology of autonomic dysreflexia 4.2 Diagnosis of autonomic dysreflexia 5. Heart rate/electrocardiography following spinal cord injury 5.1 Acute phase 5.2 Chronic phase 6. Heart rate variability 6.1 Time domain analysis 6.2 Frequency domain analysis 6.3 QT-variability index 6.4 Nonlinear (fractal) indexes 7. Echocardiography 7.1 Changes in cardiac structure following spinal cord injury 7.2 Changes in cardiac function following spinal cord injury 8. International spinal cord injury cardiovascular basic data set and international standards to document the remaining autonomic function in spinal cord injury.

  6. Role of the autonomic nervous system in modulating cardiac arrhythmias.

    PubMed

    Shen, Mark J; Zipes, Douglas P

    2014-03-14

    The autonomic nervous system plays an important role in the modulation of cardiac electrophysiology and arrhythmogenesis. Decades of research has contributed to a better understanding of the anatomy and physiology of cardiac autonomic nervous system and provided evidence supporting the relationship of autonomic tone to clinically significant arrhythmias. The mechanisms by which autonomic activation is arrhythmogenic or antiarrhythmic are complex and different for specific arrhythmias. In atrial fibrillation, simultaneous sympathetic and parasympathetic activations are the most common trigger. In contrast, in ventricular fibrillation in the setting of cardiac ischemia, sympathetic activation is proarrhythmic, whereas parasympathetic activation is antiarrhythmic. In inherited arrhythmia syndromes, sympathetic stimulation precipitates ventricular tachyarrhythmias and sudden cardiac death except in Brugada and J-wave syndromes where it can prevent them. The identification of specific autonomic triggers in different arrhythmias has brought the idea of modulating autonomic activities for both preventing and treating these arrhythmias. This has been achieved by either neural ablation or stimulation. Neural modulation as a treatment for arrhythmias has been well established in certain diseases, such as long QT syndrome. However, in most other arrhythmia diseases, it is still an emerging modality and under investigation. Recent preliminary trials have yielded encouraging results. Further larger-scale clinical studies are necessary before widespread application can be recommended.

  7. The ECG vertigo in diabetes and cardiac autonomic neuropathy.

    PubMed

    Voulgari, Christina; Tentolouris, Nicholas; Stefanadis, Christodoulos

    2011-01-01

    The importance of diabetes in the epidemiology of cardiovascular diseases cannot be overemphasized. About one third of acute myocardial infarction patients have diabetes, and its prevalence is steadily increasing. The decrease in cardiac mortality in people with diabetes is lagging behind that of the general population. Cardiovascular disease is a broad term which includes any condition causing pathological changes in blood vessels, cardiac muscle or valves, and cardiac rhythm. The ECG offers a quick, noninvasive clinical and research screen for the early detection of cardiovascular disease in diabetes. In this paper, the clinical and research value of the ECG is readdressed in diabetes and in the presence of cardiac autonomic neuropathy.

  8. Cardiac Autonomic Function in Patients With Ankylosing Spondylitis

    PubMed Central

    Wei, Cheng-Yu; Kung, Woon-Man; Chou, Yi-Sheng; Wang, Yao-Chin; Tai, Hsu-Chih; Wei, James Cheng-Chung

    2016-01-01

    Abstract Ankylosing spondylitis (AS) is a chronic inflammatory disease involing spine and enthesis. The primary aim of this study is to investigate the autonomic nervous system (ANS) function and the association between ANS and the functional status or disease activity in AS. The study included 42 AS patients, all fulfilling the modified New York criteria. All the patients are totally symptom free for ANS involvement and had normal neurological findings. These AS patients and 230 healthy volunteers receive analysis of 5 minutes heart rate variability (HRV) in lying posture. In addition, disease activity and functional status of these AS patients are assessed by Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), and Bath Ankylosing Spondylitis Global Score (BAS-G). Both groups were age and sex-matched. Although the HRV analysis indicates that the peaks of total power (TP, 0–0.5 Hz) and high-frequency power (HF, 0.15–0.40 Hz) are similar in both groups, the activities of low-frequency power (LF, 0.04–0.15 Hz), LF in normalized units (LF%), and the ratio of LF to HF (LF/HF) in AS patients are obviously lower than healthy controls. The erythrocyte sedimentation rate and C-reactive protein revealed negative relationship with HF. The AS patients without peripheral joint disease have higher LF, TP, variance, LF%, and HF than the patients with peripheral joint disease. The AS patients without uvetis have higher HF than the patients with uvetis. The total scores of BASDI, BASFI, and BAS-G do not show any association to HRV parameters. AS patients have significantly abnormal cardiac autonomic regulation. This is closely related with some inflammatory activities. Reduced autonomic function may be one of the factors of high cardiovascular risk in AS patients. PMID:27227940

  9. Dysregulation of cardiac autonomic function in offspring exposed to alcohol during antenatal period.

    PubMed

    Chandran, Sajish; Abhishekh, Hulegar A; Murthy, Pratima; Raju, Trichur R; Sathyaprabha, Talakad N

    2015-10-01

    Several lines of investigations have shown the deleterious effect of an alcohol on the autonomic nervous system. Recent evidence shows that infants exposed to alcohol during the antenatal period displayed aberration in the cardiac autonomic function after the birth. However, there is dearth of literature on the long term influence of antenatal alcohol exposure. In this study we measured the cardiac autonomic functions in children who were exposed to alcohol in the antenatal period and compared them with non-exposed control children. Twenty eight children (age: 9±2 years) in the antenatal alcohol exposed group and age, gender matched 30 non exposed healthy volunteers as a control (age: 10±2 years) were recruited. Electrocardiogram was recorded in all subjects at rest in the supine position. HRV parameters were analyzed in the time and frequency domains using customized software. The average heart rate was similar between both the groups. There was no statistical significant difference in the time domain measures between the groups. However, the low frequency power, normalized units and low frequency to high frequency ratio were significantly higher in the antenatal alcohol exposed children compared to the controls. This suggests sympathetic predominance in children who were exposed to alcohol in the antenatal period. In this study we provide evidence for the deleterious long lasting effect of antenatal exposure of alcohol on cardiac autonomic regulation. Further prospective studies are needed to confirm the causal relationship between antenatal alcohol exposure and autonomic dysregulation.

  10. Functional Imaging of Autonomic Regulation: Methods and Key Findings

    PubMed Central

    Macey, Paul M.; Ogren, Jennifer A.; Kumar, Rajesh; Harper, Ronald M.

    2016-01-01

    regions mediating postural and motoric actions, including respiration, and cardiac output. The study of pathological processes associated with autonomic disruption shows susceptibilities of different brain structures to altered timing of neural function, notably in sleep disordered breathing, such as obstructive sleep apnea and congenital central hypoventilation syndrome. The cerebellum, in particular, serves coordination roles for vestibular stimuli and blood pressure changes, and shows both injury and substantially altered timing of responses to pressor challenges in sleep-disordered breathing conditions. The insights into central autonomic processing provided by neuroimaging have assisted understanding of such regulation, and may lead to new treatment options for conditions with disrupted autonomic function. PMID:26858595

  11. Cardiac Autonomic Functions in Obese Children

    PubMed Central

    Taşçılar, Mehmet Emre; Yokuşoğlu, Mehmet; Boyraz, Mehmet; Baysan, Oben; Köz, Cem; Dündaröz, Ruşen

    2011-01-01

    Objective: The autonomic nervous system is assumed to have a role in the pathophysiology of obesity. In this study, we evaluated the autonomic system by measuring heart rate variability (HRV) in obese children. Methods: Thirty-two obese and 30 healthy children (mean ages: 11.6±2.0 years and 11.0±2.9 years, respectively) were enrolled in the study. Obesity was defined as a body mass index higher than 97th percentile for age- and gender-specific reference values. All participants were free of any disease and none of them was receiving any medication. Twenty-four-hour ambulatory electrocardiographic recordings were obtained and the time-domain and frequency-domain indices of HRV were analyzed. The study group was evaluated with respect to insulin resistance by HOMA-IR values. Results: A significant decrease in calculated HRV variables was observed in obese children as compared to controls. The HRV alteration was found in both time-domain and frequency-domain parameters. The subgroup analysis of the study group revealed a significant decrease in all investigated HRV parameters in the insulin-resistant obese children compared to the non-insulin-resistant obese ones. Conclusions: Our results indicate that HRV is decreased in obese children, which implies parasympathetic withdrawal and sympathetic predominance. A marked decrease in HRV was observed in insulin-resistant obese children compared to their non-insulin-resistant counterparts. We propose that autonomic imbalance pertaining especially to insulin resistance may be involved in the pathogenesis of obesity in pediatric patients Conflict of interest:None declared. PMID:21750633

  12. Cardiac myofilaments: mechanics and regulation

    NASA Technical Reports Server (NTRS)

    de Tombe, Pieter P.; Bers, D. M. (Principal Investigator)

    2003-01-01

    The mechanical properties of the cardiac myofilament are an important determinant of pump function of the heart. This report is focused on the regulation of myofilament function in cardiac muscle. Calcium ions form the trigger that induces activation of the thin filament which, in turn, allows for cross-bridge formation, ATP hydrolysis, and force development. The structure and protein-protein interactions of the cardiac sarcomere that are responsible for these processes will be reviewed. The molecular mechanism that underlies myofilament activation is incompletely understood. Recent experimental approaches have been employed to unravel the mechanism and regulation of myofilament mechanics and energetics by activator calcium and sarcomere length, as well as contractile protein phosphorylation mediated by protein kinase A. Central to these studies is the question whether such factors impact on muscle function simply by altering thin filament activation state, or whether modulation of cross-bridge cycling also plays a part in the responses of muscle to these stimuli.

  13. Diabetes and cardiac autonomic neuropathy: Clinical manifestations, cardiovascular consequences, diagnosis and treatment

    PubMed Central

    Balcıoğlu, Akif Serhat; Müderrisoğlu, Haldun

    2015-01-01

    Cardiac autonomic neuropathy (CAN) is a frequent chronic complication of diabetes mellitus with potentially life-threatening outcomes. CAN is caused by the impairment of the autonomic nerve fibers regulating heart rate, cardiac output, myocardial contractility, cardiac electrophysiology and blood vessel constriction and dilatation. It causes a wide range of cardiac disorders, including resting tachycardia, arrhythmias, intraoperative cardiovascular instability, asymptomatic myocardial ischemia and infarction and increased rate of mortality after myocardial infarction. Etiological factors associated with autonomic neuropathy include insufficient glycemic control, a longer period since the onset of diabetes, increased age, female sex and greater body mass index. The most commonly used methods for the diagnosis of CAN are based upon the assessment of heart rate variability (the physiological variation in the time interval between heartbeats), as it is one of the first findings in both clinically asymptomatic and symptomatic patients. Clinical symptoms associated with CAN generally occur late in the disease process and include early fatigue and exhaustion during exercise, orthostatic hypotension, dizziness, presyncope and syncope. Treatment is based on early diagnosis, life style changes, optimization of glycemic control and management of cardiovascular risk factors. Medical therapies, including aldose reductase inhibitors, angiotensin-converting enzyme inhibitors, prostoglandin analogs and alpha-lipoic acid, have been found to be effective in randomized controlled trials. The following article includes the epidemiology, clinical findings and cardiovascular consequences, diagnosis, and approaches to prevention and treatment of CAN. PMID:25685280

  14. Molecular mechanisms autonomic dysfunction and impaired cardiac contractility in critical illness

    PubMed Central

    Ackland, Gareth L.; Whittle, John; Toner, Andrew; Machhada, Asif; Gutierrez Del Arroyo, Ana; Sciuso, Alberto; Jenkins, Nicholas; Dyson, Alex; Struthers, Richard; Sneyd, Robert; Minto, Gary; Singer, Mervyn; Shah, Ajay M.; Gourine, Alexander V.

    2016-01-01

    Objectives: Molecular mechanisms linking autonomic dysfunction with poorer clinical outcomes in critical illness remain unclear. We hypothesized that baroreflex dysfunction alone is sufficient to cause cardiac impairment through neurohormonal activation of (NADPH oxidase-dependent) oxidative stress resulting in increased expression of G-protein coupled receptor kinase (GRK)-2, a key negative regulator of cardiac function. Design: Laboratory/clinical investigations. Setting: University laboratory/medical centers. Subjects: Adult rats; wild-type/NAPDH oxidase subunit-2 (NOX-2) deficient mice; elective surgical patients. Interventions: Cardiac performance was assessed by transthoracic echocardiography following experimental baroreflex dysfunction (BD, sino-aortic denervation) in rats and mice. Immunoblots assessed GPCR recycling proteins expression in rodent cardiomyocytes and patient mononuclear leukocytes. In surgical patients, heart rate recovery after cardio-pulmonary exercise testing, time/frequency measures of parasympathetic parameters were related to the presence/absence of BD (defined by spontaneous baroreflex sensitivity of <6ms.mmHg-1). The associations of BD with intraoperative cardiac function and outcomes were assessed. Measurements and Main Results: Experimental BD in rats and mice resulted in impaired cardiac contractility and upregulation of GRK-2 expression. In mice, genetic deficiency of gp91 NADPH-oxidase (NOX-2) subunit prevented upregulation of GRK-2 expression in conditions of BD and preserved cardiac function. BD was present in 81/249 (32.5%) patients, and was characterized by lower parasympathetic tone and increased GRK-2 expression in mononuclear leukocytes. BD in patients was also associated with impaired intraoperative cardiac contractility. Critical illness and mortality were more frequent in surgical patients with BD (relative risk: 1.66 [95%CI:1.16-2.39]; p=0.006). Conclusions: Reduced baroreflex sensitivity is associated with NOX-2

  15. Paroxysmal autonomic instability with dystonia (PAID) syndrome following cardiac arrest

    PubMed Central

    Kapoor, Dheeraj; Singla, Deepak; Singh, Jasveer; Jindal, Rohit

    2014-01-01

    Paroxysmal autonomic instability with dystonia (PAID) appears to be a unique syndrome following brain injury. It can echo many life-threatening conditions, making its early recognition and management a challenge for intensivists. A delay in early recognition and subsequent management may result in increased morbidity, which is preventable in affected patients. Herein, we report the case of a patient who was diagnosed with PAID syndrome following prolonged cardiac arrest, and discuss the pathophysiology, clinical presentation and management of this rare and under-recognised clinical entity. PMID:25189311

  16. HRVanalysis: A Free Software for Analyzing Cardiac Autonomic Activity.

    PubMed

    Pichot, Vincent; Roche, Frédéric; Celle, Sébastien; Barthélémy, Jean-Claude; Chouchou, Florian

    2016-01-01

    Since the pioneering studies of the 1960s, heart rate variability (HRV) has become an increasingly used non-invasive tool for examining cardiac autonomic functions and dysfunctions in various populations and conditions. Many calculation methods have been developed to address these issues, each with their strengths and weaknesses. Although, its interpretation may remain difficult, this technique provides, from a non-invasive approach, reliable physiological information that was previously inaccessible, in many fields including death and health prediction, training and overtraining, cardiac and respiratory rehabilitation, sleep-disordered breathing, large cohort follow-ups, children's autonomic status, anesthesia, or neurophysiological studies. In this context, we developed HRVanalysis, a software to analyse HRV, used and improved for over 20 years and, thus, designed to meet laboratory requirements. The main strength of HRVanalysis is its wide application scope. In addition to standard analysis over short and long periods of RR intervals, the software allows time-frequency analysis using wavelet transform as well as analysis of autonomic nervous system status on surrounding scored events and on preselected labeled areas. Moreover, the interface is designed for easy study of large cohorts, including batch mode signal processing to avoid running repetitive operations. Results are displayed as figures or saved in TXT files directly employable in statistical softwares. Recordings can arise from RR or EKG files of different types such as cardiofrequencemeters, holters EKG, polygraphs, and data acquisition systems. HRVanalysis can be downloaded freely from the Web page at: https://anslabtools.univ-st-etienne.fr HRVanalysis is meticulously maintained and developed for in-house laboratory use. In this article, after a brief description of the context, we present an overall view of HRV analysis and we describe the methodological approach of the different techniques provided

  17. Physical exercise and cardiac autonomic activity in healthy adult men.

    PubMed

    Panda, Kaninika; Krishna, Pushpa

    2014-01-01

    Physical inactivity is an important risk factor for cardiovascular mortality and morbidity. Regular exercise is known to improve health and maintain physical fitness. The heart rate response to exercise reflects autonomic control of heart and has shown to predict cardiovascular prognosis. Decreased heart rate variability (HRV) is known as a risk factor for cardiovascular mortality. The objective of this study was to study the effect of exercise on cardiac autonomic activity. Thirty two healthy adult men in the age group of 18-25 years with normal body mass index (BMI) were recruited from different physical fitness centers, who were undergoing regular exercise for past 3 months. Resting ECG was recorded for 5 minutes and analyzed for frequency analysis of HRV. HRV parameters of the subjects were compared with fifty age and BMI matched subjects who were not undergoing any exercise program. Physical activity level of all subjects was assessed by using Global Physical Activity Questionnaire. The exercising (E) subjects were found to have a lesser heart rate (73.27 ± 8.6 vs 74.41 ± 8.59) compared to non-exercising (NE) group, which was not significant. No significant difference was found in frequency domain parameters of HRV between exercising and non-exercising group with LF (47.12 ± 19.17 vs 43.55 ± 16.66), HF (41.03 ± 17.65 vs 46.03 ± 15.89) and LF/HF (1.61 ± 1.16 vs 1.22 ± 0.93) respectively. Physical activity level was significantly different between the two groups (4175 ± 1481.53 vs 1176.4?1103.83, p<0.001). This study showed 3 months of exercise did not have any effect on cardiac autonomic activity despite the difference in physical activity.

  18. HRVanalysis: A Free Software for Analyzing Cardiac Autonomic Activity

    PubMed Central

    Pichot, Vincent; Roche, Frédéric; Celle, Sébastien; Barthélémy, Jean-Claude; Chouchou, Florian

    2016-01-01

    Since the pioneering studies of the 1960s, heart rate variability (HRV) has become an increasingly used non-invasive tool for examining cardiac autonomic functions and dysfunctions in various populations and conditions. Many calculation methods have been developed to address these issues, each with their strengths and weaknesses. Although, its interpretation may remain difficult, this technique provides, from a non-invasive approach, reliable physiological information that was previously inaccessible, in many fields including death and health prediction, training and overtraining, cardiac and respiratory rehabilitation, sleep-disordered breathing, large cohort follow-ups, children's autonomic status, anesthesia, or neurophysiological studies. In this context, we developed HRVanalysis, a software to analyse HRV, used and improved for over 20 years and, thus, designed to meet laboratory requirements. The main strength of HRVanalysis is its wide application scope. In addition to standard analysis over short and long periods of RR intervals, the software allows time-frequency analysis using wavelet transform as well as analysis of autonomic nervous system status on surrounding scored events and on preselected labeled areas. Moreover, the interface is designed for easy study of large cohorts, including batch mode signal processing to avoid running repetitive operations. Results are displayed as figures or saved in TXT files directly employable in statistical softwares. Recordings can arise from RR or EKG files of different types such as cardiofrequencemeters, holters EKG, polygraphs, and data acquisition systems. HRVanalysis can be downloaded freely from the Web page at: https://anslabtools.univ-st-etienne.fr HRVanalysis is meticulously maintained and developed for in-house laboratory use. In this article, after a brief description of the context, we present an overall view of HRV analysis and we describe the methodological approach of the different techniques provided

  19. Measures of Autonomic Nervous System Regulation

    DTIC Science & Technology

    2011-04-01

    Cortisol Galvanic Skin Response (GSR) Gastro- intestinal Pupillary Response Respiratory Salivary Amylase Vascular Manipulative Body-Based...Salivary Amylase Galvanic Skin Response Vascular Gastrointestinal The ANS Measures Table in Appendix A provides a summary of over fifty tools...Measures of Autonomic Nervous System Regulation Salivary Amylase Measurement

  20. Cardiac autonomic dysfunction in obese normotensive children and adolescents

    PubMed Central

    Freitas, Isabelle Magalhães G.; Miranda, Josiane Aparecida; Mira, Pedro Augusto C.; Lanna, Carla Marcia M.; Lima, Jorge Roberto P.; Laterza, Mateus Camaroti

    2014-01-01

    OBJECTIVE: To test the hypothesis that obese normotensive children and adolescents present impaired cardiac autonomic control compared to non-obese normotensive ones. METHODS: For this cross-sectional study, 66 children and adolescents were divided into the following groups: Obese (n=31, 12±3 years old) and Non-Obese (n=35, 13±3 years old). Obesity was defined as body mass index greater than the 95th percentile for age and gender. Blood pressure was measured by oscillometric method after 15 minutes of rest in supine position. The heart rate was continuously registered during ten minutes in the supine position with spontaneous breathing. The cardiac autonomic control was assessed by heart rate variability, which was calculated from the five-minute minor variance of the signal. The derivations were the index that indicates the proportion of the number of times in which normal adjacent R-R intervals present differences >50 miliseconds (pNN50), for the time domain, and, for the spectral analysis, low (LF) and high frequency (HF) bands, besides the low and high frequencies ratio (LF/HF). The results were expressed as mean±standard deviation and compared by Student's t-test or Mann-Whitney's U-test. RESULTS: Systolic blood pressure (116±14 versus 114±13mmHg, p=0.693) and diastolic blood pressure (59±8 versus 60±11mmHg, p=0.458) were similar between the Obese and Non-Obese groups. The pNN50 index (29±21 versus 43±23, p=0.015) and HF band (54±20 versus 64±14 normalized units - n.u., p=0.023) were lower in the Obese Group. The LF band (46±20 versus 36±14 n.u., p=0.023) and LF/HF ratio (1.3±1.6 versus 0.7±0.4, p=0.044) were higher in Obese Group. CONCLUSIONS: Obese normotensive children and adolescents present impairment of cardiac autonomic control. PMID:25119757

  1. Autonomic regulation in Fragile X Syndrome

    PubMed Central

    Heilman, Keri J.; Harden, Emily R.; Zageris, Danielle M.; Berry-Kravis, Elizabeth; Porges, Stephen W.

    2011-01-01

    Autonomic reactivity was studied in individuals with fragile X syndrome (FXS), a genetic disorder partially characterized by abnormal social behavior. Relative to age-matched controls, the FXS group had faster baseline heart rate and lower amplitude respiratory sinus arrhythmia (RSA). In contrast to the typically developing controls, there was a decrease in RSA with age within the FXS group. Moreover, within the FXS group heart rate did not slow with age. The FXS group also responded with an atypical increase in RSA to the social challenge, while the control group reduced RSA. In a subset of the FXS group, the autonomic profile did not change following 2 months and 1 year of lithium treatment. The observed indices of atypical autonomic regulation, consistent with the Polyvagal Theory, may contribute to the deficits in social behavior and social communication observed in FXS. PMID:21547900

  2. Impaired regulation of cardiac function in sepsis, SIRS, and MODS.

    PubMed

    Werdan, Karl; Schmidt, Hendrik; Ebelt, Henning; Zorn-Pauly, Klaus; Koidl, Bernd; Hoke, Robert Sebastian; Heinroth, Konstantin; Müller-Werdan, Ursula

    2009-04-01

    In sepsis, systemic inflammatory response syndrome (SIRS), and multiorgan dysfunction syndrome (MODS), a severe prognostically relevant cardiac autonomic dysfunction exists, as manifested by a strong attenuation of sympathetically and vagally mediated heart rate variability (HRV). The mechanisms underlying this attenuation are not limited to the nervous system. They also include alterations of the cardiac pacemaker cells on a cellular level. As shown in human atrial cardiomyocytes, endotoxin interacts with cardiac hyperpolarization-activated cyclic nucleotide-gated (HCN) ion channels, which mediate the pacemaker current If and play an important role in transmitting sympathetic and vagal signals on heart rate and HRV. Moreover, endotoxin sensitizes cardiac HCN channels to sympathetic signals. These findings identify endotoxin as a pertinent modulator of the autonomic nervous regulation of heart function. In MODS, the vagal pathway of the autonomic nervous system is particularly compromised, leading to an attenuation of the cholinergic antiinflammatory reflex. An amelioration of the blunted vagal activity appears to be a promising novel therapeutic target to achieve a suppression of the inflammatory state and thereby an improvement of prognosis in MODS patients. Preliminary data revealed therapeutic benefits (increased survival rates and improvements of the depressed vagal activity) of the administration of statins, beta-blockers, and angiotensin-converting enzyme inhibitors in patients with MODS.

  3. Diabetic cardiac autonomic neuropathy: insights from animal models.

    PubMed

    Stables, Catherine L; Glasser, Rebecca L; Feldman, Eva L

    2013-10-01

    Cardiac autonomic neuropathy (CAN) is a relatively common and often devastating complication of diabetes. The major clinical signs are tachycardia, exercise intolerance, and orthostatic hypotension, but the most severe aspects of this complication are high rates of cardiac events and mortality. One of the earliest manifestations of CAN is reduced heart rate variability, and detection of this, along with abnormal results in postural blood pressure testing and/or the Valsalva maneuver, are central to diagnosis of the disease. The treatment options for CAN, beyond glycemic control, are extremely limited and lack evidence of efficacy. The underlying molecular mechanisms are also poorly understood. Thus, CAN is associated with a poor prognosis and there is a compelling need for research to understand, prevent, and reverse CAN. In this review of the literature we examine the use and usefulness of animal models of CAN in diabetes. Compared to other diabetic complications, the number of animal studies of CAN is very low. The published studies range across a variety of species, methods of inducing diabetes, and timescales examined, leading to high variability in study outcomes. The lack of well-characterized animal models makes it difficult to judge the relevance of these models to the human disease. One major advantage of animal studies is the ability to probe underlying molecular mechanisms, and the limited numbers of mechanistic studies conducted to date are outlined. Thus, while animal models of CAN in diabetes are crucial to better understanding and development of therapies, they are currently under-used.

  4. Cardiac autonomic neuropathy in patients with diabetes mellitus

    PubMed Central

    Dimitropoulos, Gerasimos; Tahrani, Abd A; Stevens, Martin J

    2014-01-01

    Cardiac autonomic neuropathy (CAN) is an often overlooked and common complication of diabetes mellitus. CAN is associated with increased cardiovascular morbidity and mortality. The pathogenesis of CAN is complex and involves a cascade of pathways activated by hyperglycaemia resulting in neuronal ischaemia and cellular death. In addition, autoimmune and genetic factors are involved in the development of CAN. CAN might be subclinical for several years until the patient develops resting tachycardia, exercise intolerance, postural hypotension, cardiac dysfunction and diabetic cardiomyopathy. During its sub-clinical phase, heart rate variability that is influenced by the balance between parasympathetic and sympathetic tones can help in detecting CAN before the disease is symptomatic. Newer imaging techniques (such as scintigraphy) have allowed earlier detection of CAN in the pre-clinical phase and allowed better assessment of the sympathetic nervous system. One of the main difficulties in CAN research is the lack of a universally accepted definition of CAN; however, the Toronto Consensus Panel on Diabetic Neuropathy has recently issued guidance for the diagnosis and staging of CAN, and also proposed screening for CAN in patients with diabetes mellitus. A major challenge, however, is the lack of specific treatment to slow the progression or prevent the development of CAN. Lifestyle changes, improved metabolic control might prevent or slow the progression of CAN. Reversal will require combination of these treatments with new targeted therapeutic approaches. The aim of this article is to review the latest evidence regarding the epidemiology, pathogenesis, manifestations, diagnosis and treatment for CAN. PMID:24567799

  5. Cardiac autonomic neuropathy in patients with diabetes mellitus.

    PubMed

    Dimitropoulos, Gerasimos; Tahrani, Abd A; Stevens, Martin J

    2014-02-15

    Cardiac autonomic neuropathy (CAN) is an often overlooked and common complication of diabetes mellitus. CAN is associated with increased cardiovascular morbidity and mortality. The pathogenesis of CAN is complex and involves a cascade of pathways activated by hyperglycaemia resulting in neuronal ischaemia and cellular death. In addition, autoimmune and genetic factors are involved in the development of CAN. CAN might be subclinical for several years until the patient develops resting tachycardia, exercise intolerance, postural hypotension, cardiac dysfunction and diabetic cardiomyopathy. During its sub-clinical phase, heart rate variability that is influenced by the balance between parasympathetic and sympathetic tones can help in detecting CAN before the disease is symptomatic. Newer imaging techniques (such as scintigraphy) have allowed earlier detection of CAN in the pre-clinical phase and allowed better assessment of the sympathetic nervous system. One of the main difficulties in CAN research is the lack of a universally accepted definition of CAN; however, the Toronto Consensus Panel on Diabetic Neuropathy has recently issued guidance for the diagnosis and staging of CAN, and also proposed screening for CAN in patients with diabetes mellitus. A major challenge, however, is the lack of specific treatment to slow the progression or prevent the development of CAN. Lifestyle changes, improved metabolic control might prevent or slow the progression of CAN. Reversal will require combination of these treatments with new targeted therapeutic approaches. The aim of this article is to review the latest evidence regarding the epidemiology, pathogenesis, manifestations, diagnosis and treatment for CAN.

  6. Epigenetic regulation of cardiac fibrosis

    PubMed Central

    Stratton, Matthew S.; McKinsey, Timothy A.

    2016-01-01

    Fibrosis is defined as excess deposition of extracellular matrix (ECM), resulting in tissue scarring and organ dysfunction. In the heart, fibrosis may be reparative, replacing areas of myocyte loss with a structural scar following infarction, or reactive, which is triggered in the absence of cell death and involves interstitial ECM deposition in response to long-lasting stress. Interstitial fibrosis can increase the passive stiffness of the myocardium, resulting in impaired relaxation and diastolic dysfunction. Additionally, fibrosis can lead to disruption of electrical conduction in the heart, causing arrhythmias, and can limit myocyte oxygen availability and thus exacerbate myocardial ischemia. Here, we review recent studies that have illustrated key roles for epigenetic events in the control of pro-fibrotic gene expression, and highlight the potential of small molecules that target epigenetic regulators as a means of treating fibrotic cardiac diseases. PMID:26876451

  7. Cardiac Vagal Regulation and Early Peer Status

    ERIC Educational Resources Information Center

    Graziano, Paulo A.; Keane, Susan P.; Calkins, Susan D.

    2007-01-01

    A sample of 341 5 1/2-year-old children participating in an ongoing longitudinal study was the focus of a study on the relation between cardiac vagal regulation and peer status. To assess cardiac vagal regulation, resting measures of respiratory sinus arrhythmia (RSA) and RSA change (suppression) to 3 cognitively and emotionally challenging tasks…

  8. Autonomic, locomotor and cardiac abnormalities in a mouse model of muscular dystrophy: targeting the renin-angiotensin system.

    PubMed

    Sabharwal, Rasna; Chapleau, Mark W

    2014-04-01

    New Findings What is the topic of this review? This symposium report summarizes autonomic, cardiac and skeletal muscle abnormalities in sarcoglycan-δ-deficient mice (Sgcd-/-), a mouse model of limb girdle muscular dystrophy, with emphasis on the roles of autonomic dysregulation and activation of the renin-angiotensin system at a young age. What advances does it highlight? The contributions of the autonomic nervous system and the renin-angiotensin system to the pathogenesis of muscular dystrophy are highlighted. Results demonstrate that autonomic dysregulation precedes and predicts later development of cardiac dysfunction in Sgcd-/- mice and that treatment of young Sgcd-/- mice with the angiotensin type 1 receptor antagonist losartan or with angiotensin-(1-7) abrogates the autonomic dysregulation, attenuates skeletal muscle pathology and increases spontaneous locomotor activity. Muscular dystrophies are a heterogeneous group of genetic muscle diseases characterized by muscle weakness and atrophy. Mutations in sarcoglycans and other subunits of the dystrophin-glycoprotein complex cause muscular dystrophy and dilated cardiomyopathy in animals and humans. Aberrant autonomic signalling is recognized in a variety of neuromuscular disorders. We hypothesized that activation of the renin-angiotensin system contributes to skeletal muscle and autonomic dysfunction in mice deficient in the sarcoglycan-δ (Sgcd) gene at a young age and that this early autonomic dysfunction contributes to the later development of left ventricular (LV) dysfunction and increased mortality. We demonstrated that young Sgcd-/- mice exhibit histopathological features of skeletal muscle dystrophy, decreased locomotor activity and severe autonomic dysregulation, but normal LV function. Autonomic regulation continued to deteriorate in Sgcd-/- mice with age and was accompanied by LV dysfunction and dilated cardiomyopathy at older ages. Autonomic dysregulation at a young age predicted later development of

  9. Cardiac Autonomic Dysfunction from Occupational Exposure to Polycyclic Aromatic Hydrocarbons

    PubMed Central

    Lee, Mi-Sun; Magari, Shannon; Christiani, David C.

    2013-01-01

    Objectives Polycyclic aromatic hydrocarbons (PAHs) exposures have been associated with cardiopulmonary mortality and cardiovascular events. This study investigated the association between a biological marker of PAHs exposure, assessed by urinary 1-hydroxypyrene (1-OHP), and heart rate variability (HRV) in an occupational cohort of boilermakers. Methods Continuous 24-hour monitoring of the ambulatory electrocardiogram (ECG) and pre and post shift urinary 1-OHP were repeated over extended periods of the work week. Mixed effects models were fit for the 5-minute standard deviation of normal-to-normal intervals (SDNN) in relation to urinary 1-OHP levels pre and post workshift on the day they wore the monitor, controlling for potential confounders. Results We found a significant decrease in 5-min SDNN during work of −13.6% (95% confidence interval, −17.2% to −9.8%) for every standard deviation (0.53 microgram/gram [μg/g] creatinine) increase in the next-morning pre-shift 1-OHP levels. The magnitude of reduction in 5-min SDNN were largest during the late night period after work and increased with every standard deviation (0.46 μg/g creatinine) increase in post-shift 1-OHP levels. Conclusion This is the first report providing evidence that occupational exposure to PAHs is associated with altered cardiac autonomic function. Acute exposure to PAHs may be an important predictor of cardiovascular disease risk in the work environment. PMID:21172795

  10. Diabetic cardiac autonomic neuropathy: Do we have any treatment perspectives?

    PubMed Central

    Serhiyenko, Victoria A; Serhiyenko, Alexandr A

    2015-01-01

    Cardiac autonomic neuropathy (CAN) is a serious and common complication of diabetes mellitus (DM). Despite its relationship to an increased risk of cardiovascular mortality and its association with multiple symptoms and impairments, the significance of CAN has not been fully appreciated. CAN among DM patients is characterized review the latest evidence and own data regarding the treatment and the treatment perspectives for diabetic CAN. Lifestyle modification, intensive glycemic control might prevent development or progression of CAN. Pathogenetic treatment of CAN includes: balanced diet and physical activity; optimization of glycemic control; treatment of dyslipoproteinemia; correction of metabolic abnormalities in myocardium; prevention and treatment of thrombosis; use of aldose reductase inhibitors; dihomo-γ-linolenic acid (DGLA), acetyl-L-carnitine, antioxidants, first of all α-lipoic acid (α-LA), use of long-chain ω-3 and ω-6 polyunsaturated fatty acids (ω-3 and ω-6 PUFAs), vasodilators, fat-soluble vitamin B1, aminoguanidine; substitutive therapy of growth factors, in severe cases-treatment of orthostatic hypotension. The promising methods include research and use of tools that increase blood flow through the vasa vasorum, including prostacyclin analogues, thromboxane A2 blockers and drugs that contribute into strengthening and/or normalization of Na+, K+-ATPase (phosphodiesterase inhibitor), α-LA, DGLA, ω-3 PUFAs, and the simultaneous prescription of α-LA, ω-3 PUFA and DGLA. PMID:25789106

  11. Human autonomic rhythms: vagal cardiac mechanisms in tetraplegic subjects

    NASA Technical Reports Server (NTRS)

    Koh, J.; Brown, T. E.; Beightol, L. A.; Ha, C. Y.; Eckberg, D. L.

    1994-01-01

    1. We studied eight young men (age range: 20-37 years) with chronic, clinically complete high cervical spinal cord injuries and ten age-matched healthy men to determine how interruption of connections between the central nervous system and spinal sympathetic motoneurones affects autonomic cardiovascular control. 2. Baseline diastolic pressures and R-R intervals (heart periods) were similar in the two groups. Slopes of R-R interval responses to brief neck pressure changes were significantly lower in tetraplegic than in healthy subjects, but slopes of R-R interval responses to steady-state arterial pressure reductions and increases were comparable. Plasma noradrenaline levels did not change significantly during steady-state arterial pressure reductions in tetraplegic patients, but rose sharply in healthy subjects. The range of arterial pressure and R-R interval responses to vasoactive drugs (nitroprusside and phenylephrine) was significantly greater in tetraplegic than healthy subjects. 3. Resting R-R interval spectral power at respiratory and low frequencies was similar in the two groups. During infusions of vasoactive drugs, low-frequency R-R interval spectral power was directly proportional to arterial pressure in tetraplegic patients, but was unrelated to arterial pressure in healthy subjects. Vagolytic doses of atropine nearly abolished both low- and respiratory-frequency R-R interval spectral power in both groups. 4. Our conclusions are as follows. First, since tetraplegic patients have significant levels of low-frequency arterial pressure and R-R interval spectral power, human Mayer arterial pressure waves may result from mechanisms that do not involve stimulation of spinal sympathetic motoneurones by brainstem neurones. Second, since in tetraplegic patients, low-frequency R-R interval spectral power is proportional to arterial pressure, it is likely to be mediated by a baroreflex mechanism. Third, since low-frequency R-R interval rhythms were nearly abolished

  12. Cardiac autonomic responses after resistance exercise in treated hypertensive subjects

    PubMed Central

    Trevizani, Gabriela A.; Peçanha, Tiago; Nasario-Junior, Olivassé; Vianna, Jeferson M.; Silva, Lilian P.; Nadal, Jurandir

    2015-01-01

    The aim of this study was to assess and to compare heart rate variability (HRV) after resistance exercise (RE) in treated hypertensive and normotensive subjects. Nine hypertensive men [HT: 58.0 ± 7.7 years, systolic blood pressure (SBP) = 133.6 ± 6.5 mmHg, diastolic blood pressure (DBP) = 87.3 ± 8.1 mmHg; under antihypertensive treatment] and 11 normotensive men (NT: 57.1 ± 6.0 years, SBP = 127 ± 8.5 mmHg, DBP = 82.7 ± 5.5 mmHg) performed a single session of RE (2 sets of 15–20 repetitions, 50% of 1 RM, 120 s interval between sets/exercise) for the following exercises: leg extension, leg press, leg curl, bench press, seated row, triceps push-down, seated calf flexion, seated arm curl. HRV was assessed at resting and during 10 min of recovery period by calculating time (SDNN, RMSSD, pNN50) and frequency domain (LF, HF, LF/HF) indices. Mean values of HRV indices were reduced in the post-exercise period compared to the resting period (HT: lnHF: 4.7 ± 1.4 vs. 2.4 ± 1.2 ms2; NT: lnHF: 4.8 ± 1.5 vs. 2.2 ± 1.1 ms2, p < 0.01). However, there was no group vs. time interaction in this response (p = 0.8). The results indicate that HRV is equally suppressed after RE in normotensive and hypertensive individuals. These findings suggest that a single session of RE does not bring additional cardiac autonomic stress to treated hypertensive subjects. PMID:26441677

  13. Anxiety Level and Cardiac Autonomic Modulations in Coronary Artery Disease and Cardiac Syndrome X Patients

    PubMed Central

    2017-01-01

    Background Anxiety and cardiac autonomic modulations (CAM) were thoroughly investigated in coronary artery disease (CAD) and cardiac syndrome X (CSX) patients worldwide, but not among Sudanese with similar pathology. Aims To compare levels of anxiety and CAM between Sudanese patients with CSX and CAD. Materials and Methods Anxiety was evaluated in 51 CAD and 26 CSX patients using Taylor Manifest anxiety score (TMAS) questionnaire while heart rate variability derived indices were used to assess CAM, namely natural logarithm of low frequency (LnLF), high frequency (LnHF) and LF/HF ratio (LnLF/HF). Results Low anxiety levels were achieved by 6 (23.1%) and 9 (17.6%) patients with CSX and CAD respectively. High anxiety level was achieved by only one (3.8%) patient, who was suffering from CSX. TMAS was significantly higher in CSX (31.27 (21.97)) compared to CAD (21.86 (12.97), P = 0.021). However, abnormally increased anxiety was not associated with higher risk of CSX. LnLF, LnHF and LnLF/HF were comparable in CAD and CSX patients. Conclusion CSX and CAD patients showed comparable CAM. Although anxiety levels were higher in CSX compared to CAD, TMAS ≥ 35 failed to show significant association with CSX. PMID:28068419

  14. Cardiac Autonomic Neuropathy and Early Progressive Renal Decline in Patients with Nonmacroalbuminuric Type 1 Diabetes

    PubMed Central

    Orlov, Steven; Cherney, David Z.I.; Pop-Busui, Rodica; Lovblom, Leif E.; Ficociello, Linda H.; Smiles, Adam M.; Warram, James H.; Krolewski, Andrzej S.

    2015-01-01

    Background and objectives Cardiac autonomic neuropathy predicts future adverse renal outcomes in the general population. This study sought to determine its relationship with early progressive renal decline in type 1 diabetes. Design, setting, participants, & measurements A subset of participants with normoalbuminuria (n=204) or microalbuminuria (n=166) from the First Joslin Kidney Study underwent assessment for cardiac autonomic neuropathy using heart rate variability during baseline visits performed from January 1991 to April 1992. Cardiac autonomic neuropathy was defined as an R-R variation (mean circular resultant) <20. Participants also had baseline and follow-up measurement of eGFR. Early progressive renal decline was evaluated according to two definitions: early GFR loss (slope of eGFR estimated by cystatin C <−3.3%/year) and incident advanced CKD (stage ≥3, defined by eGFR [calculated by Modification of Diet in Renal Disease method] <60 ml/min per 1.73 m2). Association with baseline cardiac autonomic neuropathy was assessed by adjusted logistic regression and Cox proportional hazards. Results Among the 370 participants, 47 (13%) had baseline cardiac autonomic neuropathy, 51 (14%) had early GFR loss, and 68 (18%) had incident advanced CKD over a median 14-year follow-up. Early GFR loss occurred in 15 (32%) of the 47 patients with baseline autonomic neuropathy and in 32 (10%) of the 323 without baseline autonomic neuropathy (P<0.001). Baseline autonomic neuropathy was strongly associated with odds of early GFR loss (adjusted odds ratio, 4.09; 95% confidence interval, 1.65 to 10.12; P=0.002). Incident advanced CKD was observed in 22 (47%) of those with baseline autonomic neuropathy and 46 (14%) of those without baseline autonomic neuropathy (P<0.001). Autonomic neuropathy was independently associated with incident advanced CKD (adjusted hazard ratio, 2.76; 95% confidence interval, 1.44 to 5.30; P=0.002). Conclusions Cardiac autonomic neuropathy was a strong

  15. Redox regulation of cardiac hypertrophy.

    PubMed

    Sag, Can M; Santos, Celio X C; Shah, Ajay M

    2014-08-01

    It is increasingly evident that redox-dependent modifications in cellular proteins and signaling pathways (or redox signaling) play important roles in many aspects of cardiac hypertrophy. Indeed, these redox modifications may be intricately linked with the process of hypertrophy wherein there is not only a significant increase in myocardial O2 consumption but also important alterations in metabolic processes and in the local generation of O2-derived reactive species (ROS) that modulate and/or amplify cell signaling pathways. This article reviews our current knowledge of redox signaling pathways and their roles in cardiac hypertrophy. This article is part of a Special Issue entitled "Redox Signalling in the Cardiovascular System".

  16. A shorter set reduces the loss of cardiac autonomic and baroreflex control after resistance exercise.

    PubMed

    Mayo, Xián; Iglesias-Soler, Eliseo; Carballeira-Fernández, Eduardo; Fernández-Del-Olmo, Miguel

    2016-11-01

    Set configuration may affect the recovery pattern of cardiac vagal autonomic and reflex modulation after a resistance exercise, since it is closely associated with intensity and volume and determines the metabolic involvement of the session. We tested the hypothesis that longer set configurations have a higher impact on cardiac autonomic control and baroreflex sensitivity compared with shorter set configurations. We studied the effects of three set configurations with the same components of work on the cardiac autonomic control and baroreflex sensitivity. Seventeen subjects performed one control session and three experimental sessions of a leg-press exercise with the same volume (40 repetitions), resting time (720 s) and intensity (10RM load): (a) 5 sets of 8 repetitions with 3 min of rest between sets (8S), (b) 10 sets of 4 repetitions with 80 s of rest between sets (4S) and (c) 40 sets of 1 repetition with 18.5 s of rest between each repetition (1S). Longer set configurations (8S and 4S) induced greater reductions of the vagal cardiac autonomic control and baroreflex sensitivity (p ≤ .001) compared with a shorter set configuration (1S). Also, 1S had non-significant reductions versus the control session (p > .05). These findings suggest that a shorter set configuration can reduce the impact of resistance exercise on the post-exercise cardiac vagal autonomic control and baroreflex sensitivity.

  17. Autonomous regulation of growth cone filopodia.

    PubMed

    Rehder, V; Cheng, S

    1998-02-05

    The fan-shaped array of filopodia is the first site of contact of a neuronal growth cone with molecules encountered during neuronal pathfinding. Filopodia are highly dynamic structures, and the "action radius" of a growth cone is strongly determined by the length and number of its filopodia. Since interactions of filopodia with instructive cues in the vicinity of the growth cone can have effects on growth cone morphology within minutes, it has to be assumed that a large part of the signaling underlying such morphological changes resides locally within the growth cone proper. In this study, we tested the hypothesis that two important growth cone parameters-namely, the length and number of its filopodia-are regulated autonomously in the growth cone. We previously demonstrated in identified neurons from the snail Helisoma trivolvis that filopodial length and number are regulated by intracellular calcium. Here, we investigated filopodial dynamics and their regulation by the second-messenger calcium in growth cones which were physically isolated from their parent neuron by neurite transection. Our results show that isolated growth cones have longer but fewer filopodia than growth cones attached to their parent cell. These isolated growth cones, however, are fully capable of undergoing calcium-induced cytoskeletal changes, suggesting that the machinery necessary to perform changes in filopodial length and number is fully intrinsic to the growth cone proper.

  18. Human autonomic rhythms: vagal cardiac mechanisms in tetraplegic subjects.

    PubMed Central

    Koh, J; Brown, T E; Beightol, L A; Ha, C Y; Eckberg, D L

    1994-01-01

    1. We studied eight young men (age range: 20-37 years) with chronic, clinically complete high cervical spinal cord injuries and ten age-matched healthy men to determine how interruption of connections between the central nervous system and spinal sympathetic motoneurones affects autonomic cardiovascular control. 2. Baseline diastolic pressures and R-R intervals (heart periods) were similar in the two groups. Slopes of R-R interval responses to brief neck pressure changes were significantly lower in tetraplegic than in healthy subjects, but slopes of R-R interval responses to steady-state arterial pressure reductions and increases were comparable. Plasma noradrenaline levels did not change significantly during steady-state arterial pressure reductions in tetraplegic patients, but rose sharply in healthy subjects. The range of arterial pressure and R-R interval responses to vasoactive drugs (nitroprusside and phenylephrine) was significantly greater in tetraplegic than healthy subjects. 3. Resting R-R interval spectral power at respiratory and low frequencies was similar in the two groups. During infusions of vasoactive drugs, low-frequency R-R interval spectral power was directly proportional to arterial pressure in tetraplegic patients, but was unrelated to arterial pressure in healthy subjects. Vagolytic doses of atropine nearly abolished both low- and respiratory-frequency R-R interval spectral power in both groups. 4. Our conclusions are as follows. First, since tetraplegic patients have significant levels of low-frequency arterial pressure and R-R interval spectral power, human Mayer arterial pressure waves may result from mechanisms that do not involve stimulation of spinal sympathetic motoneurones by brainstem neurones. Second, since in tetraplegic patients, low-frequency R-R interval spectral power is proportional to arterial pressure, it is likely to be mediated by a baroreflex mechanism. Third, since low-frequency R-R interval rhythms were nearly abolished

  19. Cardiac autonomic profile in rheumatoid arthritis and systemic lupus erythematosus.

    PubMed

    Aydemir, M; Yazisiz, V; Basarici, I; Avci, A B; Erbasan, F; Belgi, A; Terzioglu, E

    2010-03-01

    Neurological involvement is a well-documented issue in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). However, little is known about the involvement of the autonomic nervous system. This study was conducted to investigate autonomic nervous system dysfunction in patients with RA and SLE. Twenty-six RA patients, 38 SLE patients and 40 healthy controls were recruited from our in- and out-patient departments. Heart rate variability (HRV) parameters (the power of the high- [HF] and low-frequency [LF] band of haemodynamic time series, the ratio between low- and high-frequency components [LF/HF ratio], the power spectral density), baroreflex sensitivity (BRS) and beat-to-beat blood pressures were assessed by a novel non-invasive haemodynamic monitoring tool (Task Force Monitor [TFM], CNSystems Medizintechnik GmbH, Graz, Austria). Autonomic nervous system dysfunction was determined according to classical Ewing autonomic test battery. Furthermore, we implemented a secondary autonomic test score by modifying the Ewing test battery with additional criteria. Both the classical and modified Ewing test batteries have revealed that the frequencies of autonomic neuropathy were significantly higher in patient groups compared with controls (p < 0.001). Evaluation by TFM revealed that deterioration of sophisticated autonomic parameters (such as HRV and BRS) were more pronounced in the patient groups compared with controls. There was a significant association between BRS and Ewing test scores and abnormal BRS results were more frequent in patients with autonomic dysfunction according to Ewing test batteries. No relation was found between autonomic neuropathy and disease duration, disease activity and autoantibody positivity. Consequently, we believe that further large-scale studies investigating cardiovascular autonomic neuropathy in rheumatic diseases should be carried out to verify our findings and manifest clinical consequences beyond these results.

  20. Cardiac autonomic function in patients with diabetes improves with practice of comprehensive yogic breathing program

    PubMed Central

    Jyotsna, Viveka P.; Ambekar, Smita; Singla, Rajiv; Joshi, Ansumali; Dhawan, Anju; Kumar, Neeta; Deepak, K. K.; Sreenivas, V.

    2013-01-01

    Background: The aim of this study was to observe the effect comprehensive yogic breathing (Sudarshan Kriya Yoga [SKY] and Pranayam) had on cardiac autonomic functions in patients with diabetes. Materials and Methods: This is a prospective randomized controlled intervention trial. Cardiac autonomic functions were assessed in 64 diabetics. Patients were randomized into two groups, one group receiving standard therapy for diabetes and the other group receiving standard therapy for diabetes and comprehensive yogic breathing program. Standard therapy included dietary advice, brisk walking for 45 min daily, and administration of oral antidiabetic drugs. Comprehensive yogic breathing program was introduced to the participants through a course of 12 h spread over 3 days. It was an interactive session in which SKY, a rhythmic cyclical breathing, preceded by Pranayam is taught under the guidance of a certified teacher. Cardiac autonomic function tests were done before and after 6 months of intervention. Results: In the intervention group, after practicing the breathing techniques for 6 months, the improvement in sympathetic functions was statistically significant (P 0.04). The change in sympathetic functions in the standard therapy group was not significant (P 0.75). Parasympathetic functions did not show any significant change in either group. When both parasympathetic and sympathetic cardiac autonomic functions were considered, there was a trend toward improvement in patients following comprehensive yogic breathing program (P 0.06). In the standard therapy group, no change in cardiac autonomic functions was noted (P 0.99). Conclusion: Cardiac autonomic functions improved in patients with diabetes on standard treatment who followed the comprehensive yogic breathing program compared to patients who were on standard therapy alone. PMID:23869306

  1. An essential cell-autonomous role for hepcidin in cardiac iron homeostasis

    PubMed Central

    Lakhal-Littleton, Samira; Wolna, Magda; Chung, Yu Jin; Christian, Helen C; Heather, Lisa C; Brescia, Marcella; Ball, Vicky; Diaz, Rebeca; Santos, Ana; Biggs, Daniel; Clarke, Kieran; Davies, Benjamin; Robbins, Peter A

    2016-01-01

    Hepcidin is the master regulator of systemic iron homeostasis. Derived primarily from the liver, it inhibits the iron exporter ferroportin in the gut and spleen, the sites of iron absorption and recycling respectively. Recently, we demonstrated that ferroportin is also found in cardiomyocytes, and that its cardiac-specific deletion leads to fatal cardiac iron overload. Hepcidin is also expressed in cardiomyocytes, where its function remains unknown. To define the function of cardiomyocyte hepcidin, we generated mice with cardiomyocyte-specific deletion of hepcidin, or knock-in of hepcidin-resistant ferroportin. We find that while both models maintain normal systemic iron homeostasis, they nonetheless develop fatal contractile and metabolic dysfunction as a consequence of cardiomyocyte iron deficiency. These findings are the first demonstration of a cell-autonomous role for hepcidin in iron homeostasis. They raise the possibility that such function may also be important in other tissues that express both hepcidin and ferroportin, such as the kidney and the brain. DOI: http://dx.doi.org/10.7554/eLife.19804.001 PMID:27897970

  2. p53 regulates the cardiac transcriptome

    PubMed Central

    Mak, Tak W.; Hauck, Ludger; Grothe, Daniela; Billia, Filio

    2017-01-01

    The tumor suppressor Trp53 (p53) inhibits cell growth after acute stress by regulating gene transcription. The mammalian genome contains hundreds of p53-binding sites. However, whether p53 participates in the regulation of cardiac tissue homeostasis under normal conditions is not known. To examine the physiologic role of p53 in adult cardiomyocytes in vivo, Cre-loxP–mediated conditional gene targeting in adult mice was used. Genome-wide transcriptome analyses of conditional heart-specific p53 knockout mice were performed. Genome-wide annotation and pathway analyses of >5,000 differentially expressed transcripts identified many p53-regulated gene clusters. Correlative analyses identified >20 gene sets containing more than 1,000 genes relevant to cardiac architecture and function. These transcriptomic changes orchestrate cardiac architecture, excitation-contraction coupling, mitochondrial biogenesis, and oxidative phosphorylation capacity. Interestingly, the gene expression signature in p53-deficient hearts confers resistance to acute biomechanical stress. The data presented here demonstrate a role for p53, a previously unrecognized master regulator of the cardiac transcriptome. The complex contributions of p53 define a biological paradigm for the p53 regulator network in the heart under physiological conditions. PMID:28193895

  3. Autonomous Demand Response for Primary Frequency Regulation

    SciTech Connect

    Donnelly, Matt; Trudnowski, Daniel J.; Mattix, S.; Dagle, Jeffery E.

    2012-02-28

    The research documented within this report examines the use of autonomous demand response to provide primary frequency response in an interconnected power grid. The work builds on previous studies in several key areas: it uses a large realistic model (i.e., the interconnection of the western United States and Canada); it establishes a set of metrics that can be used to assess the effectiveness of autonomous demand response; and it independently adjusts various parameters associated with using autonomous demand response to assess effectiveness and to examine possible threats or vulnerabilities associated with the technology.

  4. Modulation of Cardiac Autonomic Dysfunction in Ischemic Stroke following Ayurveda (Indian System of Medicine) Treatment

    PubMed Central

    Jaideep, Sriranjini Sitaram; Nagaraja, Dindagur; Pal, Pramod Kumar; Sudhakara, D.; Talakad, Sathyaprabha N.

    2014-01-01

    Objectives. Cardiac autonomic dysfunction in stroke has implications on morbidity and mortality. Ayurveda (Indian system of medicine) describes stroke as pakshaghata. We intended to study the effect of Ayurveda therapies on the cardiac autonomic dysfunction. Methods. Fifty patients of ischemic stroke (middle cerebral artery territory) (mean age 39.26 ± 9.88 years; male 43, female 7) were recruited within one month of ictus. All patients received standard allopathic medications as advised by neurologist. In addition, patients were randomized to receive physiotherapy (Group I) or Ayurveda treatment (Group II) for 14 days. Continuous electrocardiogram and finger arterial pressure were recorded for 15 min before and after treatments and analyzed offline to obtain heart rate and blood pressure variability and baroreflex sensitivity (BRS). Results were analysed by RMANOVA. Results. Patients in Group II showed statistically significant improvement in cardiac autonomic parameters. The standard deviation of normal to normal intervals,and total and low frequency powers were significantly enhanced (F = 8.16, P = 0.007, F = 9.73, P = 0.004, F = 13.51, and P = 0.001, resp.). The BRS too increased following the treatment period (F = 10.129, P = 0.004). Conclusions. The current study is the first to report a positive modulation of cardiac autonomic activity after adjuvant Ayurveda treatment in ischemic stroke. Further long term studies are warranted. PMID:24971149

  5. An epigenome-wide association analysis of cardiac autonomic responses among a population of welders

    PubMed Central

    Zhang, Jinming; Liu, Zhonghua; Umukoro, Peter E.; Cavallari, Jennifer M.; Fang, Shona C.; Weisskopf, Marc G.; Lin, Xihong; Mittleman, Murray A.

    2017-01-01

    ABSTRACT DNA methylation is one of the potential epigenetic mechanisms associated with various adverse cardiovascular effects; however, its association with cardiac autonomic dysfunction, in particular, is unknown. In the current study, we aimed to identify epigenetic variants associated with alterations in cardiac autonomic responses. Cardiac autonomic responses were measured with two novel markers: acceleration capacity (AC) and deceleration capacity (DC). We examined DNA methylation levels at more than 472,506 CpG probes through the Illumina Infinium HumanMethylation450 BeadChip assay. We conducted separate linear mixed models to examine associations of DNA methylation levels at each CpG with AC and DC. One CpG (cg26829071) located in the GPR133 gene was negatively associated with DC values after multiple testing corrections through false discovery rate. Our study suggests the potential functional importance of methylation in cardiac autonomic responses. Findings from the current study need to be replicated in future studies in a larger population. PMID:28075199

  6. Teaching Cardiac Autonomic Function Dynamics Employing the Valsalva (Valsalva-Weber) Maneuver

    ERIC Educational Resources Information Center

    Junqueira, Luiz Fernando, Jr.

    2008-01-01

    In this report, a brief history of the Valsalva (Valsalva-Weber) maneuver is outlined, followed by an explanation on the use of this approach for the evaluation of cardiac autonomic function based on underlying heart rate changes. The most important methodological and interpretative aspects of the Valsalva-Weber maneuver are critically updated,…

  7. DAILY VARIATION OF PARTICULATE AIR POLLUTION AND POOR CARDIAC AUTONOMIC CONTROL IN THE ELDERLY

    EPA Science Inventory

    Particulate matter air pollution (PM) has been related to cardiovascular disease mortality in a number of recent studies. The pathophysiologic mechanisms for this association are under study. Low heart rate variability, a marker of poor cardiac autonomic control, is associated wi...

  8. Cardiac Autonomic Function during Submaximal Treadmill Exercise in Adults with Down Syndrome

    ERIC Educational Resources Information Center

    Mendonca, Goncalo V.; Pereira, Fernando D.; Fernhall, Bo

    2011-01-01

    This study determined whether the cardiac autonomic function of adults with Down syndrome (DS) differs from that of nondisabled persons during submaximal dynamic exercise. Thirteen participants with DS and 12 nondisabled individuals performed maximal and submaximal treadmill tests with metabolic and heart rate (HR) measurements. Spectral analysis…

  9. Slow breathing influences cardiac autonomic responses to postural maneuver: Slow breathing and HRV.

    PubMed

    Vidigal, Giovanna Ana de Paula; Tavares, Bruna S; Garner, David M; Porto, Andrey A; Carlos de Abreu, Luiz; Ferreira, Celso; Valenti, Vitor E

    2016-05-01

    Chronic slow breathing has been reported to improve Heart Rate Variability (HRV) in patients with cardiovascular disorders. However, it is not clear regarding its acute effects on HRV responses on autonomic analysis. We evaluated the acute effects of slow breathing on cardiac autonomic responses to postural change manoeuvre (PCM). The study was conducted on 21 healthy male students aged between 18 and 35 years old. In the control protocol, the volunteer remained at rest seated for 15 min under spontaneous breathing and quickly stood up within 3 s and remained standing for 15 min. In the slow breathing protocol, the volunteer remained at rest seated for 10 min under spontaneous breath, then performed slow breathing for 5 min and rapidly stood up within 3 s and remained standing for 15 min. Slow breathing intensified cardiac autonomic responses to postural maneuver.

  10. Music Improves Subjective Feelings Leading to Cardiac Autonomic Nervous Modulation: A Pilot Study

    PubMed Central

    Kume, Satoshi; Nishimura, Yukako; Mizuno, Kei; Sakimoto, Nae; Hori, Hiroshi; Tamura, Yasuhisa; Yamato, Masanori; Mitsuhashi, Rika; Akiba, Keigo; Koizumi, Jun-ichi; Watanabe, Yasuyoshi; Kataoka, Yosky

    2017-01-01

    It is widely accepted that listening to music improves subjective feelings and reduces fatigue sensations, and different kinds of music lead to different activations of these feelings. Recently, cardiac autonomic nervous modulation has been proposed as a useful objective indicator of fatigue. However, scientific considerations of the relation between feelings of fatigue and cardiac autonomic nervous modulation while listening to music are still lacking. In this study, we examined which subjective feelings of fatigue are related to participants' cardiac autonomic nervous function while they listen to music. We used an album of comfortable and relaxing environmental music, with blended sounds from a piano and violin as well as natural sound sources. We performed a crossover trial of environmental music and silent sessions for 20 healthy subjects, 12 females, and 8 males, after their daily work shift. We measured changes in eight types of subjective feelings, including healing, fatigue, sleepiness, relaxation, and refreshment, using the KOKORO scale, a subjective mood measurement system for self-reported feelings. Further, we obtained measures of cardiac autonomic nervous function on the basis of heart rate variability before and after the sessions. During the music session, subjective feelings significantly shifted toward healing and a secure/relaxed feeling and these changes were greater than those in the silent session. Heart rates (ΔHR) in the music session significantly decreased compared with those in the silent session. Other cardiac autonomic parameters such as high-frequency (HF) component and the ratio of low-frequency (LF) and HF components (LF/HF) were similar in the two sessions. In the linear regression analysis of the feelings with ΔHR and changes in LF/HF (ΔLF/HF), increases and decreases in ΔHR were correlated to the feeling axes of Fatigue-Healing and Anxiety/Tension–Security/Relaxation, whereas those in ΔLF/HF were related to the feeling axes

  11. Music Improves Subjective Feelings Leading to Cardiac Autonomic Nervous Modulation: A Pilot Study.

    PubMed

    Kume, Satoshi; Nishimura, Yukako; Mizuno, Kei; Sakimoto, Nae; Hori, Hiroshi; Tamura, Yasuhisa; Yamato, Masanori; Mitsuhashi, Rika; Akiba, Keigo; Koizumi, Jun-Ichi; Watanabe, Yasuyoshi; Kataoka, Yosky

    2017-01-01

    It is widely accepted that listening to music improves subjective feelings and reduces fatigue sensations, and different kinds of music lead to different activations of these feelings. Recently, cardiac autonomic nervous modulation has been proposed as a useful objective indicator of fatigue. However, scientific considerations of the relation between feelings of fatigue and cardiac autonomic nervous modulation while listening to music are still lacking. In this study, we examined which subjective feelings of fatigue are related to participants' cardiac autonomic nervous function while they listen to music. We used an album of comfortable and relaxing environmental music, with blended sounds from a piano and violin as well as natural sound sources. We performed a crossover trial of environmental music and silent sessions for 20 healthy subjects, 12 females, and 8 males, after their daily work shift. We measured changes in eight types of subjective feelings, including healing, fatigue, sleepiness, relaxation, and refreshment, using the KOKORO scale, a subjective mood measurement system for self-reported feelings. Further, we obtained measures of cardiac autonomic nervous function on the basis of heart rate variability before and after the sessions. During the music session, subjective feelings significantly shifted toward healing and a secure/relaxed feeling and these changes were greater than those in the silent session. Heart rates (ΔHR) in the music session significantly decreased compared with those in the silent session. Other cardiac autonomic parameters such as high-frequency (HF) component and the ratio of low-frequency (LF) and HF components (LF/HF) were similar in the two sessions. In the linear regression analysis of the feelings with ΔHR and changes in LF/HF (ΔLF/HF), increases and decreases in ΔHR were correlated to the feeling axes of Fatigue-Healing and Anxiety/Tension-Security/Relaxation, whereas those in ΔLF/HF were related to the feeling axes

  12. Gender differences in cardiac patients: a longitudinal investigation of exercise, autonomic anxiety, negative affect and depression.

    PubMed

    Hunt-Shanks, Tiffany; Blanchard, Christopher; Reid, Robert D

    2009-05-01

    Female cardiac patients frequently experience greater anxiety and depression and engage in less exercise when compared with their male counterparts. This study considered whether exercise had similar effects on male and female cardiac patients' autonomic anxiety, negative affect and depression, and whether exercise behavior explained the gender difference in their affective functioning (e.g. autonomic anxiety, negative affect and depression). Eight hundred one participants completed the Hospital and Anxiety Depression Scale (HADS) and the leisure score index (LSI) of the Godin Leisure-Time Exercise Questionnaire at baseline, 6 months, 12 months, and 24 months. Female cardiac patients had greater autonomic anxiety, negative affect and depression and reduced exercise when compared with male cardiac patients at all time points. Although exercise was significantly related to affective outcomes at various time points for both men and women, gender did not moderate any of the exercise/affective relationships, and exercise did not mediate any of the gender/affective relationships. Further research is needed to clarify the complex relationships between gender, exercise, and the affective functioning of cardiac patients.

  13. Polycystic Ovary Syndrome Presents Higher Sympathetic Cardiac Autonomic Modulation that is not altered by Strength Training

    PubMed Central

    RIBEIRO, VICTOR B.; KOGURE, GISLAINE S.; REIS, ROSANA M.; GASTALDI, ADA C.; DE ARAÚJO, JOÃO E.; MAZON, JOSÉ H.; BORGHI, AUDREY; SOUZA, HUGO C.D.

    2016-01-01

    Polycystic ovary syndrome (PCOS) may present important comorbidities, such as cardiovascular and metabolic diseases, which are often preceded by changes in cardiac autonomic modulation. Different types of physical exercises are frequently indicated for the prevention and treatment of PCOS. However, little is known about the effects of strength training on the metabolic, hormonal, and cardiac autonomic parameters. Therefore, our aim was to investigate the effects of strength training on the autonomic modulation of heart rate variability (HRV) and its relation to endocrine-metabolic parameters in women with PCOS. Fifty-three women were divided into two groups: CONTROL (n=26) and PCOS (n=27). The strength training lasted 4 months, which was divided into mesocycles of 4 weeks each. The training load started with 70% of one repetition maximum (1RM). Blood samples were collected before and after intervention for analysis of fasting insulin and glucose, HOMA-IR, testosterone, androstenedione and testosterone/androstenedione (T/A) ratio. Spectral analysis of HRV was performed to assess cardiac autonomic modulation indexes. The PCOS group presented higher insulin and testosterone levels, T/A ratio, along with increased sympathetic cardiac autonomic modulation before intervention. The training protocol used did not cause any change of endocrine-metabolic parameters in the CONTROL group. Interestingly, in the PCOS group, reduced testosterone levels and T/A ratio. Additionally, strength training did not have an effect on the spectral parameter values of HRV obtained in both groups. Strength training was not able to alter HRV autonomic modulation in women with PCOS, however may reduce testosterone levels and T/A ratio. PMID:27990221

  14. Effects of water temperature on cardiac autonomic nervous system modulation during foot immersion (foot bath)

    NASA Astrophysics Data System (ADS)

    Nishimura, M.; Ono, K.; Onodera, S.

    2005-08-01

    The purpose of this study was to make clear the effects of water temperature during foot immersion (foot bath) on heart rate, blood pressure, rectal temperature and autonomic nervous system modulation. The subjects performed foot immersion at 25, 35, 41 and 45 degrees Celsius at random, during different days, but always at the same time. Cardiac autonomic nervous system modulation was estimated with the power spectrum analysis of heart rate variability by using the Fast Fourier Transformation. The two frequency components of HRV was measured by integrate low frequency (LF; 0.04- 0.15 Hz) and high frequency (HF; 0.15- 0.40 Hz). HF was used as an indicator of cardiac vagal modulation and was showed logarithmically (LogHF). LogHF during foot immersion at 35 and 41 degrees Celsius was significantly increased. These data indicate that cardiac vagal activity was affected by water temperature during foot immersion (foot bath).

  15. Is Baseline Cardiac Autonomic Modulation Related to Performance and Physiological Responses Following a Supramaximal Judo Test?

    PubMed Central

    Blasco-Lafarga, Cristina; Martínez-Navarro, Ignacio; Mateo-March, Manuel

    2013-01-01

    Little research exists concerning Heart Rate (HR) Variability (HRV) following supramaximal efforts focused on upper-body explosive strength-endurance. Since they may be very demanding, it seems of interest to analyse the relationship among performance, lactate and HR dynamics (i.e. HR, HRV and complexity) following them; as well as to know how baseline cardiac autonomic modulation mediates these relationships. The present study aimed to analyse associations between baseline and post-exercise HR dynamics following a supramaximal Judo test, and their relationship with lactate, in a sample of 22 highly-trained male judoists (20.70±4.56 years). A large association between the increase in HR from resting to exercise condition and performance suggests that individuals exerted a greater sympathetic response to achieve a better performance (Rating of Perceived Exertion: 20; post-exercise peak lactate: 11.57±2.24 mmol/L; 95.76±4.13 % of age-predicted HRmax). Athletes with higher vagal modulation and lower sympathetic modulation at rest achieved both a significant larger ∆HR and a faster post-exercise lactate removal. A enhanced resting parasympathetic modulation might be therefore related to a further usage of autonomic resources and a better immediate metabolic recovery during supramaximal exertions. Furthermore, analyses of variance displayed a persistent increase in α1 and a decrease in lnRMSSD along the 15 min of recovery, which are indicative of a diminished vagal modulation together with a sympathovagal balance leaning to sympathetic domination. Eventually, time-domain indices (lnRMSSD) showed no lactate correlations, while nonlinear indices (α1 and lnSaEn) appeared to be moderate to strongly correlated with it, thus pointing to shared mechanisms between neuroautonomic and metabolic regulation. PMID:24205273

  16. Measuring Cardiac Autonomic Nervous System (ANS) Activity in Toddlers - Resting and Developmental Challenges

    PubMed Central

    Bush, Nicole R.; Caron, Zoe K.; Blackburn, Katherine S.; Alkon, Abbey

    2016-01-01

    The autonomic nervous system (ANS) consists of two branches, the parasympathetic and sympathetic nervous systems, and controls the function of internal organs (e.g., heart rate, respiration, digestion) and responds to everyday and adverse experiences 1. ANS measures in children have been found to be related to behavior problems, emotion regulation, and health 2-7. Therefore, understanding the factors that affect ANS development during early childhood is important. Both branches of the ANS affect young children's cardiovascular responses to stimuli and have been measured noninvasively, via external monitoring equipment, using valid and reliable measures of physiological change 8-11. However, there are few studies of very young children with simultaneous measures of the parasympathetic and sympathetic nervous systems, which limits understanding of the integrated functioning of the two systems. In addition, the majority of existing studies of young children report on infants' resting ANS measures or their reactivity to commonly used mother-child interaction paradigms, and less is known about ANS reactivity to other challenging conditions. We present a study design and standardized protocol for a non-invasive and rapid assessment of cardiac autonomic control in 18 month old children. We describe methods for continuous monitoring of the parasympathetic and sympathetic branches of the ANS under resting and challenge conditions during a home or laboratory visit and provide descriptive findings from our sample of 140 ethnically diverse toddlers using validated equipment and scoring software. Results revealed that this protocol can produce a range of physiological responses to both resting and developmentally challenging conditions, as indicated by changes in heart rate and indices of parasympathetic and sympathetic activity. Individuals demonstrated variability in resting levels, responses to challenges, and challenge reactivity, which provides additional evidence that

  17. The yin and yang of cardiac autonomic control: vago-sympathetic interactions revisited.

    PubMed

    Paton, J F R; Boscan, P; Pickering, A E; Nalivaiko, E

    2005-11-01

    We review the pattern of activity in the parasympathetic and sympathetic nerves innervating the heart. Unlike the conventional textbook picture of reciprocal control of cardiac vagal and sympathetic nervous activity, as seen during a baroreceptor reflex, many other reflexes involve simultaneous co-activation of both autonomic limbs. Indeed, even at 'rest', the heart receives tonic drives from both sympathetic and parasympathetic cardiac nerves. Autonomic co-activation occurs during peripheral chemoreceptor, diving, oculocardiac, somatic nociceptor reflex responses as well as being evoked from structures within the brain. It is suggested that simultaneous co-activation may lead to a more efficient cardiac function giving greater cardiac output than activation of the sympathetic limb alone; this permits both a longer time for ventricular filling and a stronger contraction of the myocardium. This may be important when pumping blood into a constricted vascular tree such as is the case during the diving response. We discuss that in some instances, high drive to the heart from both autonomic limbs may also be arrhythmogenic.

  18. Effect of the duration of daily aerobic physical training on cardiac autonomic adaptations.

    PubMed

    Sant'Ana, Janaina E; Pereira, Marília G A G; Dias da Silva, Valdo J; Dambrós, Camila; Costa-Neto, Claudio M; Souza, Hugo C D

    2011-01-20

    The present study has investigated in conscious rats the influence of the duration of physical training sessions on cardiac autonomic adaptations by using different approaches; 1) double blockade with methylatropine and propranolol; 2) the baroreflex sensitivity evaluated by alternating bolus injections of phenylephrine and sodium nitroprusside; and 3) the autonomic modulation of HRV in the frequency domain by means of spectral analysis. The animals were divided into four groups: one sedentary group and three training groups submitted to physical exercise (swimming) for 15, 30, and 60min a day during 10 weeks. All training groups showed similar reduction in intrinsic heart rate (IHR) after double blockade with methylatropine and propranolol. However, only 30-min and 60-min physical training presented an increase in the vagal autonomic component for determination of basal heart rate (HR) in relation to group sedentary. Spectral analysis of HR showed that the 30-min and 60-min physical training presented the reduction in low-frequency oscillations (LF=0.20-0.75Hz) and the increase in high-frequency oscillations (HF=0.75-2.5Hz) in normalized units. These both groups only showed an increased baroreflex sensitivity to tachycardiac responses in relation to group sedentary, however when compared, the physical training of 30-min exhibited a greater gain. In conclusion, cardiac autonomic adaptations, characterised by the increased predominance of the vagal autonomic component, were not proportional to the duration of daily physical training sessions. In fact, 30-minute training sessions provided similar cardiac autonomic adaptations, or even more enhanced ones, as in the case of baroreflex sensitivity compared to 60-minute training sessions.

  19. Cardiac autonomic control in high level Brazilian power and endurance track-and-field athletes.

    PubMed

    Abad, C C C; do Nascimento, A M; Gil, S; Kobal, R; Loturco, I; Nakamura, F Y; Mostarda, C T; Irigoyen, M C

    2014-08-01

    The autonomic nervous system (ANS) has an important role in physical performance. However, the cardiac ANS activity in high-level track and field athletes has been poorly explored. Thus, we tested the hypothesis that endurance and power athletes would present a markedly different cardiac autonomic control at rest. We analyzed the cardiac ANS by means of time and frequency domains heart rate variability (HRV) analyses and by symbolic analysis. Endurance athletes showed higher pulse interval than power athletes (1,265±126 vs. 1,031±98 ms respectively; p<0.05). No differences were found in time and frequency domains between the groups. However, the LF%, HF% and LF/HF ratio presented high effect sizes (1.46, 1.46 and 1.30, respectively). The symbolic analysis revealed that endurance athletes had higher 2V parasympathetic modulation (36±6.5) than power athletes (24±9.3; p<0.05). A reduced 0V sympathetic modulation was observed in endurance athletes (21±9.9) compared to power athletes (33±11; p<0.05 and ES=1.30). Our results suggest greater parasympathetic modulation and less sympathetic modulation in endurance athletes compared to power athletes. Additionally, the type of HRV analysis needs to be chosen with well-defined criteria and caution because their use in assessing cardiac autonomic modulation can interfere with the interpretation of results. In practical terms, symbolic analysis appears to better discriminate between cardiac autonomic activities of athletes with different training backgrounds than frequency domain analysis.

  20. Cardiac autonomic denervation and functional response to neurotoxins during acute experimental Chagas' disease in rats.

    PubMed

    Teixeira, A L; Fontoura, B F; Freire-Maia, L; Chiari, E; Machado, C R; Teixeira, M M; Camargos, E R

    2001-06-20

    Severe cardiac autonomic denervation occurs in the acute Chagas' disease in rats. The present study aims at verifying whether this denervation was accompanied by impairment of heart function. Scorpionic (Tityus serrulatus) crude venom was used for neurotransmitter release in isolated hearts (Langendorff's preparation). In control hearts, the venom induced significant bradycardia followed by tachycardia. In infected animals, despite the severe (sympathetic) or moderate (parasympathetic) cardiac denervation, the venom provoked similar bradycardia but the tachycardia was higher. The hearts of infected animals beat at significantly lower rate. Atropine prevented this lower rate. Our results demonstrated sympathetic dysfunction during the acute phase of Trypanosoma cruzi infection in rats, the parasympathetic function being spared.

  1. The role of the autonomic nervous system in arrhythmias and sudden cardiac death.

    PubMed

    Franciosi, Sonia; Perry, Frances K G; Roston, Thomas M; Armstrong, Kathryn R; Claydon, Victoria E; Sanatani, Shubhayan

    2017-03-31

    The autonomic nervous system (ANS) is complex and plays an important role in cardiac arrhythmia pathogenesis. A deeper understanding of the anatomy and development of the ANS has shed light on its involvement in cardiac arrhythmias. Alterations in levels of Sema-3a and NGF, both growth factors involved in innervation patterning during development of the ANS, leads to cardiac arrhythmias. Dysregulation of the ANS, including polymorphisms in genes involved in ANS development, have been implicated in sudden infant death syndrome. Disruptions in the sympathetic and/or parasympathetic systems of the ANS can lead to cardiac arrhythmias and can vary depending on the type of arrhythmia. Simultaneous stimulation of both the sympathetic and parasympathetic systems is thought to lead to atrial fibrillation whereas increased sympathetic stimulation is thought to lead to ventricular fibrillation or ventricular tachycardia. In inherited arrhythmia syndromes, such as Long QT and Catecholaminergic Polymorphic Ventricular Tachycardia, sympathetic system stimulation is thought to lead to ventricular tachycardia, subsequent arrhythmias, and in severe cases, cardiac death. On the other hand, arrhythmic events in Brugada Syndrome have been associated with periods of high parasympathetic tone. Increasing evidence suggests that modulation of the ANS as a therapeutic strategy in the treatment of cardiac arrhythmias is safe and effective. Further studies investigating the involvement of the ANS in arrhythmia pathogenesis and its modulation for the treatment of cardiac arrhythmias is warranted.

  2. Teaching cardiac autonomic function dynamics employing the Valsalva (Valsalva-Weber) maneuver.

    PubMed

    Junqueira, Luiz Fernando

    2008-03-01

    In this report, a brief history of the Valsalva (Valsalva-Weber) maneuver is outlined, followed by an explanation on the use of this approach for the evaluation of cardiac autonomic function based on underlying heart rate changes. The most important methodological and interpretative aspects of the Valsalva-Weber maneuver are critically updated, and some guidelines are established for simple application of the maneuver in a teaching or research laboratory setting. These include the hemodynamic and cardiac autonomic mechanisms involved, technical aspects such as the intensity and duration of the expiratory straining, frequency of maneuver sessions, training and posture of the individuals tested, different time- and grade change-dependent indexes of heart interval variation, and clinical application of the maneuver.

  3. Cardiac Autonomic Dysfunction in Patients With Infantile Spasm and the Effect of Adrenocorticotropic Hormone Treatment.

    PubMed

    Gencpinar, Pinar; Kocabas, Abdullah; Duman, Özgür; Dündar, Nihal Olgaç; Haspolat, Senay; Kardelen, Fırat

    2016-02-01

    Infantile spasm is an age-dependent epileptic-encephalopathy syndrome. Cardiac autonomic function is frequently altered in epilepsy. In this study, we examined heart rate variability in patients with infantile spasm before and after treatment. Nineteen patients with infantile spasm and 13 healthy comparisons were enrolled in the study. Cardiac rhythm was recorded with a Holter device for 24 hours before adrenocorticotropic hormone (ACTH) (Synacthen depot) and B6 vitamin administration and 1 month after treatment. Heart rate variability analysis found lower heart rate variability parameters in patients with infantile spasm at the onset of the syndrome, prior to treatment with ACTH. The time domain parameters of heart rate variability values showed a statistically significant increase following ACTH treatment. Our data suggest that patients with infantile spasm exhibit lower heart rate variability parameters, and the treatment of spasms with ACTH and B6 together diminished the autonomic dysfunction in our cohort.

  4. The association between anger-related personality trait and cardiac autonomic response abnormalities in elderly subjects.

    PubMed

    Narita, Kosuke; Murata, Tetsuhito; Takahashi, Tetsuya; Hamada, Toshihiko; Kosaka, Hirotaka; Yoshida, Haruyoshi; Wada, Yuji

    2007-09-01

    Cardiac autonomic response abnormality associated with trait anger has been recognized to elevate blood pressure in daily life, leading to atherosclerotic progression and cardiovascular disease. To clarify the relationship between anger-related personality traits and cardiac autonomic response in healthy elderly subjects, 54 volunteers consisting of 30 male (mean age 62.2+/-5.4) and 24 female (mean age 58.4+/-4.6) subjects underwent testing of heart rate variability (HRV) with head-up tilt. For the evaluation of trait anger, we used a questionnaire corresponding to the trait anger score taken from the State and Trait Anger Expression Inventory. Furthermore, we measured carotid intima-medial thickness (IMT) to evaluate atherosclerotic progression in subjects with anger trait. In female subjects, higher trait anger was positively associated with elevated carotid IMT and the suppression of HRV vagal attenuation from the supine to head-up position, and negatively associated with the HRV sympathetic activity in the head-up position and also with the HRV sympathetic response from the supine to head-up position. In male subjects, trait anger was not significantly associated with carotid IMT or any HRV component with or without head-up tilt testing. We conclude that a simple noninvasive measure, short-term HRV with head-up tilt testing, could be a useful method to investigate the association between cardiac autonomic imbalance and increased risk of atherosclerosis associated with trait anger in healthy elderly subjects.

  5. Gender differences in cardiac autonomic modulation during medical internship.

    PubMed

    Lin, Yu-Hsuan; Chen, Ching-Yen; Lin, Sheng-Hsuan; Liu, Chun-Hao; Weng, Wei-Hung; Kuo, Terry B J; Yang, Cheryl C H

    2013-06-01

    Medical internship is known to be a time of high stress and long working hours, which increases the risk of depression and cardiovascular disease. Gender differences in medical interns' cardiovascular risk have not been reported previously. Thirty-eight medical interns (29 males) were repeatedly tested for depressive symptoms using the Hospital Anxiety and Depression Scale and 5-min spectral analysis of heart rate variability (HRV) at 3-month intervals during their internship. Among the male interns, the variance of the heart rate decreased at 6, 9, 12 months, and a reduced high frequency, which suggests reduced cardiac parasympathetic modulation, was found at 9 and 12 months into their internship. Increased depressive symptoms were also identified at 12 months in the male group. No significant differences in depression or any of the HRV indices were identified among the female interns during their internship.

  6. Response of cardiac autonomic modulation after a single exposure to musical auditory stimulation

    PubMed Central

    Ferreira, Lucas L.; Vanderlei, Luiz Carlos M.; Guida, Heraldo L.; de Abreu, Luiz Carlos; Garner, David M.; Vanderlei, Franciele M.; Ferreira, Celso; Valenti, Vitor E.

    2015-01-01

    The acute effects after exposure to different styles of music on cardiac autonomic modulation assessed through heart rate variability (HRV) analysis have not yet been well elucidated. We aimed to investigate the recovery response of cardiac autonomic modulation in women after exposure to musical auditory stimulation of different styles. The study was conducted on 30 healthy women aged between 18 years and 30 years. We did not include subjects having previous experience with musical instruments and those who had an affinity for music styles. The volunteers remained at rest for 10 min and were exposed to classical baroque (64-84 dB) and heavy metal (75-84 dB) music for 10 min, and their HRV was evaluated for 30 min after music cessation. We analyzed the following HRV indices: Standard deviation of normal-to-normal (SDNN) intervals, root mean square of successive differences (RMSSD), percentage of normal-to-normal 50 (pNN50), low frequency (LF), high frequency (HF), and LF/HF ratio. SDNN, LF in absolute units (ms2) and normalized (nu), and LF/HF ratio increased while HF index (nu) decreased after exposure to classical baroque music. Regarding the heavy metal music style, it was observed that there were increases in SDNN, RMSSD, pNN50, and LF (ms2) after the musical stimulation. In conclusion, the recovery response of cardiac autonomic modulation after exposure to auditory stimulation with music featured an increased global activity of both systems for the two musical styles, with a cardiac sympathetic modulation for classical baroque music and a cardiac vagal tone for the heavy metal style. PMID:25774614

  7. Response of cardiac autonomic modulation after a single exposure to musical auditory stimulation.

    PubMed

    Ferreira, Lucas L; Vanderlei, Luiz Carlos M; Guida, Heraldo L; de Abreu, Luiz Carlos; Garner, David M; Vanderlei, Franciele M; Ferreira, Celso; Valenti, Vitor E

    2015-01-01

    The acute effects after exposure to different styles of music on cardiac autonomic modulation assessed through heart rate variability (HRV) analysis have not yet been well elucidated. We aimed to investigate the recovery response of cardiac autonomic modulation in women after exposure to musical auditory stimulation of different styles. The study was conducted on 30 healthy women aged between 18 years and 30 years. We did not include subjects having previous experience with musical instruments and those who had an affinity for music styles. The volunteers remained at rest for 10 min and were exposed to classical baroque (64-84 dB) and heavy metal (75-84 dB) music for 10 min, and their HRV was evaluated for 30 min after music cessation. We analyzed the following HRV indices: Standard deviation of normal-to-normal (SDNN) intervals, root mean square of successive differences (RMSSD), percentage of normal-to-normal 50 (pNN50), low frequency (LF), high frequency (HF), and LF/HF ratio. SDNN, LF in absolute units (ms 2 ) and normalized (nu), and LF/HF ratio increased while HF index (nu) decreased after exposure to classical baroque music. Regarding the heavy metal music style, it was observed that there were increases in SDNN, RMSSD, pNN50, and LF (ms 2 ) after the musical stimulation. In conclusion, the recovery response of cardiac autonomic modulation after exposure to auditory stimulation with music featured an increased global activity of both systems for the two musical styles, with a cardiac sympathetic modulation for classical baroque music and a cardiac vagal tone for the heavy metal style.

  8. Cardiac autonomic function and vascular profile in subclinical hypothyroidism: Increased beat-to-beat QT variability

    PubMed Central

    Kalra, Pramila; Yeragani, Vikram K.; Prasanna Kumar, K. M.

    2016-01-01

    Background: Patients with subclinical hypothyroidism (SH) may have higher incidence of coronary heart disease and autonomic dysfunction. Design of the Study: Prospective case control study. Aim and Objectives: To evaluate beat-to-beat QT variability and vascular stiffness in patients with SH compared to normal controls. Materials and Methods: We compared linear and nonlinear measures of cardiac repolarization liability using beat-to-beat QT intervals derived from the surface electrocardiogram during supine posture and vascular indices including pulse wave velocity and ankle-brachial index (ABI) during supine posture between female patients with SH and age- and sex-matched normal controls. Spectral analysis was done at very low frequency (LF) (0.003–0.04 Hz), Low frequency (LF) (0.04–0.15 Hz), and high frequency (HF) (0.15–0.4 Hz). The HF represents vagal regulation (parasympathetic) and LF represents both parasympathetic and sympathetic regulation. Results: We recruited 58 women with a mean age of 31.83 ± 8.9 years and 49 controls with mean age of 32.4 ± 9.9 years (P = NS). QT variability index (QTvi) was higher in cases compared to controls (P = 0.01). The ratio of LF/HF of R-R interval which is an index of sympathovagal tone was significantly more in cases compared to controls (P = 0.02). The difference in the left minus the right ABI was significant between cases and controls (P = 0.03). Conclusions: The cases had lower parasympathetic activity as compared to controls, and there was a predominance of sympathetic activity in cases. QTvi may be an important noninvasive tool in this group of patients to study the risk of cardiovascular mortality. PMID:27730068

  9. Stress-induced cardiac autonomic reactivity and preclinical atherosclerosis: does arterial elasticity modify the association?

    PubMed

    Chumaeva, Nadja; Hintsanen, Mirka; Pulkki-Råback, Laura; Merjonen, Päivi; Elovainio, Marko; Hintsa, Taina; Juonala, Markus; Kähönen, Mika; Raitakari, Olli T; Keltikangas-Järvinen, Liisa

    2015-01-01

    The effect of acute mental stress on atherosclerosis can be estimated using arterial elasticity measured by carotid artery distensibility (Cdist). We examined the interactive effect of acute stress-induced cardiac reactivity and Cdist to preclinical atherosclerosis assessed by carotid intima-media thickness (IMT) in 58 healthy adults aged 24-39 years participated in the epidemiological Young Finns Study. Cdist and IMT were measured ultrasonographically. Impedance electrocardiography was used to measure acute mental stress-induced cardiac autonomic responses: heart rate (HR), respiratory sinus arrhythmia and pre-ejection period after the mental arithmetic and the public speaking tasks. Interactions between HR reactivity and Cdist in relation to preclinical atherosclerosis were found. The results imply that elevated HR reactivity to acute mental stress is related to less atherosclerosis among healthy participants with higher arterial elasticity. Possibly, increased cardiac reactivity in response to challenging tasks is an adaptive reaction related to better cardiovascular health.

  10. Cardiac Arrest during Gamete Release in Chum Salmon Regulated by the Parasympathetic Nerve System

    PubMed Central

    Makiguchi, Yuya; Nagata, Shinya; Kojima, Takahito; Ichimura, Masaki; Konno, Yoshifumi; Murata, Hideki; Ueda, Hiroshi

    2009-01-01

    Cardiac arrest caused by startling stimuli, such as visual and vibration stimuli, has been reported in some animals and could be considered as an extraordinary case of bradycardia and defined as reversible missed heart beats. Variability of the heart rate is established as a balance between an autonomic system, namely cholinergic vagus inhibition, and excitatory adrenergic stimulation of neural and hormonal action in teleost. However, the cardiac arrest and its regulating nervous mechanism remain poorly understood. We show, by using electrocardiogram (ECG) data loggers, that cardiac arrest occurs in chum salmon (Oncorhynchus keta) at the moment of gamete release for 7.39±1.61 s in females and for 5.20±0.97 s in males. The increase in heart rate during spawning behavior relative to the background rate during the resting period suggests that cardiac arrest is a characteristic physiological phenomenon of the extraordinarily high heart rate during spawning behavior. The ECG morphological analysis showed a peaked and tall T-wave adjacent to the cardiac arrest, indicating an increase in potassium permeability in cardiac muscle cells, which would function to retard the cardiac action potential. Pharmacological studies showed that the cardiac arrest was abolished by injection of atropine, a muscarinic receptor antagonist, revealing that the cardiac arrest is a reflex response of the parasympathetic nerve system, although injection of sotalol, a β-adrenergic antagonist, did not affect the cardiac arrest. We conclude that cardiac arrest during gamete release in spawning release in spawning chum salmon is a physiological reflex response controlled by the parasympathetic nervous system. This cardiac arrest represents a response to the gaping behavior that occurs at the moment of gamete release. PMID:19543389

  11. Cardiac arrest during gamete release in chum salmon regulated by the parasympathetic nerve system.

    PubMed

    Makiguchi, Yuya; Nagata, Shinya; Kojima, Takahito; Ichimura, Masaki; Konno, Yoshifumi; Murata, Hideki; Ueda, Hiroshi

    2009-06-19

    Cardiac arrest caused by startling stimuli, such as visual and vibration stimuli, has been reported in some animals and could be considered as an extraordinary case of bradycardia and defined as reversible missed heart beats. Variability of the heart rate is established as a balance between an autonomic system, namely cholinergic vagus inhibition, and excitatory adrenergic stimulation of neural and hormonal action in teleost. However, the cardiac arrest and its regulating nervous mechanism remain poorly understood. We show, by using electrocardiogram (ECG) data loggers, that cardiac arrest occurs in chum salmon (Oncorhynchus keta) at the moment of gamete release for 7.39+/-1.61 s in females and for 5.20+/-0.97 s in males. The increase in heart rate during spawning behavior relative to the background rate during the resting period suggests that cardiac arrest is a characteristic physiological phenomenon of the extraordinarily high heart rate during spawning behavior. The ECG morphological analysis showed a peaked and tall T-wave adjacent to the cardiac arrest, indicating an increase in potassium permeability in cardiac muscle cells, which would function to retard the cardiac action potential. Pharmacological studies showed that the cardiac arrest was abolished by injection of atropine, a muscarinic receptor antagonist, revealing that the cardiac arrest is a reflex response of the parasympathetic nerve system, although injection of sotalol, a beta-adrenergic antagonist, did not affect the cardiac arrest. We conclude that cardiac arrest during gamete release in spawning release in spawning chum salmon is a physiological reflex response controlled by the parasympathetic nervous system. This cardiac arrest represents a response to the gaping behavior that occurs at the moment of gamete release.

  12. Influence of Smoking Consumption and Nicotine Dependence Degree in Cardiac Autonomic Modulation

    PubMed Central

    dos Santos, Ana Paula Soares; Ramos, Dionei; de Oliveira, Gabriela Martins; dos Santos, Ana Alice Soares; Freire, Ana Paula Coelho Figueira; It, Juliana Tiyaki; Fernandes, Renato Peretti Prieto; Vanderlei, Luiz Carlos Marques; Ramos, Ercy Mara Cipulo

    2016-01-01

    Background Smoking consumption alters cardiac autonomic function. Objective Assess the influence of the intensity of smoking and the nicotine dependence degree in cardiac autonomic modulation evaluated through index of heart rate variability (HRV). Methods 83 smokers, of both genders, between 50 and 70 years of age and with normal lung function were divided according to the intensity of smoking consumption (moderate and severe) and the nicotine dependency degree (mild, moderate and severe). The indexes of HRV were analyzed in rest condition, in linear methods in the time domain (TD), the frequency domain (FD) and through the Poincaré plot. For the comparison of smoking consumption, unpaired t test or Mann-Whitney was employed. For the analysis between the nicotine dependency degrees, we used the One-way ANOVA test, followed by Tukey's post test or Kruskal-Wallis followed by Dunn's test. The significance level was p < 0,05. Results Differences were only found when compared to the different intensities of smoking consumption in the indexes in the FD. LFun (62.89 ± 15.24 vs 75.45 ± 10.28), which corresponds to low frequency spectrum component in normalized units; HFun (37.11 ± 15.24 vs 24.55 ± 10.28), which corresponds to high frequency spectrum component in normalized units and in the LF/HF ratio (2.21 ± 1.47 vs 4.07 ± 2.94). However, in the evaluation of nicotine dependency, significant differences were not observed (p > 0.05). Conclusion Only the intensity of smoking consumption had an influence over the cardiac autonomic modulation of the assessed tobacco smokers. Tobacco smokers with severe intensity of smoking consumption presented a lower autonomic modulation than those with moderate intensity. PMID:27142649

  13. Previous exposure to musical auditory stimulation immediately influences the cardiac autonomic responses to the postural change maneuver in women

    PubMed Central

    2013-01-01

    Background Chronic exposure to musical auditory stimulation has been reported to improve cardiac autonomic regulation. However, it is not clear if music acutely influences it in response to autonomic tests. We evaluated the acute effects of music on heart rate variability (HRV) responses to the postural change maneuver (PCM) in women. Method We evaluated 12 healthy women between 18 and 28 years old and HRV was analyzed in the time (SDNN, RMSSD, NN50 and pNN50) and frequency (LF, HF and LF/HF ratio) domains. In the control protocol, the women remained at seated rest for 10 minutes and quickly stood up within three seconds and remained standing still for 15 minutes. In the music protocol, the women remained at seated rest for 10 minutes, were exposed to music for 10 minutes and quickly stood up within three seconds and remained standing still for 15 minutes. HRV was recorded at the following time: rest, music (music protocol) 0–5, 5–10 and 10–15 min during standing. Results In the control protocol the SDNN, RMSSD and pNN50 indexes were reduced at 10–15 minutes after the volunteers stood up, while the LF (nu) index was increased at the same moment compared to seated rest. In the protocol with music, the indexes were not different from control but the RMSSD, pNN50 and LF (nu) were different from the music period. Conclusion Musical auditory stimulation attenuates the cardiac autonomic responses to the PCM. PMID:23941333

  14. Abnormal left ventricular torsion and cardiac autonomic dysfunction in subjects with type 1 diabetes mellitus

    PubMed Central

    Piya, Milan K.; Shivu, Ganesh Nallur; Tahrani, Abd; Dubb, Kiran; Abozguia, Khalid; Phan, T.T.; Narendran, Parth; Pop-Busui, Rodica; Frenneaux, Michael; Stevens, Martin J.

    2011-01-01

    Left ventricular torsion is increased and cardiac energetics are reduced in uncomplicated type 1 diabetes mellitus (T1DM). Our aim was to determine the relationships of these abnormalities to cardiovascular autonomic neuropathy (CAN) in subjects with T1DM. A cross-sectional study was conducted in 20 subjects with T1DM free of known coronary heart disease attending an outpatient clinic. Cardiovascular autonomic neuropathy was assessed using heart rate variability studies and the continuous wavelet transform method. Left ventricular function was determined by speckle tracking echocardiography. Magnetic resonance spectroscopy and stress magnetic resonance imaging were used to measure cardiac energetics and myocardial perfusion reserve index, respectively. Twenty subjects (age, 35 ± 8 years; diabetes duration, 16 ± 9 years; hemoglobin A1c, 8.0% ± 1.1%) were recruited. Forty percent of the subjects exhibited definite or borderline CAN. Log peak radial strain was significantly increased in subjects with CAN compared with those without (1.56 ± 0.06 vs 1.43 ± 0.14, respectively; P = .011). Data were adjusted for log duration of diabetes, and log left ventricular torsion correlated (r = 0.593, P = .01) with log low-frequency to high-frequency ratio during the Valsalva maneuver. Log isovolumic relaxation time correlated significantly with log Valsalva ratio and log proportion of differences in consecutive RR intervals of normal beats greater than 50 milliseconds during deep breathing. However, CAN did not correlate with cardiac energetics or myocardial perfusion reserve index. Spectral analysis of low-frequency to high-frequency ratio power during the Valsalva maneuver is associated with altered left ventricular torsion in subjects with T1DM. Parasympathetic dysfunction is closely associated with diastolic deficits. Cardiovascular autonomic neuropathy is not however the principal cause of impaired cardiac energetics. The role of CAN in the development of cardiomyopathy

  15. (Non-invasive evaluation of the cardiac autonomic nervous system by PET)

    SciTech Connect

    Not Available

    1992-01-01

    The proposed research addresses the development, validation and application of cardiac PET imaging techniques to characterize the autonomic nervous system of the heart. PET technology has significantly matured over the last two decades. Instrument design, image processing and production of radiochemical compounds have formed an integrative approach to provide a powerful and novel imaging modality for the quantitative in vivo evaluation of the autonomic nervous system of the heart. Animal studies using novel tracers for the sympathetic and parasympathetic nerve terminals will be employed to characterize the functional integrity of nerve terminals. This work will be complemented by the development of agents which bind to postsynaptic receptor sites. The combined evaluation of presynaptic and postsynaptic neuronal function will allow a unique characterization of neuronal function. Initial development in animal studies will be followed by feasibility studies in humans. These studies are designed to test sophisticated imaging protocols in the human heart and validate the scintigraphic findings with independent markers of autonomic innervation. Subsequent clinical application in various cardiac diseases is expected to provide new insights into the neuropathophysiology of the heart.

  16. Silent myocardial infarction secondary to cardiac autonomic neuropathy in a patient with rheumatoid arthritis.

    PubMed

    Unnikrishnan, Dileep; Jacob, Aasems; Anthony Diaz, Mark; Lederman, Jeffrey

    2016-08-03

    An 83-year-old female patient with rheumatoid arthritis and hypertension presented to the emergency department with fever and chills of 1 day duration. On examination, temperature was 100.9 F, heart rate 111/min and she had orthostatic hypotension. Laboratory tests showed elevated blood urea nitrogen and white cell count. The patient underwent treatment for symptomatic urinary tract infection and while her fever and leucocytosis resolved, tachycardia persisted. An EKG done showed T inversions in leads II, III, arteriovenous fistula, V2 and V3. Troponin-I was elevated. Nuclear stress test revealed apical wall motion abnormality confirming myocardial infarction. Ewing's tests were carried out at bedside and these diagnosed severe autonomic neuropathy. Rheumatoid arthritis can cause cardiac autonomic neuropathy from chronic inflammation. This case entails the importance of assessing and detecting cardiac autonomic neuropathy in chronic inflammatory conditions, and the need to be cautious of acute coronary events in these patients, even for minimal or no symptoms.

  17. [Cardiac autonomic blockade in sinus disease and indication for a pacemaker].

    PubMed

    Solórzano Martín, C J; Delgado Caro, G; Lugo Peña, P

    1990-01-01

    Functional autonomic blockade (FAB) with metoprolol (0.2 mg/kg body weight) and atropine sulphate (0.04 mg/kg) was carried out in 23 patients, 20 to 81 years old (mean age 61 years) with symptomatic sick sinus syndrome with clinical indication for permanent pacing. Several measurements were determined before and after FAB, 7 had normal intrinsic heart rate (IHR) and 16 abnormal. With normal IHR, 3 had severe autonomic regulation disturbances and in only two patients the corrected sinus nodal recovery time (SNRTC) and the sinoatrial conduction time (SACT) were prolonged after FAB. On the 16 patients with abnormal IHR only 4 had severe extrinsic autonomic influence and 15 had SACT and SNRTC prolonged after FAB. All measurements were determined by standard electrocardiographic surface tracings. Indications for permanent pacing were reduced to intrinsic sick sinus syndrome and bradycardia with severe autonomic disturbances in symptomatic patients.

  18. Cardiac Autonomic Dysfunction in Patients with Schizophrenia and Their Healthy Relatives – A Small Review

    PubMed Central

    Bär, Karl-Jürgen

    2015-01-01

    The majority of excess mortality among people with schizophrenia seems to be caused by cardiovascular complications, and in particular, coronary heart disease. In addition, the prevalence of heart failure and arrhythmias is increased in this population. Reduced efferent vagal activity, which has been consistently described in these patients and their healthy first-degree relatives, might be one important mechanism contributing to their increased cardiac mortality. A decrease in heart rate variability and complexity was often shown in unmedicated patients when compared to healthy controls. In addition, faster breathing rates, accompanied by shallow breathing, seem to influence autonomic cardiac functioning in acute unmedicated patients substantially. Moreover, low-physical fitness is a further and independent cardiac risk factor present in this patient population. Interestingly, new studies describe chronotropic incompetence during physical exercise as an important additional risk factor in patients with schizophrenia. Some studies report a correlation of the autonomic imbalance with the degree of positive symptoms (i.e., delusions) and some with the duration of disease. The main body of psychiatric research is focused on mental aspects of the disease, thereby neglecting obvious physical health needs of these patients. Here, a joint effort is needed to design interventional strategies in everyday clinical settings to improve physical health and quality of life. PMID:26157417

  19. Cardiac sodium channel regulator MOG1 regulates cardiac morphogenesis and rhythm

    PubMed Central

    Zhou, Juan; Wang, Longfei; Zuo, Mengxia; Wang, Xiaojing; Ahmed, Abu Shufian Ishtiaq; Chen, Qiuyun; Wang, Qing K.

    2016-01-01

    MOG1 was initially identified as a protein that interacts with the small GTPase Ran involved in transport of macromolecules into and out of the nucleus. In addition, we have established that MOG1 interacts with the cardiac sodium channel Nav1.5 and regulates cell surface trafficking of Nav1.5. Here we used zebrafish as a model system to study the in vivo physiological role of MOG1. Knockdown of mog1 expression in zebrafish embryos significantly decreased the heart rate (HR). Consistently, the HR increases in embryos with over-expression of human MOG1. Compared with wild type MOG1 or control EGFP, mutant MOG1 with mutation E83D associated with Brugada syndrome significantly decreases the HR. Interestingly, knockdown of mog1 resulted in abnormal cardiac looping during embryogenesis. Mechanistically, knockdown of mog1 decreases expression of hcn4 involved in the regulation of the HR, and reduces expression of nkx2.5, gata4 and hand2 involved in cardiac morphogenesis. These data for the first time revealed a novel role that MOG1, a nucleocytoplasmic transport protein, plays in cardiac physiology and development. PMID:26903377

  20. An Autonomic Link Between Inhaled Diesel Exhaust and Impaired Cardiac Performance: Insight From Treadmill and Doubutamine Challenges in Heart Failure-Prone Rats

    EPA Science Inventory

    Background: Short-term exposure to vehicular emissions is associated with adverse cardiac events. Diesel exhaust (DE) is an ubiquitous air pollutant believed to provoke cardiac events partly through imbalance of the sympathetic and parasympathetic branches of the autonomic nervo...

  1. Effects of Kefir on the Cardiac Autonomic Tones and Baroreflex Sensitivity in Spontaneously Hypertensive Rats

    PubMed Central

    Klippel, Brunella F.; Duemke, Licia B.; Leal, Marcos A.; Friques, Andreia G. F.; Dantas, Eduardo M.; Dalvi, Rodolfo F.; Gava, Agata L.; Pereira, Thiago M. C.; Andrade, Tadeu U.; Meyrelles, Silvana S.; Campagnaro, Bianca P.; Vasquez, Elisardo C.

    2016-01-01

    Aims: It has been previously shown that the probiotic kefir (a symbiotic matrix containing acid bacteria and yeasts) attenuated the hypertension and the endothelial dysfunction in spontaneously hypertensive rats (SHR). In the present study, the effect of chronic administration of kefir on the cardiac autonomic control of heart rate (HR) and baroreflex sensitivity (BRS) in SHR was evaluated. Methods: SHR were treated with kefir (0.3 mL/100 g body weight) for 60 days and compared with non-treated SHR and with normotensive Wistar-Kyoto rats. Cardiac autonomic vagal (VT) and sympathetic (ST) tones were estimated through the blockade of the cardiac muscarinic receptors (methylatropine) and the blockade of β1−adrenoceptor (atenolol). The BRS was evaluated by the tachycardia and bradycardia responses to vasoactive drug-induced decreases and increases in arterial blood pressure (BP), respectively. Additionally, spontaneous BRS was estimated by autoregressive spectral analysis. Results: Kefir-treated SHR exhibited significant attenuation of basal BP, HR, and cardiac hypertrophy compared to non-treated SHR (12, 13, and 21%, respectively). Cardiac VT and ST were significantly altered in the SHR (~40 and ~90 bpm) compared with Wistar rats (~120 and ~30 bpm) and were partially recovered in SHR-kefir (~90 and ~25 bpm). SHR exhibited an impaired bradycardic BRS (~50%) compared with Wistar rats, which was reduced to ~40% in the kefir-treated SHR and abolished by methylatropine in all groups. SHR also exhibited a significant impairment of the tachycardic BRS (~23%) compared with Wistar rats and this difference was reduced to 8% in the SHR-kefir. Under the action of atenolol the residual reflex tachycardia was smaller in SHR than in Wistar rats and kefir attenuated this abnormality. Spectral analysis revealed increased low frequency components of BP (~3.5-fold) and pulse interval (~2-fold) compared with Wistar rats and these differences were reduced by kefir-treatment to ~1

  2. Neural network regulation driven by autonomous neural firings

    NASA Astrophysics Data System (ADS)

    Cho, Myoung Won

    2016-07-01

    Biological neurons naturally fire spontaneously due to the existence of a noisy current. Such autonomous firings may provide a driving force for network formation because synaptic connections can be modified due to neural firings. Here, we study the effect of autonomous firings on network formation. For the temporally asymmetric Hebbian learning, bidirectional connections lose their balance easily and become unidirectional ones. Defining the difference between reciprocal connections as new variables, we could express the learning dynamics as if Ising model spins interact with each other in magnetism. We present a theoretical method to estimate the interaction between the new variables in a neural system. We apply the method to some network systems and find some tendencies of autonomous neural network regulation.

  3. Juvenile onset depression alters cardiac autonomic balance in response to psychological and physical challenges

    PubMed Central

    Bylsma, Lauren M.; Yaroslavsky, Ilya; Rottenberg, Jonathan; Jennings, J. Richard; George, Charles J.; Kiss, Enikő; Kapornai, Krisztina; Halas, Kitti; Dochnal, Roberta; Lefkovics, Eszter; Benák, István; Baji, Ildikó; Vetró, Ágnes; Kovacs, Maria

    2015-01-01

    Cardiac autonomic balance (CAB) indexes the ratio of parasympathetic to sympathetic activation (Berntson, Norman, Hawkley, & Cacioppo, 2008), and is believed to reflect overall autonomic flexibility in the face of environmental challenges. However, CAB has not been examined in depression. We examined changes in CAB and other physiological variables in 179 youth with a history of juvenile onset depression (JOD) and 161 healthy controls, in response to two psychological (unsolvable puzzle, sad film) and two physical (handgrip, and forehead cold pressor) challenges. In repeated measures analyses, controls showed expected reductions in CAB for both the handgrip and unsolvable puzzle, reflecting a shift to sympathetic relative to parasympathetic activation. By contrast, JOD youth showed increased CAB from baseline for both tasks (ps<.05). No effects were found for the forehead cold pressor or sad film tasks, suggesting that CAB differences may arise under conditions requiring greater attentional control or sustained effort. PMID:26225465

  4. Regulation of cardiac C-protein phosphorylation

    SciTech Connect

    Titus, F.L.

    1985-01-01

    Molecular mechanisms of cardiac sympathetic and parasympathetic responses were addressed by studying subcellular changes in protein phosphorylation, cAMP-dependent protein kinase activity and protein phosphatase activity in frog hearts. B-adrenergic agonists increased and muscarinic cholinergic agonists decreased (/sup 32/P)phosphate incorporation into C-protein, a thick filament component. Regulation of protein phosphatase activity by Iso and methacholine (MCh) was assayed using extracts of drug treated frog hearts and (/sup 32/P)phospho-C-protein as substrate. Total phosphatase activity decreased 21% in extracts from hearts perfused with 0.1 ..mu..M Iso and 17% in hearts exposed to Iso plus 1 ..mu..M methacholine. This decrease reflected decreased phosphatase-2A activity. No changes in total phosphatase activity were measurable in broken cells treated with Iso or MCh. The results suggest adrenergic stimulation changes contractile activity in frog hearts by activating cAMP-dependent protein kinase associated with particulate cellular elements and inactivating soluble protein phosphatase-2A. This is the first demonstration of coordinated regulation of these enzymes by B-adrenergic agonists favoring phosphorylation of effector proteins. Coordinated regulation by methacholine in the presence of Iso was not observed.

  5. Sympathetic cardiac hyperinnervation and atrial autonomic imbalance in diet-induced obesity promote cardiac arrhythmias.

    PubMed

    McCully, Belinda H; Hasan, Wohaib; Streiff, Cole T; Houle, Jennifer C; Woodward, William R; Giraud, George D; Brooks, Virginia L; Habecker, Beth A

    2013-11-15

    Obesity increases the risk of arrhythmias and sudden cardiac death, but the mechanisms are unknown. This study tested the hypothesis that obesity-induced cardiac sympathetic outgrowth and hyperinnervation promotes the development of arrhythmic events. Male Sprague-Dawley rats (250-275 g), fed a high-fat diet (33% kcal/fat), diverged into obesity-resistant (OR) and obesity-prone (OP) groups and were compared with rats fed normal chow (13% kcal/fat; CON). In vitro experiments showed that both OR and OP rats exhibited hyperinnervation of the heart and high sympathetic outgrowth compared with CON rats, even though OR rats are not obese. Despite the hyperinnervation and outgrowth, we showed that, in vivo, OR rats were less susceptible to arrhythmic events after an intravenous epinephrine challenge compared with OP rats. On examining total and stimulus-evoked neurotransmitter levels in an ex vivo system, we demonstrate that atrial acetylcholine content and release were attenuated in OP compared with OR and CON groups. OP rats also expressed elevated atrial norepinephrine content, while norepinephrine release was suppressed. These findings suggest that the consumption of a high-fat diet, even in the absence of overt obesity, stimulates sympathetic outgrowth and hyperinnervation of the heart. However, normalized cardiac parasympathetic nervous system control may protect the heart from arrhythmic events.

  6. Effects of manual lymph drainage on cardiac autonomic tone in healthy subjects.

    PubMed

    Kim, Sung-Joong; Kwon, Oh-Yun; Yi, Chung-Hwi

    2009-01-01

    This study was designed to investigate the effects of manual lymph drainage on the cardiac autonomic tone. Thirty-two healthy male subjects were randomly assigned to manual lymph drainage (MLD) (experimental) and rest (control) groups. Electrocardiogram (ECG) parameters were recorded with bipolar electrocardiography using standard limb lead positions. The pressure-pain threshold (PPT) was quantitatively measured using an algometer. Heart rate variability differed significantly between the experimental and control groups (p < 0.05), but the PPT in the upper trapezius muscle did not (p > 0.05). These findings indicate that the application of MLD was effective in reducing the activity of the sympathetic nervous system.

  7. Regulation of Cardiac Remodeling by Cardiac Na(+)/K(+)-ATPase Isoforms.

    PubMed

    Liu, Lijun; Wu, Jian; Kennedy, David J

    2016-01-01

    Cardiac remodeling occurs after cardiac pressure/volume overload or myocardial injury during the development of heart failure and is a determinant of heart failure. Preventing or reversing remodeling is a goal of heart failure therapy. Human cardiomyocyte Na(+)/K(+)-ATPase has multiple α isoforms (1-3). The expression of the α subunit of the Na(+)/K(+)-ATPase is often altered in hypertrophic and failing hearts. The mechanisms are unclear. There are limited data from human cardiomyocytes. Abundant evidences from rodents show that Na(+)/K(+)-ATPase regulates cardiac contractility, cell signaling, hypertrophy and fibrosis. The α1 isoform of the Na(+)/K(+)-ATPase is the ubiquitous isoform and possesses both pumping and signaling functions. The α2 isoform of the Na(+)/K(+)-ATPase regulates intracellular Ca(2+) signaling, contractility and pathological hypertrophy. The α3 isoform of the Na(+)/K(+)-ATPase may also be a target for cardiac hypertrophy. Restoration of cardiac Na(+)/K(+)-ATPase expression may be an effective approach for prevention of cardiac remodeling. In this article, we will overview: (1) the distribution and function of isoform specific Na(+)/K(+)-ATPase in the cardiomyocytes. (2) the role of cardiac Na(+)/K(+)-ATPase in the regulation of cell signaling, contractility, cardiac hypertrophy and fibrosis in vitro and in vivo. Selective targeting of cardiac Na(+)/K(+)-ATPase isoform may offer a new target for the prevention of cardiac remodeling.

  8. Regulation of Cardiac Remodeling by Cardiac Na+/K+-ATPase Isoforms

    PubMed Central

    Liu, Lijun; Wu, Jian; Kennedy, David J.

    2016-01-01

    Cardiac remodeling occurs after cardiac pressure/volume overload or myocardial injury during the development of heart failure and is a determinant of heart failure. Preventing or reversing remodeling is a goal of heart failure therapy. Human cardiomyocyte Na+/K+-ATPase has multiple α isoforms (1–3). The expression of the α subunit of the Na+/K+-ATPase is often altered in hypertrophic and failing hearts. The mechanisms are unclear. There are limited data from human cardiomyocytes. Abundant evidences from rodents show that Na+/K+-ATPase regulates cardiac contractility, cell signaling, hypertrophy and fibrosis. The α1 isoform of the Na+/K+-ATPase is the ubiquitous isoform and possesses both pumping and signaling functions. The α2 isoform of the Na+/K+-ATPase regulates intracellular Ca2+ signaling, contractility and pathological hypertrophy. The α3 isoform of the Na+/K+-ATPase may also be a target for cardiac hypertrophy. Restoration of cardiac Na+/K+-ATPase expression may be an effective approach for prevention of cardiac remodeling. In this article, we will overview: (1) the distribution and function of isoform specific Na+/K+-ATPase in the cardiomyocytes. (2) the role of cardiac Na+/K+-ATPase in the regulation of cell signaling, contractility, cardiac hypertrophy and fibrosis in vitro and in vivo. Selective targeting of cardiac Na+/K+-ATPase isoform may offer a new target for the prevention of cardiac remodeling. PMID:27667975

  9. [Autonomic cardiovascular regulation in patients with tics and Tourette syndrome].

    PubMed

    Zykov, V P; Komarova, I B; Nazarova, E K; Begasheva, O I; Kabanova, S A

    2005-01-01

    Autonomic cardiovascular regulation has been assessed in patients aged 4-15 years with Tourette syndrome (n = 22) and other tic disorders (n = 48). Symptom significance was estimated by a number of hyperkinetic episodes per 20 minutes, tic scale and variants of the disease course. The functional condition of autonomic nervous system was studied clinically and using spectral analysis of heart rate variability in both upright and supine positions. Negative correlation between the ratio of sympathetic and vagus influences and severity of the disease was found: the severer were tic symptoms, the stronger was a trend to vagotonia (beta = -0.36; p < 0.0025; F > 4.0). In orthostatic test, patients with Tourette syndrome demonstrated an unfavorable hypersympathicotonic type of cardiovascular system reaction. Patients were treated during 4 weeks with glycinum (0.2 +/- 0.1 mg/day), phenibutum (0.5 +/- 0.25 mg/day), clonazepam (1.5 +/- 0.5 mg/day), tiapride (200 +/- 100 mg/day), haloperidol (1-1.5 mg/day), rispolept (2 mg/day). There was no negative effect of the drugs on heart rate variability. On the contrary, the therapy reduced hyperkinetic symptoms and corrected autonomic influences on the sinus rhythm. It is suggested that changes in autonomic cardiovascular regulation might be of secondary character and do not need any special correction.

  10. Spaceflight alters autonomic regulation of arterial pressure in humans

    NASA Technical Reports Server (NTRS)

    Fritsch-Yelle, Janice M.; Charles, John B.; Jones, Michele M.; Beightol, Larry A.; Eckberg, Dwain L.

    1994-01-01

    Spaceflight is associated with decreased orthostatic tolerance after landing. Short-duration spaceflight (4 - 5 days) impairs one neutral mechanism: the carotid baroreceptor-cardiac reflex. To understand the effects of longer-duration spaceflight on baroreflex function, we measured R-R interval power spectra, antecubital vein plasma catecholamine levels, carotid baroreceptor-cardiac reflex responses, responses to Valsalva maneuvers, and orthostatic tolerance in 16 astronauts before and after shuttle missions lasting 8 - 14 days. We found the following changes between preflight and landing day: (1) orthostatic tolerance decreased; (2) R-R interval spectral power in the 0.05- to 0.15-Hz band increased; (3) plasma norepinephrine and epinephrine levels increased; (4) the slope, range, and operational point of the carotid baroreceptor cardiac reflex response decreased; and (5) blood pressure and heart rate responses to Valsalva maneuvers were altered. Autonomic changes persisted for several days after landing. These results provide further evidence of functionally relevent reductions in parasympathetic and increases in sympathetic influences on arterial pressure control after spaceflight.

  11. Fitness, autonomic regulation and orthostatic tolerance

    NASA Technical Reports Server (NTRS)

    Buckey, Jay C.

    1991-01-01

    Work on this grant has consisted of two major studies of cardiovascular regulation in athletes along with several smaller supporting studies. This summary will give a brief overview of two major studies, and then conclude with an analysis of what the findings from these studies mean practically, and how they can be applied to current problems with post-flight orthostatic intolerance. The first study addresses a cross-sectional analysis of orthostatic intolerance in highly aerobically trained individuals; the second addresses ventricular pressure/volume relationships in athletes.

  12. Co-expression changes of lncRNAs and mRNAs in the cervical sympathetic ganglia in diabetic cardiac autonomic neuropathic rats.

    PubMed

    Li, Guilin; Sheng, Xuan; Xu, Yurong; Jiang, Huaide; Zheng, Chaoran; Guo, Jingjing; Sun, Shanshan; Yi, Zhihua; Qin, Shulan; Liu, Shuangmei; Gao, Yun; Zhang, Chunping; Xu, Hong; Wu, Bing; Zou, Lifang; Liang, Shangdong; Zhu, Gaochun

    2016-12-19

    Cardiac autonomic neuropathy in Type 2 diabetes (T2D) is often a devastating complication. Long non-coding RNAs (lncRNAs) have important effects on both normal development and disease pathogenesis. In this study, we explored the expression profiles of some lncRNAs involved in inflammation which may be co-expressed with messenger RNA (mRNA) in superior cervical and stellate ganglia after type 2 diabetic injuries. Total RNA isolated from 10 pairs of superior cervical and stellate ganglia in diabetic and normal male rats was hybridized to lncRNA arrays for detections. Pathway analysis indicated that the most significant gene ontology (GO) processes that were upregulated in diabetes were associated with immune response, cell migration, defense response, taxis, and chemotaxis. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway revealed that most of the target genes of the lncRNAs were located in cytokine-cytokine receptor interactions, the chemokine signaling pathway and cell adhesion molecules, which were involved in T2D. Gene co-expression network construction showed that the co-expression network in the experimental rats consisted of 268 regulation edges among 105 lncRNAs and 11 mRNAs. Our studies demonstrated the co-expression profile of lncRNAs and mRNAs in diabetic cardiac autonomic ganglia, suggesting possible roles for multiple lncRNAs as potential targets for the development of therapeutic strategies or biomarkers for diabetic cardiac autonomic neuropathy. © 2016 Wiley Periodicals, Inc.

  13. G0/G1 Switch Gene 2 Regulates Cardiac Lipolysis*

    PubMed Central

    Heier, Christoph; Radner, Franz P. W.; Moustafa, Tarek; Schreiber, Renate; Grond, Susanne; Eichmann, Thomas O.; Schweiger, Martina; Schmidt, Albrecht; Cerk, Ines K.; Oberer, Monika; Theussl, H.-Christian; Wojciechowski, Jacek; Penninger, Josef M.; Zimmermann, Robert; Zechner, Rudolf

    2015-01-01

    The anabolism and catabolism of myocardial triacylglycerol (TAG) stores are important processes for normal cardiac function. TAG synthesis detoxifies and stockpiles fatty acids to prevent lipotoxicity, whereas TAG hydrolysis (lipolysis) remobilizes fatty acids from endogenous storage pools as energy substrates, signaling molecules, or precursors for complex lipids. This study focused on the role of G0/G1 switch 2 (G0S2) protein, which was previously shown to inhibit the principal TAG hydrolase adipose triglyceride lipase (ATGL), in the regulation of cardiac lipolysis. Using wild-type and mutant mice, we show the following: (i) G0S2 is expressed in the heart and regulated by the nutritional status with highest expression levels after re-feeding. (ii) Cardiac-specific overexpression of G0S2 inhibits cardiac lipolysis by direct protein-protein interaction with ATGL. This leads to severe cardiac steatosis. The steatotic hearts caused by G0S2 overexpression are less prone to fibrotic remodeling or cardiac dysfunction than hearts with a lipolytic defect due to ATGL deficiency. (iii) Conversely to the phenotype of transgenic mice, G0S2 deficiency results in a de-repression of cardiac lipolysis and decreased cardiac TAG content. We conclude that G0S2 acts as a potent ATGL inhibitor in the heart modulating cardiac substrate utilization by regulating cardiac lipolysis. PMID:26350455

  14. Fetal cardiac autonomic control during breathing and non-breathing epochs: the effect of maternal exercise.

    PubMed

    Gustafson, Kathleen M; May, Linda E; Yeh, Hung-wen; Million, Stephanie K; Allen, John J B

    2012-07-01

    We explored whether maternal exercise during pregnancy moderates the effect of fetal breathing movements on fetal cardiac autonomic control assessed by metrics of heart rate (HR) and heart rate variability (HRV). Thirty women were assigned to Exercise or Control group (n=15/group) based on the modifiable physical activity questionnaire (MPAQ). Magnetocardiograms (MCG) were recorded using a dedicated fetal biomagnetometer. Periods of fetal breathing activity and apnea were identified using the fetal diaphragmatic magnetomyogram (dMMG) as a marker. MCG R-waves were marked. Metrics of fetal HR and HRV were compared using 1 breathing and 1 apneic epoch/fetus. The main effects of group (Exercise vs. Control) and condition (Apnea vs. Breathing) and their interactions were explored. Fetal breathing resulted in significantly lower fetal HR and higher vagally-mediated HRV. Maternal exercise resulted in significantly lower fetal HR, higher total HRV and vagally-mediated HRV with no difference in frequency band ratios. Significant interactions between maternal exercise and fetal breathing were found for metrics summarizing total HRV and a parasympathetic metric. Post hoc comparison showed no group difference during fetal apnea. Fetal breathing was associated with a loss of Total HRV in the Control group and no difference in the Exercise group. Both groups show enhanced vagal function during fetal breathing; greater in the Exercise group. During in utero breathing movements, the fetus of the exercising mother has enhanced cardiac autonomic function that may give the offspring an adaptive advantage.

  15. Cardiac reflexes in a warming world: thermal plasticity of barostatic control and autonomic tones in a temperate fish.

    PubMed

    Sandblom, Erik; Ekström, Andreas; Brijs, Jeroen; Sundström, L Fredrik; Jutfelt, Fredrik; Clark, Timothy D; Adill, Anders; Aho, Teija; Gräns, Albin

    2016-09-15

    Thermal plasticity of cardiorespiratory function allows ectotherms like fish to cope with seasonal temperature changes and is critical for resilience to climate change. Yet, the chronic thermal effects on cardiovascular homeostatic reflexes in fish are little understood although this may have important implications for physiological performance and overall resilience to climate warming. We compared cardiac autonomic control and baroreflex regulation of heart rate in perch (Perca fluviatilis L.) from a reference area in the Baltic Sea at 18-19°C with conspecifics from the Biotest enclosure, a chronically heated ecosystem receiving warmed effluent water (24-25°C) from a nuclear power plant. Resting heart rate of Biotest fish displayed clear thermal compensation and was 58.3±2.3 beats min(-1) compared with 52.4±2.6 beats min(-1) in reference fish at their respective environmental temperatures (Q10=1.2). The thermally compensated heart rate of Biotest fish was a combined effect of elevated inhibitory cholinergic tone (105% in Biotest fish versus 70% in reference fish) and reduced intrinsic cardiac pacemaker rate. A barostatic response was evident in both groups, as pharmacologically induced increases and decreases in blood pressure resulted in atropine-sensitive bradycardia and tachycardia, respectively. Yet, the tachycardia in Biotest fish was significantly greater, presumably due to the larger scope for vagal release. Acclimation of Biotest fish to 18°C for 3 weeks abolished differences in intrinsic heart rate and autonomic tone, suggesting considerable short-term thermal plasticity of cardiovascular control in this species. The heightened hypotensive tachycardia in Biotest perch may represent an important mechanism of ectothermic vertebrates that safeguards tissue perfusion pressure when tissue oxygen demand is elevated by environmental warming.

  16. Modulation of cardiac autonomic tone in non-hypotensive hypovolemia during blood donation.

    PubMed

    Yadav, Kavita; Singh, Akanksha; Jaryal, Ashok Kumar; Coshic, Poonam; Chatterjee, Kabita; Deepak, K K

    2016-08-02

    Non-hypotensive hypovolemia, observed during mild haemorrhage or blood donation leads to reflex readjustment of the cardiac autonomic tone. In the present study, the cardiac autonomic tone was quantified using heart rate and blood pressure variability during and after non-hypotensive hypovolemia of blood donation. 86 voluntary healthy male blood donors were recruited for the study (age 35 ± 9 years; weight 78 ± 12 kg; height 174 ± 6 cms). Continuous lead II ECG and beat-to-beat blood pressure was recorded before, during and after blood donation followed by offline time and frequency domain analysis of HRV and BPV. The overall heart rate variability (SDNN and total power) did not change during or after blood donation. However, there was a decrease in indices that represent the parasympathetic component (pNN50 %, SDSD and HF) while an increase was observed in sympathetic component (LF) along with an increase in sympathovagal balance (LF:HF ratio) during blood donation. These changes were sustained for the period immediately following blood donation. No fall of blood pressure was observed during the period of study. The blood pressure variability showed an increase in the SDNN, CoV and RMSSD time domain measures in the post donation period. These results suggest that mild hypovolemia produced by blood donation is non-hypotensive but is associated with significant changes in the autonomic tone. The increased blood pressure variability and heart rate changes that are seen only in the later part of donation period could be because of the progressive hypovolemia associated parasympathetic withdrawal and sympathetic activation that manifest during the course of blood donation.

  17. Effects of GABA, Neural Regulation, and Intrinsic Cardiac Factors on Heart Rate Variability in Zebrafish Larvae.

    PubMed

    Vargas, Rafael Antonio

    2017-04-01

    Heart rate (HR) is a periodic activity that is variable over time due to intrinsic cardiac factors and extrinsic neural control, largely by the autonomic nervous system. Heart rate variability (HRV) is analyzed by measuring consecutive beat-to-beat intervals. This variability can contain information about the factors regulating cardiac activity under normal and pathological conditions, but the information obtained from such analyses is not yet fully understood. In this article, HRV in zebrafish larvae was evaluated under normal conditions and under the effect of substances that modify intrinsic cardiac activity and cardiac activity modulated by the nervous system. We found that the factors affecting intrinsic activity have negative chronotropic and arrhythmogenic effects at this stage of development, whereas neural modulatory factors have a lesser impact. The results suggest that cardiac activity largely depends on the intrinsic properties of the heart tissue in the early stages of development and, to a lesser extent, in the maturing nervous system. We also report, for the first time, the influence of the neurotransmitter gamma amino butyric acid on HRV. The results demonstrate the larval zebrafish model as a useful tool in the study of intrinsic cardiac activity and its role in heart diseases.

  18. The cardiac cycle: regulation and energy oscillations.

    PubMed

    Wikman-Coffelt, J; Sievers, R; Coffelt, R J; Parmley, W W

    1983-08-01

    Cyclical changes in energy-related metabolites were observed in glucose-perfused but not pyruvate-perfused isolated working rat hearts. A chronological study of various phases of the cardiac cycle indicated maximum changes in metabolites occurred at half time to peak pressure (dF/dtmax). The high-energy phosphates ATP and phosphocreatine, as well as the glycolytic metabolites, glucose 6-phosphate and pyruvate, reached minimum values immediately prior to peak systole and maximum values during late diastole. The products of high-energy phosphate hydrolysis, ADP, inorganic phosphate, and creatine, as well as the regulator, adenosine 3',5'-cyclic monophosphate, showed the phase alternate. It was necessary to study cyclical changes in a maximally stressed glucose-perfused heart because the cyclical changes were small and appeared to be the result of rate-limiting steps in glycolysis and the slow transport of NADH into the mitochondria. For stressing the heart, thereby increasing ATP utilization and augmenting cyclical changes, the afterload chamber was set at 110 mmHg, and the perfusate contained high concentrations of calcium (3.5 mM, free) and isoproterenol (5 X 10(-9) M). When correction was made for binding and compartmentation of metabolites, data indicated that the free energy of ATP hydrolysis was preserved during the contraction process by a continuous binding and recycling of ADP.

  19. From Syncitium to Regulated Pump: A Cardiac Muscle Cellular Update

    ERIC Educational Resources Information Center

    Korzick, Donna H.

    2011-01-01

    The primary purpose of this article is to present a basic overview of some key teaching concepts that should be considered for inclusion in an six- to eight-lecture introductory block on the regulation of cardiac performance for graduate students. Within the context of cardiac excitation-contraction coupling, this review incorporates information…

  20. Influence of nutrients on cardiac autonomic function in nondiabetic overweight subjects.

    PubMed

    Valensi, Paul; Pariès, Jacques; Lormeau, Boris; Attia, Sandra; Attali, Jean-Raymond

    2005-10-01

    The current study sought to determine whether there is a link between cardiac autonomic dysfunction and food intake in overweight subjects. One hundred five nondiabetic overweight (body mass index >27 kg/m2) subjects were studied. Heart rate variations were analyzed during 3 bedside standard tests investigating mainly vagal control: deep breathing, lying-to-standing, and Valsalva tests. The resting metabolic rate and substrate oxidation rates were measured by indirect calorimetry. Dietary intake was estimated from a 3-day recall of food intake. Cardiac parasympathetic dysfunction (PSD) was found in 39 subjects. The sex ratio, age, anthropometric parameters, biochemical parameters and insulin resistance index, resting metabolic rate, and substrate oxidation rates did not differ in the subjects with or without PSD. The total 24-hour energy intake was similar, but the carbohydrate intake was significantly higher in the subjects with PSD (P = .006), and the fat and protein intakes were significantly lower (P = .026 and .045, respectively). In the logistic regression analyses, PSD correlated with carbohydrate and fat intake, independently of serum insulin levels. Glucose oxidation rate correlated negatively with fasting and postglucose serum insulin levels only in the subjects with PSD (P = .006 and .005, respectively). Cardiac parasympathetic dysfunction is associated with higher carbohydrate intake and lower fat and protein intakes in overweight subjects. A sympathetic override may contribute to reducing the glucose oxidation rate in subjects with PSD.

  1. Analyzing Systolic-Diastolic Interval Interaction Characteristics in Diabetic Cardiac Autonomic Neuropathy Progression

    PubMed Central

    Imam, Mohammad Hasan; Jelinek, Herbert F.; Palaniswami, Marimuthu; Khandoker, Ahsan H.

    2015-01-01

    Cardiac autonomic neuropathy (CAN), one of the major complications in diabetes, if detected at the subclinical stage allows for effective treatment and avoiding further complication including cardiovascular pathology. Surface ECG (Electrocardiogram)-based diagnosis of CAN is useful to overcome the limitation of existing cardiovascular autonomic reflex tests traditionally used for CAN identification in clinical settings. The aim of this paper is to analyze the changes in the mechanical function of the ventricles in terms of systolic-diastolic interval interaction (SDI) from a surface ECG to assess the severity of CAN progression [no CAN, early CAN (ECAN) or subclinical CAN, and definite CAN (DCAN) or clinical CAN]. ECG signals recorded in supine resting condition from 72 diabetic subjects without CAN (CAN-) and 70 diabetic subjects with CAN were analyzed in this paper. The severity of CAN was determined by Ewing’s Cardiovascular autonomic reflex tests. Fifty-five subjects of the CAN group had ECAN and 15 subjects had DCAN. In this paper, we propose an improved version of the SDI parameter (i.e., TQ/RR interval ratio) measured from the electrical diastolic interval (i.e., TQ interval) and the heart rate interval (i.e., RR interval). The performance of the proposed SDI measure was compared with the performance of the existing SDI measure (i.e., QT/TQ interval ratio). The proposed SDI parameter showed significant differences among three groups (no CAN, ECAN, and DCAN). In addition, the proposed SDI parameter was found to be more sensitive in detecting CAN progression than other ECG interval-based features traditionally used for CAN diagnosis. The modified SDI parameter might be used as an alternative measure for the Ewing autonomic reflex tests to identify CAN progression for those subjects who are unable to perform the traditional tests. These findings could also complement the echocardiographic findings of the left ventricular diastolic dysfunction by providing

  2. Analyzing Systolic-Diastolic Interval Interaction Characteristics in Diabetic Cardiac Autonomic Neuropathy Progression.

    PubMed

    Imam, Mohammad Hasan; Karmakar, Chandan K; Jelinek, Herbert F; Palaniswami, Marimuthu; Khandoker, Ahsan H

    2015-01-01

    Cardiac autonomic neuropathy (CAN), one of the major complications in diabetes, if detected at the subclinical stage allows for effective treatment and avoiding further complication including cardiovascular pathology. Surface ECG (Electrocardiogram)-based diagnosis of CAN is useful to overcome the limitation of existing cardiovascular autonomic reflex tests traditionally used for CAN identification in clinical settings. The aim of this paper is to analyze the changes in the mechanical function of the ventricles in terms of systolic-diastolic interval interaction (SDI) from a surface ECG to assess the severity of CAN progression [no CAN, early CAN (ECAN) or subclinical CAN, and definite CAN (DCAN) or clinical CAN]. ECG signals recorded in supine resting condition from 72 diabetic subjects without CAN (CAN-) and 70 diabetic subjects with CAN were analyzed in this paper. The severity of CAN was determined by Ewing's Cardiovascular autonomic reflex tests. Fifty-five subjects of the CAN group had ECAN and 15 subjects had DCAN. In this paper, we propose an improved version of the SDI parameter (i.e., TQ/RR interval ratio) measured from the electrical diastolic interval (i.e., TQ interval) and the heart rate interval (i.e., RR interval). The performance of the proposed SDI measure was compared with the performance of the existing SDI measure (i.e., QT/TQ interval ratio). The proposed SDI parameter showed significant differences among three groups (no CAN, ECAN, and DCAN). In addition, the proposed SDI parameter was found to be more sensitive in detecting CAN progression than other ECG interval-based features traditionally used for CAN diagnosis. The modified SDI parameter might be used as an alternative measure for the Ewing autonomic reflex tests to identify CAN progression for those subjects who are unable to perform the traditional tests. These findings could also complement the echocardiographic findings of the left ventricular diastolic dysfunction by providing

  3. Dysfunction of pre- and post-operative cardiac autonomic nervous system in elderly patients with diabetes mellitus.

    PubMed

    Zhang, Junlong; Tu, Weifeng; Dai, Jianqiang; Lv, Qing; Yang, Xiaoqi

    2011-01-01

    The pre- and post-operative cardiac autonomic nervous functions were compared in elderly, non-cardiac surgery patients with diabetes mellitus (DM) and without diabetes mellitus (NDM). A group of 30 unpremedicated elderly patients scheduled to undergo elective non-cardiac surgery were studied, including 15 DM patients and 15 NDM patients. Each component of heart rate variability (HRV) analysis in the frequency domain was monitored with Holter during the nights of the day before and on 1st and 2nd day after operation. After surgery, total power (TP), high frequency (HF), low frequency (LF) and very low frequency (VLF) significantly decreased as compared to the baseline values before operation in both groups (p<0.05). The LF/HF ratio was significantly changed in DM group but did not change in NDM group. On the 2nd postoperative day, TP, HF, LF and VLF in DM group were further decreased as compared to those on the 1st postoperative day and were significantly lower than those in NDM group (p<0.01 or 0.05), but these indices in NDM group did not show significant decreases. Surgery induced the cardiac autonomic nervous dysfunction in elderly patients not only with DM but also without diabetes. On the 2nd postoperative day, the disturbances of cardiac autonomic nervous activity were more sever in DM patients, compared to the 1st postoperative day, but was not significantly more sever than in the NDM patients.

  4. Gender differences in autonomic cardiovascular regulation: spectral, hormonal, and hemodynamic indexes

    NASA Technical Reports Server (NTRS)

    Evans, J. M.; Ziegler, M. G.; Patwardhan, A. R.; Ott, J. B.; Kim, C. S.; Leonelli, F. M.; Knapp, C. F.

    2001-01-01

    The autonomic nervous system drives variability in heart rate, vascular tone, cardiac ejection, and arterial pressure, but gender differences in autonomic regulation of the latter three parameters are not well documented. In addition to mean values, we used spectral analysis to calculate variability in arterial pressure, heart rate (R-R interval, RRI), stroke volume, and total peripheral resistance (TPR) and measured circulating levels of catecholamines and pancreatic polypeptide in two groups of 25 +/- 1.2-yr-old, healthy men and healthy follicular-phase women (40 total subjects, 10 men and 10 women per group). Group 1 subjects were studied supine, before and after beta- and muscarinic autonomic blockades, administered singly and together on separate days of study. Group 2 subjects were studied supine and drug free with the additional measurement of skin perfusion. In the unblocked state, we found that circulating levels of epinephrine and total spectral power of stroke volume, TPR, and skin perfusion ranged from two to six times greater in men than in women. The difference (men > women) in spectral power of TPR was maintained after beta- and muscarinic blockades, suggesting that the greater oscillations of vascular resistance in men may be alpha-adrenergically mediated. Men exhibited muscarinic buffering of mean TPR whereas women exhibited beta-adrenergic buffering of mean TPR as well as TPR and heart rate oscillations. Women had a greater distribution of RRI power in the breathing frequency range and a less negative slope of ln RRI power vs. ln frequency, both indicators that parasympathetic stimuli were the dominant influence on women's heart rate variability. The results of our study suggest a predominance of sympathetic vascular regulation in men compared with a dominant parasympathetic influence on heart rate regulation in women.

  5. Birth Weight and Its Relationship with the Cardiac Autonomic Balance in Healthy Children

    PubMed Central

    Souza, Livia Victorino; Oliveira, Vanessa; De Meneck, Franciele; Grotti Clemente, Ana Paula; Strufaldi, Maria Wany Louzada; Franco, Maria do Carmo

    2017-01-01

    Several studies indicate that the fetal environment plays a significant role in the development of cardiometabolic disease later in life. However, a few studies present conflicting data about the correlation between birth weight and the impairment of cardiac autonomic modulation. The purpose of the present study was to provide further knowledge to elucidate this contradictory relationship. One hundred children aged 5 and 14 years had anthropometric parameters, body composition and blood pressure levels determined. Heart rate variability (HRV) was evaluated by heart rate monitoring, including measurements of both the time and frequency domains. The results showed inverse correlation between the HRV parameters with BMI (RMSSD: P = 0.047; PNN50: P = 0.021; HF: P = 0.041), systolic (RMSSD: P = 0.023; PNN50: P = 0.032) and diastolic (PNN50: P = 0.030) blood pressure levels. On the other hand, there were consistent positive correlations between the HRV parameters and birth weight (RMSSD: P = 0.001; PNN50: P = 0.001; HF: P = 0.002). To determine the effect of birth weight on HRV parameters, we perform multivariate linear regression analysis adjusted for potentially confounding factors (prematurity, gender, age, BMI, physical activity index and SBP levels). These findings were preserved even after adjusting for these confounders. Our results suggested that impaired cardiac autonomic modulation characterized by a reduction in the parasympathetic activity occurs in children with low birth weight. One possible interpretation for these data is that a vagal withdrawal, rather than a sympathetic overactivity, could precede the development of hypertension and other cardiometabolic diseases in children with low birth weight. However, long-term studies should be performed to investigate this possibility. PMID:28095501

  6. Age-related decline in cardiac autonomic function is not attenuated with increased physical activity

    PubMed Central

    Njemanze, Hugo; Warren, Charlotte; Eggett, Christopher; MacGowan, Guy A.; Bates, Matthew G D; Siervo, Mario; Ivkovic, Srdjan; Trenell, Michael I.; Jakovljevic, Djordje G.

    2016-01-01

    Age and physical inactivity are important risk factors for cardiovascular mortality. Heart rate response to exercise (HRRE) and heart rate recovery (HRR), measures of cardiac autonomic function, are strong predictors of mortality. The present study defined the effect of age and physical activity on HRRE and HRR. Healthy women (N=72) grouped according to age (young, 20-30 years; middle, 40-50 years; and older, 65-81 years) and daily physical activity (low active <7500, high active >12,500 steps/day) performed a maximal cardiopulmonary exercise test. The HRRE was defined as an increase in heart rate from rest to 1, 3 and 5 minutes of exercise and at 1/3 of total exercise time, and HRR as the difference in heart rate between peak exercise and 1, 2, and 3 minutes later. Age was associated with a significant decline in HRRE at 1 min and 1/3 of exercise time (r= − 0.27, p=0.04, and r=−0.39, p=0.02) and HRR at 2 min and 3 min (r=−0.35, p=0.01, and r=−0.31, p=0.02). There was no significant difference in HRRE and HRR between high and low-active middle-age and older women (p>0.05). Increased level of habitual physical activity level appears to have a limited effect on age-related decline in cardiac autonomic function in women. PMID:27705949

  7. Cardiac autonomic responses during upper versus lower limb resistance exercise in healthy elderly men

    PubMed Central

    Machado-Vidotti, Heloisa G.; Mendes, Renata G.; Simões, Rodrigo P.; Castello-Simões, Viviane; Catai, Aparecida M.; Borghi-Silva, Audrey

    2014-01-01

    Objective To investigate the cardiac autonomic responses during upper versus lower limb discontinuous resistance exercise (RE) at different loads in healthy older men. Method Ten volunteers (65±1.2 years) underwent the one-repetition maximum (1RM) test to determine the maximum load for the bench press and the leg press. Discontinuous RE was initiated at a load of 10%1RM with subsequent increases of 10% until 30%1RM, followed by increases of 5%1RM until exhaustion. Heart rate (HR) and R-R interval were recorded at rest and for 4 minutes at each load applied. Heart rate variability (HRV) was analyzed in 5-min segments at rest and at each load in the most stable 2-min signal. Results Parasympathetic indices decreased significantly in both exercises from 30%1RM compared to rest (rMSSD: 20±2 to 11±3 and 29±5 to 12±2 ms; SD1: 15±2 to 8±1 and 23±4 to 7±1 ms, for upper and lower limb exercise respectively) and HR increased (69±4 to 90±4 bpm for upper and 66±2 to 89±1 bpm for lower). RMSM increased for upper limb exercise, but decreased for lower limb exercise (28±3 to 45±9 and 34±5 to 14±3 ms, respectively). In the frequency domain, the sympathetic (LF) and sympathovagal balance (LF/HF) indices were higher and the parasympathetic index (HF) was lower for upper limb exercise than for lower limb exercise from 35% of 1RM. Conclusions Cardiac autonomic change occurred from 30% of 1RM regardless of RE limb. However, there was more pronounced sympathetic increase and vagal decrease for upper limb exercise than for lower limb exercise. These results provide a basis for more effective prescription of RE to promote health in this population. PMID:24675908

  8. Effects of vigorous late-night exercise on sleep quality and cardiac autonomic activity.

    PubMed

    Myllymäki, Tero; Kyröläinen, Heikki; Savolainen, Katri; Hokka, Laura; Jakonen, Riikka; Juuti, Tanja; Martinmäki, Kaisu; Kaartinen, Jukka; Kinnunen, Marja-Liisa; Rusko, Heikki

    2011-03-01

    Sleep is the most important period for recovery from daily load. Regular physical activity enhances overall sleep quality, but the effects of acute exercise on sleep are not well defined. In sleep hygiene recommendations, intensive exercising is not suggested within the last 3 h before bed time, but this recommendation has not been adequately tested experimentally. Therefore, the effects of vigorous late-night exercise on sleep were examined by measuring polysomnographic, actigraphic and subjective sleep quality, as well as cardiac autonomic activity. Eleven (seven men, four women) physically fit young adults (VO(2max) 54±8 mL·kg(-1)·min(-1) , age 26±3 years) were monitored in a sleep laboratory twice in a counterbalanced order: (1) after vigorous late-night exercise; and (2) after a control day without exercise. The incremental cycle ergometer exercise until voluntary exhaustion started at 21:00±00:28 hours, lasted for 35±3 min, and ended 2:13±00:19 hours before bed time. The proportion of non-rapid eye movement sleep was greater after the exercise day than the control day (P<0.01), while no differences were seen in actigraphic or subjective sleep quality. During the whole sleep, no differences were found in heart rate (HR) variability, whereas HR was higher after the exercise day than the control day (54±7 versus 51±7, P<0.01), and especially during the first three sleeping hours. The results indicate that vigorous late-night exercise does not disturb sleep quality. However, it may have effects on cardiac autonomic control of heart during the first sleeping hours.

  9. Impaired Cardiac Autonomic Nervous System Function is Associated with Pediatric Hypertension Independent of Adiposity

    PubMed Central

    Ryder, Justin R.; O’Connell, Michael; Bosch, Tyler A.; Chow, Lisa; Rudser, Kyle D.; Dengel, Donald R.; Fox, Claudia K.; Steinberger, Julia; Kelly, Aaron S.

    2015-01-01

    Background We examined whether sympathetic nervous system activity influences hypertension status and systolic blood pressure (SBP) independent of adiposity in youth ranging from normal-weight to severe obesity. Methods We examined the association of heart rate variability (HRV) with hypertension status and SBP among youth (6-18 years old; n = 188; 103 female). Seated SBP was measured using an automated cuff. Pre-hypertension (SBP percentile≤90th-<95th) and hypertension (SBP percentile≤95th) were defined by age-, sex-, and height-norms. Autonomic nervous system activity was measured using HRV via SphygmoCorTM MM3 system and analyzed for time- and frequency-domains. Total body fat was measured via dual-energy X-ray absorptiometry. Results Logistic regression models demonstrated lower values in each time-domain HRV measure and larger LF:HF ratio to be significantly associated with higher odds of being pre-hypertensive/hypertensive (11-47% higher odds) independent of total body fat (p<0.05). In linear regression analysis, lower time-domain, but not frequency-domain, HRV measures were significantly associated with higher SBP independent of total body fat (p<0.05). Conclusion These data suggest that impaired cardiac autonomic nervous system function, at rest, is associated with higher odds of being pre-hypertensive/hypertensive and higher SBP which may be independent of adiposity in youth. PMID:26389821

  10. Cardiac autonomic responses to standing up and cognitive task in overtrained athletes.

    PubMed

    Hynynen, E; Uusitalo, A; Konttinen, N; Rusko, H

    2008-07-01

    This study compared the autonomic responses to an active orthostatic test and Stroop Color Word Test (Stroop) as well as cognitive performance in Stroop in twelve severely overtrained (OA, 6 men and 6 women) and twelve control athletes (CA, 6 men and 6 women). RR-intervals were recorded during the orthostatic test, the Stroop, and a relaxation period succeeding the Stroop. Low frequency power during standing in the orthostatic test was lower in OA than in CA (1322 +/- 955 ms2 vs. 2262 +/- 1029 ms2, p = 0.030, respectively). During Stroop, OA had higher relative total power (50 +/- 47 % vs. 19 +/- 14 % of the individual total power during supine rest after awakening, p = 0.028, respectively) and high frequency power (38.5 +/- 9.4 % vs. 13.5 +/- 2.3 % of the individual high frequency power during supine rest after awakening, p = 0.035, respectively) than CA. In the Stroop, OA made more mistakes than CA (9.7 +/- 6.5 % vs. 5.4 +/- 3.0 %, p = 0.045). The increase in absolute total power from the Stroop to relaxation correlated negatively with the amount of mistakes in the Stroop (r = - 0.588, p = 0.003). Thus, cardiac autonomic modulation during orthostatic task and responses to cognitive task and to relaxation, as well as the cognitive performance were attenuated in severe overtraining.

  11. Scintigraphic evidence for cardiac sympathetic dysinnervation in long-term IDDM patients with and without ECG-based autonomic neuropathy.

    PubMed

    Schnell, O; Kirsch, C M; Stemplinger, J; Haslbeck, M; Standl, E

    1995-11-01

    To analyse the presence and extent of global and regional distributions of cardiac sympathetic dysinnervation in long-term insulin-dependent diabetes mellitus (IDDM) without myocardial perfusion abnormalities (99mTc-methoxy isobutyl isonitrile study), 123I-metaiodobenzylguanidine (123I-MIBG) scintigraphy was performed in two clinically-comparable groups (20 diabetic patients with and 22 diabetic patients without ECG-based cardiac autonomic neuropathy). For comparison nine control subjects without heart disease were investigated. Only six diabetic patients (27%) without and one diabetic patient (5%) with ECG-based autonomic neuropathy were found to have a uniform homogeneous uptake of 123I-MIBG, in contrast to a uniform homogeneous uptake in all control subjects. The uptake of 123I-MIBG in the posterior myocardium of diabetic patients was smaller than in the anterior, lateral and septal myocardium (p < 0.001, p < 0.001, p = 0.001). In addition, diabetic patients with cardiac autonomic neuropathy (> or = two of five age-related cardiac reflex tests abnormal) demonstrated a more reduced uptake in the global, lateral and posterior myocardium than diabetic patients without (p < 0.01, p < 0.01, p < 0.001). A correlation between global or regional myocardial 123I-MIBG uptake, however, and duration of diabetes, HbA1c, body mass index or QT interval length was not observed. Our study demonstrates that cardiac sympathetic dysinnervation is common in long-term IDDM even in patients without ECG-based cardiac autonomic neuropathy and that the posterior myocardium is predominantly affected. We conclude that 123I-MIBG scintigraphy is a promising approach to further elucidate the pattern and natural history of myocardial dysinnervation in IDDM.

  12. Influence of hydrotherapy on clinical and cardiac autonomic function in migraine patients

    PubMed Central

    Sujan, M. U.; Rao, M. Raghavendra; Kisan, Ravikiran; Abhishekh, Hulegar A.; Nalini, Atchayaram; Raju, Trichur R.; Sathyaprabha, T. N.

    2016-01-01

    Background: Migraine is associated with autonomic symptoms. The growing body of literature suggests that the dysfunctional autonomic nervous system might play a pivotal role in the pathogenesis of migraine. Thermal therapies have been hypothesized to modulate these changes and alleviate pain. However, data regarding the efficacy of hydrotherapy in migraine remain scant. We evaluated the effect of add on hydrotherapy procedure (a hot arm and foot bath with ice massage to head) in migraine patients. Methods: Forty chronic migraine patients fulfilling the International Classification of Headache Disorders II criteria were recruited from the neurology outpatient clinic. Patients were randomized to receive either hydrotherapy plus conventional pharmacological care (n = 20) or conventional medication only (n = 20). Hydrotherapy group received treatment with hot arm and foot bath (103°F to 110°F) and ice massage to head daily for 20 min for 45 days. Patients were assessed using headache impact test (HIT), visual analog scale for pain and cardiac autonomic function by heart rate variability (HRV) before and after intervention period. Results: There was a significant decrease in HIT score, frequency, and intensity of headaches following treatment in both the groups. However, it was more evident in add on hydrotherapy group compared to pharmacological treatment alone group. There was also significant improvement in the HRV parameters. In particular, there was a significant decrease in heart rate (P = 0.017), increase in high frequency (HF) (P = 0.014) and decrease in low frequency/HF ratio (P = 0.004) in add on hydrotherapy group. Conclusion: Our study shows that add on hydrotherapy enhanced the vagal tone in addition to reducing the frequency and intensity of headaches in migraine patients. PMID:26933356

  13. Cardiac autonomic responses at onset of exercise: effects of aerobic fitness.

    PubMed

    D'Agosto, T; Peçanha, T; Bartels, R; Moreira, D N; Silva, L P; Nóbrega, A C L; Lima, J R P

    2014-09-01

    Analyzes of cardiac autonomic responses at the initial transient of exercise have been used for the investigation of the cardiovascular health. We evaluated the influence of aerobic fitness on HR and HRV responses at the onset of exercise. 25 male subjects (22.3±2.4 years) were divided into 2 groups: 'low aerobic fitness' (36.2±2.6ml.kg(-1).min(-1); n=10) and 'high aerobic fitness' (46.4±5.0ml.kg(-1).min(-1); n=15). The experimental session consisted of assessing the beat-to-beat HR at rest and during submaximal exercise. The autonomic responses at the onset of exercise were calculated by fitting the HR and HRV (rMSSD-index) curves during the initial 300s of exercise into a first-order exponential equation. The time constant of HR and of the rMSSD index (τonHR and τonrMSSD) were calculated for analysis. We observed lower values of τonrMSSD in the high aerobic fitness group compared to the low aerobic fitness group (26.8±5s vs. 38.0±18s, respectively; p=0.02). The τonHR (42.0±15 vs. 49.3±26s, p=0.38) for the groups showed no difference. Aerobic fitness partially influenced the autonomic responses during exercise, since individuals with higher fitness showed faster decreases in beat-to-beat HRV at the onset of exercise.

  14. Cardiac Autonomic Effects of Acute Exposures to Airborne Particulates in Men and Women

    NASA Technical Reports Server (NTRS)

    Howarth, M. S.; Schlegel, T. T.; Knapp, C. F.; Patwardhan, A. R.; Jenkins, R. A.; Ilgner, R. H.; Evans, J. M.

    2007-01-01

    The aim of this research was to investigate cardiac autonomic changes associated with acute exposures to airborne particulates. Methods: High fidelity 12-lead ECG (CardioSoft, Houston, TX) was acquired from 19 (10 male / 9 female) non-smoking volunteers (age 33.6 +/- 6.6 yrs) during 10 minutes pre-exposure, exposure and post-exposure to environmental tobacco smoke (ETS), cooking oil fumes, wood smoke and sham (water vapor). To control exposure levels, noise, subject activity, and temperature, all studies were conducted inside an environmental chamber. Results: The short-term fractal scaling exponent (Alpha-1) and the ratio of low frequency to high frequency Heart Rate Variability (HRV) powers (LF/HF, a purported sympathetic index) were both higher in males (p<0.017 and p<0.05, respectively) whereas approximate entropy (ApEn) and HF/(LF+HF) (a purported parasympathetic index) were both lower in males (p<0.036, and p<0.044, respectively). Compared to pre-exposure (p<0.0002) and sham exposure (p<0.047), male heart rates were elevated during early ETS post-exposure. Our data suggest that, in addition to tonic HRV gender differences, cardiac responses to some acute airborne particulates are gender related.

  15. Effect of Weight Gain on Cardiac Autonomic Control During Wakefulness and Sleep

    PubMed Central

    Adachi, Taro; Sert-Kuniyoshi, Fatima H.; Calvin, Andrew D.; Singh, Prachi; Romero-Corral, Abel; van der Walt, Christelle; Davison, Diane E.; Bukartyk, Jan; Konecny, Tomas; Pusalavidyasagar, Snigdha; Sierra-Johnson, Justo; Somers, Virend K.

    2012-01-01

    Obesity has been associated with increased cardiac sympathetic activation during wakefulness, but the effect on sleep-related sympathetic modulation is not known. The aim of this study was to investigate the effect of fat gain on cardiac autonomic control during wakefulness and sleep in humans. We performed a randomized controlled study to assess the effects of fat gain on heart rate variability (HRV). We recruited 36 healthy volunteers, who were randomized to either a standardized diet to gain approximately 4 kg over 8 weeks followed by an 8 week weight loss period (n=20), or to serve as a weight-maintainer control (n=16). An overnight polysomnogram with power spectral analysis of HRV was performed at baseline, after weight gain, and after weight loss to determine the ratio of low frequency (LF) to high frequency (HF) power, and to examine the relationship between changes in HRV and changes in insulin, leptin and adiponectin levels. Mean weight gain was 3.9 kg in the fat gain group versus 0.1 kg in the maintainer group. LF/HF increased both during wakefulness and sleep after fat gain and returned to baseline after fat loss in the fat gain group, and did not change in the control group. Insulin, leptin and adiponectin also increased after fat gain and fell after fat loss, but no clear pattern of changes were seen that correlated consistently with changes in HRV. Short-term fat gain in healthy subjects is associated with increased cardiac sympathetic activation during wakefulness and sleep but the mechanisms remain unclear. PMID:21357280

  16. Validation of a questionnaire measuring the regulation of autonomic function

    PubMed Central

    Kröz, M; Feder, G; von Laue, HB; Zerm, R; Reif, M; Girke, M; Matthes, H; Gutenbrunner, C; Heckmann, C

    2008-01-01

    Background To broaden the range of outcomes that we can measure for patients undergoing treatment for oncological and other chronic conditions, we aimed to validate a questionnaire measuring self-reported autonomic regulation (aR), i.e. to characterise a subject's autonomic functioning by questions on sleeping and waking, vertigo, morningness-eveningness, thermoregulation, perspiration, bowel movements and digestion. Methods We administered the questionnaire to 440 participants (♀: N = 316, ♂: N = 124): 95 patients with breast cancer, 49 with colorectal cancer, 60 with diabetes mellitus, 39 with coronary heart disease, 28 with rheumatological conditions, 32 with Hashimoto's disease, 22 with multiple morbidities and 115 healthy people. We administered the questionnaire a second time to 50.2% of the participants. External convergence criteria included the German version of the Hospital Anxiety and Depression Scale (HADS-D), a short questionnaire on morningness-eveningness, the Herdecke Quality of Life Questionnaire (HLQ) and a short version questionnaire on self-regulation. Results A principal component analysis yielded a three dimensional 18-item inventory of aR. The subscales orthostatic-circulatory, rest/activity and digestive regulation had internal consistency (Cronbach-α: rα = 0.65 – 0.75) and test-retest reliability (rrt = 0.70 – 85). AR was negatively associated with anxiety, depression, and dysmenorrhoea but positively correlated to HLQ, self-regulation and in part to morningness (except digestive aR) (0.49 – 0.13, all p < 0.05). Conclusion An internal validation of the long-version scale of aR yielded consistent relationships with health versus illness, quality of life and personality. Further studies are required to clarify the issues of external validity, clinical and physiological relevance. PMID:18533043

  17. Nine months in space: effects on human autonomic cardiovascular regulation.

    PubMed

    Cooke, W H; Ames JE, I V; Crossman, A A; Cox, J F; Kuusela, T A; Tahvanainen, K U; Moon, L B; Drescher, J; Baisch, F J; Mano, T; Levine, B D; Blomqvist, C G; Eckberg, D L

    2000-09-01

    We studied three Russian cosmonauts to better understand how long-term exposure to microgravity affects autonomic cardiovascular control. We recorded the electrocardiogram, finger photoplethysmographic pressure, and respiratory flow before, during, and after two 9-mo missions to the Russian space station Mir. Measurements were made during four modes of breathing: 1) uncontrolled spontaneous breathing; 2) stepwise breathing at six different frequencies; 3) fixed-frequency breathing; and 4) random-frequency breathing. R wave-to-R wave (R-R) interval standard deviations decreased in all and respiratory frequency R-R interval spectral power decreased in two cosmonauts in space. Two weeks after the cosmonauts returned to Earth, R-R interval spectral power was decreased, and systolic pressure spectral power was increased in all. The transfer function between systolic pressures and R-R intervals was reduced in-flight, was reduced further the day after landing, and had not returned to preflight levels by 14 days after landing. Our results suggest that long-duration spaceflight reduces vagal-cardiac nerve traffic and decreases vagal baroreflex gain and that these changes may persist as long as 2 wk after return to Earth.

  18. Acute toxicant exposure and cardiac autonomic dysfunction from smoking a single narghile waterpipe with tobacco and with a “healthy” tobacco-free alternative

    PubMed Central

    Cobb, Caroline O.; Sahmarani, Kamar; Eissenberg, Thomas; Shihadeh, Alan

    2012-01-01

    Tobacco smoking using a waterpipe (narghile, hookah, shisha) has become a global epidemic. Unlike cigarette smoking, little is known about the health effects of waterpipe use. One acute effect of cigarette smoke inhalation is dysfunction in autonomic regulation of the cardiac cycle, as indicated by reduction in heart rate variability (HRV). Reduced HRV is implicated in adverse cardiovascular health outcomes, and is associated with inhalation exposure-induced oxidative stress. Using a 32 participant cross-over study design, we investigated toxicant exposure and effects of waterpipe smoking on heart rate variability when, under controlled conditions, participants smoked a tobacco-based and a tobacco-free waterpipe product promoted as an alternative for “health-conscious” users. Outcome measures included HRV, exhaled breath carbon monoxide (CO), plasma nicotine, and puff topography, which were measured at times prior to, during, and after smoking. We found that waterpipe use acutely decreased HRV (p<0.01 for all measures), independent of product smoked. Plasma nicotine, blood pressure, and heart rate increased only with the tobacco-based product (p<0.01), while CO increased with both products (p<0.01). More smoke was inhaled during tobacco-free product use, potentially reflecting attempted regulation of nicotine intake. The data thus indicate that waterpipe smoking acutely compromises cardiac autonomic function, and does so through exposure to smoke constituents other than nicotine. PMID:23059956

  19. Cardiac Dysautonomia in Huntington's Disease.

    PubMed

    Abildtrup, Mads; Shattock, Michael

    2013-01-01

    Huntington's disease is a fatal, hereditary, neurodegenerative disorder best known for its clinical triad of progressive motor impairment, cognitive deficits and psychiatric disturbances. Although a disease of the central nervous system, mortality surveys indicate that heart disease is a leading cause of death. The nature of such cardiac abnormalities remains unknown. Clinical findings indicate a high prevalence of autonomic nervous system dysfunction - dysautonomia - which may be a result of pathology of the central autonomic network. Dysautonomia can have profound effects on cardiac health, and pronounced autonomic dysfunction can be associated with neurogenic arrhythmias and sudden cardiac death. Significant advances in the knowledge of neural mechanisms in cardiac disease have recently been made which further aid our understanding of cardiac mortality in Huntington's disease. Even so, despite the evidence of aberrant autonomic activity the potential cardiac consequences of autonomic dysfunction have been somewhat ignored. In fact, underlying cardiac abnormalities such as arrhythmias have been part of the exclusion criteria in clinical autonomic Huntington's disease research. A comprehensive analysis of cardiac function in Huntington's disease patients is warranted. Further experimental and clinical studies are needed to clarify how the autonomic nervous system is controlled and regulated in higher, central areas of the brain - and how these regions may be altered in neurological pathology, such as Huntington's disease. Ultimately, research will hopefully result in an improvement of management with the aim of preventing early death in Huntington's disease from cardiac causes.

  20. Regulation of cardiac microRNAs by serum response factor.

    PubMed

    Zhang, Xiaomin; Azhar, Gohar; Helms, Scott A; Wei, Jeanne Y

    2011-02-08

    Serum response factor (SRF) regulates certain microRNAs that play a role in cardiac and skeletal muscle development. However, the role of SRF in the regulation of microRNA expression and microRNA biogenesis in cardiac hypertrophy has not been well established. In this report, we employed two distinct transgenic mouse models to study the impact of SRF on cardiac microRNA expression and microRNA biogenesis. Cardiac-specific overexpression of SRF (SRF-Tg) led to altered expression of a number of microRNAs. Interestingly, downregulation of miR-1, miR-133a and upregulation of miR-21 occurred by 7 days of age in these mice, long before the onset of cardiac hypertrophy, suggesting that SRF overexpression impacted the expression of microRNAs which contribute to cardiac hypertrophy. Reducing cardiac SRF level using the antisense-SRF transgenic approach (Anti-SRF-Tg) resulted in the expression of miR-1, miR-133a and miR-21 in the opposite direction. Furthermore, we observed that SRF regulates microRNA biogenesis, specifically the transcription of pri-microRNA, thereby affecting the mature microRNA level. The mir-21 promoter sequence is conserved among mouse, rat and human; one SRF binding site was found to be in the mir-21 proximal promoter region of all three species. The mir-21 gene is regulated by SRF and its cofactors, including myocardin and p49/Strap. Our study demonstrates that the downregulation of miR-1, miR-133a, and upregulation of miR-21 can be reversed by one single upstream regulator, SRF. These results may help to develop novel therapeutic interventions targeting microRNA biogenesis.

  1. From syncitium to regulated pump: a cardiac muscle cellular update

    PubMed Central

    2011-01-01

    The primary purpose of this article is to present a basic overview of some key teaching concepts that should be considered for inclusion in an six- to eight-lecture introductory block on the regulation of cardiac performance for graduate students. Within the context of cardiac excitation-contraction coupling, this review incorporates information on Ca2+ microdomains and local control theory, with particular emphasis on the role of Ca2+ sparks as a key regulatory component of ventricular myocyte contraction dynamics. Recent information pertaining to local Ca2+ cycling in sinoatrial nodal cells (SANCs) as a mechanism underlying cardiac automaticity is also presented as part of the recently described coupled-clock pacemaker system. The details of this regulation are emerging; however, the notion that the sequestration and release of Ca2+ from internal stores in SANCs (similar to that observed in ventricular myocytes) regulates the rhythmic excitation of the heart (i.e., membrane ion channels) is an important advancement in this area. The regulatory role of cardiac adrenergic receptors on cardiac rate and function is also included, and fundamental concepts related to intracellular signaling are discussed. An important point of emphasis is that whole organ cardiac dynamics can be traced back to cellular events regulating intracellular Ca2+ homeostasis and, as such, provides an important conceptual framework from which students can begin to think about whole organ physiology in health and disease. Greater synchrony of Ca2+-regulatory mechanisms between ventricular and pacemaker cells should enhance student comprehension of complex regulatory phenomenon in cardiac muscle. PMID:21385997

  2. RSK3 – A Regulator of Pathological Cardiac Remodeling

    PubMed Central

    Martinez, Eliana C.; Passariello, Catherine L.; Li, Jinliang; Matheson, Christopher J.; Dodge-Kafka, Kimberly; Reigan, Philip; Kapiloff, Michael S.

    2015-01-01

    Summary The family of p90 ribosomal S6 kinases (RSK) are pleiotropic effectors for extracellular signal-regulated kinase (ERK) signaling pathways. Recently, RSK3 was shown to be important for pathological remodeling of the heart. While cardiac myocyte hypertrophy can be compensatory for increased wall stress, in chronic heart diseases this non-mitotic cell growth is usually associated with interstitial fibrosis, increased cell death, and decreased cardiac function. Although RSK3 is less abundant in the cardiac myocyte than other RSK family members, RSK3 appears to serve a unique role in cardiac myocyte stress responses. A potential mechanism conferring RSK3’s unique function in the heart is anchoring by the scaffold protein muscle A-kinase Anchoring Protein β (mAKAPβ). Recent findings suggest that RSK3 should be considered as a therapeutic target for the prevention of heart failure, a clinical syndrome of major public health significance. PMID:25988524

  3. Cardiac Organ Damage and Arterial Stiffness in Autonomic Failure: Comparison With Essential Hypertension.

    PubMed

    Milazzo, Valeria; Maule, Simona; Di Stefano, Cristina; Tosello, Francesco; Totaro, Silvia; Veglio, Franco; Milan, Alberto

    2015-12-01

    Autonomic failure (AF) is characterized by orthostatic hypotension, supine hypertension, and increased blood pressure (BP) variability. AF patients develop cardiac organ damage, similarly to essential hypertension (EH), and have higher arterial stiffness than healthy controls. Determinants of cardiovascular organ damage in AF are not well known: both BP variability and mean BP values may be involved. The aim of the study was to evaluate cardiac organ damage, arterial stiffness, and central hemodynamics in AF, compared with EH subjects with similar 24-hour BP and a group of healthy controls, and to evaluate determinants of target organ damage in patients with AF. Twenty-seven patients with primary AF were studied (mean age, 65.7±11.2 years) using transthoracic echocardiography, carotid-femoral pulse wave velocity, central hemodynamics, and 24-hour ambulatory BP monitoring. They were compared with 27 EH subjects matched for age, sex, and 24-hour mean BP and with 27 healthy controls. AF and EH had similar left ventricular mass (101.6±33.3 versus 97.7±28.1 g/m(2), P=0.59) and carotid-femoral pulse wave velocity (9.3±1.8 versus 9.2±3.0 m/s, P=0.93); both parameters were significantly lower in healthy controls (P<0.01). Compared with EH, AF patients had higher augmentation index (31.0±7.6% versus 26.1±9.2%, P=0.04) and central BP values. Nighttime systolic BP and 24-hour systolic BP predicted organ damage, independent of BP variability. AF patients develop hypertensive heart disease and increased arterial stiffness, similar to EH with comparable mean BP values. Twenty-four-hour and nighttime systolic BP were determinants of cardiovascular damage, independent of BP variability.

  4. Mechanisms regulating cardiac fuel selection in hyperthyroidism.

    PubMed Central

    Sugden, M C; Holness, M J; Liu, Y L; Smith, D M; Fryer, L G; Kruszynska, Y T

    1992-01-01

    Starvation (48 h) decreases fructose 2,6-bisphosphate (Fru-2,6-P2) concentrations and the ratio of free to acylated carnitine in hearts of euthyroid rats. These decreases, which are indicative of increased lipid fuel oxidation, are accompanied by decreased rates of glucose uptake and phosphorylation, assessed by using radioactive 2-deoxyglucose. Cardiac concentrations of acylated carnitines were increased at the expense of free carnitine even in the fed state in response to experimental hyperthyroidism, but neither Fru-2,6-P2 concentrations nor rates of glucose utilization were suppressed. Starvation (48 h) did not further increase the proportion of acylated carnitine in the heart in hyperthyroidism, and suppression of Fru-2,6-P2 concentrations and glucose utilization rates by starvation was attenuated. Although glucose utilization rates were decreased, starvation did not decrease immunoreactive GLUT 4 protein concentrations. Furthermore, although hyperthyroidism was associated with a statistically significant (30-40%) increase in relative abundance of GLUT 4 mRNA, the amount of GLUT 4 protein was not increased by hyperthyroidism in either the fed or the starved state. The results demonstrate a significant effect of hyperthyroidism to enhance cardiac glucose utilization in starvation by a mechanism which does not involve changes in GLUT 4 expression but may be secondary to changes in glucose-lipid interactions at the tissue level. PMID:1530584

  5. Tyrosine kinase FYN negatively regulates NOX4 in cardiac remodeling

    PubMed Central

    Matsushima, Shouji; Kuroda, Junya; Zhai, Peiyong; Liu, Tong; Ikeda, Shohei; Nagarajan, Narayani; Yokota, Takashi; Kinugawa, Shintaro; Hsu, Chiao-Po; Li, Hong; Tsutsui, Hiroyuki

    2016-01-01

    NADPH oxidases (Noxes) produce ROS that regulate cell growth and death. NOX4 expression in cardiomyocytes (CMs) plays an important role in cardiac remodeling and injury, but the posttranslational mechanisms that modulate this enzyme are poorly understood. Here, we determined that FYN, a Src family tyrosine kinase, interacts with the C-terminal domain of NOX4. FYN and NOX4 colocalized in perinuclear mitochondria, ER, and nuclear fractions in CMs, and FYN expression negatively regulated NOX4-induced O2– production and apoptosis in CMs. Mechanistically, we found that direct phosphorylation of tyrosine 566 on NOX4 was critical for this FYN-mediated negative regulation. Transverse aortic constriction activated FYN in the left ventricle (LV), and FYN-deficient mice displayed exacerbated cardiac hypertrophy and dysfunction and increased ROS production and apoptosis. Deletion of Nox4 rescued the exaggerated LV remodeling in FYN-deficient mice. Furthermore, FYN expression was markedly decreased in failing human hearts, corroborating its role as a regulator of cardiac cell death and ROS production. In conclusion, FYN is activated by oxidative stress and serves as a negative feedback regulator of NOX4 in CMs during cardiac remodeling. PMID:27525436

  6. Sequential modulation of cardiac autonomic control induced by cardiopulmonary and arterial baroreflex mechanisms

    NASA Technical Reports Server (NTRS)

    Furlan, R.; Jacob, G.; Palazzolo, L.; Rimoldi, A.; Diedrich, A.; Harris, P. A.; Porta, A.; Malliani, A.; Mosqueda-Garcia, R.; Robertson, D.

    2001-01-01

    BACKGROUND: Nonhypotensive lower body negative pressure (LBNP) induces a reflex increase in forearm vascular resistance and muscle sympathetic neural discharge without affecting mean heart rate. We tested the hypothesis that a reflex change of the autonomic modulation of heartbeat might arise during low intensity LBNP without changes of mean heart rate. METHODS AND RESULTS: Ten healthy volunteers underwent plasma catecholamine evaluation and a continuous recording of ECG, finger blood pressure, respiratory activity, and central venous pressure (CVP) during increasing levels of LBNP up to -40 mm Hg. Spectrum and cross-spectrum analyses assessed the changes in the spontaneous variability of R-R interval, respiration, systolic arterial pressure (SAP), and CVP and in the gain (alpha(LF)) of arterial baroreflex control of heart rate. Baroreceptor sensitivity was also evaluated by the SAP/R-R spontaneous sequences technique. LBNP began decreasing significantly: CVP at -10, R-R interval at -20, SAP at -40, and the indexes alpha(LF) and baroreceptor sensitivity at -30 and -20 mm Hg, compared with baseline conditions. Plasma norepinephrine increased significantly at -20 mm Hg. The normalized low-frequency component of R-R variability (LF(R-R)) progressively increased and was significantly higher than in the control condition at -15 mm Hg. CONCLUSIONS: Nonhypotensive LBNP elicits a reflex increase of cardiac sympathetic modulation, as evaluated by LF(R-R), which precedes the changes in the hemodynamics and in the indexes of arterial baroreflex control.

  7. Cardiac Autonomic Alteration and Metabolic Syndrome: An Ambulatory ECG-based Study in A General Population

    PubMed Central

    Ma, Yan; Tseng, Ping-Huei; Ahn, Andrew; Wu, Ming-Shiang; Ho, Yi-Lwun; Chen, Ming-Fong; Peng, Chung-Kang

    2017-01-01

    Metabolic syndrome (MetS) has been associated with chronic damage to the cardiovascular system. This study aimed to evaluate early stage cardiac autonomic dysfunction with electrocardiography (ECG)-based measures in MetS subjects. During 2012–2013, 175 subjects with MetS and 226 healthy controls underwent ECG recordings of at least 4 hours starting in the morning with ambulatory one-lead ECG monitors. MetS was diagnosed using the criteria defined in the Adult Treatment Panel III, with a modification of waist circumference for Asians. Conventional heart rate variability (HRV) analysis, and complexity index (CI1–20) calculated from 20 scales of entropy (multiscale entropy, MSE), were compared between subjects with MetS and controls. Compared with the healthy controls, subjects with MetS had significantly reduced HRV, including SDNN and pNN20 in time domain, VLF, LF and HF in frequency domain, as well as SD2 in Poincaré analysis. MetS subjects have significantly lower complexity index (CI1–20) than healthy subjects (1.69 ± 0.18 vs. 1.77 ± 0.12, p < 0.001). MetS severity was inversely associated with the CI1–20 (r = −0.27, p < 0.001). MetS is associated with significant alterations in heart rate dynamics, including HRV and complexity. PMID:28290487

  8. Regulation of autonomic nervous system in space and magnetic storms

    NASA Astrophysics Data System (ADS)

    Baevsky, R. M.; Petrov, V. M.; Chernikova, A. G.

    Variations in the earth's magnetic field and magnetic storms are known to be a risk factor for the development of cardiovascular disorders. The main ``targets'' for geomagnetic perturbations are the central nervous system and the neural regulation of vascular tone and heart rate variability. This paper presents the data about effect of geomagnetic fluctuations on human body in space. As a method for research the analysis of heart rate variability was used, which allows evaluating the state of the sympathetic and parasympathetic parts of the autonomic nervous system, vasomotor center and subcortical neural centers activity. Heart rate variability data were analyzed for 30 cosmonauts at the 2-nd day of space flight on transport spaceship Soyuz (32nd orbit). There were formed three groups of cosmonauts: without magnetic storm (n=9), on a day with magnetic storm (n=12) and 1-2 days after magnetic storm (n=9). The present study was the first to demonstrate a specific impact of geomagnetic perturbations on the system of autonomic circulatory control in cosmonauts during space flight. The increasing of highest nervous centers activity was shown for group with magnetic storms, which was more significant on 1-2 days after magnetic storm. The use of discriminate analysis allowed to classify indicated three groups with 88 % precision. Canonical variables are suggested to be used as criterions for evaluation of specific and non-specific components of cardiovascular reactions to geomagnetic perturbations. The applied aspect of the findings from the present study should be emphasized. They show, in particular, the need to supplement the medical monitoring of cosmonauts with predictions of probable geomagnetic perturbations in view of the prevention of unfavorable states appearances if the adverse reactions to geomagnetic perturbations are added to the tension experienced by regulatory systems during various stresses situations (such as work in the open space).

  9. Systematic morphology and evolutionary anatomy of the autonomic cardiac nervous system in the lesser apes, gibbons (hylobatidae).

    PubMed

    Kawashima, Tomokazu; Thorington, Richard W; Kunimatsu, Yutaka; Whatton, James F

    2008-08-01

    We examined the morphology of the autonomic cardiac nervous system (ACNS) on 20 sides of 10 gibbons (Hylobatidae) of three genera, and we have inferred the evolution of the anatomy of the primate ACNS. We report the following. (1) Several trivial intraspecific and interspecific variations are present in gibbons, but the general arrangement of the ACNS in gibbons is consistent. (2) Although the parasympathetic vagal cardiac nervous system is extremely consistent, the sympathetic cardiac nervous system, such as the composition of the sympathetic ganglia and the range of origin of the sympathetic cardiac nerves, exhibit topographical differences among primates. (3) The vertebral ganglion, seldom observed in the Old World monkeys (Cercopithecidae), was consistently present in gibbons as well as in humans. (4) There are fewer thoracic ganglia contributing to the cervicothoracic ganglion in humans than in gibbons and in gibbons than in Old World monkeys. (5) The superior cardiac nerve originating from the superior cervical ganglion, rarely observed in Old World monkeys but commonly observed in humans, was present in 13 of 20 sides (65%), mostly on the left. Accordingly, the ACNS morphology exhibits evolutionary changes within the primate lineage. These evolutionary differences between Old World monkeys, gibbons, and humans are most parsimoniously interpreted as resulting from regular changes in the lineages leading from their common ancestor to the extant species that we dissected. They include the reduction in the number of thoracic ganglia contributing to the cervicothoracic ganglion and the expansion of the range of the cardiac nervous origin.

  10. Assesment of Heart Rate Variability As A Measure of Cardiac Autonomic Status in Psychiatric Patients Exposed to Chemical Irritants

    PubMed Central

    Gupta, Supriya; Rastogi, Rajesh; Gupta, Manushree

    2015-01-01

    Background and Purpose However, little is known about the cardiac autonomic activity due to chemicals in psychiatric patients. Therefore, the objective of this study was to assess the effect of chemical irritants on the ANS of the person and measure that in the form of Heart Rate Variability (HRV), a noninvasive method to estimate the cardiac autonomic activity. The autonomic nervous system can significantly compromised by use of chemical irritants. Materials and Methods A cross-sectional hospital based study was conducted in which 33 patients (mean age: 29.94 years) of depression/anxiety were compared with 37 age matched controls (mean age: 28.10). The patients who were diagnosed as either depressed or anxious by the psychiatry were included in the study group by random sampling. Out of these 8 patients gave positive history of odour use. Thirty seven age matched healthy persons were taken as controls. Grading of patients was done according to DSMV-IV criteria and short- term HRV was recorded. Five minute HRV recording was done and time domain and frequency domain indices of HRV were assessed using RMS Polyearite D. The result in case and control groups was compared. Results We have reported a poor HRV compared to control group in patients of depression/anxiety as reflected by NN50 values (p< 0.05). Although not significant the trend shows a better HRV control in almost all the time domain and frequency domain parameters in controls compared to cases. Regarding the history of use of chemical irritants the trend showed a poor HRV control in these cases compared to the patients who did not give any such history. Conclusion Our results suggest that impaired cardiac autonomic nerve function characterized by sympathetic over activity may occur in depression/phobic patients. The study also proves a poor HRV in psychiatric subjects with history of use of odoriferous substances. PMID:26266195

  11. Cardiomyocyte Circadian Oscillations Are Cell-Autonomous, Amplified by β-Adrenergic Signaling, and Synchronized in Cardiac Ventricle Tissue

    PubMed Central

    Welsh, David K.

    2016-01-01

    Circadian clocks impact vital cardiac parameters such as blood pressure and heart rate, and adverse cardiac events such as myocardial infarction and sudden cardiac death. In mammals, the central circadian pacemaker, located in the suprachiasmatic nucleus of the hypothalamus, synchronizes cellular circadian clocks in the heart and many other tissues throughout the body. Cardiac ventricle explants maintain autonomous contractions and robust circadian oscillations of clock gene expression in culture. In the present study, we examined the relationship between intrinsic myocardial function and circadian rhythms in cultures from mouse heart. We cultured ventricular explants or dispersed cardiomyocytes from neonatal mice expressing a PER2::LUC bioluminescent reporter of circadian clock gene expression. We found that isoproterenol, a β-adrenoceptor agonist known to increase heart rate and contractility, also amplifies PER2 circadian rhythms in ventricular explants. We found robust, cell-autonomous PER2 circadian rhythms in dispersed cardiomyocytes. Single-cell rhythms were initially synchronized in ventricular explants but desynchronized in dispersed cells. In addition, we developed a method for long-term, simultaneous monitoring of clock gene expression, contraction rate, and basal intracellular Ca2+ level in cardiomyocytes using PER2::LUC in combination with GCaMP3, a genetically encoded fluorescent Ca2+ reporter. In contrast to robust PER2 circadian rhythms in cardiomyocytes, we detected no rhythms in contraction rate and only weak rhythms in basal Ca2+ level. In summary, we found that PER2 circadian rhythms of cardiomyocytes are cell-autonomous, amplified by adrenergic signaling, and synchronized by intercellular communication in ventricle explants, but we detected no robust circadian rhythms in contraction rate or basal Ca2+. PMID:27459195

  12. Exercise Type Affects Cardiac Vagal Autonomic Recovery After a Resistance Training Session.

    PubMed

    Mayo, Xián; Iglesias-Soler, Eliseo; Fariñas-Rodríguez, Juán; Fernández-Del-Olmo, Miguel; Kingsley, J Derek

    2016-09-01

    Mayo, X, Iglesias-Soler, E, Fariñas-Rodríguez, J, Fernández-del-Olmo, M, and Kingsley, JD. Exercise type affects cardiac vagal autonomic recovery after a resistance training session. J Strength Cond Res 30(9): 2565-2573, 2016-Resistance training sessions involving different exercises and set configurations may affect the acute cardiovascular recovery pattern. We explored the interaction between exercise type and set configuration on the postexercise cardiovagal withdrawal measured by heart rate variability and their hypotensive effect. Thirteen healthy participants (10 repetitions maximum [RM] bench press: 56 ± 10 kg; parallel squat: 91 ± 13 kg) performed 6 sessions corresponding to 2 exercises (Bench press vs. Parallel squat), 2 set configurations (Failure session vs. Interrepetition rest session), and a Control session of each exercise. Load (10RM), volume (5 sets), and rest (720 seconds) were equated between exercises and set configurations. Parallel squat produced higher reductions in cardiovagal recovery vs. Bench press (p = 0.001). These differences were dependent on the set configuration, with lower values in Parallel squat vs. Bench press for Interrepetition rest session (1.816 ± 0.711 vs. 2.399 ± 0.739 Ln HF/IRR × 10, p = 0.002), but not for Failure session (1.647 ± 0.904 vs. 1.808 ± 0.703 Ln HF/IRR × 10, p > 0.05). Set configuration affected the cardiovagal recovery, with lower values in Failure session in comparison with Interrepetition rest (p = 0.027) and Control session (p = 0.022). Postexercise hypotension was not dependent on the exercise type (p > 0.05) but was dependent on the set configuration, with lower values of systolic (p = 0.004) and diastolic (p = 0.011) blood pressure after the Failure session but not after an Interrepetition rest session in comparison with the Control session (p > 0.05). These results suggest that the exercise type and an Interrepetition rest design could blunt the decrease of cardiac vagal activity after

  13. Cardiac Fibroblasts Regulate Sympathetic Nerve Sprouting and Neurocardiac Synapse Stability

    PubMed Central

    Mias, Céline; Coatrieux, Christelle; Denis, Colette; Genet, Gaël; Seguelas, Marie-Hélène; Laplace, Nathalie; Rouzaud-Laborde, Charlotte; Calise, Denis; Parini, Angelo; Cussac, Daniel; Pathak, Atul; Sénard, Jean-Michel; Galés, Céline

    2013-01-01

    Sympathetic nervous system (SNS) plays a key role in cardiac homeostasis and its deregulations always associate with bad clinical outcomes. To date, little is known about molecular mechanisms regulating cardiac sympathetic innervation. The aim of the study was to determine the role of fibroblasts in heart sympathetic innervation. RT-qPCR and western-blots analysis performed in cardiomyocytes and fibroblasts isolated from healthy adult rat hearts revealed that Pro-Nerve growth factor (NGF) and pro-differentiating mature NGF were the most abundant neurotrophins expressed in cardiac fibroblasts while barely detectable in cardiomyocytes. When cultured with cardiac fibroblasts or fibroblast-conditioned medium, PC12 cells differentiated into/sympathetic-like neurons expressing axonal marker Tau-1 at neurites in contact with cardiomyocytes. This was prevented by anti-NGF blocking antibodies suggesting a paracrine action of NGF secreted by fibroblasts. When co-cultured with cardiomyocytes to mimic neurocardiac synapse, differentiated PC12 cells exhibited enhanced norepinephrine secretion as quantified by HPLC compared to PC12 cultured alone while co-culture with fibroblasts had no effect. However, when supplemented to PC12-cardiomyocytes co-culture, fibroblasts allowed long-term survival of the neurocardiac synapse. Activated fibroblasts (myofibroblasts) isolated from myocardial infarction rat hearts exhibited significantly higher mature NGF expression than normal fibroblasts and also promoted PC12 cells differentiation. Within the ischemic area lacking cardiomyocytes and neurocardiac synapses, tyrosine hydroxylase immunoreactivity was increased and associated with local anarchical and immature sympathetic hyperinnervation but tissue norepinephrine content was similar to that of normal cardiac tissue, suggesting depressed sympathetic function. Collectively, these findings demonstrate for the first time that fibroblasts are essential for the setting of cardiac sympathetic

  14. Prolonged QT period in diabetic autonomic neuropathy: a possible role in sudden cardiac death?

    PubMed Central

    Bellavere, F; Ferri, M; Guarini, L; Bax, G; Piccoli, A; Cardone, C; Fedele, D

    1988-01-01

    Twenty four men with insulin dependent diabetes and different degrees of autonomic neuropathy were studied to establish the response of the QT interval to various heart rates. Nine men with autonomic neuropathy had a longer QT interval than 13 healthy individuals and 15 patients who had diabetes without, or with only mild, autonomic neuropathy. Those with autonomic neuropathy also had a proportionally greater lengthening of the QT interval for a given increase in RR interval. The results of this study suggest a basis for the finding that sudden death is more common in patients with diabetic autonomic neuropathy. PMID:3355728

  15. Mammalian enabled (Mena) is a critical regulator of cardiac function.

    PubMed

    Aguilar, Frédérick; Belmonte, Stephen L; Ram, Rashmi; Noujaim, Sami F; Dunaevsky, Olga; Protack, Tricia L; Jalife, Jose; Todd Massey, H; Gertler, Frank B; Blaxall, Burns C

    2011-05-01

    Mammalian enabled (Mena) of the Drosophila enabled/vasodilator-stimulated phosphoprotein gene family is a cytoskeletal protein implicated in actin regulation and cell motility. Cardiac Mena expression is enriched in intercalated discs (ICD), the critical intercellular communication nexus between adjacent muscle cells. We previously identified Mena gene expression to be a key predictor of human and murine heart failure (HF). To determine the in vivo function of Mena in the heart, we assessed Mena protein expression in multiple HF models and characterized the effects of genetic Mena deletion on cardiac structure and function. Immunoblot analysis revealed significant upregulation of Mena protein expression in left ventricle tissue from patients with end-stage HF, calsequestrin-overexpressing mice, and isoproterenol-infused mice. Characterization of the baseline cardiac function of adult Mena knockout mice (Mena(-/-)) via echocardiography demonstrated persistent cardiac dysfunction, including a significant reduction in percent fractional shortening compared with wild-type littermates. Electrocardiogram PR and QRS intervals were significantly prolonged in Mena(-/-) mice, manifested by slowed conduction on optical mapping studies. Ultrastructural analysis of Mena(-/-) hearts revealed disrupted organization and widening of ICD structures, mislocalization of the gap junction protein connexin 43 (Cx43) to the lateral borders of cardiomyoycytes, and increased Cx43 expression. Furthermore, the expression of vinculin (an adherens junction protein) was significantly reduced in Mena(-/-) mice. We report for the first time that genetic ablation of Mena results in cardiac dysfunction, highlighted by diminished contractile performance, disrupted ICD structure, and slowed electrical conduction.

  16. The autonomic nervous system regulates postprandial hepatic lipid metabolism.

    PubMed

    Bruinstroop, Eveline; la Fleur, Susanne E; Ackermans, Mariette T; Foppen, Ewout; Wortel, Joke; Kooijman, Sander; Berbée, Jimmy F P; Rensen, Patrick C N; Fliers, Eric; Kalsbeek, Andries

    2013-05-15

    The liver is a key organ in controlling glucose and lipid metabolism during feeding and fasting. In addition to hormones and nutrients, inputs from the autonomic nervous system are also involved in fine-tuning hepatic metabolic regulation. Previously, we have shown in rats that during fasting an intact sympathetic innervation of the liver is essential to maintain the secretion of triglycerides by the liver. In the current study, we hypothesized that in the postprandial condition the parasympathetic input to the liver inhibits hepatic VLDL-TG secretion. To test our hypothesis, we determined the effect of selective surgical hepatic denervations on triglyceride metabolism after a meal in male Wistar rats. We report that postprandial plasma triglyceride concentrations were significantly elevated in parasympathetically denervated rats compared with control rats (P = 0.008), and VLDL-TG production tended to be increased (P = 0.066). Sympathetically denervated rats also showed a small rise in postprandial triglyceride concentrations (P = 0.045). On the other hand, in rats fed on a six-meals-a-day schedule for several weeks, a parasympathetic denervation resulted in >70% higher plasma triglycerides during the day (P = 0.001), whereas a sympathetic denervation had no effect. Our results show that abolishing the parasympathetic input to the liver results in increased plasma triglyceride levels during postprandial conditions.

  17. Neuralized functions cell autonomously to regulate Drosophila sense organ development.

    PubMed

    Yeh, E; Zhou, L; Rudzik, N; Boulianne, G L

    2000-09-01

    Neurogenic genes, including Notch and Delta, are thought to play important roles in regulating cell-cell interactions required for Drosophila sense organ development. To define the requirement of the neurogenic gene neuralized (neu) in this process, two independent neu alleles were used to generate mutant clones. We find that neu is required for determination of cell fates within the proneural cluster and that cells mutant for neu autonomously adopt neural fates when adjacent to wild-type cells. Furthermore, neu is required within the sense organ lineage to determine the fates of daughter cells and accessory cells. To gain insight into the mechanism by which neu functions, we used the GAL4/UAS system to express wild-type and epitope-tagged neu constructs. We show that Neu protein is localized primarily at the plasma membrane. We propose that the function of neu in sense organ development is to affect the ability of cells to receive Notch-Delta signals and thus modulate neurogenic activity that allows for the specification of non-neuronal cell fates in the sense organ.

  18. Sleep variability and cardiac autonomic modulation in adolescents – Penn State Child Cohort (PSCC) study

    PubMed Central

    Rodríguez-Colón, Sol M.; He, Fan; Bixler, Edward O.; Fernandez-Mendoza, Julio; Vgontzas, Alexandros N.; Calhoun, Susan; Zheng, Zhi-Jie; Liao, Duanping

    2015-01-01

    Objective To investigate the effects of objectively measured habitual sleep patterns on cardiac autonomic modulation (CAM) in a population-based sample of adolescents. Methods We used data from 421 adolescents who completed the follow-up examination in the Penn State Children Cohort study. CAM was assessed by heart rate (HR) variability (HRV) analysis of beat-to-beat normal R-R intervals from a 39-h electrocardiogram, on a 30-min basis. The HRV indices included frequency domain (HF, LF, and LF/HF ratio), and time domain (SDNN, RMSSD, and heart rate or HR) variables. Actigraphy was used for seven consecutive nights to estimate nightly sleep duration and time in bed. The seven-night mean (SD) of sleep duration and sleep efficiency were used to represent sleep duration, duration variability, sleep efficiency, and efficiency variability, respectively. HF and LF were log-transformed for statistical analysis. Linear mixed-effect models were used to analyze the association between sleep patterns and CAM. Results After adjusting for major confounders, increased sleep duration variability and efficiency variability were significantly associated with lower HRV and higher HR during the 39-h, as well as separated by daytime and nighttime. For instance, a 1-h increase in sleep duration variability is associated with −0.14(0.04), −0.12(0.06), and −0.16(0.05) ms2 decrease in total, daytime, and nighttime HF, respectively. No associations were found between sleep duration, or sleep efficiency and HRV. Conclusion Higher habitual sleep duration variability and efficiency variability are associated with lower HRV and higher HR, suggesting that an irregular sleep pattern has an adverse impact on CAM, even in healthy adolescents. PMID:25555635

  19. Role of the autonomic nervous system in the reduced maximal cardiac output at altitude.

    PubMed

    Bogaard, Harm J; Hopkins, Susan R; Yamaya, Yoshiki; Niizeki, Kyuichi; Ziegler, Michael G; Wagner, Peter D

    2002-07-01

    After acclimatization to high altitude, maximal exercise cardiac output (QT) is reduced. Possible contributing factors include 1) blood volume depletion, 2) increased blood viscosity, 3) myocardial hypoxia, 4) altered autonomic nervous system (ANS) function affecting maximal heart rate (HR), and 5) reduced flow demand from reduced muscle work capability. We tested the role of the ANS reduction of HR in this phenomenon in five normal subjects by separately blocking the sympathetic and parasympathetic arms of the ANS during maximal exercise after 2-wk acclimatization at 3,800 m to alter maximal HR. We used intravenous doses of 8.0 mg of propranolol and 0.8 mg of glycopyrrolate, respectively. At altitude, peak HR was 170 +/- 6 beats/min, reduced from 186 +/- 3 beats/min (P = 0.012) at sea level. Propranolol further reduced peak HR to 139 +/- 2 beats/min (P = 0.001), whereas glycopyrrolate increased peak HR to sea level values, 184 +/- 3 beats/min, confirming adequate dosing with each drug. In contrast, peak O(2) consumption, work rate, and QT were similar at altitude under all drug treatments [peak QT = 16.2 +/- 1.2 (control), 15.5 +/- 1.3 (propranolol), and 16.2 +/- 1.1 l/min (glycopyrrolate)]. All QT results at altitude were lower than those at sea level (20.0 +/- 1.8 l/min in air). Therefore, this study suggests that, whereas the ANS may affect HR at altitude, peak QT is unaffected by ANS blockade. We conclude that the effect of altered ANS function on HR is not the cause of the reduced maximal QT at altitude.

  20. Cardiac autonomic response following high-intensity running work-to-rest interval manipulation.

    PubMed

    Cipryan, Lukas; Laursen, Paul B; Plews, Daniel J

    2016-10-01

    The cardiorespiratory, cardiac autonomic (via heart rate variability (HRV)) and plasma volume responses to varying sequences of high-intensity interval training (HIT) of consistent external work were investigated. Twelve moderately trained males underwent three HIT bouts and one control session. The HIT trials consisted of warm-up, followed by 12 min of 15 s, 30 s or 60 s work:relief HIT sequences at an exercise intensity of 100% of the individual velocity at [Formula: see text]O2max (v[Formula: see text]O2max), interspersed by relief intervals at 60% [Formula: see text]O2max (work/relief ratio = 1). HRV was evaluated via the square root of the mean sum of the squared differences between R-R intervals (rMSSD) before, 1 h, 3 h and 24 h after the exercise. Plasma volume was assessed before, immediately after, and 3 h and 24 h after. There were no substantial between-trial differences in acute cardiorespiratory responses. The rMSSD values remained decreased 1 h after the exercise cessation in all exercise groups. The rMSSD subsequently increased between 1 h and 3 h after exercise, with the most pronounced change in the 15/15 group. There were no relationships between HRV and plasma volume. All HIT protocols resulted in similar cardiorespiratory responses with slightly varying post-exercise HRV responses, with the 30/30 protocol eliciting the least disruption to post-exercise HRV. These post-exercise HRV findings suggest that the 30/30 sequence may be the preferable HIT prescription when the between-training period is limited.

  1. A Submaximal Running Test With Postexercise Cardiac Autonomic and Neuromuscular Function in Monitoring Endurance Training Adaptation.

    PubMed

    Vesterinen, Ville; Nummela, Ari; Laine, Tanja; Hynynen, Esa; Mikkola, Jussi; Häkkinen, Keijo

    2017-01-01

    Vesterinen, V, Nummela, A, Laine, T, Hynynen, E, Mikkola, J, and Häkkinen, K. A submaximal running test with postexercise cardiac autonomic and neuromuscular function in monitoring endurance training adaptation. J Strength Cond Res 31(1): 233-243, 2017-The aim of this study was to investigate whether a submaximal running test (SRT) with postexercise heart rate recovery (HRR), heart rate variability (HRV), and countermovement jump (CMJ) measurements could be used to monitor endurance training adaptation. Thirty-five endurance-trained men and women completed an 18-week endurance training. Maximal endurance performance and maximal oxygen uptake were measured every 8 weeks. In addition, SRTs with postexercise HRR, HRV, and CMJ measurements were carried out every 4 weeks. Submaximal running test consisted of two 6-minute stages at 70 and 80% of maximum heart rate (HRmax) and a 3-minute stage at 90% HRmax, followed by a 2-minute recovery stage for measuring postexercise HRR, HRV, and CMJ test. The highest responders according to the change of maximal endurance performance showed a significant improvement in running speeds during stages 2 and 3 in SRT, whereas no changes were observed in the lowest responders. The strongest correlation was found between the change of maximal endurance performance and running speed during stage 3, whereas no significant relationships were found between the change of maximal endurance performance and the changes of postexercise HRR, HRV, and CMJ. Running speed at 90% HRmax intensity was the most sensitive variable to monitor adaptation to endurance training. The present submaximal test showed potential to monitor endurance training adaptation. Furthermore, it may serve as a practical tool for athletes and coaches to evaluate weekly the effectiveness of training program without interfering in the normal training habits.

  2. Enhancing Predictive Accuracy of Cardiac Autonomic Neuropathy Using Blood Biochemistry Features and Iterative Multitier Ensembles.

    PubMed

    Abawajy, Jemal; Kelarev, Andrei; Chowdhury, Morshed U; Jelinek, Herbert F

    2016-01-01

    Blood biochemistry attributes form an important class of tests, routinely collected several times per year for many patients with diabetes. The objective of this study is to investigate the role of blood biochemistry for improving the predictive accuracy of the diagnosis of cardiac autonomic neuropathy (CAN) progression. Blood biochemistry contributes to CAN, and so it is a causative factor that can provide additional power for the diagnosis of CAN especially in the absence of a complete set of Ewing tests. We introduce automated iterative multitier ensembles (AIME) and investigate their performance in comparison to base classifiers and standard ensemble classifiers for blood biochemistry attributes. AIME incorporate diverse ensembles into several tiers simultaneously and combine them into one automatically generated integrated system so that one ensemble acts as an integral part of another ensemble. We carried out extensive experimental analysis using large datasets from the diabetes screening research initiative (DiScRi) project. The results of our experiments show that several blood biochemistry attributes can be used to supplement the Ewing battery for the detection of CAN in situations where one or more of the Ewing tests cannot be completed because of the individual difficulties faced by each patient in performing the tests. The results show that AIME provide higher accuracy as a multitier CAN classification paradigm. The best predictive accuracy of 99.57% has been obtained by the AIME combining decorate on top tier with bagging on middle tier based on random forest. Practitioners can use these findings to increase the accuracy of CAN diagnosis.

  3. Effect of aerobic training on baroreflex regulation of cardiac and sympathetic function.

    PubMed

    Sheldahl, L M; Ebert, T J; Cox, B; Tristani, F E

    1994-01-01

    To investigate the effect of aerobic exercise training on baroreflex regulation of muscle sympathetic nerve activity (MSNA) and cardiac R-R intervals in a middle-aged to older population, 10 healthy men > 40 yr of age underwent tests of autonomic function before and after 12 wk of high-intensity training. Cardiac and peripheral baroslopes were determined from the R-R interval vs. mean arterial pressure (MAP) and peroneal MSNA vs. diastolic pressure relationships, respectively, during sequential bolus injections of nitroprusside and phenylephrine. Maximal oxygen uptake increased (P < 0.05) 17% with training. Resting R-R interval increased (881 +/- 23 to 956 +/- 38 ms, P < 0.05), MAP decreased (96 +/- 2 to 91 +/- 3 mmHg, P < 0.05), and MSNA was unaltered (23.1 +/- 2.3 to 23.6 +/- 1.9 bursts/min) with training. Before and after training, respectively, cardiac baroslopes determined with decreasing (8.7 +/- 0.9 to 9.9 +/- 5.5 ms/mmHg) and increasing MAP (9.6 +/- 2.1 to 9.9 +/- 2.2 ms/mmHg) and the peripheral sympathetic baroslope (-3.3 +/- 0.4 to -3.5 +/- 0.6 bursts.min-1 x mmHg-1) did not differ. The results suggest that short-term aerobic training does not alter resting MSNA or neurocirculatory responses to baroreceptor challenges in middle-aged and older men.

  4. [Non-invasive evaluation of the cardiac autonomic nervous system by PET]. Progress report, September 1991--September 1992

    SciTech Connect

    Not Available

    1992-09-01

    The proposed research addresses the development, validation and application of cardiac PET imaging techniques to characterize the autonomic nervous system of the heart. PET technology has significantly matured over the last two decades. Instrument design, image processing and production of radiochemical compounds have formed an integrative approach to provide a powerful and novel imaging modality for the quantitative in vivo evaluation of the autonomic nervous system of the heart. Animal studies using novel tracers for the sympathetic and parasympathetic nerve terminals will be employed to characterize the functional integrity of nerve terminals. This work will be complemented by the development of agents which bind to postsynaptic receptor sites. The combined evaluation of presynaptic and postsynaptic neuronal function will allow a unique characterization of neuronal function. Initial development in animal studies will be followed by feasibility studies in humans. These studies are designed to test sophisticated imaging protocols in the human heart and validate the scintigraphic findings with independent markers of autonomic innervation. Subsequent clinical application in various cardiac diseases is expected to provide new insights into the neuropathophysiology of the heart.

  5. Intracoronary gastrin 17 increases cardiac perfusion and function through autonomic nervous system, CCK receptors, and nitric oxide in anesthetized pigs.

    PubMed

    Grossini, Elena; Caimmi, Philippe; Molinari, Claudio; Uberti, Francesca; Mary, David; Vacca, Giovanni

    2011-01-01

    The release of gastrointestinal hormones has been reported to modulate reflex cardiovascular responses caused by gastric distension, although the role played by gastrin 17 is as yet unknown. The present study was therefore planned to determine the primary in vivo effect of gastrin 17 on coronary blood flow and cardiac function and the involvement of autonomic nervous system, CCK1/2 receptors, and nitric oxide (NO). In 40 anesthetized pigs, gastrin 17 was infused into the left anterior descending coronary artery at constant heart rate and arterial blood pressure. In 35 of the 40 pigs, the mechanisms of the observed hemodynamic responses were analyzed by repeating gastrin 17 infusion after autonomic nervous system and NO blockade, and after specific CCK receptors agonists/antagonists administration. Intracoronary gastrin 17 administration caused dose-related increases of both coronary blood flow and cardiac function. The intracoronary co-administration of CCK33/pentagastrin and gastrin 17 potentiated the coronary effects observed when the above agents were given alone (P <0.05). The potentiation of the cardiac response was observed only with the co-administration of pentagastrin and gastrin 17 (P <0.05). Moreover, blockade of muscarinic cholinoceptors (intravenous atropine) and of α-adrenoceptors (intravenous phentolamine) did not abolish the hemodynamic responses to gastrin 17. The cardiac and vascular effects of the hormone were prevented by blockade of β-adrenoceptors (intravenous atenolol and butoxamine), CCK1/2 receptors (intracoronary lorglumide and CAM-1028), and NO synthase (intracoronary Nω-nitro-l-arginine methyl ester). In conclusion, gastrin 17 primarily increased coronary blood flow and cardiac function through the involvement of CCK receptors, β-adrenoceptors, and NO release.

  6. Autonomic control of cardiac action potentials: role of potassium channel kinetics in response to sympathetic stimulation.

    PubMed

    Terrenoire, Cecile; Clancy, Colleen E; Cormier, Joseph W; Sampson, Kevin J; Kass, Robert S

    2005-03-18

    I(Ks), the slowly activating component of the delayed rectifier current, plays a major role in repolarization of the cardiac action potential (AP). Genetic mutations in the alpha- (KCNQ1) and beta- (KCNE1) subunits of I(Ks) underlie Long QT Syndrome type 1 and 5 (LQT-1 and LQT-5), respectively, and predispose carriers to the development of polymorphic ventricular arrhythmias and sudden cardiac death. beta-adrenergic stimulation increases I(Ks) and results in rate dependent AP shortening, a control system that can be disrupted by some mutations linked to LQT-1 and LQT-5. The mechanisms by which I(Ks) regulates action potential duration (APD) during beta-adrenergic stimulation at different heart rates are not known, nor are the consequences of mutation induced disruption of this regulation. Here we develop a complementary experimental and theoretical approach to address these questions. We reconstituted I(Ks) in CHO cells (ie, KCNQ1 coexpressed with KCNE1 and the adaptator protein Yotiao) and quantitatively examined the effects of beta-adrenergic stimulation on channel kinetics. We then developed theoretical models of I(Ks) in the absence and presence of beta-adrenergic stimulation. We simulated the effects of sympathetic stimulation on channel activation (speeding) and deactivation (slowing) kinetics on the whole cell action potential under different pacing conditions. The model suggests these kinetic effects are critically important in rate-dependent control of action potential duration. We also investigate the effects of two LQT-5 mutations that alter kinetics and impair sympathetic stimulation of I(Ks) and show the likely mechanism by which they lead to tachyarrhythmias and indicate a distinct role of I(KS) kinetics in this electrical dysfunction. The full text of this article is available online at http://circres.ahajournals.org.

  7. Examining the role of TRPA1 in air pollution-induced cardiac arrhythmias and autonomic imbalance

    EPA Science Inventory

    Here we describe how air pollution causes cardiac arrhythmogenesis through sensory irritation in the airways. Time-series studies show the risk of adverse cardiac events increases significantly in the hours to days after expos...

  8. Association between obesity and heart rate variability indices: an intuition toward cardiac autonomic alteration – a risk of CVD

    PubMed Central

    Yadav, Ram Lochan; Yadav, Prakash Kumar; Yadav, Laxmi Kumari; Agrawal, Kopila; Sah, Santosh Kumar; Islam, Md Nazrul

    2017-01-01

    Background Obese people have a higher prevalence of cardiovascular disease, which is supposed to be due to autonomic dysfunction and/or metabolic disorder. The alterations in cardiac autonomic functions bring out the changes in the heart rate variability (HRV) indicators, an assessing tool for cardiac autonomic conditions. Objective To compare the cardiac autonomic activity between obese and normal weight adults and find out the highest association between the indices of HRV and obesity. Methods The study was conducted in 30 adult obese persons (body mass index [BMI] >30 kg/m2) and 29 healthy normal weight controls (BMI 18–24 kg/m2). Short-term HRV variables were assessed using standard protocol. Data were compared between groups using Mann–Whitney U test. Obesity indices such as waist circumference, hip circumference, waist–hip ratio (WHR), and BMI were measured and calculated, and they were correlated with HRV indices using Spearman’s correlation analysis. Results In the obese group, there was a significant increase in the mean heart rate, whereas the HRV parasympathetic indicators were less (eg, root mean square of differences of successive RR intervals [28.75 {16.72–38.35} vs 41.55 {30.6–56.75} ms, p=0.018], number of RR intervals that differ by >50 ms, that is, NN50 [15.5 {2–39} vs 83.5 {32.75–116.25}, p=0.010], etc) and the sympathetic indicator low frequency (LF)/high frequency (HF) ratio (1.2 [0.65–2.20] vs 0.79 [0.5–1.02], p=0.045) was more than that of the normal weight group. Spearman’s correlation between HRV and obesity indices showed significant positive correlation of WHR with LF in normalized unit (r=0.478, p<0.01) and LF/HF ratio (r=0.479, p<0.01), whereas it had significant negative correlation with high frequency power ms2 (r=−0.374, p<0.05) and HF in normalized unit (r=−0.478, p<0.01). There was a nonsignificant correlation of BMI with HRV variables in obese individuals. Conclusion Increased WHR, by far an indicator of

  9. The transcription factor GATA-6 regulates pathological cardiac hypertrophy

    PubMed Central

    van Berlo, Jop H.; Elrod, John W.; van den Hoogenhof, Maarten M.G.; York, Allen J.; Aronow, Bruce J.; Duncan, Stephen A.; Molkentin, Jeffery D.

    2010-01-01

    Rationale The transcriptional code that programs maladaptive cardiac hypertrophy involves the zinc finger-containing DNA binding factor GATA-4. The highly related transcription factor GATA-6 is also expressed in the adult heart, although its role in controlling the hypertrophic program is unknown. Objective To determine the role of GATA-6 in cardiac hypertrophy and homeostasis. Methods and Results Here we performed a cardiomyocyte-specific conditional gene targeting approach for Gata6, as well as a transgenic approach to overexpress GATA-6 in the mouse heart. Deletion of Gata6-loxP with Nkx2.5-cre produced late embryonic lethality with heart defects, while deletion with β-myosin heavy chain-cre (βMHC-cre) produced viable adults with greater than 95% loss of GATA-6 protein in the heart. These later mice were subjected to pressure overload induced hypertrophy for 2 and 6 weeks, which showed a significant reduction in cardiac hypertrophy similar to that observed Gata4 heart-specific deleted mice. Gata6-deleted mice subjected to pressure overload also developed heart failure while control mice maintained proper cardiac function. Gata6-deleted mice also developed less cardiac hypertrophy following 2 weeks of angiotensin II/phenylephrine infusion. Controlled GATA-6 overexpression in the heart induced hypertrophy with aging and predisposed to greater hypertrophy with pressure overload stimulation. Combinatorial deletion of Gata4 and Gata6 from the adult heart resulted in dilated cardiomyopathy and lethality by 16 weeks of age. Mechanistically, deletion of Gata6 from the heart resulted in fundamental changes in the levels of key regulatory genes and myocyte differentiation-specific genes. Conclusions These results indicate that GATA-6 is both necessary and sufficient for regulating the cardiac hypertrophic response and differentiated gene expression, both alone and in coordination with GATA-4. PMID:20705924

  10. Regulation of cell-non-autonomous proteostasis in metazoans

    PubMed Central

    O'Brien, Daniel; van Oosten-Hawle, Patricija

    2016-01-01

    Cells have developed robust adaptation mechanisms to survive environmental conditions that challenge the integrity of their proteome and ensure cellular viability. These are stress signalling pathways that integrate extracellular signals with the ability to detect and efficiently respond to protein-folding perturbations within the cell. Within the context of an organism, the cell-autonomous effects of these signalling mechanisms are superimposed by cell-non-autonomous stress signalling pathways that allow co-ordination of stress responses across tissues. These transcellular stress signalling pathways orchestrate and maintain the cellular proteome at an organismal level. This article focuses on mechanisms in both invertebrate and vertebrate organisms that activate stress responses in a cell-non-autonomous manner. We discuss emerging insights and provide specific examples on how components of the cell-non-autonomous proteostasis network are used in cancer and protein-folding diseases to drive disease progression across tissues. PMID:27744329

  11. Regulation of cell-non-autonomous proteostasis in metazoans.

    PubMed

    O'Brien, Daniel; van Oosten-Hawle, Patricija

    2016-10-15

    Cells have developed robust adaptation mechanisms to survive environmental conditions that challenge the integrity of their proteome and ensure cellular viability. These are stress signalling pathways that integrate extracellular signals with the ability to detect and efficiently respond to protein-folding perturbations within the cell. Within the context of an organism, the cell-autonomous effects of these signalling mechanisms are superimposed by cell-non-autonomous stress signalling pathways that allow co-ordination of stress responses across tissues. These transcellular stress signalling pathways orchestrate and maintain the cellular proteome at an organismal level. This article focuses on mechanisms in both invertebrate and vertebrate organisms that activate stress responses in a cell-non-autonomous manner. We discuss emerging insights and provide specific examples on how components of the cell-non-autonomous proteostasis network are used in cancer and protein-folding diseases to drive disease progression across tissues.

  12. Autonomic regulation of anti-inflammatory activities from salivary glands.

    PubMed

    Mathison, Ronald D; Davison, Joseph S; St Laurent, Chris D; Befus, A Dean

    2012-01-01

    The cervical sympathetic nerves which innervate the medial basal hypothalamus-hypophyseal complex, primary and secondary lymph organs, and numerous glands, such as the pineal, thyroid, parathyroid and salivary glands form a relevant neuroimmunoendocrine structure that is involved in the regulation of systemic homeostasis. The superior cervical ganglia and the submandibular glands form a 'neuroendocrine axis' called the cervical sympathetic trunk submandibular gland (CST-SMG) axis. The identification of this axis usurps the traditional view of salivary glands as accessory digestive structures and reinforces the view that they are important sources of systemically active immunoregulatory and anti-inflammatory factors whose release is intimately controlled by the autonomic nervous system, and in particular the sympathetic branch. An end component of the CST-SMG axis is the synthesis, processing and release of submandibular rat-1 protein (SMR1), a prohormone, that generates several different peptides, one from near its N-terminus called sialorphin and another from its C-terminus called - submandibular gland peptide-T (SGP-T). SGP-T formed the template for tripeptide fragment (FEG) and its metabolically stable D-isomeric peptide feG, which are potent inhibitors of allergy and asthma (IgE-mediated allergic reactions) and several non-IgE-mediated inflammations. The translation from rat genetics and proteomics to humans has yielded structural and functional correlates that hopefully will lead to the development of new medications and therapeutic approaches for difficult to treat disorders. Although the CST-SMG axis has barely been explored in humans recognition of the importance of this axis could facilitate an understanding and improved management of periodontal disease, and other diseases with a more systemic and nervous system basis such as asthma, autoimmunity, graft-versus-host disease and even Parkinson's disease.

  13. Regulation of Breathing and Autonomic Outflows by Chemoreceptors

    PubMed Central

    Guyenet, Patrice G.

    2016-01-01

    Lung ventilation fluctuates widely with behavior but arterial PCO2 remains stable. Under normal conditions, the chemoreflexes contribute to PaCO2 stability by producing small corrective cardiorespiratory adjustments mediated by lower brainstem circuits. Carotid body (CB) information reaches the respiratory pattern generator (RPG) via nucleus solitarius (NTS) glutamatergic neurons which also target rostral ventrolateral medulla (RVLM) presympathetic neurons thereby raising sympathetic nerve activity (SNA). Chemoreceptors also regulate presympathetic neurons and cardiovagal preganglionic neurons indirectly via inputs from the RPG. Secondary effects of chemoreceptors on the autonomic outflows result from changes in lung stretch afferent and baroreceptor activity. Central respiratory chemosensitivity is caused by direct effects of acid on neurons and indirect effects of CO2 via astrocytes. Central respiratory chemoreceptors are not definitively identified but the retrotrapezoid nucleus (RTN) is a particularly strong candidate. The absence of RTN likely causes severe central apneas in congenital central hypoventilation syndrome. Like other stressors, intense chemosensory stimuli produce arousal and activate circuits that are wake- or attention-promoting. Such pathways (e.g., locus coeruleus, raphe, and orexin system) modulate the chemoreflexes in a state-dependent manner and their activation by strong chemosensory stimuli intensifies these reflexes. In essential hypertension, obstructive sleep apnea and congestive heart failure, chronically elevated CB afferent activity contributes to raising SNA but breathing is unchanged or becomes periodic (severe CHF). Extreme CNS hypoxia produces a stereotyped cardiorespiratory response (gasping, increased SNA). The effects of these various pathologies on brainstem cardiorespiratory networks are discussed, special consideration being given to the interactions between central and peripheral chemoreflexes. PMID:25428853

  14. Repair Injured Heart by Regulating Cardiac Regenerative Signals

    PubMed Central

    Wang, Lei; Paul, Christian

    2016-01-01

    Cardiac regeneration is a homeostatic cardiogenic process by which the sections of malfunctioning adult cardiovascular tissues are repaired and renewed employing a combination of both cardiomyogenesis and angiogenesis. Unfortunately, while high-quality regeneration can be performed in amphibians and zebrafish hearts, mammalian hearts do not respond in kind. Indeed, a long-term loss of proliferative capacity in mammalian adult cardiomyocytes in combination with dysregulated induction of tissue fibrosis impairs mammalian endogenous heart regenerative capacity, leading to deleterious cardiac remodeling at the end stage of heart failure. Interestingly, several studies have demonstrated that cardiomyocyte proliferation capacity is retained in mammals very soon after birth, and cardiac regeneration potential is correspondingly preserved in some preadolescent vertebrates after myocardial infarction. There is therefore great interest in uncovering the molecular mechanisms that may allow heart regeneration during adult stages. This review will summarize recent findings on cardiac regenerative regulatory mechanisms, especially with respect to extracellular signals and intracellular pathways that may provide novel therapeutics for heart diseases. Particularly, both in vitro and in vivo experimental evidences will be presented to highlight the functional role of these signaling cascades in regulating cardiomyocyte proliferation, cardiomyocyte growth, and maturation, with special emphasis on their responses to heart tissue injury. PMID:27799944

  15. Scaffold Proteins Regulating Extracellular Regulated Kinase Function in Cardiac Hypertrophy and Disease

    PubMed Central

    Liang, Yan; Sheikh, Farah

    2016-01-01

    The mitogen activated protein kinase (MAPK)-extracellular regulated kinase 1/2 (ERK1/2) pathway is a central downstream signaling pathway that is activated in cardiac muscle cells during mechanical and agonist-mediated hypertrophy. Studies in genetic mouse models deficient in ERK-associated MAPK components pathway have further reinforced a direct role for this pathway in stress-induced cardiac hypertrophy and disease. However, more recent studies have highlighted that these signaling pathways may exert their regulatory functions in a more compartmentalized manner in cardiac muscle. Emerging data has uncovered specific MAPK scaffolding proteins that tether MAPK/ERK signaling specifically at the sarcomere and plasma membrane in cardiac muscle and show that deficiencies in these scaffolding proteins alter ERK activity and phosphorylation, which are then critical in altering the cardiac myocyte response to stress-induced hypertrophy and disease progression. In this review, we provide insights on ERK-associated scaffolding proteins regulating cardiac myofilament function and their impact on cardiac hypertrophy and disease. PMID:26973524

  16. Maladaptive autonomic regulation in PTSD accelerates physiological aging

    PubMed Central

    Williamson, John B.; Porges, Eric C.; Lamb, Damon G.; Porges, Stephen W.

    2015-01-01

    A core manifestation of post-traumatic stress disorder (PTSD) is a disconnection between physiological state and psychological or behavioral processes necessary to adequately respond to environmental demands. Patients with PTSD experience abnormal oscillations in autonomic states supporting either fight and flight behaviors or withdrawal, immobilization, and dissociation without an intervening “calm” state that would provide opportunities for positive social interactions. This defensive autonomic disposition is adaptive in dangerous and life threatening situations, but in the context of every-day life may lead to significant psychosocial distress and deteriorating social relationships. The perpetuation of these maladaptive autonomic responses may contribute to the development of comorbid mental health issues such as depression, loneliness, and hostility that further modify the nature of cardiovascular behavior in the context of internal and external stressors. Over time, changes in autonomic, endocrine, and immune function contribute to deteriorating health, which is potently expressed in brain dysfunction and cardiovascular disease. In this theoretical review paper, we present an overview of the literature on the chronic health effects of PTSD. We discuss the brain networks underlying PTSD in the context of autonomic efferent and afferent contributions and how disruption of these networks leads to poor health outcomes. Finally, we discuss treatment approaches based on our theoretical model of PTSD. PMID:25653631

  17. Gross anatomical study on the human myocardial bridges with special reference to the spatial relationship among coronary arteries, cardiac veins, and autonomic nerves.

    PubMed

    Watanabe, Yuko; Arakawa, Takamitsu; Kageyama, Ikuo; Aizawa, Yukio; Kumaki, Katsuji; Miki, Akinori; Terashima, Toshio

    2016-04-01

    Coronary arteries are frequently covered by cardiac muscles. This arrangement is termed a myocardial bridge. Previous studies have shown that myocardial bridges can cause myocardial ischemic diseases or cardiac arrhythmia, but the relevant pathogenic mechanisms remain unknown. We examined 60 hearts from Japanese cadavers macroscopically to clarify the spatial relationships among coronary arteries, cardiac veins and autonomic nerves. We found 86 myocardial bridges in 47 hearts from the 60 cadavers examined (78.3%). Next, we dissected out nine hearts with myocardial bridges in detail under the operating microscope. We found no additional branches of coronary arteries on the myocardial bridge surfaces. However, the cardiac veins, which usually accompany the coronary arteries, ran independently on the myocardial bridge surfaces in the same region. Cardiac autonomic nerves comprised two rami: one was associated with the coronary artery under the myocardial bridge and the other ran on the surface of the bridge. Such spatial relationships among the coronary arteries, cardiac veins and cardiac autonomic nerves at the myocardial bridges are quite similar to those in mouse embryo hearts.

  18. AMPK in cardiac fibrosis and repair: Actions beyond metabolic regulation.

    PubMed

    Daskalopoulos, Evangelos P; Dufeys, Cécile; Bertrand, Luc; Beauloye, Christophe; Horman, Sandrine

    2016-02-01

    Fibrosis is a general term encompassing a plethora of pathologies that span all systems and is marked by increased deposition of collagen. Injury of variable etiology gives rise to complex cascades involving several cell-types and molecular signals, leading to the excessive accumulation of extracellular matrix that promotes fibrosis and eventually leads to organ failure. Cardiac fibrosis is a dynamic process associated notably with ischemia, hypertrophy, volume- and pressure-overload, aging and diabetes mellitus. It has profoundly deleterious consequences on the normal architecture and functioning of the myocardium and is associated with considerable mortality and morbidity. The AMP-activated protein kinase (AMPK) is a ubiquitously expressed cellular energy sensor and an essential component of the adaptive response to cardiomyocyte stress that occurs during ischemia. Nevertheless, its actions extend well beyond its energy-regulating role and it appears to possess an essential role in regulating fibrosis of the myocardium. In this review paper, we will summarize the main elements and crucial players of cardiac fibrosis. In addition, we will provide an overview of the diverse roles of AMPK in the heart and discuss in detail its implication in cardiac fibrosis. Lastly, we will highlight the recently published literature concerning AMPK-targeting current therapy and novel strategies aiming to attenuate fibrosis.

  19. Acute psychosocial challenge and cardiac autonomic response in women: the role of estrogens, corticosteroids, and behavioral coping styles.

    PubMed

    Pico-Alfonso, M Angeles; Mastorci, Francesca; Ceresini, Graziano; Ceda, Gian Paolo; Manghi, Massimo; Pino, Olimpia; Troisi, Alfonso; Sgoifo, Andrea

    2007-06-01

    Theoretical statements, as well as clinical and experimental data, suggest that the amplitude of cardiovascular reactivity to acute stressors can be a good predictor of preclinical and clinical cardiovascular states. The aim of the present study is to investigate the role of estrogens, the hypothalamic-pituitary-adrenocortical activity, and the behavioral profile in individual cardiac autonomic reactivity to brief laboratory stressors in women. Thirty-six adult, healthy women were exposed to a stress interview and a mental task test, each lasting 5 min. They were assigned to two experimental groups: D4, i.e. 4 days after menses beginning (follicular phase, n=18), and D14, i.e. 14 days after menses beginning (ovulatory phase, n=18). The cardiac measurements in the baseline, stress and recovery periods consisted in heart rate (average R-R interval) and parasympathetic tone (r-MSSD) quantification, while the HPA axis activity and stress reactivity were assessed via plasma cortisol and dehydroepiandrosterone concentrations. The ethological profile during the interview was drawn by means of non-verbal behavior analysis. The cardiac, adrenocortical and behavioral responses to the two stressors were similar in groups D4 and D14, despite significantly higher estradiol levels in the latter. Subjects with higher pre-stress cortisol levels had higher heart rate and lower vagal activity in the baseline, stress and recovery phases. Women showing higher level of submission were characterized by higher heart rate acceleration and vagal withdrawal during both the interview and the recovery phase. In addition, the subjects that exhibited greater displacement during the interview were also characterized by lower heart rate increments and less pronounced vagal suppression during post-stress recovery. In conclusion, the present results do not support a clear buffering role of estrogens in cardiovascular response to acute stressors. However, they confirm that baseline HPA axis activity

  20. Alterations in the ultrastructure of cardiac autonomic nervous system triggered by crotoxin from rattlesnake (Crotalus durissus cumanensis) venom.

    PubMed

    Hernández, Miguelina; Scannone, Héctor; Finol, Héctor J; Pineda, Maria E; Fernández, Irma; Vargas, Alba M; Girón, María E; Aguilar, Irma; Rodríguez-Acosta, Alexis

    2007-10-01

    This study explored the toxic effects of crotoxin isolated from Crotalus durissus cumanensis venom on the ultrastructure of mice cardiac autonomic nervous system. Mice were intravenously injected with saline (control group) and crotoxin diluted in saline venom (study group) at a dose of 0.107 mg/kg mouse body weight. Samples from the inter-ventricular septum were prepared for electron microscopy after 6 h (G1), 12 h (G2), 24 h (G3) and 48 h (G4). The G1 group showed some cardiomyocyte with pleomorphic mitochondria. Capillary swollen walls, nerve cholinergic endings with depleted acetylcholine vesicles in their interior and other depletions were observed. A space completely lacking in contractile elements was noticed. The G2 group demonstrated a myelinic figure, a subsarcolemic region with few myofibrils and nervous cholinergic terminal with scarce vacuoles in their interior. The G3 group demonstrated a structure with a depleted axonic terminal, mitochondrias varying in size and enhanced electron density. In addition, muscular fibers with myofibrillar structure disorganization, a depleted nervous structure surrounded by a Schwann cell along with an abundance of natriuretic peptides, were seen. An amyelinic terminal with depleted Schwann cell and with scarce vesicles was also observed. Finally, axonic lysis with autophagic vacuoles in their interior and condensed mitochondria was observed in the G4 group. This work describes the first report of ultrastructural damage caused by crotoxin on mice cardiac autonomic nervous system.

  1. Short-term ECG recording for the identification of cardiac autonomic neuropathy in people with diabetes mellitus

    NASA Astrophysics Data System (ADS)

    Jelinek, Herbert F.; Pham, Phuong; Struzik, Zbigniew R.; Spence, Ian

    2007-07-01

    Diabetes mellitus (DM) is a serious and increasing health problem worldwide. Compared to non-diabetics, patients experience an increased risk of all cardiovascular diseases, including dysfunctional neural control of the heart. Poor diagnoses of cardiac autonomic neuropathy (CAN) may result in increased incidence of silent myocardial infarction and ischaemia, which can lead to sudden death. Traditionally the Ewing battery of tests is used to identify CAN. The purpose of this study is to examine the usefulness of heart rate variability (HRV) analyses of short-term ECG recordings as a method for detecting CAN. HRV may be able to identify asymptomatic individuals, which the Ewing battery is not able to do. Several HRV parameters are assessed, including time and frequency domain, as well as nonlinear parameters. Eighteen out of thirty-eight individuals with diabetes were positive for two or more of the Ewing battery of tests indicating CAN. Approximate Entropy (ApEn), log normalized total power (LnTP) and log normalized high frequency (LnHF) power demonstrate a significant difference at p < 0.05 between CAN+ and CAN-. This indicates that nonlinear scaling parameters are able to identify people with cardiac autonomic neuropathy in short ECG recordings. Our study paves the way to assess the utility of nonlinear parameters in identifying asymptomatic CAN.

  2. Effects of psychological stress test on the cardiac response of public safety workers: alternative parameters to autonomic balance

    NASA Astrophysics Data System (ADS)

    Huerta-Franco, M. R.; Vargas-Luna, F. M.; Delgadillo-Holtfort, I.

    2015-01-01

    It is well known that public safety workers (PSW) face many stressful situations that yield them as high-risk population for suffering chronic stress diseases. In this multidisciplinary research the cardiac response to induced psychological stress by a short duration Stroop test was evaluated in 20 female and 19 male PSW, in order to compare traditionally used cardiac response parameters with alternative ones. Electrocardiograms have been recorded using the Eindhoven electrodes configuration for 1 min before, 3 min during and 1 min after the test. Signals analysis has been performed for the heart rate and the power spectra of its variability and of the variability of the amplitude of the R-wave, i.e. the highest peak of the electrocardiographic signal periodic sequence. The results demonstrated that the traditional autonomic balance index shows no significant differences between stages. In contrast, the median of the area of the power spectrum of the R-wave amplitude variability in the frequency region dominated by the autonomous nervous system (0.04-to-0.4 Hz) is the more sensitive parameter. Moreover, this parameter allows to identify gender differences consistent with those encountered in other studies.

  3. Regulation of fibronectin gene expression in cardiac fibroblasts by scleraxis.

    PubMed

    Bagchi, Rushita A; Lin, Justin; Wang, Ryan; Czubryt, Michael P

    2016-11-01

    The glycoprotein fibronectin is a key component of the extracellular matrix. By interacting with numerous matrix and cell surface proteins, fibronectin plays important roles in cell adhesion, migration and intracellular signaling. Up-regulation of fibronectin occurs in tissue fibrosis, and previous studies have identified the pro-fibrotic factor TGFβ as an inducer of fibronectin expression, although the mechanism responsible remains unknown. We have previously shown that a key downstream effector of TGFβ signaling in cardiac fibroblasts is the transcription factor scleraxis, which in turn regulates the expression of a wide variety of extracellular matrix genes. We noted that fibronectin expression tracked closely with scleraxis expression, but it was unclear whether scleraxis directly regulated the fibronectin gene. Here, we report that scleraxis acts via two E-box binding sites in the proximal human fibronectin promoter to govern fibronectin expression, with the second E-box being both sufficient and necessary for scleraxis-mediated fibronectin expression to occur. A combination of electrophoretic mobility shift and chromatin immunoprecipitation assays indicated that scleraxis interacted to a greater degree with the second E-box. Over-expression or knockdown of scleraxis resulted in increased or decreased fibronectin expression, respectively, and scleraxis null mice presented with dramatically decreased immunolabeling for fibronectin in cardiac tissue sections compared to wild-type controls. Furthermore, scleraxis was required for TGFβ-induced fibronectin expression: TGFβ lost its ability to induce fibronectin expression following scleraxis knockdown. Together, these results demonstrate a novel and required role for scleraxis in the regulation of cardiac fibroblast fibronectin gene expression basally or in response to TGFβ.

  4. Impact of traffic-related air pollution on acute changes in cardiac autonomic modulation during rest and physical activity: a cross-over study.

    PubMed

    Cole-Hunter, Tom; Weichenthal, Scott; Kubesch, Nadine; Foraster, Maria; Carrasco-Turigas, Glòria; Bouso, Laura; Martínez, David; Westerdahl, Dane; de Nazelle, Audrey; Nieuwenhuijsen, Mark

    2016-01-01

    People are often exposed to traffic-related air pollution (TRAP) during physical activity (PA), but it is not clear if PA modifies the impact of TRAP on cardiac autonomic modulation. We conducted a panel study among 28 healthy adults in Barcelona, Spain to examine how PA may modify the impact of TRAP on cardiac autonomic regulation. Participants completed four 2-h exposure scenarios that included either rest or intermittent exercise in high- and low-traffic environments. Time- and frequency-domain measures of heart rate variability (HRV) were monitored during each exposure period along with continuous measures of TRAP. Linear mixed-effects models were used to estimate the impact of TRAP on HRV as well as potential effect modification by PA. Exposure to TRAP was associated with consistent decreases in HRV; however, exposure-response relationships were not always linear over the broad range of exposures. For example, each 10 μg/m(3) increase in black carbon was associated with a 23% (95% CI: -31, -13) decrease in high frequency power at the low-traffic site, whereas no association was observed at the high-traffic site. PA modified the impact of TRAP on HRV at the high-traffic site and tended to weaken inverse associations with measures reflecting parasympathetic modulation (P ≤ 0.001). Evidence of effect modification at the low-traffic site was less consistent. The strength and direction of the relationship between TRAP and HRV may vary across exposure gradients. PA may modify the impact of TRAP on HRV, particularly at higher concentrations.

  5. Assessment of cardiac autonomic functions by heart rate recovery, heart rate variability and QT dynamicity parameters in patients with acromegaly.

    PubMed

    Dural, Muhammet; Kabakcı, Giray; Cınar, Neşe; Erbaş, Tomris; Canpolat, Uğur; Gürses, Kadri Murat; Tokgözoğlu, Lale; Oto, Ali; Kaya, Ergün Barış; Yorgun, Hikmet; Sahiner, Levent; Dağdelen, Selçuk; Aytemir, Kudret

    2014-04-01

    Cardiovascular complications are the most common causes of morbidity and mortality in acromegaly. However, there is little data regarding cardiac autonomic functions in these patients. Herein, we aimed to investigate several parameters of cardiac autonomic functions in patients with acromegaly compared to healthy subjects. We enrolled 20 newly diagnosed acromegalic patients (55% female, age:45.7 ± 12.6 years) and 32 age- and gender-matched healthy subjects. All participants underwent 24 h Holter recording. Heart rate recovery (HRR) indices were calculated by subtracting 1st, 2nd and 3rd minute heart rates from maximal heart rate. All patients underwent heart rate variability (HRV) and QT dynamicity analysis. Baseline characteristics were similar except diabetes mellitus and hypertension among groups. Mean HRR1 (29.2 ± 12.3 vs 42.6 ± 6.5, p = 0.001), HRR2 (43.5 ± 15.6 vs 61.1 ± 10.8, p = 0.001) and HRR3 (46.4 ± 16.2 vs 65.8 ± 9.8, p = 0.001) values were significantly higher in control group. HRV parameters as, SDNN [standard deviation of all NN intervals] (p = 0.001), SDANN [SD of the 5 min mean RR intervals] (p = 0.001), RMSSD [root square of successive differences in RR interval] (p = 0.001), PNN50 [proportion of differences in successive NN intervals >50 ms] (p = 0.001) and high-frequency [HF] (p = 0.001) were significantly decreased in patients with acromegaly; but low frequency [LF] (p = 0.046) and LF/HF (p = 0.001) were significantly higher in acromegaly patients. QTec (p = 0.009), QTac/RR slope (p = 0.017) and QTec/RR slope (p = 0.01) were significantly higher in patients with acromegaly. Additionally, there were significant negative correlation of disease duration with HRR2, HRR3, SDNN, PNN50, RMSSD, variability index. Our study results suggest that cardiac autonomic functions are impaired in patients with acromegaly. Further large scale studies are needed to exhibit the prognostic significance of impaired autonomic functions in patients with

  6. Selective contribution of diabetes and other cardiovascular risk factors to cardiac autonomic dysfunction in the general population.

    PubMed

    Ziegler, D; Zentai, C; Perz, S; Rathmann, W; Haastert, B; Meisinger, C; Löwel, H

    2006-04-01

    Both cardiac autonomic dysfunction adn cardiovascular risk factors are related to and excess risk of mortality. We sought to determine whether the major cardiovascular risk factors are associated with diminished heart rate variability (HRV), prolonged QTc interval, or increased QT dispersion (QTD). Male (n = 1030) and female (n = 957) subjects, aged 55-74 years, who participated in the population-based MONICA Augsburg survey 1989/90 were assessed for the presence of cardiovascular risk factors such as diabetes, hypertension, obesity, dyslipidemia, smoking, and low physical activity. Lowest quartiles for time domain indexes of HRV (SD of R-R intervals [SDNN], max-min difference), QTc > 440 ms, and QTD > 60 ms determined from 12-lead resting ECG were used as cutpoints. In men, after adjustment for age and alcohol consumption, significant independent determinants for the lowest quartiles of SDNN were diabetes, obesity, and smoking. Independent contributors to prolonged QTc were hypertension, obesity, smoking, and low physical activity, whereas for increased QTD it was only hypertension. In women, diabetes was the only contributor to low SDNN, and hypertension was the only determinant of prolonged QTc. In conclusion, diabetes is the primary determinant of reduced HRV in the general population, while hypertension is the primary contributor to prolonged QTc in both sexes. However, obesity and smoking contribute to autonomic dysfunction in men but not women. Thus, a selectivity and sex-related differences exist among the various cardiovascular risk factors as to their influence on autonomic dysfunction.

  7. Periodic variation in R-R intervals and cardiovascular autonomic regulation in young adult Syrian hamsters.

    PubMed

    Mongue-Din, H; Salmon, A; Fiszman, M Y; Fromes, Y

    2009-03-01

    Several hamster strains are commonly used as models for cardiomyopathic phenotypes evolving toward heart failure. However, little is known about heart rate variability (HRV) in this species. Prolonged surface ECG recording, a prerequisite to HRV studies, can be obtained either by telemetry or by restraints. Here, we performed long time ECG recording using telemetry on young adult Syrian hamsters and we analyzed time series of interbeat intervals. Standard statistics showed that the mean of normal R-R intervals slightly increased with age, with standard deviation of normal R-R intervals remaining stable over time. However, time domain analysis using Poincaré plots revealed dynamic changes in the HRV. Analysis of frequency domains revealed that the ratio of spectral components (low frequency/high frequency) exhibited a maturation pattern. Thus refined analysis of HRV revealed a more complex pattern than common statistical analysis would translate. Unlike other rodents, hamsters display a great spontaneous variability of their heart rate. As the complexity canvas of HRV might be the consequence of extracardiac regulation factors, we assessed the sympathovagal balance in both time and frequency domain of heart rate. Pharmacological tests revealed that both sympathetic and vagal tones contribute to HRV in Syrian hamsters. Thus Syrian hamsters have a broad intrinsic HRV with large influences of the neurovegetative system. However, the influence of the previous beat seems to prevail over the autonomic oscillators. These animals present a high sensitivity to artificially altered cardiac regulation and might be great models for the diagnosis of early alterations in the HRV related to pathology. Therefore, Syrian hamsters represent a unique model for HRV studies.

  8. Evidence of defective cardiovascular regulation in insulin-dependent diabetic patients without clinical autonomic dysfunction.

    PubMed

    Weston, P J; James, M A; Panerai, R B; McNally, P G; Potter, J F; Thurston, H

    1998-12-01

    (1) Autonomic dysfunction is a well recognised complication of diabetes mellitus and early detection may allow therapeutic manoeuvres to reduce the associated mortality and morbidity. We sought to identify early cardiovascular autonomic neuropathy using spectral analysis of heart rate and systolic blood pressure variability. (2) Thirty patients with Type 1 (insulin-dependent) diabetes mellitus (DM) and 30 matched control subjects were studied. In addition to standard tests of autonomic function, heart rate and systolic blood pressure variability were assessed using power spectral analysis. From the frequency domain analysis of systolic blood pressure and R-R interval, the overall gain of baroreflex mechanisms was assessed. (3) Standard tests of autonomic function were normal in both groups. Total spectral power of R-R interval was reduced in the Type 1 DM group for low-frequency (473 +/- 63 vs. 747 +/- 78 ms2, mean +/- S.E.M., P = 0.002) and high-frequency bands (125 +/- 13 vs. 459+/-90 ms2, P < 0.0001). Systolic blood pressure low-frequency power was increased in the diabetic group (9.3 +/- 1.2 vs. 6.6+/-0.7 mmHg2, P < 0.05). The low frequency/high frequency ratio for heart rate variability was significantly higher in the Type 1 DM patients (4.6+/-0.5 vs. 2.9+/-0.5, P = 0.002), implying a relative sympathetic predominance. When absolute powers were expressed in normalised units, these differences persisted. There were significant reductions in baroreceptor-cardiac reflex sensitivity in Type 1 DM patients compared to controls while supine (9.7+/-0.7 vs. 18.5 +/- 1.7 ms/mmHg, P < 0.0001) and standing (2.9+/-0.9 vs. 7.18+/-1.9 ms/mmHg, P < 0.001). (4) Spectral analysis of cardiovascular variability detects autonomic dysfunction more frequently in Type 1 DM patients than conventional tests, and is suggestive of an abnormality of parasympathetic function. The abnormality of baroreceptor-cardiac reflex sensitivity could be explained by this impairment of parasympathetic

  9. Epigenetic regulation of cardiac myofibril gene expression during heart development.

    PubMed

    Zhao, Weian; Liu, Lingjuan; Pan, Bo; Xu, Yang; Zhu, Jing; Nan, Changlong; Huang, Xupei; Tian, Jie

    2015-07-01

    Cardiac gene expression regulation is controlled not only by genetic factors but also by environmental, i.e., epigenetic factors. Several environmental toxic effects such as oxidative stress and ischemia can result in abnormal myofibril gene expression during heart development. Troponin, one of the regulatory myofibril proteins in the heart, is a well-known model in study of cardiac gene regulation during the development. In our previous studies, we have demonstrated that fetal form troponin I (ssTnI) expression in the heart is partially regulated by hormones, such as thyroid hormone. In the present study, we have explored the epigenetic role of histone modification in the regulation of ssTnI expression. Mouse hearts were collected at different time of heart development, i.e., embryonic day 15.5, postnatal day 1, day 7, day 14 and day 21. Levels of histone H3 acetylation (acH3) and histone H3 lysine 9 trimethylation (H3K9me(3)) were detected using chromatin immunoprecipitation assays in slow upstream regulatory element (SURE) domain (TnI slow upstream regulatory element), 300-bp proximal upstream domain and the first intron of ssTnI gene, which are recognized as critical regions for ssTnI regulation. We found that the levels of acH3 on the SURE region were gradually decreased, corresponding to a similar decrease of ssTnI expression in the heart, whereas the levels of H3K9me(3) in the first intron of ssTnI gene were gradually increased. Our results indicate that both histone acetylation and methylation are involved in the epigenetic regulation of ssTnI expression in the heart during the development, which are the targets for environmental factors.

  10. Cardiac Cyclic Nucleotide Phosphodiesterases: Function, Regulation, and Therapeutic Prospects

    PubMed Central

    Knight, W. E.; Yan, C.

    2014-01-01

    The second messengers cAMP and cGMP exist in multiple discrete compartments and regulate a variety of biological processes in the heart. The cyclic nucleotide phosphodiesterases, by catalyzing the hydrolysis of cAMP and cGMP, play crucial roles in controlling the amplitude, duration, and compartmentalization of cyclic nucleotide signaling. Over 60 phosphodiesterase isoforms, grouped into 11 families, have been discovered to date. In the heart, both cAMP- and cGMP-hydrolyzing phosphodiesterases play important roles in physiology and pathology. At least 7 of the 11 phosphodiesterase family members appear to be expressed in the myocardium, and evidence supports phosphodiesterase involvement in regulation of many processes important for normal cardiac function including pacemaking and contractility, as well as many pathological processes including remodeling and myocyte apoptosis. Pharmacological inhibitors for a number of phosphodiesterase families have also been used clinically or preclinically to treat several types of cardiovascular disease. In addition, phosphodiesterase inhibitors are also being considered for treatment of many forms of disease outside the cardiovascular system, raising the possibility of cardiovascular side effects of such agents. This review will discuss the roles of phosphodiesterases in the heart, in terms of expression patterns, regulation, and involvement in physiological and pathological functions. Additionally, the cardiac effects of various phosphodiesterase inhibitors, both potentially beneficial and detrimental, will be discussed. PMID:22951903

  11. B-vitamin Supplementation Mitigates Effects of Fine Particles on Cardiac Autonomic Dysfunction and Inflammation: A Pilot Human Intervention Trial

    PubMed Central

    Zhong, Jia; Trevisi, Letizia; Urch, Bruce; Lin, Xinyi; Speck, Mary; Coull, Brent A.; Liss, Gary; Thompson, Aaron; Wu, Shaowei; Wilson, Ander; Koutrakis, Petros; Silverman, Frances; Gold, Diane R.; Baccarelli, Andrea A.

    2017-01-01

    Ambient fine particle (PM2.5) pollution triggers acute cardiovascular events. Individual-level preventions are proposed to complement regulation in reducing the global burden of PM2.5–induced cardiovascular diseases. We determine whether B vitamin supplementation mitigates PM2.5 effects on cardiac autonomic dysfunction and inflammation in a single-blind placebo-controlled crossover pilot trial. Ten healthy adults received two-hour controlled-exposure-experiment to sham under placebo, PM2.5 (250 μg/m3) under placebo, and PM2.5 (250 μg/m3) under B-vitamin supplementation (2.5 mg/d folic acid, 50 mg/d vitamin B6, and 1 mg/d vitamin B12), respectively. At pre-, post-, 24 h-post-exposure, we measured resting heart rate (HR) and heart rate variability (HRV) with electrocardiogram, and white blood cell (WBC) counts with hematology analyzer. Compared to sham, PM2.5 exposure increased HR (3.8 bpm, 95% CI: 0.3, 7.4; P = 0.04), total WBC count (11.5%, 95% CI: 0.3%, 24.0%; P = 0.04), lymphocyte count (12.9%, 95% CI: 4.4%, 22.1%; P = 0.005), and reduced low-frequency power (57.5%, 95% CI: 2.5%, 81.5%; P = 0.04). B-vitamin supplementation attenuated PM2.5 effect on HR by 150% (P = 0.003), low-frequency power by 90% (P = 0.01), total WBC count by 139% (P = 0.006), and lymphocyte count by 106% (P = 0.02). In healthy adults, two-hour PM2.5 exposure substantially increases HR, reduces HRV, and increases WBC. These effects are reduced by B vitamin supplementation. PMID:28367952

  12. B-vitamin Supplementation Mitigates Effects of Fine Particles on Cardiac Autonomic Dysfunction and Inflammation: A Pilot Human Intervention Trial.

    PubMed

    Zhong, Jia; Trevisi, Letizia; Urch, Bruce; Lin, Xinyi; Speck, Mary; Coull, Brent A; Liss, Gary; Thompson, Aaron; Wu, Shaowei; Wilson, Ander; Koutrakis, Petros; Silverman, Frances; Gold, Diane R; Baccarelli, Andrea A

    2017-04-03

    Ambient fine particle (PM2.5) pollution triggers acute cardiovascular events. Individual-level preventions are proposed to complement regulation in reducing the global burden of PM2.5-induced cardiovascular diseases. We determine whether B vitamin supplementation mitigates PM2.5 effects on cardiac autonomic dysfunction and inflammation in a single-blind placebo-controlled crossover pilot trial. Ten healthy adults received two-hour controlled-exposure-experiment to sham under placebo, PM2.5 (250 μg/m(3)) under placebo, and PM2.5 (250 μg/m(3)) under B-vitamin supplementation (2.5 mg/d folic acid, 50 mg/d vitamin B6, and 1 mg/d vitamin B12), respectively. At pre-, post-, 24 h-post-exposure, we measured resting heart rate (HR) and heart rate variability (HRV) with electrocardiogram, and white blood cell (WBC) counts with hematology analyzer. Compared to sham, PM2.5 exposure increased HR (3.8 bpm, 95% CI: 0.3, 7.4; P = 0.04), total WBC count (11.5%, 95% CI: 0.3%, 24.0%; P = 0.04), lymphocyte count (12.9%, 95% CI: 4.4%, 22.1%; P = 0.005), and reduced low-frequency power (57.5%, 95% CI: 2.5%, 81.5%; P = 0.04). B-vitamin supplementation attenuated PM2.5 effect on HR by 150% (P = 0.003), low-frequency power by 90% (P = 0.01), total WBC count by 139% (P = 0.006), and lymphocyte count by 106% (P = 0.02). In healthy adults, two-hour PM2.5 exposure substantially increases HR, reduces HRV, and increases WBC. These effects are reduced by B vitamin supplementation.

  13. SPARC regulates collagen interaction with cardiac fibroblast cell surfaces.

    PubMed

    Harris, Brett S; Zhang, Yuhua; Card, Lauren; Rivera, Lee B; Brekken, Rolf A; Bradshaw, Amy D

    2011-09-01

    Cardiac tissue from mice that do not express secreted protein acidic and rich in cysteine (SPARC) have reduced amounts of insoluble collagen content at baseline and in response to pressure overload hypertrophy compared with wild-type (WT) mice. However, the cellular mechanism by which SPARC affects myocardial collagen is not clearly defined. Although expression of SPARC by cardiac myocytes has been detected in vitro, immunohistochemistry of hearts demonstrated SPARC staining primarily associated with interstitial fibroblastic cells. Primary cardiac fibroblasts isolated from SPARC-null and WT mice were assayed for collagen I synthesis by [(3)H]proline incorporation into procollagen and by immunoblot analysis of procollagen processing. Bacterial collagenase was used to discern intracellular from extracellular forms of collagen I. Increased amounts of collagen I were found associated with SPARC-null versus WT cells, and the proportion of total collagen I detected on SPARC-null fibroblasts without propeptides [collagen-α(1)(I)] was higher than in WT cells. In addition, the amount of total collagen sensitive to collagenase digestion (extracellular) was greater in SPARC-null cells than in WT cells, indicating an increase in cell surface-associated collagen in the absence of SPARC. Furthermore, higher levels of collagen type V, a fibrillar collagen implicated in collagen fibril initiation, were found in SPARC-null fibroblasts. The absence of SPARC did not result in significant differences in proliferation or in decreased production of procollagen I by cardiac fibroblasts. We conclude that SPARC regulates collagen in the heart by modulating procollagen processing and interactions with fibroblast cell surfaces. These results are consistent with decreased levels of interstitial collagen in the hearts of SPARC-null mice being due primarily to inefficient collagen deposition into the extracellular matrix rather than to differences in collagen production.

  14. Cardiac myosin binding protein-C Ser302 phosphorylation regulates cardiac β-adrenergic reserve

    PubMed Central

    Mamidi, Ranganath; Gresham, Kenneth S.; Li, Jiayang; Stelzer, Julian E.

    2017-01-01

    Phosphorylation of cardiac myosin binding protein-C (MyBP-C) modulates cardiac contractile function; however, the specific roles of individual serines (Ser) within the M-domain that are targets for β-adrenergic signaling are not known. Recently, we demonstrated that significant accelerations in in vivo pressure development following β-agonist infusion can occur in transgenic (TG) mouse hearts expressing phospho-ablated Ser282 (that is, TGS282A) but not in hearts expressing phospho-ablation of all three serines [that is, Ser273, Ser282, and Ser302 (TG3SA)], suggesting an important modulatory role for other Ser residues. In this regard, there is evidence that Ser302 phosphorylation may be a key contributor to the β-agonist–induced positive inotropic responses in the myocardium, but its precise functional role has not been established. Thus, to determine the in vivo and in vitro functional roles of Ser302 phosphorylation, we generated TG mice expressing nonphosphorylatable Ser302 (that is, TGS302A). Left ventricular pressure-volume measurements revealed that TGS302A mice displayed no accelerations in the rate of systolic pressure rise and an inability to maintain systolic pressure following dobutamine infusion similar to TG3SA mice, implicating Ser302 phosphorylation as a critical regulator of enhanced systolic performance during β-adrenergic stress. Dynamic strain–induced cross-bridge (XB) measurements in skinned myocardium isolated from TGS302A hearts showed that the molecular basis for impaired β-adrenergic–mediated enhancements in systolic function is due to the absence of protein kinase A–mediated accelerations in the rate of cooperative XB recruitment. These results demonstrate that Ser302 phosphorylation regulates cardiac contractile reserve by enhancing contractile responses during β-adrenergic stress. PMID:28345052

  15. Mathematical biomarkers for the autonomic regulation of cardiovascular system.

    PubMed

    Campos, Luciana A; Pereira, Valter L; Muralikrishna, Amita; Albarwani, Sulayma; Brás, Susana; Gouveia, Sónia

    2013-10-07

    Heart rate and blood pressure are the most important vital signs in diagnosing disease. Both heart rate and blood pressure are characterized by a high degree of short term variability from moment to moment, medium term over the normal day and night as well as in the very long term over months to years. The study of new mathematical algorithms to evaluate the variability of these cardiovascular parameters has a high potential in the development of new methods for early detection of cardiovascular disease, to establish differential diagnosis with possible therapeutic consequences. The autonomic nervous system is a major player in the general adaptive reaction to stress and disease. The quantitative prediction of the autonomic interactions in multiple control loops pathways of cardiovascular system is directly applicable to clinical situations. Exploration of new multimodal analytical techniques for the variability of cardiovascular system may detect new approaches for deterministic parameter identification. A multimodal analysis of cardiovascular signals can be studied by evaluating their amplitudes, phases, time domain patterns, and sensitivity to imposed stimuli, i.e., drugs blocking the autonomic system. The causal effects, gains, and dynamic relationships may be studied through dynamical fuzzy logic models, such as the discrete-time model and discrete-event model. We expect an increase in accuracy of modeling and a better estimation of the heart rate and blood pressure time series, which could be of benefit for intelligent patient monitoring. We foresee that identifying quantitative mathematical biomarkers for autonomic nervous system will allow individual therapy adjustments to aim at the most favorable sympathetic-parasympathetic balance.

  16. Mathematical biomarkers for the autonomic regulation of cardiovascular system

    PubMed Central

    Campos, Luciana A.; Pereira, Valter L.; Muralikrishna, Amita; Albarwani, Sulayma; Brás, Susana; Gouveia, Sónia

    2013-01-01

    Heart rate and blood pressure are the most important vital signs in diagnosing disease. Both heart rate and blood pressure are characterized by a high degree of short term variability from moment to moment, medium term over the normal day and night as well as in the very long term over months to years. The study of new mathematical algorithms to evaluate the variability of these cardiovascular parameters has a high potential in the development of new methods for early detection of cardiovascular disease, to establish differential diagnosis with possible therapeutic consequences. The autonomic nervous system is a major player in the general adaptive reaction to stress and disease. The quantitative prediction of the autonomic interactions in multiple control loops pathways of cardiovascular system is directly applicable to clinical situations. Exploration of new multimodal analytical techniques for the variability of cardiovascular system may detect new approaches for deterministic parameter identification. A multimodal analysis of cardiovascular signals can be studied by evaluating their amplitudes, phases, time domain patterns, and sensitivity to imposed stimuli, i.e., drugs blocking the autonomic system. The causal effects, gains, and dynamic relationships may be studied through dynamical fuzzy logic models, such as the discrete-time model and discrete-event model. We expect an increase in accuracy of modeling and a better estimation of the heart rate and blood pressure time series, which could be of benefit for intelligent patient monitoring. We foresee that identifying quantitative mathematical biomarkers for autonomic nervous system will allow individual therapy adjustments to aim at the most favorable sympathetic-parasympathetic balance. PMID:24109456

  17. Isoform-targeted regulation of cardiac adenylyl cyclase.

    PubMed

    Ishikawa, Yoshihiro

    2003-01-01

    Numerous attempts have been made to develop strategies for regulating the intracellular cyclic AMP signal pharmacologically, with an intention to establish either new medical therapeutic methods or experimental tools. In the past decades, many pharmacological reagents have been identified that regulate this pathway at the level of the receptor. G protein, adenylyl cyclase, cyclic AMP, protein kinase A and phosphodiesterase. Since the cloning of adenylyl cyclase isoforms during the 1990s, investigators including ourselves have tried to find reagents that regulate the activity of this enzyme directly in an isoform-dependent manner. The ultimate goal of developing such reagents would be to regulate the cyclic AMP signal in an organ-dependent manner. Ourselves and other workers have reported that such reagents may vary from a simple cation to kinases. In a more recent study, using the results from crystallographic studies and computer-assisted drug design programs, we have identified subtype-selective regulators of adenylyl cyclase. Such regulators are mostly based upon forskolin, a diterpene compound obtained from Coleus forskolii, that acts directly on adenylyl cyclase to increase the intracellular levels of cyclic AMP. Similarly, novel reagents have been identified that inhibit a specific adenylyl cyclase isoform (e.g. type 5 adenylyl cyclase). Such reagents would potentially provide a new therapeutic strategy to treat hypertension, for example, as well as methods to selectively stimulate or inhibit this adenylyl cyclase isoform, which may be reminiscent of overexpression or knocking out of the cardiac adenylyl cyclase isoform by the use of a pharmacological method.

  18. Phenotypic screen quantifying differential regulation of cardiac myocyte hypertrophy identifies CITED4 regulation of myocyte elongation

    PubMed Central

    Ryall, Karen A.; Bezzerides, Vassilios J.; Rosenzweig, Anthony; Saucerman, Jeffrey J.

    2014-01-01

    Cardiac hypertrophy is controlled by a highly connected signaling network with many effectors of cardiac myocyte size. Quantification of the contribution of individual pathways to specific changes in shape and transcript abundance is needed to better understand hypertrophy signaling and to improve heart failure therapies. We stimulated cardiac myocytes with 15 hypertrophic agonists and quantitatively characterized differential regulation of 5 shape features using high-throughput microscopy and transcript levels of 12 genes using qPCR. Transcripts measured were associated with phenotypes including fibrosis, cell death, contractility, proliferation, angiogenesis, inflammation, and the fetal cardiac gene program. While hypertrophy pathways are highly connected, the agonist screen revealed distinct hypertrophy phenotypic signatures for the 15 receptor agonists. We then used k-means clustering of inputs and outputs to identify a network map linking input modules to output modules. Five modules were identified within inputs and outputs with many maladaptive outputs grouping together in one module: Bax, C/EBPβ, Serca2a, TNFα, and CTGF. Subsequently, we identified mechanisms underlying two correlations revealed in the agonist screen: correlation between regulators of fibrosis and cell death signaling (CTGF and Bax mRNA) caused by AngII; and myocyte proliferation (CITED4 mRNA) and elongation caused by Nrg1. Follow-up experiments revealed positive regulation of Bax mRNA level by CTGF and an incoherent feedforward loop linking Nrg1, CITED4 and elongation. With this agonist screen, we identified the most influential inputs in the cardiac hypertrophy signaling network for a variety of features related to pathological and protective hypertrophy signaling and shared regulation among cardiac myocyte phenotypes. PMID:24613264

  19. Quantifying Effects of Pharmacological Blockers of Cardiac Autonomous Control Using Variability Parameters

    PubMed Central

    Miyabara, Renata; Berg, Karsten; Kraemer, Jan F.; Baltatu, Ovidiu C.; Wessel, Niels; Campos, Luciana A.

    2017-01-01

    Objective: The aim of this study was to identify the most sensitive heart rate and blood pressure variability (HRV and BPV) parameters from a given set of well-known methods for the quantification of cardiovascular autonomic function after several autonomic blockades. Methods: Cardiovascular sympathetic and parasympathetic functions were studied in freely moving rats following peripheral muscarinic (methylatropine), β1-adrenergic (metoprolol), muscarinic + β1-adrenergic, α1-adrenergic (prazosin), and ganglionic (hexamethonium) blockades. Time domain, frequency domain and symbolic dynamics measures for each of HRV and BPV were classified through paired Wilcoxon test for all autonomic drugs separately. In order to select those variables that have a high relevance to, and stable influence on our target measurements (HRV, BPV) we used Fisher's Method to combine the p-value of multiple tests. Results: This analysis led to the following best set of cardiovascular variability parameters: The mean normal beat-to-beat-interval/value (HRV/BPV: meanNN), the coefficient of variation (cvNN = standard deviation over meanNN) and the root mean square differences of successive (RMSSD) of the time domain analysis. In frequency domain analysis the very-low-frequency (VLF) component was selected. From symbolic dynamics Shannon entropy of the word distribution (FWSHANNON) as well as POLVAR3, the non-linear parameter to detect intermittently decreased variability, showed the best ability to discriminate between the different autonomic blockades. Conclusion: Throughout a complex comparative analysis of HRV and BPV measures altered by a set of autonomic drugs, we identified the most sensitive set of informative cardiovascular variability indexes able to pick up the modifications imposed by the autonomic challenges. These indexes may help to increase our understanding of cardiovascular sympathetic and parasympathetic functions in translational studies of experimental diseases. PMID

  20. Role of cardiac output and the autonomic nervous system in the antinatriuretic response to acute constriction of the thoracic superior vena cava.

    NASA Technical Reports Server (NTRS)

    Schrier, R. W.; Humphreys, M. H.; Ufferman, R. C.

    1971-01-01

    Study of the differential characteristics of hepatic congestion and decreased cardiac output in terms of potential afferent stimuli in the antinatriuretic effect of acute thoracic inferior vena cava (TIVC) constriction. An attempt is made to see if the autonomic nervous system is involved in the antinatriuretic effect of acute TIVC or thoracic superior vena cava constriction.

  1. Measures of Autonomic Nervous System

    DTIC Science & Technology

    2011-04-01

    Gastro- intestinal Pupillary Response Respiratory Salivary Amylase Vascular Manipulative Body-Based/ Tension-Release Practices Trauma...Physiological Activities ANS Physiological Activities Cardiac Pupillary Response Catecholamines Respiration Cortisol Salivary Amylase Galvanic Skin...Measures of Autonomic Nervous System Regulation Salivary Amylase Measurement Most measures of salivary amylase

  2. Vestibular autonomic regulation (including motion sickness and the mechanism of vomiting)

    NASA Technical Reports Server (NTRS)

    Balaban, C. D.

    1999-01-01

    Autonomic manifestations of vestibular dysfunction and motion sickness are well established in the clinical literature. Recent studies of 'vestibular autonomic regulation' have focused predominantly on autonomic responses to stimulation of the vestibular sense organs in the inner ear. These studies have shown that autonomic responses to vestibular stimulation are regionally selective and have defined a 'vestibulosympathetic reflex' in animal experiments. Outside the realm of experimental preparations, however, the importance of vestibular inputs in autonomic regulation is unclear because controls for secondary factors, such as affective/emotional responses and cardiovascular responses elicited by muscle contraction and regional blood pooling, have been inadequate. Anatomic and physiologic evidence of an extensive convergence of vestibular and autonomic information in the brainstem suggests though that there may be an integrated representation of gravitoinertial acceleration from vestibular, somatic, and visceral receptors for somatic and visceral motor control. In the case of vestibular dysfunction or motion sickness, the unpleasant visceral manifestations (e.g. epigastric discomfort, nausea or vomiting) may contribute to conditioned situational avoidance and the development of agoraphobia.

  3. [Status of the mechanisms of autonomic regulation in Raynaud's disease].

    PubMed

    Tabeeva, G R

    1991-01-01

    Patients suffering from Raynaud's disease underwent clinicoelectrophysiological studies for the status of the segmental and autonomous nervous system. Based on the distribution of the patients' group with Raynaud's disease according to the type of the disease course and intensity of Raynaud's phenomenon, the author shows a relationship between the clinical manifestations of the leading phenomenon and disorders of sympathetic conduction in the limbs. That made it possible to suggest that peripheral vegetative neuropathy together with the well-defined psychovegetative syndrome may be implicated in the pathogenesis of Raynaud's disease.

  4. Fatalities after taking ibogaine in addiction treatment could be related to sudden cardiac death caused by autonomic dysfunction.

    PubMed

    Maas, U; Strubelt, S

    2006-01-01

    Ibogaine is the most important alkaloid of the Central African Iboga-shrub. It is the central drug in Gabonian initiation ceremonies in which it is used to cause a near-death experience. In Western countries it is used in private clinics to treat addiction. However, in the United States and most European countries it is classified as an illegal drug because at least eight persons have died after having taken Ibogaine. These fatalities occurred in most cases several days after ingestion or following the intake of very small doses. There is no conclusive explanation at the present time for these deaths. We hypothesize, that these deaths may be a result of cardiac arrhythmias, caused by a dysregulation of the autonomic nervous system. Ibogaine affects the autonomic nervous system by influencing several neurotransmitter-systems and the fastigial nucleus. The cerebellar nucleus responds to small doses with a stimulation of the sympathetic system, leading to a fight or flight reaction. High doses, however, lead to a vagal dominance: a "feigned death". The risk of cardiac arrhythmias is increased in situations of sympathetic stimulation or coincidence of a high parasympathetic tonus and a left-sided sympathetic stimulation. This could occur under influence of small doses of ibogaine and also at times of exhaustion with a high vagal tonus, when sudden fear reactions could cause a critical left-sided sympathetic stimulation. Gabonian healers prevent these risks by isolating their patients from normal life and by inducing a trance-state with right-hemispheric and vagal dominance for several days.

  5. Electrochemical Skin Conductance May Be Used to Screen for Diabetic Cardiac Autonomic Neuropathy in a Chinese Population with Diabetes

    PubMed Central

    He, Tianyi; Wang, Chuan; Zuo, Anju; Liu, Pan; Li, Wenjuan

    2017-01-01

    Aims. This study aimed to assess whether the electrochemical skin conductance (ESC) could be used to screen for diabetic cardiac autonomic neuropathy (DCAN) in a Chinese population with diabetes. Methods. We recruited 75 patients with type 2 diabetes mellitus (T2DM) and 45 controls without diabetes. DCAN was diagnosed by the cardiovascular autonomic reflex tests (CARTs) as gold standard. In all subjects ESCs of hands and feet were also detected by SUDOSCAN™ as a new screening method. The efficacy was assessed by receiver operating characteristic (ROC) curve analysis. Results. The ESCs of both hands and feet were significantly lower in T2DM patients with DCAN than those without DCAN (67.33 ± 15.37 versus 78.03 ± 13.73, P = 0.002, and 57.77 ± 20.99 versus 75.03 ± 11.41, P < 0.001). The ROC curve analysis showed the areas under the ROC curve were both 0.75 for ESCs of hands and feet in screening DCAN. And the optimal cut-off values of ESCs, sensitivities, and specificities were 76 μS, 76.7%, and 75.6% for hands and 75 μS, 80.0%, and 60.0% for feet, respectively. Conclusions. ESC measurement is a reliable and feasible method to screen DCAN in the Chinese population with diabetes before further diagnosis with CARTs. PMID:28280746

  6. Cardiac autonomic functions and the emergence of violence in a highly realistic model of social conflict in humans

    PubMed Central

    Haller, Jozsef; Raczkevy-Deak, Gabriella; Gyimesine, Katalin P.; Szakmary, Andras; Farkas, Istvan; Vegh, Jozsef

    2014-01-01

    Among the multitude of factors that can transform human social interactions into violent conflicts, biological features received much attention in recent years as correlates of decision making and aggressiveness especially in critical situations. We present here a highly realistic new model of human aggression and violence, where genuine acts of aggression are readily performed and which at the same time allows the parallel recording of biological concomitants. Particularly, we studied police officers trained at the International Training Centre (Budapest, Hungary), who are prepared to perform operations under extreme conditions of stress. We found that aggressive arousal can transform a basically peaceful social encounter into a violent conflict. Autonomic recordings show that this change is accompanied by increased heart rates, which was associated earlier with reduced cognitive complexity of perceptions (“attentional myopia”) and promotes a bias toward hostile attributions and aggression. We also observed reduced heart rate variability in violent subjects, which is believed to signal a poor functioning of prefrontal-subcortical inhibitory circuits and reduces self-control. Importantly, these autonomic particularities were observed already at the beginning of social encounters i.e., before aggressive acts were initiated, suggesting that individual characteristics of the stress-response define the way in which social pressure affects social behavior, particularly the way in which this develops into violence. Taken together, these findings suggest that cardiac autonomic functions are valuable external symptoms of internal motivational states and decision making processes, and raise the possibility that behavior under social pressure can be predicted by the individual characteristics of stress responsiveness. PMID:25374519

  7. The effects of chewing versus caffeine on alertness, cognitive performance and cardiac autonomic activity during sleep deprivation.

    PubMed

    Kohler, Mark; Pavy, Alan; van den Heuvel, Cameron

    2006-12-01

    Chewing has been shown to alleviate feelings of sleepiness and improve cognitive performance during the day. This study investigated the effect of chewing on alertness and cognitive performance across one night without sleep as well as the possible mediating role of cardiac autonomic activity. Fourteen adults participated in a randomized, counterbalanced protocol employing a chewing, placebo and caffeine condition. Participants completed tasks assessing psychomotor vigilance, tracking, grammatical reasoning, alertness and sleepiness each hour across the night. All participants received either placebo or caffeine (200 mg), while the chewing condition also chewed on a tasteless and odorless substance for 15 min each hour. Heart rate (HR), root mean square of the successive differences in R-R intervals on the ECG (RMSSD), and preejection period (PEP) were simultaneously recorded. Alertness and cognitive performance amongst the chewing condition did not differ or were in fact worse when compared with placebo. Similarly, measures of HR and RMSSD remained the same between these two conditions; however, PEP was reduced in the later part of the night in the chewing condition compared with a relative increase for placebo. Caffeine led to improved speed and accuracy on cognitive tasks and increased alertness when compared with chewing. Relative increases in RMSSD and reductions in HR were demonstrated following caffeine; however, no change in PEP was seen. Strong associations between cardiac parasympathetic activity and complex cognitive tasks, as well as between subjective alertness and simpler cognitive tasks, suggest a differential process mediating complex versus simple cognitive performance during sleep deprivation.

  8. Dynamic response of cardiac autonomic nervous system activity to habitual exercise during gradual variation of breathing frequency.

    PubMed

    Nakamura, H

    2015-01-01

    The purpose of this study is to measure cardiac autonomic nervous system activity during breathing control with gradual alteration of the frequency between habitual exercise and sedentary young male subjects. In this study, to evaluate CANS activity, Tone-Entropy analysis, which is based on statistical property of acceleration between consecutive R-R intervals, was used. Sixteen healthy young male subjects (21.6+/-1.4yrs) were participated in these experiments and their R-R interval sequences were recorded. The controlled breathing trials let the subjects synchronize their breathing frequency ranging 3 to 30 breathing per minute. After that, breathing frequency was gradually and reversely decreased from 30 to 3 breathing per minute. Before and after the breathing controlled trials, 5 minute voluntary breathing trials were performed. Our results showed that total CANS activities of HE group were activated more than those of SE group in the entire sections and also that, as compared with HE group, maximum of average HR in SE group was appeared at 30 breathing per minute and it is recognized that the statistically significant difference between HE and SE group was shown. In conclusion, our results suggest that efficiency of cardiac function on habitual exercise in breathing control may be quantitatively and graphically evaluated with HR and Tone-Entropy analysis without any physical stimulation.

  9. [Researches of autonomic regulation of blood circulation in the condition of long-term space flight].

    PubMed

    Baevskiĭ, R M; Luchitskaia, E S; Funtova, I I; Chernikova, A G

    2013-01-01

    In the article is presented five-year experience of experimentation in autonomic regulation of blood circulation onboard the International space station. The heart rate variability (HRV) analysis was the basic methodical approach in the researches. We described probabilistic approach created on the basis of HRV analysis to an estimation of risk of pathology development in the conditions of long space flight. The individual type of autonomic regulation had essential value during the analysis of results. It is shown that the type of regulation, which is inherent in every cosmonaut in the conditions of weightlessness, remains even during following flights. We obtained the new scientific data on connection of character of adaptable reaction of an organism to the space flight factors with individual type of autonomic regulation. It is shown that staying in weightlessness is connected with changeover of regulatory systems and with transition in a zone of prenosological states. Adaptable reactions in weightlessness are characterized by tension growth of regulatory systems at preservation of sufficient functional reserves. The mobilization of additional resources after returning to the Earth is required and consequently functional reserve of mechanisms of regulation decreases. Cosmonauts with vagotonic and normo-sympatotonic types of autonomic regulation appear to be the most resistant. Knowing the type of autonomic regulation we will be able to foresee possible reaction of the cosmonaut to the factors of space flight. As a result of HRV analysis during the flight of the past few months likelihood estimations were calculated and risk categories were defined. Consequently, 3 groups of risk of pathology development were distinguished. In conclusion, theoretical and applied relevance of the conducted experiments were considered.

  10. Engineered hybrid cardiac patches with multifunctional electronics for online monitoring and regulation of tissue function

    NASA Astrophysics Data System (ADS)

    Feiner, Ron; Engel, Leeya; Fleischer, Sharon; Malki, Maayan; Gal, Idan; Shapira, Assaf; Shacham-Diamand, Yosi; Dvir, Tal

    2016-06-01

    In cardiac tissue engineering approaches to treat myocardial infarction, cardiac cells are seeded within three-dimensional porous scaffolds to create functional cardiac patches. However, current cardiac patches do not allow for online monitoring and reporting of engineered-tissue performance, and do not interfere to deliver signals for patch activation or to enable its integration with the host. Here, we report an engineered cardiac patch that integrates cardiac cells with flexible, freestanding electronics and a 3D nanocomposite scaffold. The patch exhibited robust electronic properties, enabling the recording of cellular electrical activities and the on-demand provision of electrical stimulation for synchronizing cell contraction. We also show that electroactive polymers containing biological factors can be deposited on designated electrodes to release drugs in the patch microenvironment on demand. We expect that the integration of complex electronics within cardiac patches will eventually provide therapeutic control and regulation of cardiac function.

  11. Engineered hybrid cardiac patches with multifunctional electronics for online monitoring and regulation of tissue function

    PubMed Central

    Feiner, Ron; Engel, Leeya; Fleischer, Sharon; Malki, Maayan; Gal, Idan; Shapira, Assaf; Shacham-Diamand, Yosi; Dvir, Tal

    2016-01-01

    In cardiac tissue engineering approaches to treat myocardial infarction, cardiac cells are seeded within three-dimensional porous scaffolds to create functional cardiac patches. However, current cardiac patches do not allow for online monitoring and reporting of engineered-tissue performance, and do not interfere to deliver signals for patch activation or to enable its integration with the host. Here, we report an engineered cardiac patch that integrates cardiac cells with flexible, free-standing electronics and a 3D nanocomposite scaffold. The patch exhibited robust electronic properties, enabling the recording of cellular electrical activities and the on-demand provision of electrical stimulation for synchronizing cell contraction. We also show that electroactive polymers containing biological factors can be deposited on designated electrodes to release drugs in the patch microenvironment on-demand. We expect that the integration of complex electronics within cardiac patches will eventually provide therapeutic control and regulation of cardiac function. PMID:26974408

  12. Updates on the Methodological Approaches for Carrying Out an In-Depth Study of the Cardiac Conduction System and the Autonomic Nervous System of Victims of Sudden Unexplained Fetal and Infant Death

    PubMed Central

    Alfonsi, Graziella; Crippa, Marina

    2016-01-01

    This article contains a set of protocols for histopathological techniques that can be used for carrying out in-depth studies of cases of sudden infant death syndrome and sudden intrauterine unexplained fetal death syndrome. In order to enable researchers to advance hypotheses regarding the causes of the unexpected death of infants and fetuses, the authors propose three innovative and accurate methodologies for studying the cardiac conduction system, the peripheral cardiac nervous system, and the central autonomic nervous system. Over the years, these protocols have been developed, modified, and improved on a vast number of cases which has enabled pathologists to carry out the microscopic analyses of the structures which regulate life, in order to highlight all the possible morphological substrates of pathophysiological mechanisms that may underlie these syndromes. In memory of our research professor Lino Rossi (1923–2004). PMID:27917382

  13. Autonomous and nonautonomous roles of Hedgehog signaling in regulating limb muscle formation

    PubMed Central

    Hu, Jimmy Kuang-Hsien; McGlinn, Edwina; Harfe, Brian D.; Kardon, Gabrielle; Tabin, Clifford J.

    2012-01-01

    Muscle progenitor cells migrate from the lateral somites into the developing vertebrate limb, where they undergo patterning and differentiation in response to local signals. Sonic hedgehog (Shh) is a secreted molecule made in the posterior limb bud that affects patterning and development of multiple tissues, including skeletal muscles. However, the cell-autonomous and non-cell-autonomous functions of Shh during limb muscle formation have remained unclear. We found that Shh affects the pattern of limb musculature non-cell-autonomously, acting through adjacent nonmuscle mesenchyme. However, Shh plays a cell-autonomous role in maintaining cell survival in the dermomyotome and initiating early activation of the myogenic program in the ventral limb. At later stages, Shh promotes slow muscle differentiation cell-autonomously. In addition, Shh signaling is required cell-autonomously to regulate directional muscle cell migration in the distal limb. We identify neuroepithelial cell transforming gene 1 (Net1) as a downstream target and effector of Shh signaling in that context. PMID:22987639

  14. Analysis of cardiac autonomic modulation of children with attention deficit hyperactivity disorder

    PubMed Central

    de Carvalho, Tatiana Dias; Wajnsztejn, Rubens; de Abreu, Luiz Carlos; Marques Vanderlei, Luiz Carlos; Godoy, Moacir Fernandes; Adami, Fernando; Valenti, Vitor E; Monteiro, Carlos B M; Leone, Claudio; da Cruz Martins, Karen Cristina; Ferreira, Celso

    2014-01-01

    Background Attention deficit hyperactivity disorder (ADHD) is characterized by decreased attention span, impulsiveness, and hyperactivity. Autonomic nervous system imbalance was previously described in this population. We aim to compare the autonomic function of children with ADHD and controls by analyzing heart rate variability (HRV). Methods Children rested in supine position with spontaneous breathing for 20 minutes. Heart rate was recorded beat by beat. HRV analysis was performed in the time and frequency domains and Poincaré plot. Results Twenty-eight children with ADHD (22 boys, aged 9.964 years) and 28 controls (15 boys, age 9.857 years) participated in this study. It was determined that the mean and standard deviation of indexes which indicate parasympathetic activity is higher in children with ADHD than in children without the disorder: high frequency in normalized units, 46.182 (14.159) versus 40.632 (12.247); root mean square of successive differences, 41.821 (17.834) versus 38.150 (18.357); differences between adjacent normal-to-normal intervals greater than 50 milliseconds, 199.75 (144.00) versus 127.46 (102.21) (P<0.05); percentage of differences between adjacent normal-to-normal intervals greater than 50 milliseconds, 23.957 (17.316) versus 16.211 (13.215); standard deviation of instantaneous beat-to-beat interval, 29.586 (12.622) versus 26.989 (12.983). Conclusion Comparison of the autonomic function by analyzing HRV suggests an increase in the activity of the parasympathetic autonomic nervous systems in children with ADHD in relation to the control group. PMID:24748797

  15. Reduced cardiac autonomic response to deep breathing: A heritable vulnerability trait in patients with schizophrenia and their healthy first-degree relatives.

    PubMed

    Liu, Yu-Wen; Tzeng, Nian-Sheng; Yeh, Chin-Bin; Kuo, Terry B J; Huang, San-Yuan; Chang, Chuan-Chia; Chang, Hsin-An

    2016-09-30

    Reduced resting heart rate variability (HRV) has been observed in patients with schizophrenia and their relatives, suggesting genetic predispositions. However, findings have not been consistent. We assessed cardiac autonomic response to deep breathing in first-degree relatives of patients with schizophrenia (n=45; 26 female; aged 39.69±14.82 years). Data were compared to healthy controls (n=45; 26 female; aged 38.27±9.79 years) matched for age, gender, body mass index and physical activity as well as to unmedicated patients with acute schizophrenia (n=45; 25 female; aged 37.31±12.65 years). Electrocardiograms were recorded under supine resting and deep-breathing conditions (10-12breaths/min). We measured HRV components including variance, low-frequency (LF) power, which may reflect baroreflex function, high-frequency (HF) power, which reflects cardiac parasympathetic activity, and LF/HF ratio, which may reflect sympatho-vagal balance. Patients rather than relatives exhibited lower resting-state HRV (variance, LF, and HF) than controls. As expected, deep breathing induced an increase in variance and HF-HRV in controls. However, such a response was significantly reduced in both patients and their relatives. In conclusion, the diminished cardiac autonomic reactivity to deep breathing seen in patients and their unaffected relatives indicates that this pattern of cardiac autonomic dysregulation may be regarded as a genetic trait marker for schizophrenia.

  16. Belousov-Zhabotinsky autonomic hydrogel composites: Regulating waves via asymmetry

    PubMed Central

    Buskohl, Philip R.; Vaia, Richard A.

    2016-01-01

    Belousov-Zhabotinsky (BZ) autonomic hydrogel composites contain active nodes of immobilized catalyst (Ru) encased within a nonactive matrix. Designing functional hierarchies of chemical and mechanical communication between these nodes enables applications ranging from encryption, sensors, and mechanochemical actuators to artificial skin. However, robust design rules and verification of computational models are challenged by insufficient understanding of the relative importance of local (molecular) heterogeneities, active node shape, and embedment geometry on transient and steady-state behavior. We demonstrate the predominance of asymmetric embedment and node shape in low-strain, BZ-gelatin composites and correlate behavior with gradients in BZ reactants. Asymmetric embedment of square and rectangular nodes results in directional steady-state waves that initiate at the embedded edge and propagate toward the free edge. In contrast, symmetric embedment does not produce preferential wave propagation because of a lack of diffusion gradient across the catalyzed region. The initiation at the embedded edge is correlated with bromide absorption by the inactive matrix, which locally elevates the bromate concentration required for catalyst oxidation. The competition between embedment asymmetry and node geometry was used to demonstrate a repeatable switch in wave direction that functions as a signal delay. Furthermore, signal propagation in or out of the composite was demonstrated via embedment asymmetry and relative dimensions of a T-shaped active network node. Overall, structural asymmetry provides a robust approach to controlling initiation and orientation of chemical-mechanical communication within composite BZ gels. PMID:27679818

  17. Short-Term Complexity of Cardiac Autonomic Control during Sleep: REM as a Potential Risk Factor for Cardiovascular System in Aging

    PubMed Central

    Chellappa, Sarah L.; Casali, Karina Rabello; Porta, Alberto; Montano, Nicola

    2011-01-01

    Introduction Sleep is a complex phenomenon characterized by important modifications throughout life and by changes of autonomic cardiovascular control. Aging is associated with a reduction of the overall heart rate variability (HRV) and a decrease of complexity of autonomic cardiac regulation. The aim of our study was to evaluate the HRV complexity using two entropy-derived measures, Shannon Entropy (SE) and Corrected Conditional Entropy (CCE), during sleep in young and older subjects. Methods A polysomnographic study was performed in 12 healthy young (21.1±0.8 years) and 12 healthy older subjects (64.9±1.9 years). After the sleep scoring, heart period time series were divided into wake (W), Stage 1–2 (S1-2), Stage 3–4 (S3-4) and REM. Two complexity indexes were assessed: SE(3) measuring the complexity of a distribution of 3-beat patterns (SE(3) is higher when all the patterns are identically distributed and it is lower when some patterns are more likely) and CCEmin measuring the minimum amount of information that cannot be derived from the knowledge of previous values. Results Across the different sleep stages, young subjects had similar RR interval, total variance, SE(3) and CCEmin. In the older group, SE(3) and CCEmin were reduced during REM sleep compared to S1-2, S3-4 and W. Compared to young subjects, during W and sleep the older subjects showed a lower RR interval and reduced total variance as well as a significant reduction of SE(3) and CCEmin. This decrease of entropy measures was more evident during REM sleep. Conclusion Our study indicates that aging is characterized by a reduction of entropy indices of cardiovascular variability during wake/sleep cycle, more evident during REM sleep. We conclude that during aging REM sleep is associated with a simplification of cardiac control mechanisms that could lead to an impaired ability of the cardiovascular system to react to cardiovascular adverse events. PMID:21544202

  18. Changes in autonomic regulation with age: implications for psychopharmacologic treatments in children and adolescents.

    PubMed

    Galanter, C A; Wasserman, G; Sloan, R P; Pine, D S

    1999-01-01

    Developmental changes in the cardiovascular system could have an impact on risks associated with psychopharmacological interventions. Children may be more vulnerable to adverse cardiac events due to immaturity in autonomic control of the heart. These changes are incompletely understood and are characterized in this study. A consecutive series of 70 boys, aged 6-14 years, was recruited. Developmental variation in the autonomic nervous system was evaluated by assessing heart period variability (HPV), pulse, and blood pressure in response to orthostasis. Increased age correlated significantly with greater heart rate and diastolic blood pressure response to orthostasis. HPV at rest and in response to tilt did not significantly correlate with age. Boys with family histories of hypertension had a significantly greater blood pressure response to orthostasis. These findings suggest that developmental age-related changes in the sympathetic nervous system, as reflected by changes of pulse and blood pressure response to tilt, occur across this age range. Parasympathetic changes, as reflected by HPV, do not. In light of these findings, more research is needed on children's and adolescents' relative cardiac risk with psychotropic medications as opposed to adults'.

  19. Acute ingestion of alcohol and cardiac autonomic modulation in healthy volunteers.

    PubMed

    Bau, Paulo F D; Moraes, Ruy S; Bau, Claiton H D; Ferlin, Elton L; Rosito, Guido A; Fuchs, Flávio D

    2011-03-01

    Arrhythmogenic effects of alcohol may be intermediated by its effects over heart rate variability (HRV). Most studies about the effects of alcohol over HRV were observational and did not explore the temporal influence of alcohol ingestion over autonomic modulation. The aim of this study was to verify if an acute ingestion of alcohol has a time-dependent influence over time-domain indices of HRV. The effect of the ingestion of 60 g of ethanol or placebo over autonomic modulation was compared in healthy men (35 per group), with 18-25 years of age, before and during 17 h after ingestion. Alcohol promoted a fall in the standard deviation of all normal R-R intervals, root mean square of successive differences, and percentage of pairs of adjacent R-R intervals differing by more than 50 ms and in two indices of the three-dimensional return map, by a period up to 10 h after the ingestion of alcohol, accompanied by an increase in heart rate. The indices returned to values similar of the control group 10 h after ingestion. The effects over HRV indices were attenuated by adjustment for heart rate. The ingestion of alcohol induces a broad cardiovascular adaptation secondary to vagal withdrawal and sympathetic activation that may be responsible for arrhythmogenic effects of alcohol ingestion.

  20. Cardiac autonomic modulation in healthy elderly after different intensities of dynamic exercise

    PubMed Central

    Droguett, Viviane Santos López; Santos, Amilton da Cruz; de Medeiros, Carlos Eduardo; Marques, Douglas Porto; do Nascimento, Leone Severino; Brasileiro-Santos, Maria do Socorro

    2015-01-01

    Purpose To investigate the heart rate (HR) and its autonomic modulation at baseline and during dynamic postexercise (PEX) with intensities of 40% and 60% of the maximum HR in healthy elderly. Methods This cross-sectional study included ten apparently healthy people who had been submitted to a protocol on a cycle ergometer for 35 minutes. Autonomic modulation was evaluated by spectral analysis of HR variability (HRV). Results A relevant increase in HR response was observed at 15 minutes postexercise with intensities of 60% and 40% of the maximum HR (10±2 bpm versus 5±1 bpm, respectively; P=0.005), and a significant reduction in HRV was also noted with 40% and 60% intensities during the rest period, and significant reduction in HRV (RR variance) was also observed in 40% and 60% intensities when compared to the baseline, as well as between the post-exercise intensities (1032±32 ms versus 905±5 ms) (P<0.001). In the HRV spectral analysis, a significant increase in the low frequency component HRV and autonomic balance at 40% of the maximum HR (68±2 normalized units [nu] versus 55±1 nu and 2.0±0.1 versus 1.2±0.1; P<0.001) and at 60% of the maximum HR (77±1 nu versus 55±1 nu and 3.2±0.1 versus 1.2±0.1 [P<0.001]) in relation to baseline was observed. A significant reduction of high frequency component at 40% and 60% intensities, however, was observed when compared to baseline (31±2 nu and 23±1 nu versus 45±1 nu, respectively; P<0.001). Moreover, significant differences were observed for the low frequency and high frequency components, as well as for the sympathovagal balance between participants who reached 40% and 60% of the maximum HR. Conclusion There was an increase in the HR, sympathetic modulation, and sympathovagal balance, as well as a reduction in vagal modulation in the elderly at both intensities of the PEX. PMID:25653509

  1. Effect of Head-Down Bed Rest and Artificial Gravity Countermeasure on Cardiac Autonomic and Advanced Electrocardiographic Function

    NASA Technical Reports Server (NTRS)

    Schlegel, T. T.; Platts, S.; Stenger, M.; Ribeiro, C.; Natapoff, A.; Howarth, M.; Evans, J.

    2007-01-01

    To study the effects of 21 days of head-down bed rest (HDBR), with versus without an artificial gravity (AG) countermeasure, on cardiac autonomic and advanced electrocardiographic function. Fourteen healthy men participated in the study: seven experienced 21 days of HDBR alone ("HDBR controls") and seven the same degree and duration of HDBR but with approximately 1hr daily short-arm centrifugation as an AG countermeasure ("AG-treated"). Five minute supine high-fidelity 12-lead ECGs were obtained in all subjects: 1) 4 days before HDBR; 2) on the last day of HDBR; and 3) 7 days after HDBR. Besides conventional 12-lead ECG intervals and voltages, all of the following advanced ECG parameters were studied: 1) both stochastic (time and frequency domain) and deterministic heart rate variability (HRV); 2) beat-to-beat QT interval variability (QTV); 3) T-wave morphology, including signal-averaged T-wave residua (TWR) and principal component analysis ratios; 4) other SAECG-related parameters including high frequency QRS ECG and late potentials; and 5) several advanced ECG estimates of left ventricular (LV) mass. The most important results by repeated measures ANOVA were that: 1) Heart rates, Bazett-corrected QTc intervals, TWR, LF/HF power and the alpha 1 of HRV were significantly increased in both groups (i.e., by HDBR), but with no relevant HDBR*group differences; 2) All purely "vagally-mediated" parameters of HRV (e.g., RMSSD, HF power, Poincare SD1, etc.), PR intervals, and also several parameters of LV mass (Cornell and Sokolow-Lyon voltages, spatial ventricular activation times, ventricular gradients) were all significantly decreased in both groups (i.e., by HDBR), but again with no relevant HDBR*group differences); 3) All "generalized" or "vagal plus sympathetic" parameters of stochastic HRV (i.e., SDNN, total power, LF power) were significantly more decreased in the AG-treated group than in the HDBR-only group (i.e., here there was a relevant HDBR*group difference

  2. AKAP-scaffolding proteins and regulation of cardiac physiology.

    PubMed

    Mauban, J R H; O'Donnell, M; Warrier, S; Manni, S; Bond, M

    2009-04-01

    A kinase anchoring proteins (AKAPs) compose a growing list of diverse but functionally related proteins defined by their ability to bind to the regulatory subunit of protein kinase A. AKAPs perform an integral role in the spatiotemporal modulation of a multitude of cellular signaling pathways. This review highlights the extensive role of AKAPs in cardiac excitation/contraction coupling and cardiac physiology. The literature shows that particular AKAPs are involved in cardiac Ca(2+) influx, release, reuptake, and myocyte repolarization. Studies have also suggested roles for AKAPs in cardiac remodeling. Transgenic studies show functional effects of AKAPs, not only in the cardiovascular system but in other organ systems as well.

  3. Validation of the state version questionnaire on autonomic regulation (state-aR) for cancer patients

    PubMed Central

    2011-01-01

    Objectives Current quality of life inventories used in oncology mainly measure the effects of chemo- or radiotherapy alongside functional and role scales. A new approach is to measure the autonomic state of regulation with the trait-inventory of autonomic regulation (Trait-aR). Loss of Trait-aR has been shown in different medical conditions such as breast cancer (BC) but not in colorectal cancer patients (CRC). In this paper we report the validation of a new state autonomic regulation scale (State-aR) of the last week. Methods Study 1 included 114 participants: (41 women/16 men with cancer and 57 age- and gender-matched healthy people) to conduct a reliability-, factor- and validity-analysis. Concurrent and convergent validity was evaluated with Trait-aR, Fatigue-Numeri-cal-Scale, Hospital Anxiety and Depression Scale (HADS-D) and the self-regulation scale, 65 participants were retested. Study 2 completed 42 participants: 17 with BC and 25 with CRC receiving chemotherapy. The State-aR was administered prior, during and after chemotherapy for measuring responsiveness. Results The factor analysis loaded to four subscales of State-aR (rest-activity, orthostatic-circulatory, thermosweating and digestive regulation) with a: Cronbach-α rα = 0.77-0.83 and a test-retest-reliability rrt = 0.60-0.80. The sum- and sub scales correlated with their concurrent subscales in the Trait-aR (0.48-0.74) and with the sum-scale moderately with all convergent criteria (r = 0.41 --0.44; p < 0.001). During chemotherapy the State-aR-sum and rest-activity-scale decreased significantly compared to the change in the Trait-aR (p < 0.05). Conclusions These findings support that the state autonomic regulation scale has satisfactory to good reliability, good validity and acceptable responsiveness in the context of chemotherapy treatment. PMID:22024425

  4. Evolutionary origin of autonomic regulation of physiological activities in vertebrate phyla.

    PubMed

    Shimizu, Hiroshi; Okabe, Masataka

    2007-10-01

    Proper regulation of physiological activities is crucial for homeostasis in animals. Autonomic regulation of these activities is most developed in mammals, in which a part of peripheral nervous system, termed the autonomic nervous system plays the dominant role. Circulatory activity and digestive activity in vertebrates change in opposite phases to each other. The stage where circulatory activity is high and digestive activity is low is termed the "fight or flight stage" while the stage where circulatory activity is low and digestive activity is high is termed the "rest and digest stage". It has been thought that the autonomic nervous system originated in early vertebrate phyla and developed to its greatest extent in mammals. In this study, we compared the pattern of change of circulatory and digestive activities in several invertebrates and found that the two stages seen in mammals are also present in a wide variety of animals, including evolutionarily early-diverging invertebrate taxa. From this and other arguments we propose a novel possibility that the basic properties of the autonomic nervous system were established very early in metazoan evolution.

  5. Evidence for vestibular regulation of autonomic functions in a mouse genetic model

    NASA Technical Reports Server (NTRS)

    Murakami, Dean M.; Erkman, Linda; Hermanson, Ola; Rosenfeld, Michael G.; Fuller, Charles A.

    2002-01-01

    Physiological responses to changes in the gravitational field and body position, as well as symptoms of patients with anxiety-related disorders, have indicated an interrelationship between vestibular function and stress responses. However, the relative significance of cochlear and vestibular information in autonomic regulation remains unresolved because of the difficulties in distinguishing the relative contributions of other proprioceptive and interoceptive inputs, including vagal and somatic information. To investigate the role of cochlear and vestibular function in central and physiological responses, we have examined the effects of increased gravity in wild-type mice and mice lacking the POU homeodomain transcription factor Brn-3.1 (Brn-3bPou4f3). The only known phenotype of the Brn-3.1(-/-) mouse is related to hearing and balance functions, owing to the failure of cochlear and vestibular hair cells to differentiate properly. Here, we show that normal physiological responses to increased gravity (2G exposure), such as a dramatic drop in body temperature and concomitant circadian adjustment, were completely absent in Brn-3.1(-/-) mice. In line with the lack of autonomic responses, the massive increase in neuronal activity after 2G exposure normally detected in wild-type mice was virtually abolished in Brn-3.1(-/-) mice. Our results suggest that cochlear and vestibular hair cells are the primary regulators of autonomic responses to altered gravity and provide genetic evidence that these cells are sufficient to alter neural activity in regions involved in autonomic and neuroendocrine control.

  6. Executive Cognitive Functioning and Cardiovascular Autonomic Regulation in a Population-Based Sample of Working Adults

    PubMed Central

    Stenfors, Cecilia U. D.; Hanson, Linda M.; Theorell, Töres; Osika, Walter S.

    2016-01-01

    Objective: Executive cognitive functioning is essential in private and working life and is sensitive to stress and aging. Cardiovascular (CV) health factors are related to cognitive decline and dementia, but there is relatively few studies of the role of CV autonomic regulation, a key component in stress responses and risk factor for cardiovascular disease (CVD), and executive processes. An emerging pattern of results from previous studies suggest that different executive processes may be differentially associated with CV autonomic regulation. The aim was thus to study the associations between multiple measures of CV autonomic regulation and measures of different executive cognitive processes. Method: Participants were 119 healthy working adults (79% women), from the Swedish Longitudinal Occupational Survey of Health. Electrocardiogram was sampled for analysis of heart rate variability (HRV) measures, including the Standard Deviation of NN, here heart beats (SDNN), root of the mean squares of successive differences (RMSSD), high frequency (HF) power band from spectral analyses, and QT variability index (QTVI), a measure of myocardial repolarization patterns. Executive cognitive functioning was measured by seven neuropsychological tests. The relationships between CV autonomic regulation measures and executive cognitive measures were tested with bivariate and partial correlational analyses, controlling for demographic variables, and mental health symptoms. Results: Higher SDNN and RMSSD and lower QTVI were significantly associated with better performance on cognitive tests tapping inhibition, updating, shifting, and psychomotor speed. After adjustments for demographic factors however (age being the greatest confounder), only QTVI was clearly associated with these executive tests. No such associations were seen for working memory capacity. Conclusion: Poorer CV autonomic regulation in terms of lower SDNN and RMSSD and higher QTVI was associated with poorer executive

  7. Executive Cognitive Functioning and Cardiovascular Autonomic Regulation in a Population-Based Sample of Working Adults.

    PubMed

    Stenfors, Cecilia U D; Hanson, Linda M; Theorell, Töres; Osika, Walter S

    2016-01-01

    Objective: Executive cognitive functioning is essential in private and working life and is sensitive to stress and aging. Cardiovascular (CV) health factors are related to cognitive decline and dementia, but there is relatively few studies of the role of CV autonomic regulation, a key component in stress responses and risk factor for cardiovascular disease (CVD), and executive processes. An emerging pattern of results from previous studies suggest that different executive processes may be differentially associated with CV autonomic regulation. The aim was thus to study the associations between multiple measures of CV autonomic regulation and measures of different executive cognitive processes. Method: Participants were 119 healthy working adults (79% women), from the Swedish Longitudinal Occupational Survey of Health. Electrocardiogram was sampled for analysis of heart rate variability (HRV) measures, including the Standard Deviation of NN, here heart beats (SDNN), root of the mean squares of successive differences (RMSSD), high frequency (HF) power band from spectral analyses, and QT variability index (QTVI), a measure of myocardial repolarization patterns. Executive cognitive functioning was measured by seven neuropsychological tests. The relationships between CV autonomic regulation measures and executive cognitive measures were tested with bivariate and partial correlational analyses, controlling for demographic variables, and mental health symptoms. Results: Higher SDNN and RMSSD and lower QTVI were significantly associated with better performance on cognitive tests tapping inhibition, updating, shifting, and psychomotor speed. After adjustments for demographic factors however (age being the greatest confounder), only QTVI was clearly associated with these executive tests. No such associations were seen for working memory capacity. Conclusion: Poorer CV autonomic regulation in terms of lower SDNN and RMSSD and higher QTVI was associated with poorer executive

  8. Effect of pioglitazone on systemic inflammation is independent of metabolic control and cardiac autonomic function in patients with type 2 diabetes.

    PubMed

    Nerla, Roberto; Pitocco, Dario; Zaccardi, Francesco; Scalone, Giancarla; Coviello, Ilaria; Mollo, Roberto; Ghirlanda, Giovanni; Lanza, Gaetano A; Crea, Filippo

    2010-12-01

    The aim of this article is to investigate the relation of the anti-inflammatory effect of pioglitazone with cardiac autonomic function and metabolic control in diabetic patients. In this prospective open label trial, 36 type 2 diabetic patients (age 60 ± 10, 20 M) without overt cardiovascular disease were randomized to add pioglitazone (30 mg) to their therapy or to continue standard therapy. C-reactive protein (CRP) serum levels, metabolic parameters and cardiac autonomic function (assessed by heart rate variability [HRV] on 24-h ECG Holter monitoring) were measured at baseline and after 3 months. Clinical and laboratory variables were similar in the two groups. No significant changes were observed after 3 months for metabolic and anthropometric parameters, except for a mild increase in HDL levels in the pioglitazone group only (P = 0.04 vs. controls). CRP levels decreased significantly at follow-up in the pioglitazone group (3.2 ± 1.97 vs. 2.37 ± 1.56 mg/l) but not in the control group (3.0 ± 1.92 vs. 3.93 ± 2.14 mg/l; P = 0.003). No differences were found in basal and follow-up HRV variables between the two groups. In type 2 diabetic patients pioglitazone exerts favourable effects on inflammation even after short-term therapy. This effect precedes those on metabolic and anthropometric parameters and is not associated with changes in cardiac autonomic function.

  9. Creative motivation: creative achievement predicts cardiac autonomic markers of effort during divergent thinking.

    PubMed

    Silvia, Paul J; Beaty, Roger E; Nusbaum, Emily C; Eddington, Kari M; Kwapil, Thomas R

    2014-10-01

    Executive approaches to creativity emphasize that generating creative ideas can be hard and requires mental effort. Few studies, however, have examined effort-related physiological activity during creativity tasks. Using motivational intensity theory as a framework, we examined predictors of effort-related cardiac activity during a creative challenge. A sample of 111 adults completed a divergent thinking task. Sympathetic (PEP and RZ) and parasympathetic (RSA and RMSSD) outcomes were assessed using impedance cardiography. As predicted, people with high creative achievement (measured with the Creative Achievement Questionnaire) showed significantly greater increases in sympathetic activity from baseline to task, reflecting higher effort. People with more creative achievements generated ideas that were significantly more creative, and creative performance correlated marginally with PEP and RZ. The results support the view that creative thought can be a mental challenge.

  10. Impact of aging on cardiac function in a female rat model of menopause: role of autonomic control, inflammation, and oxidative stress

    PubMed Central

    Machi, Jacqueline Freire; Dias, Danielle da Silva; Freitas, Sarah Cristina; de Moraes, Oscar Albuquerque; da Silva, Maikon Barbosa; Cruz, Paula Lázara; Mostarda, Cristiano; Salemi, Vera M C; Morris, Mariana; De Angelis, Kátia; Irigoyen, Maria-Cláudia

    2016-01-01

    Objective The aim of this study was to evaluate the effects of aging on metabolic, cardiovascular, autonomic, inflammatory, and oxidative stress parameters after ovarian hormone deprivation (OVX). Methods Female Wistar rats (3 or 22 months old) were divided into: young controls, young ovariectomized, old controls, and old ovariectomized (bilateral ovaries removal). After a 9-week follow-up, physical capacity, metabolic parameters, and morphometric and cardiac functions were assessed. Subsequently, arterial pressure was recorded and cardiac autonomic control was evaluated. Oxidative stress was measured on the cardiac tissue, while inflammatory profile was assessed in the plasma. Results Aging or OVX caused an increase in body and fat weight and triglyceride concentration and a decrease in both insulin sensitivity and aerobic exercise capacity. Left ventricular diastolic dysfunction and increased cardiac overload (myocardial performance index) were reported in old groups when compared with young groups. Aging and OVX led to an increased sympathetic tonus, and vagal tonus was lower only for the old groups. Tumor necrosis factor-α and interleukin-6 were increased in old groups when compared with young groups. Glutathione redox balance (GSH/GSSG) was reduced in young ovariectomized, old controls, and old ovariectomized groups when compared with young controls, indicating an increased oxidative stress. A negative correlation was found between GSH/GSSG and tumor necrosis factor-α (r=−0.6, P<0.003). Correlations were found between interleukin-6 with adipose tissue (r=0.5, P<0.009) and vagal tonus (r=−0.7, P<0.0002); and among myocardial performance index with interleukin-6 (r=0.65, P<0.0002), sympathetic tonus (r=0.55, P<0.006), and physical capacity (r=−0.55, P<0.003). The findings in this trial showed that ovariectomy aggravated the impairment of cardiac and functional effects of aging in female rats, probably associated with exacerbated autonomic dysfunction

  11. Intracellular Energetic Units regulate metabolism in cardiac cells.

    PubMed

    Saks, Valdur; Kuznetsov, Andrey V; Gonzalez-Granillo, Marcela; Tepp, Kersti; Timohhina, Natalja; Karu-Varikmaa, Minna; Kaambre, Tuuli; Dos Santos, Pierre; Boucher, François; Guzun, Rita

    2012-02-01

    This review describes developments in historical perspective as well as recent results of investigations of cellular mechanisms of regulation of energy fluxes and mitochondrial respiration by cardiac work - the metabolic aspect of the Frank-Starling law of the heart. A Systems Biology solution to this problem needs the integration of physiological and biochemical mechanisms that take into account intracellular interactions of mitochondria with other cellular systems, in particular with cytoskeleton components. Recent data show that different tubulin isotypes are involved in the regular arrangement exhibited by mitochondria and ATP-consuming systems into Intracellular Energetic Units (ICEUs). Beta II tubulin association with the mitochondrial outer membrane, when co-expressed with mitochondrial creatine kinase (MtCK) specifically limits the permeability of voltage-dependent anion channel for adenine nucleotides. In the MtCK reaction this interaction changes the regulatory kinetics of respiration through a decrease in the affinity for adenine nucleotides and an increase in the affinity for creatine. Metabolic Control Analysis of the coupled MtCK-ATP Synthasome in permeabilized cardiomyocytes showed a significant increase in flux control by steps involved in ADP recycling. Mathematical modeling of compartmentalized energy transfer represented by ICEUs shows that cyclic changes in local ADP, Pi, phosphocreatine and creatine concentrations during contraction cycle represent effective metabolic feedback signals when amplified in the coupled non-equilibrium MtCK-ATP Synthasome reactions in mitochondria. This mechanism explains the regulation of respiration on beat to beat basis during workload changes under conditions of metabolic stability. This article is part of a Special Issue entitled "Local Signaling in Myocytes."

  12. Effort Deficits and Depression: The Influence of Anhedonic Depressive Symptoms on Cardiac Autonomic Activity During a Mental Challenge

    PubMed Central

    Silvia, Paul J.; Nusbaum, Emily C.; Eddington, Kari M.; Beaty, Roger E.; Kwapil, Thomas R.

    2014-01-01

    Motivational approaches to depression emphasize the role of dysfunctional motivational dynamics, particularly diminished reward and incentive processes associated with anhedonia. A study examined how anhedonic depressive symptoms, measured continuously across a wide range of severity, influenced the physiological mobilization of effort during a cognitive task. Using motivational intensity theory as a guide, we expected that the diminished incentive value associated with anhedonic depressive symptoms would reduce effort during a “do your best” challenge (also known as an unfixed or self-paced challenge), in which effort is a function of the value of achieving the task’s goal. Using impedance cardiography, two cardiac autonomic responses were assessed: pre-ejection period (PEP), a measure of sympathetic activity and our primary measure of interest, and respiratory sinus arrhythmia (RSA), a measure of parasympathetic activity. As expected, PEP slowed from baseline to task as anhedonic depressive symptoms increased (as measured with the DASS Depression scale), indicating diminished effort-related sympathetic activity. No significant effects appeared for RSA. The findings support motivational intensity theory as a translational model of effort processes in depression and clarify some inconsistent effects of depressive symptoms on effort-related physiology found in past work. PMID:25431505

  13. Effort Deficits and Depression: The Influence of Anhedonic Depressive Symptoms on Cardiac Autonomic Activity During a Mental Challenge.

    PubMed

    Silvia, Paul J; Nusbaum, Emily C; Eddington, Kari M; Beaty, Roger E; Kwapil, Thomas R

    2014-12-01

    Motivational approaches to depression emphasize the role of dysfunctional motivational dynamics, particularly diminished reward and incentive processes associated with anhedonia. A study examined how anhedonic depressive symptoms, measured continuously across a wide range of severity, influenced the physiological mobilization of effort during a cognitive task. Using motivational intensity theory as a guide, we expected that the diminished incentive value associated with anhedonic depressive symptoms would reduce effort during a "do your best" challenge (also known as an unfixed or self-paced challenge), in which effort is a function of the value of achieving the task's goal. Using impedance cardiography, two cardiac autonomic responses were assessed: pre-ejection period (PEP), a measure of sympathetic activity and our primary measure of interest, and respiratory sinus arrhythmia (RSA), a measure of parasympathetic activity. As expected, PEP slowed from baseline to task as anhedonic depressive symptoms increased (as measured with the DASS Depression scale), indicating diminished effort-related sympathetic activity. No significant effects appeared for RSA. The findings support motivational intensity theory as a translational model of effort processes in depression and clarify some inconsistent effects of depressive symptoms on effort-related physiology found in past work.

  14. Autonomous CaMKII Activity as a Drug Target for Histological and Functional Neuroprotection after Resuscitation from Cardiac Arrest.

    PubMed

    Deng, Guiying; Orfila, James E; Dietz, Robert M; Moreno-Garcia, Myriam; Rodgers, Krista M; Coultrap, Steve J; Quillinan, Nidia; Traystman, Richard J; Bayer, K Ulrich; Herson, Paco S

    2017-01-31

    The Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) is a major mediator of physiological glutamate signaling, but its role in pathological glutamate signaling (excitotoxicity) remains less clear, with indications for both neuro-toxic and neuro-protective functions. Here, the role of CaMKII in ischemic injury is assessed utilizing our mouse model of cardiac arrest and cardiopulmonary resuscitation (CA/CPR). CaMKII inhibition (with tatCN21 or tatCN19o) at clinically relevant time points (30 min after resuscitation) greatly reduces neuronal injury. Importantly, CaMKII inhibition also works in combination with mild hypothermia, the current standard of care. The relevant drug target is specifically Ca(2+)-independent "autonomous" CaMKII activity generated by T286 autophosphorylation, as indicated by substantial reduction in injury in autonomy-incompetent T286A mutant mice. In addition to reducing cell death, tatCN19o also protects the surviving neurons from functional plasticity impairments and prevents behavioral learning deficits, even at extremely low doses (0.01 mg/kg), further highlighting the clinical potential of our findings.

  15. A comparison of autonomous regulation and negative self-evaluative emotions as predictors of smoking behavior change among college students.

    PubMed

    Lee, Hyoung S; Catley, Delwyn; Harris, Kari Jo

    2012-05-01

    This study compared autonomous self-regulation and negative self-evaluative emotions as predictors of smoking behavior change in college student smokers (N = 303) in a smoking cessation intervention study. Although the two constructs were moderately correlated, latent growth curve modeling revealed that only autonomous regulation, but not negative self-evaluative emotions, was negatively related to the number of days smoked. Results suggest that the two variables tap different aspects of motivation to change smoking behaviors, and that autonomous regulation predicts smoking behavior change better than negative self-evaluative emotions.

  16. Cardiac MyBP-C regulates the rate and force of contraction in mammalian myocardium Cardiac Myosin Binding Protein C

    PubMed Central

    Moss, Richard L.; Fitzsimons, Daniel P.; Ralphe, J. Carter

    2014-01-01

    Cardiac myosin binding protein-C (cMyBP-C) is a thick filament-associated protein that appears to contribute to the regulation of cardiac contraction through interactions with either myosin or actin or both. Several studies over the past several years have suggested that the interactions of cMyBP-C with its binding partners vary with its phosphorylation state, binding predominantly to myosin when dephosphorylated and to actin when it is phosphorylated by PKA or other kinases. Here, we summarize evidence suggesting that phosphorylation of cMyBP-C is a key regulator of the kinetics and amplitude of cardiac contraction during β-adrenergic stimulation and increased stimulus frequency. We propose a model for these effects via a phosphorylation-dependent regulation of the kinetics and extent of cooperative recruitment of cross-bridges to the thin filament – phosphorylation of cMyBP-C accelerates cross-bridge binding to actin, thereby accelerating recruitment and increasing the amplitude of the cardiac twitch. In contrast, enhanced lusitropy as a result of phosphorylation appears to be due to a direct effect of phosphorylation to accelerate cross-bridge detachment rate. Depression or elimination of one or both of these processes in a disease such as end-stage heart failure appears to contribute to the systolic and diastolic dysfunction that characterizes the disease. PMID:25552695

  17. Metalloproteinases in hypertension and cardiac disease: differential expression and mutual regulation.

    PubMed

    Bosonea, Ana-Maria; Wang, Xiang; Odenbach, Jeffrey; Fernandez-Patron, Carlos

    2011-01-01

    Arterial hypertension, a condition characterized by sustained elevated blood pressure, is associated with pathological cardiac remodeling (i.e. cardiac hypertrophy and fibrosis) and is a major risk factor for cardiac failure. These processes can be triggered by excess vasoconstrictive agonists, which induce metalloproteinase-dependent shedding of growth factors to transactivate growth factor receptors and initiate disease signaling. Here, we review emerging evidence that agonist-activated metalloproteinases exhibit different expression patterns and mutual transcriptional regulation during the development of hypertension and cardiac remodeling.

  18. Timing of obstetrical assistance affects peripartal cardiac autonomic function and early maternal behavior of dairy cows.

    PubMed

    Kovács, Levente; Kézér, Fruzsina Luca; Ruff, Ferenc; Szenci, Ottó

    2016-10-15

    Peripartal autonomic nervous system function and early maternal behavior were investigated in 79 multiparous Holstein-Friesian cows. Animals were allocated into four groups based on the technology of calving management: 1) unassisted calving in a group pen (UCG; N=19), 2) unassisted calving in an individual pen (UCI; N=21), 3) assisted calving with appropriately timed obstetrical assistance (ACA; N=20), and 4) assisted calving with premature obstetrical assistance (ACP; N=19). Heart rate, the high frequency (HF) component of heart rate variability (HRV) as a measure of vagal activity and the ratio between the low frequency (LF) and HF components (LF/HF ratio) as a parameter of sympathetic nervous system activity were calculated. Heart rate and HRV parameters were presented as areas under the curves (AUC) for the following periods: 1) prepartum period (between 96h before the onset of calving restlessness and the onset of restlessness), 2) parturition (between the onset calving restlessness and delivery), and 3) postpartum period (during a 48-h period after delivery). Pain-related behaviors were recorded during parturition (i.e., the occurrence of vocalization and stretching the neck towards the abdomen) and during a 2-h observation period after calving (i.e., the occurrence of vocalization, stretching the neck towards the abdomen and the duration of standing with an arched back). Early maternal behavior was observed during the first 2h following calving as follows: 1) latency and duration of sniffing calf's head/body, and 2) latency and duration of licking calf's head/body. No difference was found across groups in autonomic function before the onset of calving restlessness. Area under the heart rate curve was higher in ACP cows during parturition (39.6±2.5beats/min×h) compared to UCG, UCI and ACA animals (AUC=13.1±0.9beats/min×h, AUC=22.3±1.4beats/min×h and AUC=25.0±2.1beats/min×h, respectively). Area under the heart rate curve did not differ across the UCG

  19. Roles of Calcium Regulating MicroRNAs in Cardiac Ischemia-Reperfusion Injury

    PubMed Central

    Choi, Eunhyun; Cha, Min-Ji; Hwang, Ki-Chul

    2014-01-01

    Cardiac Ca2+ cycling and signaling are closely associated with cardiac function. Changes in cellular Ca2+ homeostasis may lead to aberrant cardiac rhythm and may play a critical role in the pathogenesis of cardiac diseases, due to their exacerbation of heart failure. MicroRNAs (miRNAs) play a key role in the regulation of gene expression at the post-transcriptional level and participate in regulating diverse biological processes. The emerging evidence indicates that the expression profiles of miRNAs vary among human diseases, including cardiovascular diseases. Cardiac Ca2+-handling and signaling proteins are also regulated by miRNAs. Given the relationship between cardiac Ca2+ homeostasis and signaling and miRNA, Ca2+-related miRNAs may serve as therapeutic targets during the treatment of heart failure. In this review, we summarize the knowledge currently available regarding the role of Ca2+ in cardiac function, as well as changes in Ca2+ cycling and homeostasis and the handling of these processes by miRNAs during cardiac ischemia-reperfusion injury. PMID:25216032

  20. Spontaneous awakening from nocturnal sleep and cardiac autonomic function in preschool children.

    PubMed

    Sampei, Mari; Dakeishi, Miwako; Wood, Donald C; Iwata, Toyoto; Murata, Katsuyuki

    2007-05-30

    A cross-sectional study was carried out to clarify the physiological features of spontaneous awakening from nocturnal sleep (i.e., whether a child can spontaneously wake up on weekday mornings). The study population comprised 116 children at ages 5 and 6 years. Heart rate variability reflecting cardiac sympathetic and parasympathetic activities was measured. Children's typical bedtimes and wake times for weekdays and the presence/absence of spontaneous awakening from nocturnal sleep were reported by parents, and information about obligatory naptimes was provided by preschool teachers. The mean total sleep duration in the children was 625+/-56 (standard deviation) min. Total and nocturnal sleep durations were significantly shorter in 52 children without spontaneous awakening than in 64 children with it. Similarly, the parasympathetic activity was significantly lower in the children without spontaneous awakening, even in using analysis of covariance. Heart rate was significantly increased in the children without spontaneous awakening, but neither total nor nocturnal sleep durations were significant covariates in the analysis of covariance. In conclusion, the absence of spontaneous awakening from nocturnal sleep in preschool children is suggested to be characterized by short sleep duration, parasympathetic hypoactivity, and elevated heart rate.

  1. [Non-invasive evaluation of the cardiac autonomic nervous system by PET]. Progress report

    SciTech Connect

    Not Available

    1992-12-01

    C-11 hydroxy ephedrine, introduced as the first clinically usable norepinephrine analogue, studies employing normal volunteers and patients with various cardiac disorders was found to valuable as a nonadreneric tracer. Simultaneously, animal studies been used to assess its use following ischemic injury in order to define neuronal damage. Current research focuses on the comparison of C-11 hydroxyephedrine with other neurotransmitters such as C-11 epinephrine and C-11 threohydroxyephedrine. Epinephrine is primarily stored in vesicles of the nerve terminal, while threo-hydroxyephedrine is only substrate to uptake I mechanism. Such a combination of radiotracers may allow the dissection of uptake I mechanism as well as vesicular storage. In parallel to the refinement of presynaptic tracers for the sympathetic nervous system, we are developing radiopharmaceuticals to delineate the adrenergic receptors in the heart. The combined evaluation of pre- and postsynaptic nerve function will improve our ability to identify abnormalides. We are currently developing a new radiosynthesis of the hydrophilic adrenergic receptor antagonist C-11 CGP-12177 which has been used by others for the visualization of adrenergic receptors in the heart. We are developing radiopharmaceuticals, for the delineation of presynaptic cholinergic nerve terminals. Derivatives of benzovesamicol have been labeled in our institution and are currently under investigation. The most promising agent is F-18 benzovesamicol (FEBOBV) which allows the visualization of parasympathetic nerve terminals in the canine heart as demonstrated by, preliminary PET data.

  2. [Non-invasive evaluation of the cardiac autonomic nervous system by PET

    SciTech Connect

    Not Available

    1992-01-01

    C-11 hydroxy ephedrine, introduced as the first clinically usable norepinephrine analogue, studies employing normal volunteers and patients with various cardiac disorders was found to valuable as a nonadreneric tracer. Simultaneously, animal studies been used to assess its use following ischemic injury in order to define neuronal damage. Current research focuses on the comparison of C-11 hydroxyephedrine with other neurotransmitters such as C-11 epinephrine and C-11 threohydroxyephedrine. Epinephrine is primarily stored in vesicles of the nerve terminal, while threo-hydroxyephedrine is only substrate to uptake I mechanism. Such a combination of radiotracers may allow the dissection of uptake I mechanism as well as vesicular storage. In parallel to the refinement of presynaptic tracers for the sympathetic nervous system, we are developing radiopharmaceuticals to delineate the adrenergic receptors in the heart. The combined evaluation of pre- and postsynaptic nerve function will improve our ability to identify abnormalides. We are currently developing a new radiosynthesis of the hydrophilic adrenergic receptor antagonist C-11 CGP-12177 which has been used by others for the visualization of adrenergic receptors in the heart. We are developing radiopharmaceuticals, for the delineation of presynaptic cholinergic nerve terminals. Derivatives of benzovesamicol have been labeled in our institution and are currently under investigation. The most promising agent is F-18 benzovesamicol (FEBOBV) which allows the visualization of parasympathetic nerve terminals in the canine heart as demonstrated by, preliminary PET data.

  3. Cardiac autonomic innervation of the western pygmy possum (Cercatetus concinnus) and golden bandicoot (Isoodon auratus).

    PubMed

    Zosky, Graeme R; O'Shea, James E

    2017-01-01

    Evidence for a functional ventricular parasympathetic innervation of the mammalian heart between and within taxa remains controversial. We have previously proposed that the presence of a functional parasympathetic innervation of the ventricle was indicative of heterothermy, and is essential for maintaining ventricular stability at low body temperature. However, it is possible that the presence of such an innervation is also representative of the primitive mammalian state. In this study, we aimed to determine whether a functional parasympathetic innervation of the ventricle, that is capable of actively reducing the force of contraction, is present across metatherian mammals. Using in vitro isolated cardiac preparations, we examined evidence for a functional ventricular parasympathetic innervation of the ventricle in two species of metatherian mammal, one heterotherm (Western pygmy possum; Cercatetus concinnus) and one homeotherm (Golden bandicoot; Isoodon auratus), from different families to complement existing data from a heterothermic dasyurid. Both C. concinnus and I. auratus had a potent biphasic response to transmural electrical stimulation in both atrial and ventricular preparations. Both the decrease and increase in the force of contraction in response to stimulation were almost entirely blocked by the cholinergic and adrenergic antagonists, atropine and propranolol, respectively. These observations provide clear evidence for a parasympathetic innervation of the ventricle that is capable of directly influencing the force of contraction across metatherian mammals with different thermoregulatory strategies. While this innervation may facilitate heterothermy, this suggests that the presence of such an innervation pattern is indicative of the primitive mammalian state.

  4. Effects of negative air ions on activity of neural substrates involved in autonomic regulation in rats

    NASA Astrophysics Data System (ADS)

    Suzuki, Satoko; Yanagita, Shinya; Amemiya, Seiichiro; Kato, Yumi; Kubota, Natsuko; Ryushi, Tomoo; Kita, Ichiro

    2008-07-01

    The neural mechanism by which negative air ions (NAI) mediate the regulation of autonomic nervous system activity is still unknown. We examined the effects of NAI on physiological responses, such as blood pressure (BP), heart rate (HR), and heart rate variability (HRV) as well as neuronal activity, in the paraventricular nucleus of the hypothalamus (PVN), locus coeruleus (LC), nucleus ambiguus (NA), and nucleus of the solitary tract (NTS) with c-Fos immunohistochemistry in anesthetized, spontaneously breathing rats. In addition, we performed cervical vagotomy to reveal the afferent pathway involved in mediating the effects of NAI on autonomic regulation. NAI significantly decreased BP and HR, and increased HF power of the HRV spectrum. Significant decreases in c-Fos positive nuclei in the PVN and LC, and enhancement of c-Fos expression in the NA and NTS were induced by NAI. After vagotomy, these physiological and neuronal responses to NAI were not observed. These findings suggest that NAI can modulate autonomic regulation through inhibition of neuronal activity in PVN and LC as well as activation of NA neurons, and that these effects of NAI might be mediated via the vagus nerves.

  5. Physical therapy for airway clearance improves cardiac autonomic modulation in children with acute bronchiolitis

    PubMed Central

    Jacinto, Cynthia P.; Gastaldi, Ada C.; Aguiar, Daniela Y.; Maida, Karina D.; Souza, Hugo C. D.

    2013-01-01

    Background The effects of physical therapy on heart rate variability (HRV), especially in children, are still inconclusive. Objective We investigated the effects of conventional physical therapy (CPT) for airway clearance and nasotracheal suction on the HRV of pediatric patients with acute bronchiolitis. Method 24 children were divided into two groups: control group (CG, n=12) without respiratory diseases and acute bronchiolitis group (BG, n=12). The heart rate was recorded in the BG at four different moments: basal recording (30 minutes), 5 minutes after the CPT (10 minutes), 5 minutes after nasotracheal suction (10 minutes), and 40 minutes after nasotracheal suction (30 minutes). The CG was subjected to the same protocol, except for nasotracheal suction. To assess the HRV, we used spectrum analysis, which decomposes the heart rate oscillations into frequency bands: low frequency (LF=0.04-0.15Hz), which corresponds mainly to sympathetic modulation; and high frequency (HF=0.15-1.2Hz), corresponding to vagal modulation. Results Under baseline conditions, the BG showed higher values in LF oscillations, lower values in HF oscillations, and increased LF/HF ratio when compared to the CG. After CPT, the values for HRV in the BG were similar to those observed in the CG during basal recording. Five minutes after nasotracheal suction, the BG showed a decrease in LF and HF oscillations; however, after 40 minutes, the values were similar to those observed after application of CPT. Conclusions The CPT and nasotracheal suction, both used for airway clearance, promote improvement in autonomic modulation of HRV in children with acute bronchiolitis. PMID:24271093

  6. Cardiac ferroportin regulates cellular iron homeostasis and is important for cardiac function

    PubMed Central

    Lakhal-Littleton, Samira; Wolna, Magda; Carr, Carolyn A.; Miller, Jack J. J.; Christian, Helen C.; Ball, Vicky; Santos, Ana; Diaz, Rebeca; Biggs, Daniel; Stillion, Richard; Holdship, Philip; Clarke, Kieran; Davies, Benjamin; Robbins, Peter A.

    2015-01-01

    Iron is essential to the cell. Both iron deficiency and overload impinge negatively on cardiac health. Thus, effective iron homeostasis is important for cardiac function. Ferroportin (FPN), the only known mammalian iron-exporting protein, plays an essential role in iron homeostasis at the systemic level. It increases systemic iron availability by releasing iron from the cells of the duodenum, spleen, and liver, the sites of iron absorption, recycling, and storage respectively. However, FPN is also found in tissues with no known role in systemic iron handling, such as the heart, where its function remains unknown. To explore this function, we generated mice with a cardiomyocyte-specific deletion of Fpn. We show that these animals have severely impaired cardiac function, with a median survival of 22 wk, despite otherwise unaltered systemic iron status. We then compared their phenotype with that of ubiquitous hepcidin knockouts, a recognized model of the iron-loading disease hemochromatosis. The phenotype of the hepcidin knockouts was far milder, with normal survival up to 12 mo, despite far greater iron loading in the hearts. Histological examination demonstrated that, although cardiac iron accumulates within the cardiomyocytes of Fpn knockouts, it accumulates predominantly in other cell types in the hepcidin knockouts. We conclude, first, that cardiomyocyte FPN is essential for intracellular iron homeostasis and, second, that the site of deposition of iron within the heart determines the severity with which it affects cardiac function. Both findings have significant implications for the assessment and treatment of cardiac complications of iron dysregulation. PMID:25713362

  7. Role of GTP-binding proteins in the regulation of mammalian cardiac chloride conductance

    PubMed Central

    1992-01-01

    insensitive to propranolol or ACh, but could still be abolished by pipette application of PKI. The data indicate that stimulation of beta-adrenergic or histaminergic receptors in the presence of nonhydrolyzable GTP analogues causes persistent activation of Gs and uncouples it from the receptors. We conclude that autonomic regulation of cardiac Cl- conductance reflects accurately the underlying modulation of adenylyl cyclase activity and, hence, that this system is a suitable mammalian model for in situ studies of the interactions between adenylyl cyclase, Gs, Gi, and forskolin. PMID:1375958

  8. Spontaneous Calcium Oscillations Regulate Human Cardiac Progenitor Cell Growth

    PubMed Central

    Ferreira-Martins, João; Rondon-Clavo, Carlos; Tugal, Derin; Korn, Justin A; Rizzi, Roberto; Padin-Iruegas, Maria Elena; Ottolenghi, Sergio; De Angelis, Antonella; Urbanek, Konrad; Iwata, Noriko; D’Amario, Domenico; Hosoda, Toru; Leri, Annarosa; Kajstura, Jan; Anversa, Piero; Rota, Marcello

    2009-01-01

    Rationale The adult heart possesses a pool of progenitor cells stored in myocardial niches but the mechanisms involved in the activation of this cell compartment are currently unknown. Objective Ca2+ promotes cell growth raising the possibility that changes in intracellular Ca2+ initiate division of c-kit-positive human cardiac progenitor cells (hCPCs) and determine their fate. Methods and Results Ca2+ oscillations were identified in hCPCs and these events occurred independently from coupling with cardiomyocytes or the presence of extracellular Ca2+. These findings were confirmed in the heart of transgenic mice in which EGFP was under the control of the c-kit-promoter. Ca2+ oscillations in hCPCs were regulated by the release of Ca2+ from the ER through activation of inositol 1,4,5-triphosphate receptors (IP3Rs) and the re-uptake of Ca2+ by the sarco/endoplasmic reticulum Ca2+ pump (SERCA). IP3Rs and SERCA were highly expressed in hCPCs while ryanodine receptors were not detected. Although Na+-Ca2+ exchanger, store-operated Ca2+-channels and plasma membrane Ca2+-pump were present and functional in hCPCs, they had no direct effects on Ca2+ oscillations. Conversely, Ca2+ oscillations and their frequency markedly increased with ATP and histamine which activated purinoceptors and histamine-1 receptors highly expressed in hCPCs. Importantly, Ca2+ oscillations in hCPCs were coupled with the entry of cells into the cell cycle and BrdUrd incorporation. Induction of Ca2+ oscillations in hCPCs prior to their intramyocardial delivery to infarcted hearts was associated with enhanced engraftment and expansion of these cells promoting the generation of a large myocyte progeny. Conclusion IP3R-mediated Ca2+ mobilization control hCPC growth and their regenerative potential. PMID:19745162

  9. Pioglitazone reverses down-regulation of cardiac PPAR{gamma} expression in Zucker diabetic fatty rats

    SciTech Connect

    Pelzer, Theo . E-mail: pelzer_t@klinik.uni-wuerzburg.de; Jazbutyte, Virginija; Arias-Loza, Paula Anahi; Segerer, Stephan; Lichtenwald, Margit; Law, Marilyn P.; Schaefers, Michael; Ertl, Georg; Neyses, Ludwig

    2005-04-08

    Peroxisome proliferator-activated receptor-{gamma} (PPAR{gamma}) plays a critical role in peripheral glucose homeostasis and energy metabolism, and inhibits cardiac hypertrophy in non-diabetic animal models. The functional role of PPAR{gamma} in the diabetic heart, however, is not fully understood. Therefore, we analyzed cardiac gene expression, metabolic control, and cardiac glucose uptake in male Zucker diabetic fatty rats (ZDF fa/fa) and lean ZDF rats (+/+) treated with the high affinity PPAR{gamma} agonist pioglitazone or placebo from 12 to 24 weeks of age. Hyperglycemia, hyperinsulinemia, and hypertriglyceridemia as well as lower cardiac PPAR{gamma}, glucose transporter-4 and {alpha}-myosin heavy chain expression levels were detected in diabetic ZDF rats compared to lean animals. Pioglitazone increased body weight and improved metabolic control, cardiac PPAR{gamma}, glut-4, and {alpha}-MHC expression levels in diabetic ZDF rats. Cardiac [{sup 18}F]fluorodeoxyglucose uptake was not detectable by micro-PET studies in untreated and pioglitazone treated ZDF fa/fa rats but was observed after administration of insulin to pioglitazone treated ZDF fa/fa rats. PPAR{gamma} agonists favorably affect cardiac gene expression in type-2 diabetic rats via activation and up-regulation of cardiac PPAR{gamma} expression whereas improvement of impaired cardiac glucose uptake in advanced type-2 diabetes requires co-administration of insulin.

  10. How to Calculate Renyi Entropy from Heart Rate Variability, and Why it Matters for Detecting Cardiac Autonomic Neuropathy.

    PubMed

    Cornforth, David J; Tarvainen, Mika P; Jelinek, Herbert F

    2014-01-01

    Cardiac autonomic neuropathy (CAN) is a disease that involves nerve damage leading to an abnormal control of heart rate. An open question is to what extent this condition is detectable from heart rate variability (HRV), which provides information only on successive intervals between heart beats, yet is non-invasive and easy to obtain from a three-lead ECG recording. A variety of measures may be extracted from HRV, including time domain, frequency domain, and more complex non-linear measures. Among the latter, Renyi entropy has been proposed as a suitable measure that can be used to discriminate CAN from controls. However, all entropy methods require estimation of probabilities, and there are a number of ways in which this estimation can be made. In this work, we calculate Renyi entropy using several variations of the histogram method and a density method based on sequences of RR intervals. In all, we calculate Renyi entropy using nine methods and compare their effectiveness in separating the different classes of participants. We found that the histogram method using single RR intervals yields an entropy measure that is either incapable of discriminating CAN from controls, or that it provides little information that could not be gained from the SD of the RR intervals. In contrast, probabilities calculated using a density method based on sequences of RR intervals yield an entropy measure that provides good separation between groups of participants and provides information not available from the SD. The main contribution of this work is that different approaches to calculating probability may affect the success of detecting disease. Our results bring new clarity to the methods used to calculate the Renyi entropy in general, and in particular, to the successful detection of CAN.

  11. Heart rate variability and heart rate turbulence in patients with type 2 diabetes mellitus with versus without cardiac autonomic neuropathy.

    PubMed

    Balcioğlu, Serhat; Arslan, Uğur; Türkoğlu, Sedat; Ozdemir, Murat; Cengel, Atiye

    2007-09-01

    Cardiac autonomic neuropathy (CAN) is an important complication of diabetes mellitus (DM) and confers an increased cardiovascular risk. The aim of this study was to disclose the place of heart rate (HR) variability and HR turbulence for the detection of CAN in patients with type 2 DM and no obvious heart disease. Ninety patients who were <75 years old and had type 2 DM for >/=2 years were studied. CAN was diagnosed with a battery of cardiovascular reflex tests and the degree of neuropathic involvement was graded by the Ewing score. Time-domain HR variability and HR turbulence parameters were assessed on 24-hour digital Holter recordings. Thirty-five patients were found to have CAN. The clinical characteristics of patients with and without CAN were similar, except that the mean duration of DM and the number of patients using insulin were significantly increased in the group with CAN. All time-domain HR variability parameters were significantly lower in the group with CAN. Of the 2 HR turbulence parameters studied, turbulence onset was similar but turbulence slope was significantly lower in the group with CAN. The Ewing score significantly correlated negatively with all HR variability parameters and turbulence slope, and among all, turbulence slope was the most strongly correlated (r = -0.617, p <0.01). Receiver-operating characteristics analysis revealed a sensitivity of 97% and a specificity of 71% at a turbulence slope cut-off value of 3.32 for the detection of CAN. In conclusion, time-domain HR variability and HR turbulence parameters, except turbulence, onset were found to be significantly depressed in patients with type 2 DM and CAN. Decreases in all these parameters were found to correlate significantly with degree of neuropathic involvement. The most strongly correlated parameter, turbulence slope, was found to be highly sensitive and specific for the detection of CAN at a cut-off value of 3.32.

  12. Exposure to medium and high ambient levels of ozone causes adverse systemic inflammatory and cardiac autonomic effects.

    PubMed

    Arjomandi, Mehrdad; Wong, Hofer; Donde, Aneesh; Frelinger, Jessica; Dalton, Sarah; Ching, Wendy; Power, Karron; Balmes, John R

    2015-06-15

    Epidemiological evidence suggests that exposure to ozone increases cardiovascular morbidity. However, the specific biological mechanisms mediating ozone-associated cardiovascular effects are unknown. To determine whether short-term exposure to ambient levels of ozone causes changes in biomarkers of cardiovascular disease including heart rate variability (HRV), systemic inflammation, and coagulability, 26 subjects were exposed to 0, 100, and 200 ppb ozone in random order for 4 h with intermittent exercise. HRV was measured and blood samples were obtained immediately before (0 h), immediately after (4 h), and 20 h after (24 h) each exposure. Bronchoscopy with bronchoalveolar lavage (BAL) was performed 20 h after exposure. Regression modeling was used to examine dose-response trends between the endpoints and ozone exposure. Inhalation of ozone induced dose-dependent adverse changes in the frequency domains of HRV across exposures consistent with increased sympathetic tone [increase of (parameter estimate ± SE) 0.4 ± 0.2 and 0.3 ± 0.1 in low- to high-frequency domain HRV ratio per 100 ppb increase in ozone at 4 h and 24 h, respectively (P = 0.02 and P = 0.01)] and a dose-dependent increase in serum C-reactive protein (CRP) across exposures at 24 h [increase of 0.61 ± 0.24 mg/l in CRP per 100 ppb increase in ozone (P = 0.01)]. Changes in HRV and CRP did not correlate with ozone-induced local lung inflammatory responses (BAL granulocytes, IL-6, or IL-8), but changes in HRV and CRP were associated with each other after adjustment for age and ozone level. Inhalation of ozone causes adverse systemic inflammatory and cardiac autonomic effects that may contribute to the cardiovascular mortality associated with short-term exposure.

  13. Exposure to medium and high ambient levels of ozone causes adverse systemic inflammatory and cardiac autonomic effects

    PubMed Central

    Wong, Hofer; Donde, Aneesh; Frelinger, Jessica; Dalton, Sarah; Ching, Wendy; Power, Karron; Balmes, John R.

    2015-01-01

    Epidemiological evidence suggests that exposure to ozone increases cardiovascular morbidity. However, the specific biological mechanisms mediating ozone-associated cardiovascular effects are unknown. To determine whether short-term exposure to ambient levels of ozone causes changes in biomarkers of cardiovascular disease including heart rate variability (HRV), systemic inflammation, and coagulability, 26 subjects were exposed to 0, 100, and 200 ppb ozone in random order for 4 h with intermittent exercise. HRV was measured and blood samples were obtained immediately before (0 h), immediately after (4 h), and 20 h after (24 h) each exposure. Bronchoscopy with bronchoalveolar lavage (BAL) was performed 20 h after exposure. Regression modeling was used to examine dose-response trends between the endpoints and ozone exposure. Inhalation of ozone induced dose-dependent adverse changes in the frequency domains of HRV across exposures consistent with increased sympathetic tone [increase of (parameter estimate ± SE) 0.4 ± 0.2 and 0.3 ± 0.1 in low- to high-frequency domain HRV ratio per 100 ppb increase in ozone at 4 h and 24 h, respectively (P = 0.02 and P = 0.01)] and a dose-dependent increase in serum C-reactive protein (CRP) across exposures at 24 h [increase of 0.61 ± 0.24 mg/l in CRP per 100 ppb increase in ozone (P = 0.01)]. Changes in HRV and CRP did not correlate with ozone-induced local lung inflammatory responses (BAL granulocytes, IL-6, or IL-8), but changes in HRV and CRP were associated with each other after adjustment for age and ozone level. Inhalation of ozone causes adverse systemic inflammatory and cardiac autonomic effects that may contribute to the cardiovascular mortality associated with short-term exposure. PMID:25862833

  14. Tumor necrosis factor receptor-associated factor 3 is a positive regulator of pathological cardiac hypertrophy.

    PubMed

    Jiang, Xi; Deng, Ke-Qiong; Luo, Yuxuan; Jiang, Ding-Sheng; Gao, Lu; Zhang, Xiao-Fei; Zhang, Peng; Zhao, Guang-Nian; Zhu, Xueyong; Li, Hongliang

    2015-08-01

    Cardiac hypertrophy, a common early symptom of heart failure, is regulated by numerous signaling pathways. Here, we identified tumor necrosis factor receptor-associated factor 3 (TRAF3), an adaptor protein in tumor necrosis factor-related signaling cascades, as a key regulator of cardiac hypertrophy in response to pressure overload. TRAF3 expression was upregulated in hypertrophied mice hearts and failing human hearts. Four weeks after aortic banding, cardiac-specific conditional TRAF3-knockout mice exhibited significantly reduced cardiac hypertrophy, fibrosis, and dysfunction. Conversely, transgenic mice overexpressing TRAF3 in the heart developed exaggerated cardiac hypertrophy in response to pressure overload. TRAF3 also promoted an angiotensin II- or phenylephrine-induced hypertrophic response in isolated cardiomyocytes. Mechanistically, TRAF3 directly bound to TANK-binding kinase 1 (TBK1), causing increased TBK1 phosphorylation in response to hypertrophic stimuli. This interaction between TRAF3 and TBK1 further activated AKT signaling, which ultimately promoted the development of cardiac hypertrophy. Our findings not only reveal a key role of TRAF3 in regulating the hypertrophic response but also uncover TRAF3-TBK1-AKT as a novel signaling pathway in the development of cardiac hypertrophy and heart failure. This pathway may represent a potential therapeutic target for this pathological process.

  15. Prolongation of heart rate-corrected QT interval is a predictor of cardiac autonomic dysfunction in patients with systemic lupus erythematosus.

    PubMed

    Nomura, Atsushi; Kishimoto, Mitsumasa; Takahashi, Osamu; Deshpande, Gautam A; Yamaguchi, Kenichi; Okada, Masato

    2014-05-01

    Heart rate-corrected QT interval duration (QTc) has been shown to be related to cardiac autonomic dysfunction in patients with diabetes mellitus, although this association has not been previously described in patients with systemic lupus erythematosus (SLE). We retrospectively reviewed the medical records of 91 SLE patients and 144 non-SLE connective tissue disease patients visiting our clinic from November 2010 to April 2011. We compared ambulatory heart rate identified by pulse measured by automated machine in an outpatient waiting area versus resting heart rate identified on prior screening electrocardiogram. Heart rate differences were analyzed in relation to QTc interval and other characteristics. Ambulatory and resting heart rate differences were larger among SLE patients with QTc prolongation (QTc > 430 ms) than those without QTc prolongation (mean difference, 15.9 vs. 9.6, p = 0.001). In multivariate analysis, differences in heart rate were associated with QTc prolongation (OR 1.10, 95 % CI 1.01-1.21; p = 0.038), independent of age, duration of disease, immunosuppressant use, hydroxychloroquine use, diabetes mellitus, cardiac abnormality, anti-Ro/SS-A antibody positivity, or resting heart rate. Cardiac autonomic dysfunction is a common manifestation of SLE and may be related to QTc prolongation.

  16. Identification of genes regulated during mechanical load-induced cardiac hypertrophy

    NASA Technical Reports Server (NTRS)

    Johnatty, S. E.; Dyck, J. R.; Michael, L. H.; Olson, E. N.; Abdellatif, M.; Schneider, M. (Principal Investigator)

    2000-01-01

    Cardiac hypertrophy is associated with both adaptive and adverse changes in gene expression. To identify genes regulated by pressure overload, we performed suppressive subtractive hybridization between cDNA from the hearts of aortic-banded (7-day) and sham-operated mice. In parallel, we performed a subtraction between an adult and a neonatal heart, for the purpose of comparing different forms of cardiac hypertrophy. Sequencing more than 100 clones led to the identification of an array of functionally known (70%) and unknown genes (30%) that are upregulated during cardiac growth. At least nine of those genes were preferentially expressed in both the neonatal and pressure over-load hearts alike. Using Northern blot analysis to investigate whether some of the identified genes were upregulated in the load-independent calcineurin-induced cardiac hypertrophy mouse model, revealed its incomplete similarity with the former models of cardiac growth. Copyright 2000 Academic Press.

  17. Fast retrieval and autonomous regulation of single spontaneously recycling synaptic vesicles.

    PubMed

    Leitz, Jeremy; Kavalali, Ege T

    2014-11-21

    Presynaptic terminals release neurotransmitters spontaneously in a manner that can be regulated by Ca(2+). However, the mechanisms underlying this regulation are poorly understood because the inherent stochasticity and low probability of spontaneous fusion events has curtailed their visualization at individual release sites. Here, using pH-sensitive optical probes targeted to synaptic vesicles, we visualized single spontaneous fusion events and found that they are retrieved extremely rapidly with faster re-acidification kinetics than their action potential-evoked counterparts. These fusion events were coupled to postsynaptic NMDA receptor-driven Ca(2+) signals, and at elevated Ca(2+) concentrations there was an increase in the number of vesicles that would undergo fusion. Furthermore, spontaneous vesicle fusion propensity in a synapse was Ca(2+)-dependent but regulated autonomously: independent of evoked fusion probability at the same synapse. Taken together, these results expand classical quantal analysis to incorporate endocytic and exocytic phases of single fusion events and uncover autonomous regulation of spontaneous fusion.

  18. Carotid body denervation improves autonomic and cardiac function and attenuates disordered breathing in congestive heart failure

    PubMed Central

    Marcus, Noah J; Rio, Rodrigo; Schultz, Evan P; Xia, Xiao-Hong; Schultz, Harold D

    2014-01-01

    ± 0.06), and was attenuated in CHF–CBD animals (0.59 ± 0.05) (P < 0.05 for all comparisons). Arrhythmia incidence was increased in CHF–sham and reduced in CHF–CBD animals (213 ± 58 events h–1 CHF, 108 ± 48 events h–1 CHF–CBD, P < 0.05). Furthermore, ventricular systolic (3.8 ± 0.7 vs. 6.3 ± 0.5 ml, P < 0.05) and diastolic (6.3 ± 1.0 vs. 9.1 ± 0.5 ml, P < 0.05) volumes were reduced, and ejection fraction preserved (41 ± 5% vs. 54 ± 2% reduction from pre-pace, P < 0.05) in CHF–CBD compared to CHF–sham rabbits. Similar patterns of changes were observed longitudinally within the CHF–CBD group before and after CBD. In conclusion, CBD is effective in reducing RSNA, SRC and arrhythmia incidence, while improving breathing stability and cardiac function in pacing-induced CHF rabbits. Key points A strong correlation between disordered breathing patterns, elevated sympathetic nerve activity and enhanced chemoreflex sensitivity exists in patients with heart failure. Evidence indicates that disordered breathing patterns and increased sympathetic nerve activity increases arrhythmia incidence in patients with heart failure. Enhanced coupling between sympathetic and respiratory neural drive underlies elevated sympathetic nerve activity in an animal model of sleep apnoea. We investigated the impact of carotid body chemoreceptor denervation on sympathetic nerve activity, disordered breathing and sympatho-respiratory coupling in an animal model of heart failure. Renal sympathetic nerve activity, apnoea/hypopnoea incidence, variability measures of tidal volume and respiratory rate and arrhythmia incidence were quantified during resting breathing in heart failure animals with and without carotid body ablation. Our results indicate that carotid body chemoreceptor denervation reduces sympathetic nerve activity, disordered breathing patterns, arrhythmia incidence and sympatho-respiratory coupling in

  19. β-adrenergic Responsiveness in the Type 2 Diabetic Heart: Effects on Cardiac Reserve.

    PubMed

    Wilson, Genevieve A; Wilson, Luke C; Lamberts, Regis R; Majeed, Kamran; Lal, Sudish; Wilkins, Gerard T; Baldi, James C

    2016-12-14

    Type 2 diabetes (T2D) is associated with reduced cardiac reserve and aerobic capacity. Altered myocardial autonomic nervous regulation has been demonstrated in humans with diabetes (indirectly) and animal models (directly).

  20. The transcriptional repressor Nab1 is a specific regulator of pathological cardiac hypertrophy.

    PubMed

    Buitrago, Monika; Lorenz, Kristina; Maass, Alexander H; Oberdorf-Maass, Silke; Keller, Ursula; Schmitteckert, Eva M; Ivashchenko, Yuri; Lohse, Martin J; Engelhardt, Stefan

    2005-08-01

    Hypertrophy represents the major physiological response of the heart to adapt to chronically enhanced workload, but is also crucial in the development of heart failure. Although we know of numerous inducers of cardiac hypertrophy, little is known about mechanisms that limit cardiac hypertrophy. Here, we describe the transcriptional repressor NAB1 as an endogenous regulator of cardiac growth. We identified NAB1 as being upregulated in both mouse and human heart failure. Nab1 is highly expressed in mammalian cardiac myocytes and it inhibited cardiomyocyte hypertrophy through repression of its targets, transcription factor Egr. Transgenic mice with cardiac-specific overexpression of Nab1 showed that Nab1 is a potent inhibitor of cardiac growth in response to pathological stimuli in vivo. Nab1 overexpression suppressed adrenergically induced and pressure overload-induced hypertrophy, whereas physiological growth during development and in response to exercise was not affected. These findings implicate the Nab1-Egr1 axis as a crucial regulator of pathological cardiac growth.

  1. microRNA expression in autonomous thyroid adenomas: Correlation with mRNA regulation.

    PubMed

    Floor, Sébastien L; Trésallet, Christophe; Hébrant, Aline; Desbuleux, Alice; Libert, Frédérick; Hoang, Catherine; Capello, Matteo; Andry, Guy; van Staveren, Wilma C G; Maenhaut, Carine

    2015-08-15

    The objective of the study was to identify the deregulated miRNA in autonomous adenoma and to correlate the data with mRNA regulation. Seven autonomous adenoma with adjacent healthy thyroid tissues were investigated. Twelve miRNAs were downregulated and one was upregulated in the tumors. Combining bioinformatic mRNA target prediction and microarray data on mRNA regulations allowed to identify mRNA targets of our deregulated miRNAs. A large enrichment in mRNA encoding proteins involved in extracellular matrix organization and different phosphodiesterases were identified among these putative targets. The direct interaction between miR-101-3p and miR-144-3p and PDE4D mRNA was experimentally validated. The global miRNA profiles were not greatly modified, confirming the definition of these tumors as minimal deviation tumors. These results support a role for miRNA in the regulation of extracellular matrix proteins and tissue remodeling occurring during tumor development, and in the important negative feedback of the cAMP pathway, which limits the consequences of its constitutive activation in these tumors.

  2. Childhood Psychopathology and Autonomic Dysregulation: Exploring the Links Using Heart Rate Variability

    ERIC Educational Resources Information Center

    Srinivasan, Krishnamachari

    2007-01-01

    Changes in cardiovascular reactivity have been used as a psychophysiological marker of various emotional states in both children and adults. Recent decades have seen increasing use of heart rate variability as a non-invasive marker of cardiac autonomic function and of central processes involved in autonomic function regulation. Developmental…

  3. Suppressor of IKKɛ is an essential negative regulator of pathological cardiac hypertrophy

    PubMed Central

    Deng, Ke-Qiong; Wang, Aibing; Ji, Yan-Xiao; Zhang, Xiao-Jing; Fang, Jing; Zhang, Yan; Zhang, Peng; Jiang, Xi; Gao, Lu; Zhu, Xue-Yong; Zhao, Yichao; Gao, Lingchen; Yang, Qinglin; Zhu, Xue-Hai; Wei, Xiang; Pu, Jun; Li, Hongliang

    2016-01-01

    Although pathological cardiac hypertrophy represents a leading cause of morbidity and mortality worldwide, our understanding of the molecular mechanisms underlying this disease is still poor. Here, we demonstrate that suppressor of IKKɛ (SIKE), a negative regulator of the interferon pathway, attenuates pathological cardiac hypertrophy in rodents and non-human primates in a TANK-binding kinase 1 (TBK1)/AKT-dependent manner. Sike-deficient mice develop cardiac hypertrophy and heart failure, whereas Sike-overexpressing transgenic (Sike-TG) mice are protected from hypertrophic stimuli. Mechanistically, SIKE directly interacts with TBK1 to inhibit the TBK1-AKT signalling pathway, thereby achieving its anti-hypertrophic action. The suppression of cardiac remodelling by SIKE is further validated in rats and monkeys. Collectively, these findings identify SIKE as a negative regulator of cardiac remodelling in multiple animal species due to its inhibitory regulation of the TBK1/AKT axis, suggesting that SIKE may represent a therapeutic target for the treatment of cardiac hypertrophy and heart failure. PMID:27249321

  4. [Autonomic regulation at emotional stress under hypoxic conditions in the elderly with physiological and accelerated aging: effect of hypoxic training].

    PubMed

    Os'mak, E D; Asanov, É O

    2014-01-01

    The effect of hypoxic training on autonomic regulation in psycho-emotional stress conditions in hypoxic conditions in older people with physiological (25 people) and accelerated (28 people) aging respiratory system. It is shown that hypoxic training leads to an increase in vagal activity indicators (HF) and reduced simpatovagal index (LF/HF), have a normalizing effect on the autonomic balance during stress loads in older people with different types of aging respiratory system.

  5. Metabolic syndrome burden in apparently healthy adolescents are adversely associated with cardiac autonomic modulation- Penn State Children Cohort

    PubMed Central

    Rodríguez-Colón, Sol M.; He, Fan; Bixler, Edward O.; Fernandez-Mendoza, Julio; Vgontzas, Alexandros N.; Calhoun, Susan; Zheng, Zhi-Jie; Liao, Duanping

    2015-01-01

    Background Reduced cardiac autonomic modulation (CAM) has been associated with metabolic syndrome (MetS) in adults. However, the association between MetS component cluster and CAM has not been examined in adolescents. Methods We conducted a cross-sectional analysis using data from the Penn State Child Cohort follow-up examination. CAM was assessed by heart rate variability (HRV) analysis of 39-hour RR intervals, including frequency (high frequency, HF; low frequency, LF; and LF/HF ratio) and time (SDNN, standard deviation of all RR intervals; RMSSD, square root of the mean of the sum of the squares of differences between adjacent RR intervals; and HR, heart rate) domain variables. To assess the MetS burden, we used continuous MetS score (cMetS)–sum of the age and sex-adjusted standardized residual (Z-score) of five established MetS components. Linear mixed-effect models were used to analyze the association between cMetS and CAM in the entire population and stratified by gender. Results After adjusting for age, sex, and race, cMetS was significantly associated with reduced HRV and higher HR. With 1 standard deviation increase in cMetS, there was a significant decrease in HF(−0.10(SE=0.02)), LF(−0.07(SE=0.01)), SDNN(−1.97(SE=0.50)), and RMSSD(−1.70(SE=0.72)), and increase in LF/HF(0.08(SE=0.02)) and HR(1.40(SE=0.26)). All cMetS components, with the exception of high-density lipoprotein (HDL), were associated with significantly decreased HRV and increased HR. High blood pressure (MAP) and triglyceride (TG) levels were also associated with an increase in LF/HF and decrease in RMSSD. An increase in high-density lipoprotein was only associated with higher LF and SDNN. Moreover, cMetS and HRV associations were more pronounced in males than in females. The associations between HRV and. MAP, TG, and HDL were more pronounced in females. Conclusions cMetS score is associated with lower HRV, suggesting an adverse impact on CAM, even in apparently healthy adolescents

  6. Acute effects of tai chi exercise on cardiac autonomic function in healthy adults with tai chi experience.

    PubMed

    Kalsaria, Pratik; Li, Hongtao; Waite, Gabi N; Moga, Margaret M; Kingsley, Derek J; Geib, Roy W

    2012-01-01

    About 1 in 3 American adults have cardiovascular disease associated with risk factors such as physical inactivity, obesity, and stress. Heart rate variability (HRV) analysis is considered a non-invasive procedure for analyzing cardiovascular autonomic influence. Depressed HRV has been linked to abnormal cardiovascular autonomic modulation.

  7. Interferon Regulatory Factor 7 Functions as a Novel Negative Regulator of Pathological Cardiac Hypertrophy

    PubMed Central

    Jiang, Ding-Sheng; Liu, Yu; Zhou, Heng; Zhang, Yan; Zhang, Xiao-Dong; Zhang, Xiao-Fei; Chen, Ke; Gao, Lu; Peng, Juan; Gong, Hui; Chen, Yingjie; Yang, Qinglin; Liu, Peter P.; Fan, Guo-Chang; Zou, Yunzeng; Li, Hongliang

    2017-01-01

    Cardiac hypertrophy is a complex pathological process that involves multiple factors including inflammation and apoptosis. Interferon regulatory factor 7 (IRF7) is a multifunctional regulator that participates in immune regulation, cell differentiation, apoptosis, and oncogenesis. However, the role of IRF7 in cardiac hypertrophy remains unclear. We performed aortic banding in cardiac-specific IRF7 transgenic mice, IRF7 knockout mice, and the wild-type littermates of these mice. Our results demonstrated that IRF7 was downregulated in aortic banding–induced animal hearts and cardiomyocytes that had been treated with angiotensin II or phenylephrine for 48 hours. Accordingly, heart-specific overexpression of IRF7 significantly attenuated pressure overload–induced cardiac hypertrophy, fibrosis, and dysfunction, whereas loss of IRF7 led to opposite effects. Moreover, IRF7 protected against angiotensin II–induced cardiomyocyte hypertrophy in vitro. Mechanistically, we identified that IRF7-dependent cardioprotection was mediated through IRF7 binding to inhibitor of κB kinase-β, and subsequent nuclear factor-κB inactivation. In fact, blocking nuclear factor-κB signaling with cardiac-specific inhibitors of κBαS32A/S36A super-repressor transgene counteracted the adverse effect of IRF7 deficiency. Conversely, activation of nuclear factor-κB signaling via a cardiac-specific conditional inhibitor of κB kinase-βS177E/S181E (constitutively active) transgene negated the antihypertrophic effect of IRF7 overexpression. Our data demonstrate that IRF7 acts as a novel negative regulator of pathological cardiac hypertrophy by inhibiting nuclear factor-κB signaling and may constitute a potential therapeutic target for pathological cardiac hypertrophy. PMID:24396025

  8. A kinase interacting protein (AKIP1) is a key regulator of cardiac stress

    PubMed Central

    Sastri, Mira; Haushalter, Kristofer J.; Panneerselvam, Mathivadhani; Chang, Philip; Fridolfsson, Heidi; Finley, J. Cameron; Ng, Daniel; Schilling, Jan M.; Miyanohara, Atsushi; Day, Michele E.; Hakozaki, Hiro; Petrosyan, Susanna; Koller, Antonius; King, Charles C.; Darshi, Manjula; Blumenthal, Donald K.; Ali, Sameh Saad; Roth, David M.; Patel, Hemal H.; Taylor, Susan S.

    2013-01-01

    cAMP-dependent protein kinase (PKA) regulates a myriad of functions in the heart, including cardiac contractility, myocardial metabolism, and gene expression. However, a molecular integrator of the PKA response in the heart is unknown. Here, we show that the PKA adaptor A-kinase interacting protein 1 (AKIP1) is up-regulated in cardiac myocytes in response to oxidant stress. Mice with cardiac gene transfer of AKIP1 have enhanced protection to ischemic stress. We hypothesized that this adaptation to stress was mitochondrial-dependent. AKIP1 interacted with the mitochondrial localized apoptosis inducing factor (AIF) under both normal and oxidant stress. When cardiac myocytes or whole hearts are exposed to oxidant and ischemic stress, levels of both AKIP1 and AIF were enhanced. AKIP1 is preferentially localized to interfibrillary mitochondria and up-regulated in this cardiac mitochondrial subpopulation on ischemic injury. Mitochondria isolated from AKIP1 gene-transferred hearts showed increased mitochondrial localization of AKIP1, decreased reactive oxygen species generation, enhanced calcium tolerance, decreased mitochondrial cytochrome C release, and enhance phosphorylation of mitochondrial PKA substrates on ischemic stress. These observations highlight AKIP1 as a critical molecular regulator and a therapeutic control point for stress adaptation in the heart. PMID:23319652

  9. Autonomous regulation of sex-specific developmental programming in mouse fetal germ cells.

    PubMed

    Iwahashi, Kazuhiro; Yoshioka, Hirotaka; Low, Eleanor W; McCarrey, John R; Yanagimachi, Ryuzo; Yamazaki, Yukiko

    2007-10-01

    In mice, unique events regulating epigenetic programming (e.g., genomic imprinting) and replication state (mitosis versus meiosis) occur during fetal germ cell development. To determine whether these processes are autonomously programmed in fetal germ cells or are dependent upon ongoing instructive interactions with surrounding gonadal somatic cells, we isolated male and female germ cells at 13.5 days postcoitum (dpc) and maintained them in culture for 6 days, either alone or in the presence of feeder cells or gonadal somatic cells. We examined allele-specific DNA methylation in the imprinted H19 and Snrpn genes, and we also determined whether these cells remained mitotic or entered meiosis. Our results show that isolated male germ cells are able to establish a characteristic "paternal" methylation pattern at imprinted genes in the absence of any support from somatic cells. On the other hand, cultured female germ cells maintain a hypomethylated status at these loci, characteristic of the normal "maternal" methylation pattern in endogenous female germ cells before birth. Further, the surviving female germ cells entered first meiotic prophase and reached the pachytene stage, whereas male germ cells entered mitotic arrest. These results indicate that mechanisms controlling both epigenetic programming and replication state are autonomously regulated in fetal germ cells that have been exposed to the genital ridge prior to 13.5 dpc.

  10. Increased Efferent Cardiac Sympathetic Nerve Activity and Defective Intrinsic Heart Rate Regulation in Type 2 Diabetes.

    PubMed

    Thaung, H P Aye; Baldi, J Chris; Wang, Heng-Yu; Hughes, Gillian; Cook, Rosalind F; Bussey, Carol T; Sheard, Phil W; Bahn, Andrew; Jones, Peter P; Schwenke, Daryl O; Lamberts, Regis R

    2015-08-01

    Elevated sympathetic nerve activity (SNA) coupled with dysregulated β-adrenoceptor (β-AR) signaling is postulated as a major driving force for cardiac dysfunction in patients with type 2 diabetes; however, cardiac SNA has never been assessed directly in diabetes. Our aim was to measure the sympathetic input to and the β-AR responsiveness of the heart in the type 2 diabetic heart. In vivo recording of SNA of the left efferent cardiac sympathetic branch of the stellate ganglion in Zucker diabetic fatty rats revealed an elevated resting cardiac SNA and doubled firing rate compared with nondiabetic rats. Ex vivo, in isolated denervated hearts, the intrinsic heart rate was markedly reduced. Contractile and relaxation responses to β-AR stimulation with dobutamine were compromised in externally paced diabetic hearts, but not in diabetic hearts allowed to regulate their own heart rate. Protein levels of left ventricular β1-AR and Gs (guanine nucleotide binding protein stimulatory) were reduced, whereas left ventricular and right atrial β2-AR and Gi (guanine nucleotide binding protein inhibitory regulatory) levels were increased. The elevated resting cardiac SNA in type 2 diabetes, combined with the reduced cardiac β-AR responsiveness, suggests that the maintenance of normal cardiovascular function requires elevated cardiac sympathetic input to compensate for changes in the intrinsic properties of the diabetic heart.

  11. Long term regulation of cardiac L-type calcium channel by small G proteins.

    PubMed

    Magyar, J; Jenes, A; Kistamás, K; Ruzsnavszky, F; Nánási, P P; Satin, J; Szentandrássy, N; Bányász, T

    2011-01-01

    Calcium ions are crucial elements of excitation-contraction coupling in cardiac myocytes. The intracellular Ca(2+ ) concentration changes continously during the cardiac cycle, but the Ca(2+ ) entering to the cell serves as an intracellular second messenger, as well. The Ca(2+ ) as a second messenger influences the activity of many intracellular signalling pathways and regulates gene expression. In cardiac myocytes the major pathway for Ca(2+ ) entry into cells is L-type calcium channel (LTCC). The precise control of LTCC function is essential for maintaining the calcium homeostasis of cardiac myocytes. Dysregulation of LTCC may result in different diseases like cardiac hypertrophy, arrhytmias, heart failure. The physiological and pathological structural changes in the heart are induced in part by small G proteins. These proteins are involved in wide spectrum of cell biological functions including protein transport, regulation of cell proliferation, migration, apoptosis, and cytoskeletal rearrangement. Understanding the crosstalk between small G proteins and LTCC may help to understand the pathomechanism of different cardiac diseases and to develop a new generation of genetically-encoded Ca(2+ ) channel inhibitors.

  12. Global transcriptomic analysis of induced cardiomyocytes predicts novel regulators for direct cardiac reprogramming.

    PubMed

    Talkhabi, Mahmood; Razavi, Seyed Morteza; Salari, Ali

    2017-04-04

    Heart diseases are the most significant cause of morbidity and mortality in the world. De novo generated cardiomyocytes (CMs) are a great cellular source for cell-based therapy and other potential applications. Direct cardiac reprogramming is the newest method to produce CMs, known as induced cardiomyocytes (iCMs). During a direct cardiac reprogramming, also known as transdifferentiation, non-cardiac differentiated adult cells are reprogrammed to cardiac identity by forced expression of cardiac-specific transcription factors (TFs) or microRNAs. To this end, many different combinations of TFs (±microRNAs) have been reported for direct reprogramming of mouse or human fibroblasts to iCMs, although their efficiencies remain very low. It seems that the investigated TFs and microRNAs are not sufficient for efficient direct cardiac reprogramming and other cardiac specific factors may be required for increasing iCM production efficiency, as well as the quality of iCMs. Here, we analyzed gene expression data of cardiac fibroblast (CFs), iCMs and adult cardiomyocytes (aCMs). The up-regulated and down-regulated genes in CMs (aCMs and iCMs) were determined as CM and CF specific genes, respectively. Among CM specific genes, we found 153 transcriptional activators including some cardiac and non-cardiac TFs that potentially activate the expression of CM specific genes. We also identified that 85 protein kinases such as protein kinase D1 (PKD1), protein kinase A (PRKA), calcium/calmodulin-dependent protein kinase (CAMK), protein kinase C (PRKC), and insulin like growth factor 1 receptor (IGF1R) that are strongly involved in establishing CM identity. CM gene regulatory network constructed using protein kinases, transcriptional activators and intermediate proteins predicted some new transcriptional activators such as myocyte enhancer factor 2A (MEF2A) and peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PPARGC1A), which may be required for qualitatively and

  13. Apigenin ameliorates hypertension-induced cardiac hypertrophy and down-regulates cardiac hypoxia inducible factor-lα in rats.

    PubMed

    Zhu, Zeng-Yan; Gao, Tian; Huang, Yan; Xue, Jie; Xie, Mei-Lin

    2016-04-01

    Apigenin is a natural flavonoid compound that can inhibit hypoxia-inducible factor (HIF)-1α expression in cultured tumor cells under hypoxic conditions. Hypertension-induced cardiac hypertrophy is always accompanied by abnormal myocardial glucolipid metabolism due to an increase of HIF-1α. However, whether or not apigenin may ameliorate the cardiac hypertrophy and abnormal myocardial glucolipid metabolism remains unknown. This study aimed to examine the effects of apigenin. Rats with cardiac hypertrophy induced by renovascular hypertension were treated with apigenin 50-100 mg kg(-1) (the doses can be achieved by pharmacological or dietary supplementation for an adult person) by gavage for 4 weeks. The results showed that after treatment with apigenin, the blood pressure, heart weight, heart weight index, cardiomyocyte cross-sectional area, serum angiotensin II, and serum and myocardial free fatty acids were reduced. It is important to note that apigenin decreased the expression level of myocardial HIF-1α protein. Moreover, apigenin simultaneously increased the expression levels of myocardial peroxisome proliferator-activated receptor (PPAR) α, carnitine palmitoyltransferase (CPT)-1, and pyruvate dehydrogenase kinase (PDK)-4 proteins and decreased the expression levels of myocardial PPARγ, glycerol-3-phosphate acyltransferase genes (GPAT), and glucose transporter (GLUT)-4 proteins. These findings demonstrated that apigenin could improve hypertensive cardiac hypertrophy and abnormal myocardial glucolipid metabolism in rats, and its mechanisms might be associated with the down-regulation of myocardial HIF-1α expression and, subsequently increasing the expressions of myocardial PPARα and its target genes CPT-1 and PDK-4, and decreasing the expressions of myocardial PPARγ and its target genes GPAT and GLUT-4.

  14. Trigeminal Cardiac Reflex and Cerebral Blood Flow Regulation

    PubMed Central

    Lapi, Dominga; Scuri, Rossana; Colantuoni, Antonio

    2016-01-01

    The stimulation of some facial regions is known to trigger the trigemino-cardiac reflex: the main stimulus is represented by the contact of the face with water. This phenomenon called diving reflex induces a set of reactions in the cardiovascular and respiratory systems occurring in all mammals, especially marine (whales, seals). During the immersion of the face in the water, the main responses are aimed at reducing the oxygen consumption of the organism. Accordingly reduction in heart rate, peripheral vasoconstriction, blood pooling in certain organs, especially the heart, and brain and an increase in blood pressure have been reported. Moreover, the speed and intensity of the reflex is inversely proportional to the temperature of the water: more cold the water, more reactions as described are strong. In the case of deep diving an additional effect, such as blood deviation, has been reported: the blood is sequestered within the lungs, to compensate for the increase in the external pressure, preventing them from collapsing. The trigeminal-cardiac reflex is not just confined to the diving reflex; recently it has been shown that a brief proprioceptive stimulation (10 min) by jaw extension in rats produces interesting effects both at systemic and cerebral levels, reducing the arterial blood pressure, and vasodilating the pial arterioles. The arteriolar dilation is associated with rhythmic diameter changes characterized by an increase in the endothelial activity. Fascinating the stimulation of trigeminal nerve is able to activate the nitric oxide release by vascular endothelial cells. Therefore, the aim of this review was to highlight the effects due to trigeminal cardiac reflex induced by a simple mandibular extension. Opposite effects, such as hypotension, and modulation of cerebral arteriolar tone, were observed, when these responses were compared to those elicited by the diving reflex. PMID:27812317

  15. Diabetic autonomic neuropathy.

    PubMed

    Vinik, Aaron I; Erbas, Tomris

    2013-01-01

    Autonomic neuropathy, once considered to be the Cinderella of diabetes complications, has come of age. The autonomic nervous system innervates the entire human body, and is involved in the regulation of every single organ in the body. Thus, perturbations in autonomic function account for everything from abnormalities in pupillary function to gastroparesis, intestinal dysmotility, diabetic diarrhea, genitourinary dysfunction, amongst others. "Know autonomic function and one knows the whole of medicine!" It is now becoming apparent that before the advent of severe pathological damage to the autonomic nervous system there may be an imbalance between the two major arms, namely the sympathetic and parasympathetic nerve fibers that innervate the heart and blood vessels, resulting in abnormalities in heart rate control and vascular dynamics. Cardiac autonomic neuropathy (CAN) has been linked to resting tachycardia, postural hypotension, orthostatic bradycardia and orthostatic tachycardia (POTTS), exercise intolerance, decreased hypoxia-induced respiratory drive, loss of baroreceptor sensitivity, enhanced intraoperative or perioperative cardiovascular lability, increased incidence of asymptomatic ischemia, myocardial infarction, and decreased rate of survival after myocardial infarction and congestive heart failure. Autonomic dysfunction can affect daily activities of individuals with diabetes and may invoke potentially life-threatening outcomes. Intensification of glycemic control in the presence of autonomic dysfunction (more so if combined with peripheral neuropathy) increases the likelihood of sudden death and is a caveat for aggressive glycemic control. Advances in technology, built on decades of research and clinical testing, now make it possible to objectively identify early stages of CAN with the use of careful measurement of time and frequency domain analyses of autonomic function. Fifteen studies using different end points report prevalence rates of 1% to 90

  16. Regulation of cardiac microRNAs induced by aerobic exercise training during heart failure.

    PubMed

    Souza, Rodrigo W A; Fernandez, Geysson J; Cunha, João P Q; Piedade, Warlen P; Soares, Luana C; Souza, Paula A T; de Campos, Dijon H S; Okoshi, Katashi; Cicogna, Antonio C; Dal-Pai-Silva, Maeli; Carvalho, Robson F

    2015-11-15

    Exercise training (ET) has beneficial effects on the myocardium in heart failure (HF) patients and in animal models of induced cardiac hypertrophy and failure. We hypothesized that if microRNAs (miRNAs) respond to changes following cardiac stress, then myocardial profiling of these miRNAs may reveal cardio-protective mechanisms of aerobic ET in HF. We used ascending aortic stenosis (AS) inducing HF in Wistar rats. Controls were sham-operated animals. At 18 wk after surgery, rats with cardiac dysfunction were randomized to 10 wk of aerobic ET (HF-ET) or to a heart failure sedentary group (HF-S). ET attenuated cardiac remodeling as well as clinical and pathological signs of HF with maintenance of systolic and diastolic function when compared with that of the HF-S. Global miRNA expression profiling of the cardiac tissue revealed 53 miRNAs exclusively dysregulated in animals in the HF-ET, but only 11 miRNAs were exclusively dysregulated in the HF-S. Out of 23 miRNAs that were differentially regulated in both groups, 17 miRNAs exhibited particularly high increases in expression, including miR-598, miR-429, miR-224, miR-425, and miR-221. From the initial set of deregulated miRNAs, 14 miRNAs with validated targets expressed in cardiac tissue that respond robustly to ET in HF were used to construct miRNA-mRNA regulatory networks that revealed a set of 203 miRNA-target genes involved in programmed cell death, TGF-β signaling, cellular metabolic processes, cytokine signaling, and cell morphogenesis. Our findings reveal that ET attenuates cardiac abnormalities during HF by regulating cardiac miRNAs with a potential role in cardio-protective mechanisms through multiple effects on gene expression.

  17. Exhaustive endurance training for 6-9 weeks did not induce changes in intrinsic heart rate and cardiac autonomic modulation in female athletes.

    PubMed

    Uusitalo, A L; Uusitalo, A J; Rusko, H K

    1998-11-01

    We investigated the effects of progressively increased training load and overtraining on resting and intrinsic heart rate (IHR) and cardiac autonomic modulation (CAM), and their relationships to performance variables. Nine athletes (ETG) increased training volume at 70-90% of maximal oxygen uptake (VO2max) by 130% (p<0.01) and training volume at <70% VO2max by 100% (p < 0.01) during 6-9 weeks. The corresponding increases in six female control athletes (CG) were 5 and 10%. Pharmacological blocking through atropine and propranolol and the Rosenblueth and Simeone model were used to calculate the sympathovagal balance index (Abal) and to measure IHR. The results were analysed using two-way analysis of variance. VO2max, IHR and Abal did not change. Resting heart rate had a tendency to decrease in the ETG and increase in the CG during the training period (interaction p < 0.01). Five ETG athletes demonstrated overtraining state (OA subgroup). Their VO2max (mean+/-SEM) decreased from 53.0+/-2.2 ml x kg(-1) x min(-1) to 50.2+/-2.3 ml x kg(-1) x min(-1) (p < 0.01), but no changes in resting HR, IHR and Abal were found. A significant correlation between the baseline values of VO2max and the parasympathetic activity index was found (r=-0.59, p < 0.05). In conclusion, progressively increased training load and overtraining did not induce significant changes in intrinsic heart rate or cardiac autonomic modulation in female endurance athletes. Resting heart rate rather decreased with heavy endurance training and overtraining. High maximal oxygen uptake was correlated with high cardiac parasympathetic modulation.

  18. The Role of the Autonomic Nervous System in the Regulation of Aortic Stiffness

    PubMed Central

    Barrett, Sharon M.L.; Evans, Sarah V.; Cheriyan, Joseph; McEniery, Carmel M.; Wilkinson, Ian B.

    2016-01-01

    The autonomic nervous system is important in regulating blood pressure, but whether it regulates aortic stiffness is more contentious. We conducted 3 studies in young, healthy individuals to address this important question. Study 1 was a cross-sectional study of 347 subjects with detailed measurements of hemodynamics and heart rate variability. In study 2, 9 subjects were given a bolus of intravenous nicotinic ganglion blocker, pentolinium, or saline in a random order and hemodynamics and heart rate variability were assessed before and after. In study 3, changes in hemodynamics and heart rate variability were assessed during stimulation of the sympathetic nervous system with the use of isometric handgrip exercise in 12 subjects. Study 1: aortic pulse wave velocity (P=0.003) was lowest in the subjects with the highest parasympathetic activity, but after adjusting for mean arterial pressure, the effect was abolished (P=0.3). Study 2: after pentolinium, sympathetic and parasympathetic activity fell (P=0.001 for both), mean arterial pressure, and heart rate increased (P=0.004 and P=0.04, respectively), but there was no change in pulse wave velocity in comparison to placebo (P=0.1). Study 3: during handgrip exercise, sympathetic activity (P=0.003), mean arterial pressure (P<0.0001), and aortic pulse wave velocity increased (P=0.013). However, pulse wave velocity adjusted for mean arterial pressure did not change (P=0.1). The main finding of these studies is that in young healthy subjects, the autonomic nervous system does not have a pressure-independent role in the regulation of aortic stiffness. However, these findings may not apply to patients with increased sympathetic tone or hypertension. PMID:27672029

  19. Developmental profiling of postnatal dentate gyrus progenitors provides evidence for dynamic cell-autonomous regulation

    PubMed Central

    Gilley, Jennifer A.; Yang, Cui-Ping; Kernie, Steven G.

    2009-01-01

    The dentate gyrus of the hippocampus is one of the most prominent regions in the postnatal mammalian brain where neurogenesis continues throughout life. There is tremendous speculation regarding the potential implications of adult hippocampal neurogenesis, though it remains unclear to what extent this ability becomes attenuated during normal aging, and what genetic changes in the progenitor population ensue over time. Using defined elements of the nestin promoter, we developed a transgenic mouse that reliably labels neural stem and early progenitors with green fluorescent protein (GFP). Using a combination of immunohistochemical and flow cytometry techniques, we characterized the progenitor cells within the dentate gyrus and created a developmental profile from postnatal day 7 (P7) until 6 months of age. In addition, we demonstrate that the proliferative potential of these progenitors is controlled at least in part by cell-autonomous cues. Finally, in order to identify what may underlie these differences, we performed stem cell-specific microarrays on GFP-expressing sorted cells from isolated P7 and postnatal day 28 (P28) dentate gyrus. We identified several differentially expressed genes that may underlie the functional differences that we observe in neurosphere assays from sorted cells and differentiation assays at these different ages. These data suggest that neural progenitors from the dentate gyrus are differentially regulated by cell-autonomous factors that change over time. PMID:20014381

  20. Crucial Role of miR-433 in Regulating Cardiac Fibrosis

    PubMed Central

    Tao, Lichan; Bei, Yihua; Chen, Ping; Lei, Zhiyong; Fu, Siyi; Zhang, Haifeng; Xu, Jiahong; Che, Lin; Chen, Xiongwen; Sluijter, Joost PG; Das, Saumya; Cretoiu, Dragos; Xu, Bin; Zhong, Jiuchang; Xiao, Junjie; Li, Xinli

    2016-01-01

    Dysregulation of microRNAs has been implicated in many cardiovascular diseases including fibrosis. Here we report that miR-433 was consistently elevated in three models of heart disease with prominent cardiac fibrosis, and was enriched in fibroblasts compared to cardiomyocytes. Forced expression of miR-433 in neonatal rat cardiac fibroblasts increased proliferation and their differentiation into myofibroblasts as determined by EdU incorporation, α-SMA staining, and expression levels of fibrosis-associated genes. Conversely, inhibition of miR-433 exhibited opposite results. AZIN1 and JNK1 were identified as two target genes of miR-433. Decreased level of AZIN1 activated TGF-β1 while down-regulation of JNK1 resulted in activation of ERK and p38 kinase leading to Smad3 activation and ultimately cardiac fibrosis. Importantly, systemic neutralization of miR-433 or adeno-associated virus 9 (AAV9)-mediated cardiac transfer of a miR-433 sponge attenuated cardiac fibrosis and ventricular dysfunction following myocardial infarction. Thus, our work suggests that miR-433 is a potential target for amelioration of cardiac fibrosis. PMID:27698941

  1. Cardiac sodium channel palmitoylation regulates channel availability and myocyte excitability with implications for arrhythmia generation

    PubMed Central

    Pei, Zifan; Xiao, Yucheng; Meng, Jingwei; Hudmon, Andy; Cummins, Theodore R.

    2016-01-01

    Cardiac voltage-gated sodium channels (Nav1.5) play an essential role in regulating cardiac electric activity by initiating and propagating action potentials in the heart. Altered Nav1.5 function is associated with multiple cardiac diseases including long-QT3 and Brugada syndrome. Here, we show that Nav1.5 is subject to palmitoylation, a reversible post-translational lipid modification. Palmitoylation increases channel availability and late sodium current activity, leading to enhanced cardiac excitability and prolonged action potential duration. In contrast, blocking palmitoylation increases closed-state channel inactivation and reduces myocyte excitability. We identify four cysteines as possible Nav1.5 palmitoylation substrates. A mutation of one of these is associated with cardiac arrhythmia (C981F), induces a significant enhancement of channel closed-state inactivation and ablates sensitivity to depalmitoylation. Our data indicate that alterations in palmitoylation can substantially control Nav1.5 function and cardiac excitability and this form of post-translational modification is likely an important contributor to acquired and congenital arrhythmias. PMID:27337590

  2. Kaempferol Attenuates Cardiac Hypertrophy via Regulation of ASK1/MAPK Signaling Pathway and Oxidative Stress.

    PubMed

    Feng, Hong; Cao, Jianlei; Zhang, Guangyu; Wang, Yanggan

    2017-02-20

    Kaempferol has been demonstrated to provide benefits for the treatment of atherosclerosis, coronary heart disease, hyperlipidemia, and diabetes through its antioxidant and anti-inflammatory properties. However, its role in cardiac hypertrophy remains to be elucidated. The aim of our study was to investigate the effects of kaempferol on cardiac hypertrophy and the underlying mechanism. Mice subjected to aorta banding were treated with or without kaempferol (100 mg/kg/d, p. o.) for 6 weeks. Echocardiography was performed to evaluate cardiac function. Mice hearts were collected for pathological observation and molecular mechanism investigation. H9c2 cardiomyocytes were stimulated with or without phenylephrine for in vitro study. Kaempferol significantly attenuated cardiac hypertrophy induced by aorta banding as evidenced by decreased cardiomyocyte areas and interstitial fibrosis, accompanied with improved cardiac functions and decreased apoptosis. The ASK1/MAPK signaling pathways (JNK1/2 and p38) were markedly activated in the aorta banding mouse heart but inhibited by kaempferol treatment. In in vitro experiments, kaempferol also inhibited the activity of ASK1/JNK1/2/p38 signaling pathway and the enlargement of H9c2 cardiomyocytes. Furthermore, our study revealed that kaempferol could protect the mouse heart and H9c2 cells from pathological oxidative stress. Our investigation indicated that treatment with kaempferol protects against cardiac hypertrophy, and its cardioprotection may be partially explained by the inhibition of the ASK1/MAPK signaling pathway and the regulation of oxidative stress.

  3. Physiological Self-Regulation and Information Processing in Infancy: Cardiac Vagal Tone and Habituation.

    ERIC Educational Resources Information Center

    Bornstein, Marc H.; Suess, Patricia E.

    2000-01-01

    Investigated the role of physiological self-regulation (cardiac vagal tone) in information processing (habituation) in infants. Found that decreases in vagal tone consistently related to habituation efficiency at 2 and 5 months. Within- and between- age suppression of vagal tone predicted accumulated looking time (ALT), but ALT did not predict…

  4. Self-esteem and autonomic physiology: parallels between self-esteem and cardiac vagal tone as buffers of threat.

    PubMed

    Martens, Andy; Greenberg, Jeff; Allen, John J B

    2008-11-01

    In this article a potential physiological connection to self-esteem is suggested: cardiac vagal tone, the degree of influence on the heart by the vagus, a primary nerve of the parasympathetic nervous system. This hypothesis emerges from parallels between the two literatures that suggest both self-esteem and cardiac vagal tone function to provide protection from threat responding. This article reviews these literatures and evidence and preliminary findings that suggest in some contexts self-esteem and cardiac vagal tone may exert an influence on each other. Last, the article discusses theoretical and applied health implications of this potential physiological connection to self-esteem.

  5. RNA splicing regulated by RBFOX1 is essential for cardiac function in zebrafish.

    PubMed

    Frese, Karen S; Meder, Benjamin; Keller, Andreas; Just, Steffen; Haas, Jan; Vogel, Britta; Fischer, Simon; Backes, Christina; Matzas, Mark; Köhler, Doreen; Benes, Vladimir; Katus, Hugo A; Rottbauer, Wolfgang

    2015-08-15

    Alternative splicing is one of the major mechanisms through which the proteomic and functional diversity of eukaryotes is achieved. However, the complex nature of the splicing machinery, its associated splicing regulators and the functional implications of alternatively spliced transcripts are only poorly understood. Here, we investigated the functional role of the splicing regulator rbfox1 in vivo using the zebrafish as a model system. We found that loss of rbfox1 led to progressive cardiac contractile dysfunction and heart failure. By using deep-transcriptome sequencing and quantitative real-time PCR, we show that depletion of rbfox1 in zebrafish results in an altered isoform expression of several crucial target genes, such as actn3a and hug. This study underlines that tightly regulated splicing is necessary for unconstrained cardiac function and renders the splicing regulator rbfox1 an interesting target for investigation in human heart failure and cardiomyopathy.

  6. Scl binds to primed enhancers in mesoderm to regulate hematopoietic and cardiac fate divergence

    PubMed Central

    Org, Tõnis; Duan, Dan; Ferrari, Roberto; Montel-Hagen, Amelie; Van Handel, Ben; Kerényi, Marc A; Sasidharan, Rajkumar; Rubbi, Liudmilla; Fujiwara, Yuko; Pellegrini, Matteo; Orkin, Stuart H; Kurdistani, Siavash K; Mikkola, Hanna KA

    2015-01-01

    Scl/Tal1 confers hemogenic competence and prevents ectopic cardiomyogenesis in embryonic endothelium by unknown mechanisms. We discovered that Scl binds to hematopoietic and cardiac enhancers that become epigenetically primed in multipotent cardiovascular mesoderm, to regulate the divergence of hematopoietic and cardiac lineages. Scl does not act as a pioneer factor but rather exploits a pre-established epigenetic landscape. As the blood lineage emerges, Scl binding and active epigenetic modifications are sustained in hematopoietic enhancers, whereas cardiac enhancers are decommissioned by removal of active epigenetic marks. Our data suggest that, rather than recruiting corepressors to enhancers, Scl prevents ectopic cardiogenesis by occupying enhancers that cardiac factors, such as Gata4 and Hand1, use for gene activation. Although hematopoietic Gata factors bind with Scl to both activated and repressed genes, they are dispensable for cardiac repression, but necessary for activating genes that enable hematopoietic stem/progenitor cell development. These results suggest that a unique subset of enhancers in lineage-specific genes that are accessible for regulators of opposing fates during the time of the fate decision provide a platform where the divergence of mutually exclusive fates is orchestrated. PMID:25564442

  7. [Characteristics of autonomic regulations in miners working in hard conditions of coal mines].

    PubMed

    Perederiĭ, H S; Ivanov, V V

    2004-01-01

    72 miners aged from 30 till 40 years have been surveyed. It was established that to achieve socially acceptable results the miners use corresponding strategy doing their job. Under the influence of the work the functional states mediated not only by conditions of working environment but also by resistivity of the organism are developed. It is shown that highly productive, reliable and effective work is possible under adequate interactions of central and autonomic mechanisms of regulation. Alteration in these interactions, particularly, non-adequate centralization of management processes decreases physical capacity for work. Enhancement of sympathetic effects on periphery that leads to development of hypertensive reactions has been observed. Such alterations are accompanied by an increase in physiological cost of work and decreased productivity of labor.

  8. [Intrinsic cardiac ganglia].

    PubMed

    Birand, Ahmet

    2008-12-01

    Heart has been considered as the source and the seat of emotions, passion and love. But from the dawn of XIXth century, scientists have emphasized that the heart, though life depends on its ceaseless activity, is merely a electromechanical pump, pumping oxygenated blood. Nowadays, we all know that heart pumps blood commensurate with the needs of the body and this unending toil, and its regulation depends on the intrinsic properties of the myocardium, Frank-Starling Law and neurohumoral contribution. It has been understood, though not clearly enough, that these time-tensions may cause structural or functional cardiac impairments and arrhythmias are related to the autonomic nervous system. Less well known and less taken in account in daily cardiology practice is the fact that heart has an intrinsic cardiac nervous system, or "heart brain" consisting of complex ganglia, intrinsic cardiac ganglia containing afferent (receiving), local circuit (interneurons) and efferent (transmitting) sympathetic and parasympathetic neurons. This review enlightens structural and functional aspects of intrinsic cardiac ganglia as the very first step in the regulation of cardiac function. This issue is important for targets of pharmacological treatment and techniques of cardiac surgery interventions as repair of septal defects, valvular interventions and congenital corrections.

  9. Cell-Autonomous and Non-Cell-Autonomous Regulation of a Feeding State-Dependent Chemoreceptor Gene via MEF-2 and bHLH Transcription Factors.

    PubMed

    Gruner, Matthew; Grubbs, Jeremy; McDonagh, Aja; Valdes, Dominic; Winbush, Ari; van der Linden, Alexander M

    2016-08-01

    Food and feeding-state dependent changes in chemoreceptor gene expression may allow Caenorhabditis elegans to modify their chemosensory behavior, but the mechanisms essential for these expression changes remain poorly characterized. We had previously shown that expression of a feeding state-dependent chemoreceptor gene, srh-234, in the ADL sensory neuron of C. elegans is regulated via the MEF-2 transcription factor. Here, we show that MEF-2 acts together with basic helix-loop-helix (bHLH) transcription factors to regulate srh-234 expression as a function of feeding state. We identify a cis-regulatory MEF2 binding site that is necessary and sufficient for the starvation-induced down regulation of srh-234 expression, while an E-box site known to bind bHLH factors is required to drive srh-234 expression in ADL. We show that HLH-2 (E/Daughterless), HLH-3 and HLH-4 (Achaete-scute homologs) act in ADL neurons to regulate srh-234 expression. We further demonstrate that the expression levels of srh-234 in ADL neurons are regulated remotely by MXL-3 (Max-like 3 homolog) and HLH-30 (TFEB ortholog) acting in the intestine, which is dependent on insulin signaling functioning specifically in ADL neurons. We also show that this intestine-to-neuron feeding-state regulation of srh-234 involves a subset of insulin-like peptides. These results combined suggest that chemoreceptor gene expression is regulated by both cell-autonomous and non-cell-autonomous transcriptional mechanisms mediated by MEF2 and bHLH factors, which may allow animals to fine-tune their chemosensory responses in response to changes in their feeding state.

  10. Cell-Autonomous and Non-Cell-Autonomous Regulation of a Feeding State-Dependent Chemoreceptor Gene via MEF-2 and bHLH Transcription Factors

    PubMed Central

    Winbush, Ari; van der Linden, Alexander M.

    2016-01-01

    Food and feeding-state dependent changes in chemoreceptor gene expression may allow Caenorhabditis elegans to modify their chemosensory behavior, but the mechanisms essential for these expression changes remain poorly characterized. We had previously shown that expression of a feeding state-dependent chemoreceptor gene, srh-234, in the ADL sensory neuron of C. elegans is regulated via the MEF-2 transcription factor. Here, we show that MEF-2 acts together with basic helix-loop-helix (bHLH) transcription factors to regulate srh-234 expression as a function of feeding state. We identify a cis-regulatory MEF2 binding site that is necessary and sufficient for the starvation-induced down regulation of srh-234 expression, while an E-box site known to bind bHLH factors is required to drive srh-234 expression in ADL. We show that HLH-2 (E/Daughterless), HLH-3 and HLH-4 (Achaete-scute homologs) act in ADL neurons to regulate srh-234 expression. We further demonstrate that the expression levels of srh-234 in ADL neurons are regulated remotely by MXL-3 (Max-like 3 homolog) and HLH-30 (TFEB ortholog) acting in the intestine, which is dependent on insulin signaling functioning specifically in ADL neurons. We also show that this intestine-to-neuron feeding-state regulation of srh-234 involves a subset of insulin-like peptides. These results combined suggest that chemoreceptor gene expression is regulated by both cell-autonomous and non-cell-autonomous transcriptional mechanisms mediated by MEF2 and bHLH factors, which may allow animals to fine-tune their chemosensory responses in response to changes in their feeding state. PMID:27487365

  11. The VITAH Trial—Vitamin D Supplementation and Cardiac Autonomic Tone in Patients with End-Stage Kidney Disease on Hemodialysis: A Blinded, Randomized Controlled Trial

    PubMed Central

    Mann, Michelle C.; Exner, Derek V.; Hemmelgarn, Brenda R.; Hanley, David A.; Turin, Tanvir C.; MacRae, Jennifer M.; Wheeler, David C.; Sola, Darlene Y.; Ramesh, Sharanya; Ahmed, Sofia B.

    2016-01-01

    End-stage kidney disease (ESKD) patients are at increased cardiovascular risk. Vitamin D deficiency is associated with depressed heart rate variability (HRV), a risk factor depicting poor cardiac autonomic tone and risk of cardiovascular death. Vitamin D deficiency and depressed HRV are highly prevalent in the ESKD population. We aimed to determine the effects of oral vitamin D supplementation on HRV ((low frequency (LF) to high frequency (HF) spectral ratio (LF:HF)) in ESKD patients on hemodialysis. Fifty-six subjects with ESKD requiring hemodialysis were recruited from January 2013–March 2015 and randomized 1:1 to either conventional (0.25 mcg alfacalcidol plus placebo 3×/week) or intensive (0.25 mcg alfacalcidol 3×/week plus 50,000 international units (IU) ergocalciferol 1×/week) vitamin D for six weeks. The primary outcome was the change in LF:HF. There was no difference in LF:HF from baseline to six weeks for either vitamin D treatment (conventional: p = 0.9 vs. baseline; intensive: p = 0.07 vs. baseline). However, participants who remained vitamin D-deficient (25-hydroxyvitamin D < 20 ng/mL) after treatment demonstrated an increase in LF:HF (conventional: n = 13, ∆LF:HF: 0.20 ± 0.06, p < 0.001 vs. insufficient and sufficient vitamin D groups; intensive: n = 8: ∆LF:HF: 0.15 ± 0.06, p < 0.001 vs. sufficient vitamin D group). Overall, six weeks of conventional or intensive vitamin D only augmented LF:HF in ESKD subjects who remained vitamin D-deficient after treatment. Our findings potentially suggest that while activated vitamin D, with or without additional nutritional vitamin D, does not appear to improve cardiac autonomic tone in hemodialysis patients with insufficient or sufficient baseline vitamin D levels, supplementation in patients with severe vitamin D deficiency may improve cardiac autonomic tone in this higher risk sub-population of ESKD. Trial Registration: ClinicalTrials.gov, NCT01774812. PMID:27690095

  12. The VITAH Trial-Vitamin D Supplementation and Cardiac Autonomic Tone in Patients with End-Stage Kidney Disease on Hemodialysis: A Blinded, Randomized Controlled Trial.

    PubMed

    Mann, Michelle C; Exner, Derek V; Hemmelgarn, Brenda R; Hanley, David A; Turin, Tanvir C; MacRae, Jennifer M; Wheeler, David C; Sola, Darlene Y; Ramesh, Sharanya; Ahmed, Sofia B

    2016-09-28

    End-stage kidney disease (ESKD) patients are at increased cardiovascular risk. Vitamin D deficiency is associated with depressed heart rate variability (HRV), a risk factor depicting poor cardiac autonomic tone and risk of cardiovascular death. Vitamin D deficiency and depressed HRV are highly prevalent in the ESKD population. We aimed to determine the effects of oral vitamin D supplementation on HRV ((low frequency (LF) to high frequency (HF) spectral ratio (LF:HF)) in ESKD patients on hemodialysis. Fifty-six subjects with ESKD requiring hemodialysis were recruited from January 2013-March 2015 and randomized 1:1 to either conventional (0.25 mcg alfacalcidol plus placebo 3×/week) or intensive (0.25 mcg alfacalcidol 3×/week plus 50,000 international units (IU) ergocalciferol 1×/week) vitamin D for six weeks. The primary outcome was the change in LF:HF. There was no difference in LF:HF from baseline to six weeks for either vitamin D treatment (conventional: p = 0.9 vs. baseline; intensive: p = 0.07 vs. baseline). However, participants who remained vitamin D-deficient (25-hydroxyvitamin D < 20 ng/mL) after treatment demonstrated an increase in LF:HF (conventional: n = 13, ∆LF:HF: 0.20 ± 0.06, p < 0.001 vs. insufficient and sufficient vitamin D groups; intensive: n = 8: ∆LF:HF: 0.15 ± 0.06, p < 0.001 vs. sufficient vitamin D group). Overall, six weeks of conventional or intensive vitamin D only augmented LF:HF in ESKD subjects who remained vitamin D-deficient after treatment. Our findings potentially suggest that while activated vitamin D, with or without additional nutritional vitamin D, does not appear to improve cardiac autonomic tone in hemodialysis patients with insufficient or sufficient baseline vitamin D levels, supplementation in patients with severe vitamin D deficiency may improve cardiac autonomic tone in this higher risk sub-population of ESKD.

  13. Cytoskeletal prestress regulates nuclear shape and stiffness in cardiac myocytes

    PubMed Central

    Lee, Hyungsuk; Adams, William J; Alford, Patrick W; McCain, Megan L; Feinberg, Adam W; Sheehy, Sean P; Goss, Josue A

    2015-01-01

    Mechanical stresses on the myocyte nucleus have been associated with several diseases and potentially transduce mechanical stimuli into cellular responses. Although a number of physical links between the nuclear envelope and cytoplasmic filaments have been identified, previous studies have focused on the mechanical properties of individual components of the nucleus, such as the nuclear envelope and lamin network. The mechanical interaction between the cytoskeleton and chromatin on nuclear deformability remains elusive. Here, we investigated how cytoskeletal and chromatin structures influence nuclear mechanics in cardiac myocytes. Rapid decondensation of chromatin and rupture of the nuclear membrane caused a sudden expansion of DNA, a consequence of prestress exerted on the nucleus. To characterize the prestress exerted on the nucleus, we measured the shape and the stiffness of isolated nuclei and nuclei in living myocytes during disruption of cytoskeletal, myofibrillar, and chromatin structure. We found that the nucleus in myocytes is subject to both tensional and compressional prestress and its deformability is determined by a balance of those opposing forces. By developing a computational model of the prestressed nucleus, we showed that cytoskeletal and chromatin prestresses create vulnerability in the nuclear envelope. Our studies suggest the cytoskeletal–nuclear–chromatin interconnectivity may play an important role in mechanics of myocyte contraction and in the development of laminopathies by lamin mutations. PMID:25908635

  14. Cytoskeletal prestress regulates nuclear shape and stiffness in cardiac myocytes.

    PubMed

    Lee, Hyungsuk; Adams, William J; Alford, Patrick W; McCain, Megan L; Feinberg, Adam W; Sheehy, Sean P; Goss, Josue A; Parker, Kevin Kit

    2015-11-01

    Mechanical stresses on the myocyte nucleus have been associated with several diseases and potentially transduce mechanical stimuli into cellular responses. Although a number of physical links between the nuclear envelope and cytoplasmic filaments have been identified, previous studies have focused on the mechanical properties of individual components of the nucleus, such as the nuclear envelope and lamin network. The mechanical interaction between the cytoskeleton and chromatin on nuclear deformability remains elusive. Here, we investigated how cytoskeletal and chromatin structures influence nuclear mechanics in cardiac myocytes. Rapid decondensation of chromatin and rupture of the nuclear membrane caused a sudden expansion of DNA, a consequence of prestress exerted on the nucleus. To characterize the prestress exerted on the nucleus, we measured the shape and the stiffness of isolated nuclei and nuclei in living myocytes during disruption of cytoskeletal, myofibrillar, and chromatin structure. We found that the nucleus in myocytes is subject to both tensional and compressional prestress and its deformability is determined by a balance of those opposing forces. By developing a computational model of the prestressed nucleus, we showed that cytoskeletal and chromatin prestresses create vulnerability in the nuclear envelope. Our studies suggest the cytoskeletal-nuclear-chromatin interconnectivity may play an important role in mechanics of myocyte contraction and in the development of laminopathies by lamin mutations.

  15. Negative feedback regulation of Homer 1a on norepinephrine-dependent cardiac hypertrophy

    SciTech Connect

    Chiarello, Carmelina; Bortoloso, Elena; Carpi, Andrea; Furlan, Sandra; Volpe, Pompeo

    2013-07-15

    Homers are scaffolding proteins that modulate diverse cell functions being able to assemble signalling complexes. In this study, the presence, sub-cellular distribution and function of Homer 1 was investigated. Homer 1a and Homer 1b/c are constitutively expressed in cardiac muscle of both mouse and rat and in HL-1 cells, a cardiac cell line. As judged by confocal immunofluorescence microscopy, Homer 1a displays sarcomeric and peri-nuclear localization. In cardiomyocytes and cultured HL-1 cells, the hypertrophic agonist norepinephrine (NE) induces α{sub 1}-adrenergic specific Homer 1a over-expression, with a two-to-three-fold increase within 1 h, and no up-regulation of Homer 1b/c, as judged by Western blot and qPCR. In HL-1 cells, plasmid-driven over-expression of Homer 1a partially antagonizes activation of ERK phosphorylation and ANF up-regulation, two well-established, early markers of hypertrophy. At the morphometric level, NE-induced increase of cell size is likewise and partially counteracted by exogenous Homer 1a. Under the same experimental conditions, Homer 1b/c does not have any effect on ANF up-regulation nor on cell hypertrophy. Thus, Homer 1a up-regulation is associated to early stages of cardiac hypertrophy and appears to play a negative feedback regulation on molecular transducers of hypertrophy. -- Highlights: • Homer 1a is constitutively expressed in cardiac tissue. • In HL-1 cells, norepinephrine activates signaling pathways leading to hypertrophy. • Homer 1a up-regulation is an early event of norepinephrine-induced hypertrophy. • Homer 1a plays a negative feedback regulation modulating pathological hypertrophy. • Over-expression of Homer 1a per se does not induce hypertrophy.

  16. Class IA phosphoinositide 3-kinase regulates heart size and physiological cardiac hypertrophy.

    PubMed

    Luo, Ji; McMullen, Julie R; Sobkiw, Cassandra L; Zhang, Li; Dorfman, Adam L; Sherwood, Megan C; Logsdon, M Nicole; Horner, James W; DePinho, Ronald A; Izumo, Seigo; Cantley, Lewis C

    2005-11-01

    Class I(A) phosphoinositide 3-kinases (PI3Ks) are activated by growth factor receptors, and they regulate, among other processes, cell growth and organ size. Studies using transgenic mice overexpressing constitutively active and dominant negative forms of the p110alpha catalytic subunit of class I(A) PI3K have implicated the role of this enzyme in regulating heart size and physiological cardiac hypertrophy. To further understand the role of class I(A) PI3K in controlling heart growth and to circumvent potential complications from the overexpression of dominant negative and constitutively active proteins, we generated mice with muscle-specific deletion of the p85alpha regulatory subunit and germ line deletion of the p85beta regulatory subunit of class I(A) PI3K. Here we show that mice with cardiac deletion of both p85 subunits exhibit attenuated Akt signaling in the heart, reduced heart size, and altered cardiac gene expression. Furthermore, exercise-induced cardiac hypertrophy is also attenuated in the p85 knockout hearts. Despite such defects in postnatal developmental growth and physiological hypertrophy, the p85 knockout hearts exhibit normal contractility and myocardial histology. Our results therefore provide strong genetic evidence that class I(A) PI3Ks are critical regulators for the developmental growth and physiological hypertrophy of the heart.

  17. Bioinformatics Analysis Reveals MicroRNAs Regulating Biological Pathways in Exercise-Induced Cardiac Physiological Hypertrophy

    PubMed Central

    Xu, Jiahong; Liu, Yang; Xie, Yuan

    2017-01-01

    Exercise-induced physiological cardiac hypertrophy is generally considered to be a type of adaptive change after exercise training and is beneficial for cardiovascular diseases. This study aims at investigating exercise-regulated microRNAs (miRNAs) and their potential biological pathways. Here, we collected 23 miRNAs from 8 published studies. MirPath v.3 from the DIANA tools website was used to execute the analysis, and TargetScan was used to predict the target genes. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses were performed to identify potential pathways and functional annotations associated with exercise-induced physiological cardiac hypertrophy. Various miRNA targets and molecular pathways, such as Fatty acid elongation, Arrhythmogenic right ventricular cardiomyopathy (ARVC), and ECM-receptor interaction, were identified. This study could prompt the understanding of the regulatory mechanisms underlying exercise-induced physiological cardiac hypertrophy. PMID:28286759

  18. Bioinformatics Analysis Reveals MicroRNAs Regulating Biological Pathways in Exercise-Induced Cardiac Physiological Hypertrophy.

    PubMed

    Xu, Jiahong; Liu, Yang; Xie, Yuan; Zhao, Cuimei; Wang, Hongbao

    2017-01-01

    Exercise-induced physiological cardiac hypertrophy is generally considered to be a type of adaptive change after exercise training and is beneficial for cardiovascular diseases. This study aims at investigating exercise-regulated microRNAs (miRNAs) and their potential biological pathways. Here, we collected 23 miRNAs from 8 published studies. MirPath v.3 from the DIANA tools website was used to execute the analysis, and TargetScan was used to predict the target genes. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses were performed to identify potential pathways and functional annotations associated with exercise-induced physiological cardiac hypertrophy. Various miRNA targets and molecular pathways, such as Fatty acid elongation, Arrhythmogenic right ventricular cardiomyopathy (ARVC), and ECM-receptor interaction, were identified. This study could prompt the understanding of the regulatory mechanisms underlying exercise-induced physiological cardiac hypertrophy.

  19. A Temporal Chromatin Signature in Human Embryonic Stem Cells Identifies Regulators of Cardiac Development

    PubMed Central

    Paige, Sharon L.; Thomas, Sean; Stoick-Cooper, Cristi L.; Wang, Hao; Maves, Lisa; Sandstrom, Richard; Pabon, Lil; Reinecke, Hans; Pratt, Gabriel; Keller, Gordon; Moon, Randall T.; Stamatoyannopoulos, John; Murry, Charles E.

    2012-01-01

    Summary Directed differentiation of human embryonic stem cells (ESCs) into cardiovascular cells provides a model for studying molecular mechanisms of human cardiovascular development. Though it is known that chromatin modification patterns in ESCs differ markedly from those in lineage-committed progenitors and differentiated cells, the temporal dynamics of chromatin alterations during differentiation along a defined lineage have not been studied. We show that differentiation of human ESCs into cardiovascular cells is accompanied by programmed temporal alterations in chromatin structure that distinguish key regulators of cardiovascular development from other genes. We used this temporal chromatin signature to identify regulators of cardiac development, including the homeobox gene MEIS2. We demonstrate using the zebrafish model that MEIS2 is critical for proper heart tube formation and subsequent cardiac looping. Temporal chromatin signatures should be broadly applicable to other models of stem cell differentiation to identify regulators and provide key insights into major developmental decisions. PMID:22981225

  20. RBFox1-mediated RNA splicing regulates cardiac hypertrophy and heart failure

    PubMed Central

    Gao, Chen; Ren, Shuxun; Lee, Jae-Hyung; Qiu, Jinsong; Chapski, Douglas J.; Rau, Christoph D.; Zhou, Yu; Abdellatif, Maha; Nakano, Astushi; Vondriska, Thomas M.; Xiao, Xinshu; Fu, Xiang-Dong; Chen, Jau-Nian; Wang, Yibin

    2015-01-01

    RNA splicing is a major contributor to total transcriptome complexity; however, the functional role and regulation of splicing in heart failure remain poorly understood. Here, we used a total transcriptome profiling and bioinformatic analysis approach and identified a muscle-specific isoform of an RNA splicing regulator, RBFox1 (also known as A2BP1), as a prominent regulator of alternative RNA splicing during heart failure. Evaluation of developing murine and zebrafish hearts revealed that RBFox1 is induced during postnatal cardiac maturation. However, we found that RBFox1 is markedly diminished in failing human and mouse hearts. In a mouse model, RBFox1 deficiency in the heart promoted pressure overload–induced heart failure. We determined that RBFox1 is a potent regulator of RNA splicing and is required for a conserved splicing process of transcription factor MEF2 family members that yields different MEF2 isoforms with differential effects on cardiac hypertrophic gene expression. Finally, induction of RBFox1 expression in murine pressure overload models substantially attenuated cardiac hypertrophy and pathological manifestations. Together, this study identifies regulation of RNA splicing by RBFox1 as an important player in transcriptome reprogramming during heart failure that influence pathogenesis of the disease. PMID:26619120

  1. RBFox1-mediated RNA splicing regulates cardiac hypertrophy and heart failure.

    PubMed

    Gao, Chen; Ren, Shuxun; Lee, Jae-Hyung; Qiu, Jinsong; Chapski, Douglas J; Rau, Christoph D; Zhou, Yu; Abdellatif, Maha; Nakano, Astushi; Vondriska, Thomas M; Xiao, Xinshu; Fu, Xiang-Dong; Chen, Jau-Nian; Wang, Yibin

    2016-01-01

    RNA splicing is a major contributor to total transcriptome complexity; however, the functional role and regulation of splicing in heart failure remain poorly understood. Here, we used a total transcriptome profiling and bioinformatic analysis approach and identified a muscle-specific isoform of an RNA splicing regulator, RBFox1 (also known as A2BP1), as a prominent regulator of alternative RNA splicing during heart failure. Evaluation of developing murine and zebrafish hearts revealed that RBFox1 is induced during postnatal cardiac maturation. However, we found that RBFox1 is markedly diminished in failing human and mouse hearts. In a mouse model, RBFox1 deficiency in the heart promoted pressure overload-induced heart failure. We determined that RBFox1 is a potent regulator of RNA splicing and is required for a conserved splicing process of transcription factor MEF2 family members that yields different MEF2 isoforms with differential effects on cardiac hypertrophic gene expression. Finally, induction of RBFox1 expression in murine pressure overload models substantially attenuated cardiac hypertrophy and pathological manifestations. Together, this study identifies regulation of RNA splicing by RBFox1 as an important player in transcriptome reprogramming during heart failure that influence pathogenesis of the disease.

  2. A Review of Cardiac Autonomic Measures: Considerations for Examination of Physiological Response in Children with Autism Spectrum Disorder

    ERIC Educational Resources Information Center

    Benevides, Teal W.; Lane, Shelly J.

    2015-01-01

    The autonomic nervous system (ANS) is responsible for multiple physiological responses, and dysfunction of this system is often hypothesized as contributing to cognitive, affective, and behavioral responses in children. Research suggests that examination of ANS activity may provide insight into behavioral dysregulation in children with autism…

  3. Differential Regulation of Cardiac Function and Intracardiac Cytokines by Rapamycin in Healthy and Diabetic Rats

    PubMed Central

    Luck, Christian; DeMarco, Vincent G.; Mahmood, Abuzar; Gavini, Madhavi P.

    2017-01-01

    Diabetes is comorbid with cardiovascular disease and impaired immunity. Rapamycin improves cardiac functions and extends lifespan by inhibiting the mechanistic target of rapamycin complex 1 (mTORC1). However, in diabetic murine models, Rapamycin elevates hyperglycemia and reduces longevity. Since Rapamycin is an immunosuppressant, we examined whether Rapamycin (750 μg/kg/day) modulates intracardiac cytokines, which affect the cardiac immune response, and cardiac function in male lean (ZL) and diabetic obese Zucker (ZO) rats. Rapamycin suppressed levels of fasting triglycerides, insulin, and uric acid in ZO but increased glucose. Although Rapamycin improved multiple diastolic parameters (E/E′, E′/A′, E/Vp) initially, these improvements were reversed or absent in ZO at the end of treatment, despite suppression of cardiac fibrosis and phosphoSer473Akt. Intracardiac cytokine protein profiling and Ingenuity® Pathway Analysis indicated suppression of intracardiac immune defense in ZO, in response to Rapamycin treatment in both ZO and ZL. Rapamycin increased fibrosis in ZL without increasing phosphoSer473Akt and differentially modulated anti-fibrotic IL-10, IFNγ, and GM-CSF in ZL and ZO. Therefore, fundamental difference in intracardiac host defense between diabetic ZO and healthy ZL, combined with differential regulation of intracardiac cytokines by Rapamycin in ZO and ZL hearts, underlies differential cardiac outcomes of Rapamycin treatment in health and diabetes.

  4. Gene regulation, alternative splicing, and posttranslational modification of troponin subunits in cardiac development and adaptation: a focused review.

    PubMed

    Sheng, Juan-Juan; Jin, Jian-Ping

    2014-01-01

    Troponin plays a central role in regulating the contraction and relaxation of vertebrate striated muscles. This review focuses on the isoform gene regulation, alternative RNA splicing, and posttranslational modifications of troponin subunits in cardiac development and adaptation. Transcriptional and posttranscriptional regulations such as phosphorylation and proteolysis modifications, and structure-function relationships of troponin subunit proteins are summarized. The physiological and pathophysiological significances are discussed for impacts on cardiac muscle contractility, heart function, and adaptations in health and diseases.

  5. Calcitonin gene-related peptide (CGRP) in autonomic cardiovascular regulation and vascular structure.

    PubMed

    Mai, Tu H; Wu, Jing; Diedrich, André; Garland, Emily M; Robertson, David

    2014-05-01

    Calcitonin gene-related peptide (CGRP) is reported to play important roles in cardiovascular regulation in human and animal models. In spite of this, its role remains controversial. We aim to clarify this by studying the autonomic cardiovascular function and vascular structure in CGRP knockout (CGRP(-/-)) mice. Blood pressure (BP) and heart rate (HR) were assessed by telemeters. Urine (24-hour) and blood were collected for catecholamines measurements. Baroreflex sensitivity was assessed using phenylephrine and sodium nitroprusside administered in an acute study. Daytime mean arterial pressure (MAP; 12-hour period) was significantly higher in the CGRP(-/-) mice than in the wild type (WT) mice (114.5 vs. 104.5 mm Hg; P = .04). Norepinephrine was elevated in plasma and 24-hour urine in the knockouts (Urine, 956 vs. 618 pg/mL; P = .004; Plasma, 2505 vs. 1168 pg/mL; P = .04). Paradoxically, cardiovagal baroreflex sensitivity was higher in CGRP(-/-) mice (3.2 vs. 1.4 ms/mm Hg; P = .03). To increase insight, we studied aortic stiffness in CGRP(-/-) mice and found it increased compared with age-matched WT mice, as evidenced by the depression of the compliance curve (P < .05). CGRP(-/-) mice have higher BP due to elevated sympathetic signals and abnormalities in blood vessel structure. Moreover, our data also showed that CGRP plays an important role in the regulation of the cardio-vagal tone.

  6. Developmental regulation of cation pumps in skeletal and cardiac muscle.

    PubMed

    Dauncey, M J; Harrison, A P

    1996-03-01

    The prenatal and early postnatal periods are critical stages during which long-term development can be affected. For example, retardation of growth during these periods is closely linked to the occurrence of adult degenerative diseases. Appropriate development of muscle is essential for numerous functions, including movement, posture, thermogenesis, breathing and maintenance of the circulation. Defects in normal muscle development could thus impair any of these functions in the neonate and may also have long-term consequences for the health of the individual. Central to normal muscle structure and function is the appropriate development not only of the sarcomeric proteins but also of the sarcolemma, transverse-tubules, sarcoplasmic reticulum and associated membrane-bound ATPases. Long-term regulation of these ATPases is by changes in their concentration, whereas short-term regulation is mediated by alterations in enzyme activity. This review focuses on changes in total concentrations of Na+, K+, and Ca(2+)-ATPases during prenatal and postnatal life, in functionally diverse muscles of mammalian species born at different stages of maturity. Both these cation pumps belong to multigene families and changes in relative abundance of their specific isoforms are also considered because they may have important consequences for contractile performance during distinct stages of development. Finally, potential regulatory mechanisms which alter markedly during normal ontogeny are discussed. These include intrinsic factors such as hormones and contractile activity, extrinsic factors such as nutrition and environmental temperature, and interactions between these variables which are known to be especially important during postnatal development.

  7. Autonomous and controlled motivational regulations for multiple health-related behaviors: between- and within-participants analyses.

    PubMed

    Hagger, M S; Hardcastle, S J; Chater, A; Mallett, C; Pal, S; Chatzisarantis, N L D

    2014-01-01

    Self-determination theory has been applied to the prediction of a number of health-related behaviors with self-determined or autonomous forms of motivation generally more effective in predicting health behavior than non-self-determined or controlled forms. Research has been confined to examining the motivational predictors in single health behaviors rather than comparing effects across multiple behaviors. The present study addressed this gap in the literature by testing the relative contribution of autonomous and controlling motivation to the prediction of a large number of health-related behaviors, and examining individual differences in self-determined motivation as a moderator of the effects of autonomous and controlling motivation on health behavior. Participants were undergraduate students (N = 140) who completed measures of autonomous and controlled motivational regulations and behavioral intention for 20 health-related behaviors at an initial occasion with follow-up behavioral measures taken four weeks later. Path analysis was used to test a process model for each behavior in which motivational regulations predicted behavior mediated by intentions. Some minor idiosyncratic findings aside, between-participants analyses revealed significant effects for autonomous motivational regulations on intentions and behavior across the 20 behaviors. Effects for controlled motivation on intentions and behavior were relatively modest by comparison. Intentions mediated the effect of autonomous motivation on behavior. Within-participants analyses were used to segregate the sample into individuals who based their intentions on autonomous motivation (autonomy-oriented) and controlled motivation (control-oriented). Replicating the between-participants path analyses for the process model in the autonomy- and control-oriented samples did not alter the relative effects of the motivational orientations on intention and behavior. Results provide evidence for consistent effects

  8. Autonomic regulation across phases of the menstrual cycle and sleep stages in women with premenstrual syndrome and healthy controls.

    PubMed

    de Zambotti, Massimiliano; Nicholas, Christian L; Colrain, Ian M; Trinder, John A; Baker, Fiona C

    2013-11-01

    To investigate the influence of menstrual cycle phase and the presence of severe premenstrual symptoms on cardiac autonomic control during sleep, we performed heart rate variability (HRV) analysis during stable non-rapid eye movement (NREM) and REM sleep in 12 women with severe premenstrual syndrome and 14 controls in the mid-follicular, mid-luteal, and late-luteal phases of the menstrual cycle. Heart rate was higher, along with lower high frequency (HF) power, reflecting reduced vagal activity, and a higher ratio of low frequency (LF) to high frequency power, reflecting a shift to sympathetic dominance, in REM sleep compared with NREM sleep in both groups of women. Both groups of women had higher heart rate during NREM and REM sleep in the luteal phase recordings compared with the mid-follicular phase. HF power in REM sleep was lowest in the mid-luteal phase, when progesterone was highest, in both groups of women. The mid-luteal phase reduction in HF power was also evident in NREM sleep in control women but not in women with PMS, suggesting some impact of premenstrual syndrome on autonomic responses to the hormone environment of the mid-luteal phase. In addition, mid-luteal phase progesterone levels correlated positively with HF power and negatively with LF/HF ratio in control women in NREM sleep and with the LF/HF ratio during REM sleep in both groups of women. Our findings suggest the involvement of female reproductive steroids in cardiac autonomic control during sleep in women with and without premenstrual syndrome.

  9. The relationships between self-assessed habitual physical activity and non-invasive measures of cardiac autonomic modulation in young healthy volunteers.

    PubMed

    Sandercock, Gavin R H; Hardy-Shepherd, Darren; Nunan, David; Brodie, David

    2008-09-01

    Heart rate variability estimates cardiac autonomic modulation, but the relationship between habitual physical activity and heart rate variability remains unclear. The aims of this study were to compare RR-interval and heart rate variability indices in individuals of different habitual physical activity levels, and examine the relationship between habitual physical activity and heart rate variability. Ninety-two healthy volunteers (47 men, 45 women; mean age 23.1 years, s = 2.1) were divided into tertiles according to the Baecke Questionnaire score. Standard heart rate variability indices were derived from 5-min resting RR-interval recordings with paced respiration (0.25 Hz). Between-group differences and the relationship between habitual physical activity and heart rate variability were assessed. More active participants (tertiles 2-3) had longer RR-intervals than those in tertile 1 (P < 0.05). Participants in tertile 2 had higher root mean squared differences of successive normal RR-intervals than those in tertile 1 and a higher standard deviation of normal RR-intervals than those in tertiles 1 and 3. There was a positive linear relationship between habitual activity and RR-interval. Differing RR-interval lengths were found in subgroups of young individuals according to level of habitual physical activity. More active individuals showed resting bradycardia without evidence of enhanced cardiac parasympathetic modulation. The mechanism linking habitual physical activity and RR-interval length appears to be independent of physiological mechanisms that can be measured by heart rate variability.

  10. Behavioural asymmetry is involved in regulation of autonomic processes: Left side presentation of food improves reproduction and lactation in cows.

    PubMed

    Rizhova, Larissa Yu; Kokorina, Elvina P

    2005-06-03

    It is known that the right and left brain hemispheres differ in their ability to regulate autonomic processes in the organism. Direct unilateral stimulation of the brain provokes side-dependent endocrine, immune and other visceral reactions. Since brain hemispheres are mainly involved in the regulation of muscles and sensory organs on the contra lateral side of the body the activation of behavioural asymmetry stimulates the contra lateral half of the brain. The important theoretical and practical question of whether autonomic processes can be regulated via the behavioural asymmetry route remains unexplored. In this study, we report that the chronic presentation of an emotionally important stimulus-food-from the left side, improves reproductive performance in animals in a broad range of feeding conditions. The unilateral presentation of food can also influence lactation, but in this case the side-dependent effects are different under varying feeding conditions. This finding opens a simple practical approach to influence basic somatic functions in the organism.

  11. Sensitivity Analysis of Vagus Nerve Stimulation Parameters on Acute Cardiac Autonomic Responses: Chronotropic, Inotropic and Dromotropic Effects

    PubMed Central

    Ojeda, David; Le Rolle, Virginie; Romero-Ugalde, Hector M.; Gallet, Clément; Bonnet, Jean-Luc; Henry, Christine; Bel, Alain; Mabo, Philippe; Carrault, Guy; Hernández, Alfredo I.

    2016-01-01

    Although the therapeutic effects of Vagus Nerve Stimulation (VNS) have been recognized in pre-clinical and pilot clinical studies, the effect of different stimulation configurations on the cardiovascular response is still an open question, especially in the case of VNS delivered synchronously with cardiac activity. In this paper, we propose a formal mathematical methodology to analyze the acute cardiac response to different VNS configurations, jointly considering the chronotropic, dromotropic and inotropic cardiac effects. A latin hypercube sampling method was chosen to design a uniform experimental plan, composed of 75 different VNS configurations, with different values for the main parameters (current amplitude, number of delivered pulses, pulse width, interpulse period and the delay between the detected cardiac event and VNS onset). These VNS configurations were applied to 6 healthy, anesthetized sheep, while acquiring the associated cardiovascular response. Unobserved VNS configurations were estimated using a Gaussian process regression (GPR) model. In order to quantitatively analyze the effect of each parameter and their combinations on the cardiac response, the Sobol sensitivity method was applied to the obtained GPR model and inter-individual sensitivity markers were estimated using a bootstrap approach. Results highlight the dominant effect of pulse current, pulse width and number of pulses, which explain respectively 49.4%, 19.7% and 6.0% of the mean global cardiovascular variability provoked by VNS. More interestingly, results also quantify the effect of the interactions between VNS parameters. In particular, the interactions between current and pulse width provoke higher cardiac effects than the changes on the number of pulses alone (between 6 and 25% of the variability). Although the sensitivity of individual VNS parameters seems similar for chronotropic, dromotropic and inotropic responses, the interacting effects of VNS parameters provoke

  12. High-Intensity Resistance Exercise Promotes Postexercise Hypotension Greater than Moderate Intensity and Affects Cardiac Autonomic Responses in Women Who Are Hypertensive.

    PubMed

    de Freitas Brito, Aline; Brasileiro-Santos, Maria do S; Coutinho de Oliveira, Caio V; Sarmento da Nóbrega, Thereza K; Lúcia de Moraes Forjaz, Cláudia; da Cruz Santos, Amilton

    2015-12-01

    The purpose of this study was to evaluate the effect of high-intensity resistance exercise (RE) sessions on blood pressure (BP), heart rate (HR), cardiac autonomic modulation, and forearm blood flow (FBF). Sixteen trained hypertensive women (n = 16, 56 ± 3 years) completed the following 3 experimental sessions: control (CS), RE at 50% (EX50%), and RE at 80% (EX80%) of 1 repetition maximum (1RM). Both EX50% and EX80% comprised a set of 10 repetitions of 10 exercises, with an interval of 90 seconds between exercises. Measurements were taken preintervention and postintervention (at 10, 30, 50, 70, and 90 minutes of recovery). Reductions in systolic/diastolic BP after exercise were greater in EX80% (largest declines, -29 ± 4/-14 ± 5 mm Hg) than EX50% (largest declines, -18 ± 6/-8 ± 5 mm Hg, p ≤ 0.05). Heart rate and cardiac sympathovagal balance (LF/HF) increased more in relation to pre-exercise values in EX80% than EX50% (largest increases 96 ± 3 vs. 90 ± 4 b·min, LF/HF = 1.77 ± 0.25 vs. 1.40 ± 0.20, respectively, p ≤ 0.05). Increases in FBF and hyperemia was also higher in EX80% than EX50% compared with pre-exercise (4.97 ± 0.28 vs. 4.36 ± 0.27 ml·min·100 ml and 5.90 ± 0.20 vs. 5.38 ± 0.25 ml·min·100 ml; p ≤ 0.05, respectively). These results suggest that RE of higher intensity promoted greater postexercise hypotension accompanied by greater increases in FBF, vasodilator response, HR, and cardiac sympathovagal balance.

  13. Gritty people try harder: grit and effort-related cardiac autonomic activity during an active coping challenge.

    PubMed

    Silvia, Paul J; Eddington, Kari M; Beaty, Roger E; Nusbaum, Emily C; Kwapil, Thomas R

    2013-05-01

    Grit, a recently proposed personality trait associated with persistence for long-range goals, predicts achievement in a wide range of important life outcomes. Using motivational intensity theory, the present research examined the physiological underpinnings of grit during an active coping task. Forty young adults completed the Short Grit Scale and worked on a self-paced mental effort task. Effort-related autonomic nervous system (ANS) activity was assessed using impedance cardiography, which yielded measures of sympathetic activity (pre-ejection period; PEP) and parasympathetic activity (respiratory sinus arrhythmia; RSA). Multilevel models revealed that people high on the Perseverance of Effort subscale showed autonomic coactivation: both PEP and RSA became stronger during the task, reflecting higher activity of both ANS divisions. The Consistency of Interest subscale, in contrast, predicted only weaker sympathetic activity (slower PEP). Taken together, the findings illuminate autonomic processes associated with how "gritty" people pursue goals, and they suggest that more attention should be paid to the facets' distinct effects.

  14. Relationship between changes in pulmonary V̇O₂ kinetics and autonomic regulation of blood flow.

    PubMed

    McNarry, M A; Kingsley, M I C; Lewis, M J

    2014-08-01

    Various regulatory mechanisms of pulmonary oxygen uptake (V̇O2) kinetics have been postulated. The purpose of this study was to investigate the relationship between vagal withdrawal, measured using RMSSDRR, the root mean square of successive differences in cardiac interval (RR) kinetics, a mediator of oxygen delivery, and V̇O2 kinetics. Forty-nine healthy adults (23 ± 3 years; 72 ± 13 kg; 1.80 ± 0.08 m) performed multiple repeat transitions to moderate- and heavy-intensity exercise. Electrocardiography, impedance cardiography, and pulmonary gas exchange parameters were measured throughout; time domain measures of heart rate variability were subsequently derived. The parameters describing the dynamic response of V̇O2, cardiac output (Q) and RMSSDRR were determined using a mono-exponential model. During heavy-intensity exercise, the phase II τ of V̇O2 was significantly correlated with the τ of RR (r = 0.36, P < 0.05), Q (r = 0.67, P < 0.05), and RMSSDRR (r = 0.38, P < 0.05). The τ describing the rise in Q explained 47% of the variation in V̇O2 τ, with 30% of the rate of this rise in Q explained by the τ of RR and RMSSDRR. No relationship was evident between V̇O2 kinetics and those of Q, RR, or RMSSDRR during moderate exercise. Vagal withdrawal kinetics support the concept of a centrally mediated oxygen delivery limitation partly regulating V̇O2 kinetics during heavy-, but not moderate-, intensity exercise.

  15. Cardiac thin filament regulation and the Frank-Starling mechanism.

    PubMed

    Kobirumaki-Shimozawa, Fuyu; Inoue, Takahiro; Shintani, Seine A; Oyama, Kotaro; Terui, Takako; Minamisawa, Susumu; Ishiwata, Shin'ichi; Fukuda, Norio

    2014-07-01

    The heart has an intrinsic ability to increase systolic force in response to a rise in ventricular filling (the Frank-Starling law of the heart). It is widely accepted that the length dependence of myocardial activation underlies the Frank-Starling law of the heart. Recent advances in muscle physiology have enabled the identification of the factors involved in length-dependent activation, viz., titin (connectin)-based interfilament lattice spacing reduction and thin filament "on-off" regulation, with the former triggering length-dependent activation and the latter determining the number of myosin molecules recruited to thin filaments. Patients with a failing heart have demonstrated reduced exercise tolerance at least in part via depression of the Frank-Starling mechanism. Recent studies revealed that various mutations occur in the thin filament regulatory proteins, such as troponin, in the ventricular muscle of failing hearts, which consequently alter the Frank-Starling mechanism. In this article, we review the molecular mechanisms of length-dependent activation, and the influence of troponin mutations on the phenomenon.

  16. Beta adrenergic receptor blockade of feline myocardium. Cardiac mechanics, energetics, and beta adrenoceptor regulation.

    PubMed Central

    Cooper, G; Kent, R L; McGonigle, P; Watanabe, A M

    1986-01-01

    Myocardial oxygen consumption is regulated by interrelated mechanical and inotropic conditions; there is a parallel increase in the aerobic metabolism and inotropic state during beta-adrenergic stimulation under fixed mechanical conditions. In contrast, there is some evidence that beta-blockade may reduce oxygen consumption through effects independent of its influence on mechanical conditions and contractile state, and that prolonged beta-blockade may sensitize the myocardium to beta-adrenergic stimulation. To clarify these two points, the present study examined the relationship of myocardial energetics to mechanics and inotropism during acute beta-blockade and after the withdrawal of long-term beta-blockade, whereupon the basis for any effect observed was sought by characterizing the number, affinity, and affinity states of the beta-receptors as well as the coupling of activated beta-receptors to cyclic AMP generation. Studies of right ventricular papillary muscles from control and chronically beta-blocked cats demonstrated contractile and energetic properties as well as dose-response behavior and inotropic specificity suggestive of an increase in myocardial sensitivity to beta-adrenoceptor stimulation in the latter group. Assays of cardiac beta-adrenoceptors from further groups of control and pretreated cats, both in cardiac tissue and in isolated cardiac muscle cells, failed to define a difference between the two groups either in terms of receptor number and affinity or in terms of the proportion of receptors in the high-affinity state. However, coupling of the activated beta-adrenoceptors to cyclic AMP generation was enhanced in cardiac muscle cells from chronically beta-blocked cats. These data demonstrate that beta-adrenoceptor blockade (a) produces parallel effects on inotropic state and oxygen consumption without an independent effect on either and (b) increases myocardial sensitivity to beta-adrenergic stimulation after beta-blockade withdrawal, not by "up-regulation

  17. Regulation of human cardiac potassium channels by full-length KCNE3 and KCNE4

    PubMed Central

    Abbott, Geoffrey W.

    2016-01-01

    Voltage-gated potassium (Kv) channels comprise pore-forming α subunits and a multiplicity of regulatory proteins, including the cardiac-expressed and cardiac arrhythmia-linked transmembrane KCNE subunits. After recently uncovering novel, N-terminally extended (L) KCNE3 and KCNE4 isoforms and detecting their transcripts in human atrium, reported here are their functional effects on human cardiac Kv channel α subunits expressed in Xenopus laevis oocytes. As previously reported for short isoforms KCNE3S and KCNE4S, KCNE3L inhibited hERG; KCNE4L inhibited Kv1.1; neither form regulated the HCN1 pacemaker channel. Unlike KCNE4S, KCNE4L was a potent inhibitor of Kv4.2 and Kv4.3; co-expression of cytosolic β subunit KChIP2, which regulates Kv4 channels in cardiac myocytes, partially relieved Kv4.3 but not Kv4.2 inhibition. Inhibition of Kv4.2 and Kv4.3 by KCNE3L was weaker, and its inhibition of Kv4.2 abolished by KChIP2. KCNE3L and KCNE4L also exhibited subunit-specific effects on Kv4 channel complex inactivation kinetics, voltage dependence and recovery. Further supporting the potential physiological significance of the robust functional effects of KCNE4L on Kv4 channels, KCNE4L protein was detected in human atrium, where it co-localized with Kv4.3. The findings establish functional effects of novel human cardiac-expressed KCNE isoforms and further contribute to our understanding of the potential mechanisms influencing cardiomyocyte repolarization. PMID:27922120

  18. Relations Between Autonomous Motivation and Leisure-Time Physical Activity Participation: The Mediating Role of Self-Regulation Techniques.

    PubMed

    Nurmi, Johanna; Hagger, Martin S; Haukkala, Ari; Araújo-Soares, Vera; Hankonen, Nelli

    2016-04-01

    This study tested the predictive validity of a multitheory process model in which the effect of autonomous motivation from self-determination theory on physical activity participation is mediated by the adoption of self-regulatory techniques based on control theory. Finnish adolescents (N = 411, aged 17-19) completed a prospective survey including validated measures of the predictors and physical activity, at baseline and after one month (N = 177). A subsample used an accelerometer to objectively measure physical activity and further validate the physical activity self-report assessment tool (n = 44). Autonomous motivation statistically significantly predicted action planning, coping planning, and self-monitoring. Coping planning and self-monitoring mediated the effect of autonomous motivation on physical activity, although self-monitoring was the most prominent. Controlled motivation had no effect on self-regulation techniques or physical activity. Developing interventions that support autonomous motivation for physical activity may foster increased engagement in self-regulation techniques and positively affect physical activity behavior.

  19. Validation of Spectral Analysis as a Noninvasive Tool to Assess Autonomic Regulation of Cardiovascular Function

    NASA Technical Reports Server (NTRS)

    Knapp, Charles F.; Evans, Joyce M.

    1996-01-01

    A major focus of our program has been to develop a sensitive noninvasive procedure to quantify early weightlessness-induced changes in cardiovascular function or potential dysfunction. Forty studies of healthy young volunteers (10 men and 10 women, each studied twice) were conducted to determine changes in the sympatho-vagal balance of autonomic control of cardiovascular regulation during graded headward and footward blood volume shifts. Changes in sympatho-vagal balance were classified by changes in the mean levels and spectral content of cardiovascular variables and verified by changes in circulating levels of catecholamines and pancreatic polypeptide. Possible shifts in intra/extravascular fluid were assessed from changes in hematocrit and plasma mass density while changes in the stimulus to regulate plasma volume were determined from Plasma Renin Activity (PRA). Autonomic blockade was used to unmask the relative contribution of sympathetic and parasympathetic efferent influences in response to 10 min each of 0, 20 and 40 mmHg Lower Body Negative Pressure (LBNP) and 15 and 30 mmHg Positive Pressure (LBPP). The combination of muscarinic blockade with graded LBNP and LBPP was used to evoke graded increases and decreases in sympathetic activity without parasympathetic contributions. The combination of beta blockade with graded LBNP and LBPP was used to produce graded increases and decreases in parasympathetic activity without beta sympathetic contributions. Finally, a combination of both beta and muscarinic blockades with LBNP and LBPP was used to determine the contribution from other, primarily alpha adrenergic, sources. Mean values, spectral analyses and time frequency analysis of R-R interval (HR), Arterial Pressure (AP), peripheral blood flow (RF), Stroke Volume (SV) and peripheral resistance (TPR) were performed for all phases of the study. Skin blood Flow (SF) was also measured in other studies and similarly analyzed. Spectra were examined for changes in

  20. Circadian clock and cardiac vulnerability: A time stamp on multi-scale neuroautonomic regulation

    NASA Astrophysics Data System (ADS)

    Ivanov, Plamen Ch.

    2005-03-01

    Cardiovascular vulnerability displays a 24-hour pattern with a peak between 9AM and 11AM. This daily pattern in cardiac risk is traditionally attributed to external factors including activity levels and sleep-wake cycles. However,influences from the endogenous circadian pacemaker independent from behaviors may also affect cardiac control. We investigate heartbeat dynamics in healthy subjects recorded throughout a 10-day protocol wherein the sleep/wake and behavior cycles are desynchronized from the endogenous circadian cycle,enabling assessment of circadian factors while controlling for behavior-related factors. We demonstrate that the scaling exponent characterizing temporal correlations in heartbeat dynamics over multiple time scales does exhibit a significant circadian rhythm with a sharp peak at the circadian phase corresponding to the period 9-11AM, and that this rhythm is independent from scheduled behaviors and mean heart rate. Our findings of strong circadian rhythms in the multi-scale heartbeat dynamics of healthy young subjects indicate that the underlying mechanism of cardiac regulation is strongly influenced by the endogenous circadian pacemaker. A similar circadian effect in vulnerable individuals with underlying cardiovascular disease would contribute to the morning peak of adverse cardiac events observed in epidemiological studies.

  1. Symptoms of anxiety and mood disturbance alter cardiac and peripheral autonomic control in patients with metabolic syndrome.

    PubMed

    Toschi-Dias, Edgar; Trombetta, Ivani C; da Silva, Valdo José Dias; Maki-Nunes, Cristiane; Alves, Maria Janieire N N; Angelo, Luciana F; Cepeda, Felipe X; Martinez, Daniel G; Negrão, Carlos Eduardo; Rondon, Maria Urbana P B

    2013-03-01

    Previous investigations show that metabolic syndrome (MetSyn) causes sympathetic hyperactivation. Symptoms of anxiety and mood disturbance (AMd) provoke sympatho-vagal imbalance. We hypothesized that AMd would alter even further the autonomic function in patients with MetSyn. Twenty-six never-treated patients with MetSyn (ATP-III) were allocated to two groups, according to the levels of anxiety and mood disturbance: (1) with AMd (MetSyn + AMd, n = 15), and (2) without AMd (MetSyn, n = 11). Ten healthy control subjects were also studied (C, n = 10). AMd was determined using quantitative questionnaires. Muscle sympathetic nerve activity (MSNA, microneurography), blood pressure (oscillometric beat-to-beat basis), and heart rate (ECG) were measured during a baseline 10-min period. Spectral analysis of RR interval and systolic arterial pressure were analyzed, and the power of low (LF) and high (HF) frequency bands were determined. Sympatho-vagal balance was obtained by LF/HF ratio. Spontaneous baroreflex sensitivity (BRS) was evaluated by calculation of α-index. MSNA was greater in patients with MetSyn + AMd compared with MetSyn and C. Patients with MetSyn + AMd showed higher LF and lower HF power compared with MetSyn and C. In addition, LF/HF balance was higher in MetSyn + AMd than in MetSyn and C groups. BRS was decreased in MetSyn + AMd compared with MetSyn and C groups. Anxiety and mood disturbance alter autonomic function in patients with MetSyn. This autonomic dysfunction may contribute to the increased cardiovascular risk observed in patients with mood alterations.

  2. Transcription of minute virus of mice, an autonomous parvovirus, may be regulated by attenuation.

    PubMed Central

    Ben-Asher, E; Aloni, Y

    1984-01-01

    To characterize the transcriptional organization and regulation of minute virus of mice, an autonomous parvovirus, viral transcriptional complexes were isolated and cleaved with restriction enzymes. The in vivo preinitiated nascent RNA was elongated in vitro in the presence of [alpha-32P]UTP to generate runoff transcripts. The lengths of the runoff transcripts were analyzed by gel electrophoresis under denaturing conditions. On the basis of the map locations of the restriction sites and the lengths of the runoff transcripts, the in vivo initiation sites were determined. Two major initiation sites having similar activities were thus identified at residues 201 +/- 5 and 2005 +/- 5; both of them were preceded by a TATAA sequence. When uncleaved viral transcriptional complexes or isolated nuclei were incubated in vitro in the presence of [alpha-32P]UTP or [alpha-32P]CTP, they synthesized labeled RNA that, as determined by polyacrylamide gel electrophoresis, contained a major band of 142 nucleotides. The RNA of the major band was mapped between the initiation site at residue 201 +/- 5 and residue 342. We noticed the potential of forming two mutually exclusive stem-and-loop structures in the 142-nucleotide RNA; one of them is followed by a string of uridylic acid residues typical of a procaryotic transcription termination signal. We propose that, as in the transcription of simian virus 40, RNA transcription in minute virus of mice may be regulated by attenuation and may involve eucaryotic polymerase B, which can respond to a transcription termination signal similar to that of the procaryotic polymerase. Images PMID:6090703

  3. The cell-autonomous role of excitatory synaptic transmission in the regulation of neuronal structure and function.

    PubMed

    Lu, Wei; Bushong, Eric A; Shih, Tiffany P; Ellisman, Mark H; Nicoll, Roger A

    2013-05-08

    The cell-autonomous role of synaptic transmission in the regulation of neuronal structural and electrical properties is unclear. We have now employed a genetic approach to eliminate glutamatergic synaptic transmission onto individual CA1 pyramidal neurons in a mosaic fashion in vivo. Surprisingly, while electrical properties are profoundly affected in these neurons, as well as inhibitory synaptic transmission, we found little perturbation of neuronal morphology, demonstrating a functional segregation of excitatory synaptic transmission from neuronal morphological development.

  4. Transcranial direct current stimulation improves the QT variability index and autonomic cardiac control in healthy subjects older than 60 years

    PubMed Central

    Piccirillo, Gianfranco; Ottaviani, Cristina; Fiorucci, Claudia; Petrocchi, Nicola; Moscucci, Federica; Di Iorio, Claudia; Mastropietri, Fabiola; Parrotta, Ilaria; Pascucci, Matteo; Magrì, Damiano

    2016-01-01

    Background Noninvasive brain stimulation technique is an interesting tool to investigate the causal relation between cortical functioning and autonomic nervous system (ANS) responses. Objective The objective of this report is to evaluate whether anodal transcranial direct current stimulation (tDCS) over the temporal cortex influences short-period temporal ventricular repolarization dispersion and cardiovascular ANS control in elderly subjects. Subjects and methods In 50 healthy subjects (29 subjects younger than 60 years and 21 subjects older than 60 years) matched for gender, short-period RR and systolic blood pressure spectral variability, QT variability index (QTVI), and noninvasive hemodynamic data were obtained during anodal tDCS or sham stimulation. Results In the older group, the QTVI, low-frequency (LF) power expressed in normalized units, the ratio between LF and high-frequency (HF) power, and systemic peripheral resistances decreased, whereas HF power expressed in normalized units and α HF power increased during the active compared to the sham condition (P<0.05). Conclusion In healthy subjects older than 60 years, tDCS elicits cardiovascular and autonomic changes. Particularly, it improves temporal ventricular repolarization dispersion, reduces sinus sympathetic activity and systemic peripheral resistance, and increases vagal sinus activity and baroreflex sensitivity. PMID:27895475

  5. Energy metabolism regulated by HDAC inhibitor attenuates cardiac injury in hemorrhagic rat model.

    PubMed

    Kuai, Qiyuan; Wang, Chunyan; Wang, Yanbing; Li, Weijing; Zhang, Gongqing; Qiao, Zhixin; He, Min; Wang, Xuanlin; Wang, Yu; Jiang, Xingwei; Su, Lihua; He, Yuezhong; Ren, Suping; Yu, Qun

    2016-12-02

    A disturbance of energy metabolism reduces cardiac function in acute severe hemorrhagic patients. Alternatively, adequate energy supply reduces heart failure and increases survival. However, the approach to regulating energy metabolism conductive to vital organs is limited, and the underlying molecular mechanism remains unknown. This study assesses the ability of histone deacetylase inhibitors (HDACIs) to preserve cardiac energy metabolism during lethal hemorrhagic injury. In the lethally hemorrhagic rat and hypoxic myocardial cells, energy metabolism and heart function were well maintained following HDACI treatment, as evident by continuous ATP production with normal cardiac contraction. Valproic acid (VPA) regulated the energy metabolism of hemorrhagic heart by reducing lactate synthesis and protecting the mitochondrial ultrastructure and respiration, which were attributable to the inhibition of lactate dehydrogenase A activity and the increased myeloid cell leukemia-1 (mcl-1) gene expression, ultimately facilitating ATP production and consumption. MCL-1, the key target of VPA, mediated this cardioprotective effect under acute severe hemorrhage conditions. Our results suggest that HDACIs promote cardioprotection by improving energy metabolism during hemorrhagic injury and could therefore be an effective strategy to counteract this process in the clinical setting.

  6. Energy metabolism regulated by HDAC inhibitor attenuates cardiac injury in hemorrhagic rat model

    PubMed Central

    Kuai, Qiyuan; Wang, Chunyan; Wang, Yanbing; Li, Weijing; Zhang, Gongqing; Qiao, Zhixin; He, Min; Wang, Xuanlin; Wang, Yu; Jiang, Xingwei; Su, Lihua; He, Yuezhong; Ren, Suping; Yu, Qun

    2016-01-01

    A disturbance of energy metabolism reduces cardiac function in acute severe hemorrhagic patients. Alternatively, adequate energy supply reduces heart failure and increases survival. However, the approach to regulating energy metabolism conductive to vital organs is limited, and the underlying molecular mechanism remains unknown. This study assesses the ability of histone deacetylase inhibitors (HDACIs) to preserve cardiac energy metabolism during lethal hemorrhagic injury. In the lethally hemorrhagic rat and hypoxic myocardial cells, energy metabolism and heart function were well maintained following HDACI treatment, as evident by continuous ATP production with normal cardiac contraction. Valproic acid (VPA) regulated the energy metabolism of hemorrhagic heart by reducing lactate synthesis and protecting the mitochondrial ultrastructure and respiration, which were attributable to the inhibition of lactate dehydrogenase A activity and the increased myeloid cell leukemia-1 (mcl-1) gene expression, ultimately facilitating ATP production and consumption. MCL-1, the key target of VPA, mediated this cardioprotective effect under acute severe hemorrhage conditions. Our results suggest that HDACIs promote cardioprotection by improving energy metabolism during hemorrhagic injury and could therefore be an effective strategy to counteract this process in the clinical setting. PMID:27910887

  7. Signaling molecules, transcription growth factors and other regulators revealed from in-vivo and in-vitro models for the regulation of cardiac development.

    PubMed

    Meganathan, Kesavan; Sotiriadou, Isaia; Natarajan, Karthick; Hescheler, Jürgen; Sachinidis, Agapios

    2015-03-15

    Several in-vivo heart developmental models have been applied to decipher the cardiac developmental patterning encompassing early, dorsal, cardiac and visceral mesoderm as well as various transcription factors such as Gata, Hand, Tin, Dpp, Pnr. The expression of cardiac specific transcription factors, such as Gata4, Tbx5, Tbx20, Tbx2, Tbx3, Mef2c, Hey1 and Hand1 are of fundamental significance for the in-vivo cardiac development. Not only the transcription factors, but also the signaling molecules involved in cardiac development were conserved among various species. Enrichment of the bone morphogenic proteins (BMPs) in the anterior lateral plate mesoderm is essential for the initiation of myocardial differentiation and the cardiac developmental process. Moreover, the expression of a number of cardiac transcription factors and structural genes initiate cardiac differentiation in the medial mesoderm. Other signaling molecules such as TGF-beta, IGF-1/2 and the fibroblast growth factor (FGF) play a significant role in cardiac repair/regeneration, ventricular heart development and specification of early cardiac mesoderm, respectively. The role of the Wnt signaling in cardiac development is still controversial discussed, as in-vitro results differ dramatically in relation to the animal models. Embryonic stem cells (ESC) were utilized as an important in-vitro model for the elucidation of the cardiac developmental processes since they can be easily manipulated by numerous signaling molecules, growth factors, small molecules and genetic manipulation. Finally, in the present review the dynamic role of the long noncoding RNA and miRNAs in the regulation of cardiac development are summarized and discussed.

  8. Cardiac expression of ms1/STARS, a novel gene involved in cardiac development and disease, is regulated by GATA4.

    PubMed

    Ounzain, Samir; Kobayashi, Satoru; Peterson, Richard E; He, Aibin; Motterle, Anna; Samani, Nilesh J; Menick, Donald R; Pu, William T; Liang, Qiangrong; Chong, Nelson W

    2012-05-01

    Ms1/STARS is a novel muscle-specific actin-binding protein that specifically modulates the myocardin-related transcription factor (MRTF)-serum response factor (SRF) regulatory axis within striated muscle. This ms1/STARS-dependent regulatory axis is of central importance within the cardiac gene regulatory network and has been implicated in cardiac development and postnatal cardiac function/homeostasis. The dysregulation of ms1/STARS is associated with and causative of pathological cardiac phenotypes, including cardiac hypertrophy and cardiomyopathy. In order to gain an understanding of the mechanisms governing ms1/STARS expression in the heart, we have coupled a comparative genomic in silico analysis with reporter, gain-of-function, and loss-of-function approaches. Through this integrated analysis, we have identified three evolutionarily conserved regions (ECRs), α, SINA, and DINA, that act as cis-regulatory modules and confer differential cardiac cell-specific activity. Two of these ECRs, α and DINA, displayed distinct regulatory sensitivity to the core cardiac transcription factor GATA4. Overall, our results demonstrate that within embryonic, neonatal, and adult hearts, GATA4 represses ms1/STARS expression with the pathologically associated depletion of GATA4 (type 1/type 2 diabetic models), resulting in ms1/STARS upregulation. This GATA4-dependent repression of ms1/STARS expression has major implications for MRTF-SRF signaling in the context of cardiac development and disease.

  9. Kruppel-like factor 4 protein regulates isoproterenol-induced cardiac hypertrophy by modulating myocardin expression and activity.

    PubMed

    Yoshida, Tadashi; Yamashita, Maho; Horimai, Chihiro; Hayashi, Matsuhiko

    2014-09-19

    Kruppel-like factor 4 (KLF4) plays an important role in vascular diseases, including atherosclerosis and vascular injury. Although KLF4 is expressed in the heart in addition to vascular cells, the role of KLF4 in cardiac disease has not been fully determined. The goals of this study were to investigate the role of KLF4 in cardiac hypertrophy and to determine the underlying mechanisms. Cardiomyocyte-specific Klf4 knockout (CM Klf4 KO) mice were generated by the Cre/LoxP technique. Cardiac hypertrophy was induced by chronic infusion of the β-adrenoreceptor agonist isoproterenol (ISO). Results showed that ISO-induced cardiac hypertrophy was enhanced in CM Klf4 KO mice compared with control mice. Accelerated cardiac hypertrophy in CM Klf4 KO mice was accompanied by the augmented cellular enlargement of cardiomyocytes as well as the exaggerated expression of fetal cardiac genes, including atrial natriuretic factor (Nppa). Additionally, induction of myocardin, a transcriptional cofactor regulating fetal cardiac genes, was enhanced in CM Klf4 KO mice. Interestingly, KLF4 regulated Nppa expression by modulating the expression and activity of myocardin, providing a mechanical basis for accelerated cardiac hypertrophy in CM Klf4 KO mice. Moreover, we showed that KLF4 mediated the antihypertrophic effect of trichostatin A, a histone deacetylase inhibitor, because ISO-induced cardiac hypertrophy in CM Klf4 KO mice was attenuated by olmesartan, an angiotensin II type 1 antagonist, but not by trichostatin A. These results provide novel evidence that KLF4 is a regulator of cardiac hypertrophy by modulating the expression and the activity of myocardin.

  10. Modular organization of cardiac energy metabolism: energy conversion, transfer and feedback regulation

    PubMed Central

    Guzun, R.; Kaambre, T.; Bagur, R.; Grichine, A.; Usson, Y.; Varikmaa, M.; Anmann, T.; Tepp, K.; Timohhina, N.; Shevchuk, I.; Chekulayev, V.; Boucher, F.; Santos, P. Dos; Schlattner, U.; Wallimann, T.; Kuznetsov, A. V.; Dzeja, P.; Aliev, M.; Saks, V.

    2014-01-01

    To meet high cellular demands, the energy metabolism of cardiac muscles is organized by precise and coordinated functioning of intracellular energetic units (ICEUs). ICEUs represent structural and functional modules integrating multiple fluxes at sites of ATP generation in mitochondria and ATP utilization by myofibrillar, sarcoplasmic reticulum and sarcolemma ion-pump ATPases. The role of ICEUs is to enhance the efficiency of vectorial intracellular energy transfer and fine tuning of oxidative ATP synthesis maintaining stable metabolite levels to adjust to intracellular energy needs through the dynamic system of compartmentalized phosphoryl transfer networks. One of the key elements in regulation of energy flux distribution and feedback communication is the selective permeability of mitochondrial outer membrane (MOM) which represents a bottleneck in adenine nucleotide and other energy metabolite transfer and microcompartmentalization. Based on the experimental and theoretical (mathematical modelling) arguments, we describe regulation of mitochondrial ATP synthesis within ICEUs allowing heart workload to be linearly correlated with oxygen consumption ensuring conditions of metabolic stability, signal communication and synchronization. Particular attention was paid to the structure–function relationship in the development of ICEU, and the role of mitochondria interaction with cytoskeletal proteins, like tubulin, in the regulation of MOM permeability in response to energy metabolic signals providing regulation of mitochondrial respiration. Emphasis was given to the importance of creatine metabolism for the cardiac energy homoeostasis. PMID:24666671

  11. Cardiac and autonomic responses to change in posture or vitamin C supplementation in sickle cell anemia subjects.

    PubMed

    Jaja, S I; Kehinde, M O; Ogungbemi, S I

    2008-06-01

    Autonomic function following change in posture with or without vitamin C supplementation was studied in ten (10) sickle cell anemia (SCA) and twelve (12) non-sickle cell anemia (NSCA) subjects. Arterial blood pressure and electrocardiographic measurements were taken in the supine position on a couch 80cm high and immediately on assumption of the upright position. Vitamin C was then administered orally (300mg/day for 6 weeks). At the end of the period, blood pressure and ECG measurements were again made in the supine position and in response to change in posture. Change in posture significantly decreased QRS amplitude, QRS duration, PR interval, RR interval and MABP but increased HR and rate pressure product (RPP) in both groups of subjects. The HR and RPP responses were significantly higher in NSCA than in SCA subjects (p<0.001, respectively). Vitamin C caused greater reductions in QRS duration (p<0.01), PR duration p<0.001) in the NSCA subjects than in SCA subjects. It caused, however, greater reduction in RR duration (p<0.001) and MABP in SCA subjects than in NSCA subjects. It also caused significantly greater increases in HR and RPP (p<0.001, respectively) in the SCA subjects than in NSCA subjects. After vitamin C supplementation, change in posture decreased RR interval (p<0.001), QT interval (p<0.01) and MABP (p<0.05) but increased RPP (p<0.01) in NSCA subjects. In SCA subjects, there was a fall in RR interval (p<0.001) and MABP (p<0.01), but elevated RPP (p<0.001). Changes (Delta) in MABP, HR and RPP were similar between NSCA and SCA subjects. In conclusion, these findings indicate a blunted cardiovascular autonomic response to change in posture in sickle cell anemia subjects. Chronic, oral, low-dose vitamin C supplementation equilibrates this response with those of non-sickle cell anemia subjects.

  12. NF-κB signaling regulates cell-autonomous regulation of CXCL10 in breast cancer 4T1 cells

    PubMed Central

    Jin, Won Jong; Kim, Bongjun; Kim, Darong; Park Choo, Hea-Young; Kim, Hong-Hee; Ha, Hyunil; Lee, Zang Hee

    2017-01-01

    The chemokine CXCL10 and its receptor CXCR3 play a role in breast cancer metastasis to bone and osteoclast activation. However, the mechanism of CXCL10/CXCR3-induced intracellular signaling has not been fully investigated. To evaluate CXCL10-induced cellular events in the mouse breast cancer cell line 4T1, we developed a new synthetic CXCR3 antagonist JN-2. In this study, we observed that secretion of CXCL10 in the supernatant of 4T1 cells was gradually increased during cell growth. JN-2 inhibited basal and CXCL10-induced CXCL10 expression and cell motility in 4T1 cells. Treatment of 4T1 cells with CXCL10 increased the expression of P65, a subunit of the NF-κB pathway, via activation of the NF-κB transcriptional activity. Ectopic overexpression of P65 increased CXCL10 secretion and blunted JN-2-induced suppression of CXCL10 secretion, whereas overexpression of IκBα suppressed CXCL10 secretion. These results indicate that the CXCL10/CXCR3 axis creates a positive feedback loop through the canonical NF-κB signaling pathway in 4T1 cells. In addition, treatment of osteoblasts with conditioned medium from JN-2-treated 4T1 cells inhibited the expression of RANKL, a crucial cytokine for osteoclast differentiation, which resulted in an inhibitory effect on osteoclast differentiation in the co-culture system of bone marrow-derived macrophages and osteoblasts. Direct intrafemoral injection of 4T1 cells induced severe bone destruction; however, this effect was suppressed by the CXCR3 antagonist via downregulation of P65 expression in an animal model. Collectively, these results suggest that the CXCL10/CXCR3-mediated NF-κB signaling pathway plays a role in the control of autonomous regulation of CXCL10 and malignant tumor properties in breast cancer 4T1 cells. PMID:28209986

  13. Effect of upper torso inclination in Fowler's position on autonomic cardiovascular regulation.

    PubMed

    Kubota, Satoshi; Endo, Yutaka; Kubota, Mitsue

    2013-09-01

    The present study investigates autonomic cardiovascular regulation during postural changes while in Fowler's position. Respiratory sinus arrhythmia (RSA) and sequence baroreflex sensitivity (sBRS) were measured in 12 healthy individuals in three positions (Experiment 1). We also measured RSA, sBRS, tidal volume (TV), lung volume spectrum (LV spectrum), and transfer gain and phase between lung volume and RR interval (RSA-TF, RSATF-phase) in 11 healthy individuals in two positions (Experiment 2). All participants maintained respiratory frequency at 15 breaths/min. The three positions in Experiment 1 were 30°, 45°, and 60° of upper torso inclination with a lower torso inclination of 30° throughout all evaluations. The two positions in Experiment 2 were 30° and 60° of upper torso backrest inclination with a lower torso inclination of 30° throughout all evaluations. The results of Experiment 1 showed significantly higher RSA and sBRS at 60° and 45° than at 30°, whereas RR interval (RRI), systolic blood pressure (SBP), and diastolic blood pressure (DBP) did not differ significantly under any condition. The results of Experiment 2 showed that RSA, RSA-TF, sBRS, TV, and LV spectrum were significantly higher at 60° than at 30°, and that RRI, SBP, DBP, and the RSATF phase did not significantly differ under any condition. These findings suggested that slight flexion of the upper torso in Fowler's position activates respiratory function and increases the contribution of vagal nerve activity to the cardiovascular system in young participants under conditions of a fixed respiratory rate.

  14. Autonomic nervous system regulation of the sinoatrial cell depolarization rate: Unifying computational models.

    PubMed

    Castellanos, P; Godinez, R

    2015-01-01

    In the last years different computational models have been proposed to simulate the sinoatrial node cell (SANC) action potential. Also, there has been a great effort to model the heart regulation mechanism by the autonomic nervous system (ANS) through the sympathetic and parasympathetic pathways. Both computational models have tried to fit the rabbit and/or the guinea-pig experimental heart rate data with an increasing success. Thus, the aim of this work was to unify the available models that have been reported to study the heart rate behavior when the SANC is stimulated by using different frequency patterns. Our results contribute to the unification of part of the Scepanovic's model [1] (involved with second messengers dynamics and its influence over specific SANC ionic channels), and the SANC ionic channels computational model proposed by Severi et al. [2] in 2012. In this model unification we did refit some parameters, particularly, those related to the Hill functions in the dynamic modeling of phosphokinase and its effect on the ionic channels currents If and ICaL, and over the Pup, parameter that is related to the Ca(++) uptake by the sarcoplasmic reticulum. Also, we eliminated the neurotransmitter effect over the ionic current IKr that is not presented in the Severi's model. These modifications were enough to successfully reproduce the heart rate experimental recordings under acetylcholine (Ach) or norepinephrine (NE) for independent stimulation: Ach 10 nM stimulation showed a 21.54% action potential shift compared with the 20% reported for experimental recordings; Isoprenaline 1 μM, also displayed a depolarization increased rate of 29.3%, compared with the experimental data of 28.2%. Furthermore, we were able to reproduce the guinea-pig experimental heart rate recordings, when the SANC model was vagal stimulated by using a 2 Hz, 10 Hz and 20 Hz frequency for 10 seconds and the experimental heart rate data for a sympathetic stimulation of 10 Hz frequency for

  15. Regulating the regulator: Insights into the cardiac protein phosphatase 1 interactome.

    PubMed

    Chiang, David Y; Heck, Albert J R; Dobrev, Dobromir; Wehrens, Xander H T

    2016-12-01

    Reversible phosphorylation of proteins is a delicate yet dynamic balancing act between kinases and phosphatases, the disturbance of which underlies numerous disease processes. While our understanding of protein kinases has grown tremendously over the past decades, relatively little is known regarding protein phosphatases. This may be because protein kinases are great in number and relatively specific in function, and thereby amenable to be studied in isolation, whereas protein phosphatases are much less abundant and more nonspecific in their function. To achieve subcellular localization and substrate specificity, phosphatases depend on partnering with a large number of regulatory subunits, protein scaffolds and/or other interactors. This added layer of complexity presents a significant barrier to their study, but holds the key to unexplored opportunities for novel pharmacologic intervention. In this review we focus on serine/threonine protein phosphatase type-1 (PP1), which plays an important role in cardiac physiology and pathophysiology. Although much work has been done to investigate the role of PP1 in cardiac diseases including atrial fibrillation and heart failure, most of these studies were limited to examining and manipulating the catalytic subunit(s) of PP1 without adequately considering the PP1 interactors, which give specificity to PP1's functions. To complement these studies, three unbiased methods have been developed and applied to the mapping of the PP1 interactome: bioinformatics approaches, yeast two-hybrid screens, and affinity-purification mass spectrometry. The application of these complementary methods has the potential to generate a detailed cardiac PP1 interactome, which is an important step in identifying novel and targeted pharmacological interventions.

  16. Blood pressure regulation, autonomic control and sleep disordered breathing in children.

    PubMed

    Nisbet, Lauren C; Yiallourou, Stephanie R; Walter, Lisa M; Horne, Rosemary S C

    2014-04-01

    Sleep disordered breathing (SDB) ranges in severity from primary snoring (PS) to obstructive sleep apnoea (OSA). In adults, SDB is associated with adverse cardiovascular consequences which are mediated, in part, by autonomic dysfunction. Although SDB is common in children, fewer paediatric studies have investigated these cardiovascular effects. Initial research focused on those with OSA, indeed children with PS were occasionally utilised as the comparison control group. However, it is essential to understand the ramifications of this disorder in all its severities, as currently the milder forms of SDB are often untreated. Methodologies used to assess autonomic function in children with SDB include blood pressure (BP), BP variability, baroreflex sensitivity, heart rate variability, peripheral arterial tonometry and catecholamine assays. The aim of this review was to summarise the findings of paediatric studies to date and explore the relationship between autonomic dysfunction and SDB in children, paying particular attention to the roles of disease severity and/or age. This review found evidence of autonomic dysfunction in children with SDB during both wakefulness and sleep. BP dysregulation, elevated generalised sympathetic activity and impairment of autonomic reflexes occur in school-aged children and adolescents with SDB. The adverse effects of SDB seem somewhat less in young children, although more studies are needed. There is mounting evidence that the cardiovascular and autonomic consequences of SDB are not limited to those with OSA, but are also evident in children with PS. The severity of disease and age of onset of autonomic consequences may be important guides for the treatment of SDB.

  17. Phosphorylation sites required for regulation of cardiac calcium channels in the fight-or-flight response.

    PubMed

    Fu, Ying; Westenbroek, Ruth E; Scheuer, Todd; Catterall, William A

    2013-11-26

    L-type Ca(2+) currents conducted by CaV1.2 channels initiate excitation-contraction coupling in the heart. Their activity is increased by β-adrenergic/cAMP signaling via phosphorylation by PKA in the fight-or-flight response, but the sites of regulation are unknown. We describe the functional role of phosphorylation of Ser1700 and Thr1704-sites of phosphorylation by PKA and casein kinase II at the interface between the proximal and distal C-terminal regulatory domains. Mutation of both residues to Ala in STAA mice reduced basal L-type Ca(2+) currents, due to a small decrease in expression and a substantial decrease in functional activity. The increase in L-type Ca(2+) current caused by isoproterenol was markedly reduced at physiological levels of stimulation (3-10 nM). Maximal increases in calcium current at nearly saturating concentrations of isoproterenol (100 nM) were also significantly reduced, but the mutation effects were smaller, suggesting that alternative regulatory mechanisms are engaged at maximal levels of stimulation. The β-adrenergic increase in cell contraction was also diminished. STAA ventricular myocytes exhibited arrhythmic contractions in response to isoproterenol, and up to 20% of STAA cells failed to sustain contractions when stimulated at 1 Hz. STAA mice have reduced exercise capacity, and cardiac hypertrophy is evident at 3 mo. We conclude that phosphorylation of Ser1700 and Thr1704 is essential for regulation of basal activity of CaV1.2 channels and for up-regulation by β-adrenergic signaling at physiological levels of stimulation. Disruption of phosphorylation at those sites leads to impaired cardiac function in vivo, as indicated by reduced exercise capacity and cardiac hypertrophy.

  18. Regulation of mitochondrial oxidative stress by β-arrestins in cultured human cardiac fibroblasts

    PubMed Central

    Philip, Jennifer L.; Razzaque, Md. Abdur; Han, Mei; Li, Jinju; Theccanat, Tiju; Xu, Xianyao; Akhter, Shahab A.

    2015-01-01

    ABSTRACT Oxidative stress in cardiac fibroblasts (CFs) promotes transformation to myofibroblasts and collagen synthesis leading to myocardial fibrosis, a precursor to heart failure (HF). NADPH oxidase 4 (Nox4) is a major source of cardiac reactive oxygen species (ROS); however, mechanisms of Nox4 regulation are unclear. β-arrestins are scaffold proteins that signal in G-protein-dependent and -independent pathways; for example, in ERK activation. We hypothesize that β-arrestins regulate oxidative stress in a Nox4-dependent manner and increase fibrosis in HF. CFs were isolated from normal and failing adult human left ventricles. Mitochondrial ROS/superoxide production was quantitated using MitoSox. β-arrestin and Nox4 expressions were manipulated using adenoviral overexpression or short interfering RNA (siRNA)-mediated knockdown. Mitochondrial oxidative stress and Nox4 expression in CFs were significantly increased in HF. Nox4 knockdown resulted in inhibition of mitochondrial superoxide production and decreased basal and TGF-β-stimulated collagen and α-SMA expression. CF β-arrestin expression was upregulated fourfold in HF. β-arrestin knockdown in failing CFs decreased ROS and Nox4 expression by 50%. β-arrestin overexpression in normal CFs increased mitochondrial superoxide production twofold. These effects were prevented by inhibition of either Nox or ERK. Upregulation of Nox4 seemed to be a primary mechanism for increased ROS production in failing CFs, which stimulates collagen deposition. β-arrestin expression was upregulated in HF and plays an important and newly identified role in regulating mitochondrial superoxide production via Nox4. The mechanism for this effect seems to be ERK-mediated. Targeted inhibition of β-arrestins in CFs might decrease oxidative stress as well as pathological cardiac fibrosis. PMID:26449263

  19. On site assessment of cardiac function and neural regulation in amateur half marathon runners

    PubMed Central

    Dalla Vecchia, Laura; Traversi, Egidio; Porta, Alberto; Lucini, Daniela; Pagani, Massimo

    2014-01-01

    Objective Strenuous exercise variably modifies cardiovascular function. Only few data are available on intermediate levels of effort. We therefore planned a study in order to address the hypothesis that a half marathon distance would result in transient changes of cardiac mechanics, neural regulation and biochemical profile suggestive of a complex, integrated adaptation. Methods We enrolled 35 amateur athletes (42±7 years). Supine and standing heart rate variability and a complete echocardiographic evaluation were assessed on site after the completion of a half marathon (postrace) and about 1 month after (baseline). Biochemical tests were also measured postrace. Results Compared to baseline, the postrace left ventricular end-diastolic volume was smaller, peak velocity of E wave was lower, peak velocity of A wave higher, and accordingly the E/A ratio lower. The postrace heart and respiratory rate were higher and variance of RR interval lower, together with a clear shift towards a sympathetic predominance in supine position and a preserved response to orthostasis. At baseline, athletes were characterised by a lower, although still predominant, sympathetic drive with a preserved physiological response to standing. Conclusions Immediately after a half marathon there are clear marks that an elevated sympathetic cardiac drive outlasts the performance, together with decreased left ventricular diastolic volumes and slight modifications of the left ventricular filling pattern without additional signs of diastolic dysfunction or indices of transient left or right ventricular systolic abnormalities. Furthermore, no biochemical indices of any permanent cardiac damage were found. PMID:25332775

  20. KChIP2 is a core transcriptional regulator of cardiac excitability

    PubMed Central

    Nassal, Drew M; Wan, Xiaoping; Liu, Haiyan; Maleski, Danielle; Ramirez-Navarro, Angelina; Moravec, Christine S; Ficker, Eckhard; Laurita, Kenneth R; Deschênes, Isabelle

    2017-01-01

    Arrhythmogenesis from aberrant electrical remodeling is a primary cause of death among patients with heart disease. Amongst a multitude of remodeling events, reduced expression of the ion channel subunit KChIP2 is consistently observed in numerous cardiac pathologies. However, it remains unknown if KChIP2 loss is merely a symptom or involved in disease development. Using rat and human derived cardiomyocytes, we identify a previously unobserved transcriptional capacity for cardiac KChIP2 critical in maintaining electrical stability. Through interaction with genetic elements, KChIP2 transcriptionally repressed the miRNAs miR-34b and miR-34c, which subsequently targeted key depolarizing (INa) and repolarizing (Ito) currents altered in cardiac disease. Genetically maintaining KChIP2 expression or inhibiting miR-34 under pathologic conditions restored channel function and moreover, prevented the incidence of reentrant arrhythmias. This identifies the KChIP2/miR-34 axis as a central regulator in developing electrical dysfunction and reveals miR-34 as a therapeutic target for treating arrhythmogenesis in heart disease. DOI: http://dx.doi.org/10.7554/eLife.17304.001 PMID:28263709

  1. PTPIP51 regulates mouse cardiac ischemia/reperfusion through mediating the mitochondria-SR junction

    PubMed Central

    Qiao, Xue; Jia, Shi; Ye, Jingjing; Fang, Xuan; Zhang, Chenglin; Cao, Yangpo; Xu, Chunling; Zhao, Lifang; Zhu, Yi; Wang, Lu; Zheng, Ming

    2017-01-01

    Protein tyrosine phosphatase interacting protein 51 (PTPIP51) participates in multiple cellular processes, and dysfunction of PTPIP51 is implicated in diseases such as cancer and neurodegenerative disorders. However, there is no functional evidence showing the physiological or pathological roles of PTPIP51 in the heart. We have therefore investigated the role and mechanisms of PTPIP51 in regulating cardiac function. We found that PTPIP51 was markedly upregulated in ischemia/reperfusion heart. Upregulation of PTPIP51 by adenovirus-mediated overexpression markedly increased the contact of mitochondria-sarcoplasmic reticulum (SR), elevated mitochondrial Ca2+ uptake from SR release through mitochondrial Ca2+uniporter. Inhibition or knockdown of mitochondrial Ca2+uniporter reversed PTPIP51-mediated increase of mitochondrial Ca2+ and protected cardiomyocytes against PTPIP51-mediated apoptosis. More importantly, cardiac specific knockdown of PTPIP51 largely reduced myocardium infarction size and heart injury after ischemia/reperfusion. Our study defines a novel and essential function of PTPIP51 in the cardiac ischemia/reperfusion process by mediating mitochondria-SR contact. Downregulation of PTPIP51 improves heart function after ischemia/reperfusion injury, suggesting PTPIP51 as a therapeutic target for ischemic heart diseases. PMID:28345618

  2. A role for matrix stiffness in the regulation of cardiac side population cell function.

    PubMed

    Qiu, Yiling; Bayomy, Ahmad F; Gomez, Marcus V; Bauer, Michael; Du, Ping; Yang, Yanfei; Zhang, Xin; Liao, Ronglih

    2015-05-01

    The mechanical properties of the local microenvironment may have important influence on the fate and function of adult tissue progenitor cells, altering the regenerative process. This is particularly critical following a myocardial infarction, in which the normal, compliant myocardial tissue is replaced with fibrotic, stiff scar tissue. In this study, we examined the effects of matrix stiffness on adult cardiac side population (CSP) progenitor cell behavior. Ovine and murine CSP cells were isolated and cultured on polydimethylsiloxane substrates, replicating the elastic moduli of normal and fibrotic myocardium. Proliferation capacity and cell cycling were increased in CSP cells cultured on the stiff substrate with an associated reduction in cardiomyogeneic differentiation and accelerated cell ageing. In addition, culture on stiff substrate stimulated upregulation of extracellular matrix and adhesion proteins gene expression in CSP cells. Collectively, we demonstrate that microenvironment properties, including matrix stiffness, play a critical role in regulating progenitor cell functions of endogenous resident CSP cells. Understanding the effects of the tissue microenvironment on resident cardiac progenitor cells is a critical step toward achieving functional cardiac regeneration.

  3. Endothelial Nogo-B regulates sphingolipid biosynthesis to promote pathological cardiac hypertrophy during chronic pressure overload

    PubMed Central

    Huang, Yan; Azevedo, Paula S.; Siragusa, Mauro; Bielawski, Jacek; Giordano, Frank J.

    2016-01-01

    We recently discovered that endothelial Nogo-B, a membrane protein of the ER, regulates vascular function by inhibiting the rate-limiting enzyme, serine palmitoyltransferase (SPT), in de novo sphingolipid biosynthesis. Here, we show that endothelium-derived sphingolipids, particularly sphingosine-1-phosphate (S1P), protect the heart from inflammation, fibrosis, and dysfunction following pressure overload and that Nogo-B regulates this paracrine process. SPT activity is upregulated in banded hearts in vivo as well as in TNF-α–activated endothelium in vitro, and loss of Nogo removes the brake on SPT, increasing local S1P production. Hence, mice lacking Nogo-B, systemically or specifically in the endothelium, are resistant to the onset of pathological cardiac hypertrophy. Furthermore, pharmacological inhibition of SPT with myriocin restores permeability, inflammation, and heart dysfunction in Nogo-A/B–deficient mice to WT levels, whereas SEW2871, an S1P1 receptor agonist, prevents myocardial permeability, inflammation, and dysfunction in WT banded mice. Our study identifies a critical role of endothelial sphingolipid biosynthesis and its regulation by Nogo-B in the development of pathological cardiac hypertrophy and proposes a potential therapeutic target for the attenuation or reversal of this clinical condition. PMID:27158676

  4. Inhibition of serum and glucocorticoid regulated kinase-1 as novel therapy for cardiac arrhythmia disorders.

    PubMed

    Bezzerides, Vassilios J; Zhang, Aifeng; Xiao, Ling; Simonson, Bridget; Khedkar, Santosh A; Baba, Shiro; Ottaviano, Filomena; Lynch, Stacey; Hessler, Katherine; Rigby, Alan C; Milan, David; Das, Saumya; Rosenzweig, Anthony

    2017-03-23

    Alterations in sodium flux (INa) play an important role in the pathogenesis of cardiac arrhythmias and may also contribute to the development of cardiomyopathies. We have recently demonstrated a critical role for the regulation of the voltage-gated sodium channel NaV1.5 in the heart by the serum and glucocorticoid regulated kinase-1 (SGK1). Activation of SGK1 in the heart causes a marked increase in both the peak and late sodium currents leading to prolongation of the action potential duration and an increased propensity to arrhythmia. Here we show that SGK1 directly regulates NaV1.5 channel function, and genetic inhibition of SGK1 in a zebrafish model of inherited long QT syndrome rescues the long QT phenotype. Using computer-aided drug discovery coupled with in vitro kinase assays, we identified a novel class of SGK1 inhibitors. Our lead SGK1 inhibitor (5377051) selectively inhibits SGK1 in cultured cardiomyocytes, and inhibits phosphorylation of an SGK1-specific target as well as proliferation in the prostate cancer cell line, LNCaP. Finally, 5377051 can reverse SGK1's effects on NaV1.5 and shorten the action potential duration in induced pluripotent stem cell (iPSC)-derived cardiomyocytes from a patient with a gain-of-function mutation in Nav 1.5 (Long QT3 syndrome). Our data suggests that SGK1 inhibitors warrant further investigation in the treatment of cardiac arrhythmias.

  5. TRPC3 positively regulates reactive oxygen species driving maladaptive cardiac remodeling

    PubMed Central

    Kitajima, Naoyuki; Numaga-Tomita, Takuro; Watanabe, Masahiko; Kuroda, Takuya; Nishimura, Akiyuki; Miyano, Kei; Yasuda, Satoshi; Kuwahara, Koichiro; Sato, Yoji; Ide, Tomomi; Birnbaumer, Lutz; Sumimoto, Hideki; Mori, Yasuo; Nishida, Motohiro

    2016-01-01

    Reactive oxygen species (ROS) produced by NADPH oxidase 2 (Nox2) function as key mediators of mechanotransduction during both physiological adaptation to mechanical load and maladaptive remodeling of the heart. This is despite low levels of cardiac Nox2 expression. The mechanism underlying the transition from adaptation to maladaptation remains obscure, however. We demonstrate that transient receptor potential canonical 3 (TRPC3), a Ca2+-permeable channel, acts as a positive regulator of ROS (PRROS) in cardiomyocytes, and specifically regulates pressure overload-induced maladaptive cardiac remodeling in mice. TRPC3 physically interacts with Nox2 at specific C-terminal sites, thereby protecting Nox2 from proteasome-dependent degradation and amplifying Ca2+-dependent Nox2 activation through TRPC3-mediated background Ca2+ entry. Nox2 also stabilizes TRPC3 proteins to enhance TRPC3 channel activity. Expression of TRPC3 C-terminal polypeptide abolished TRPC3-regulated ROS production by disrupting TRPC3-Nox2 interaction, without affecting TRPC3-mediated Ca2+ influx. The novel TRPC3 function as a PRROS provides a mechanistic explanation for how diastolic Ca2+ influx specifically encodes signals to induce ROS-mediated maladaptive remodeling and offers new therapeutic possibilities. PMID:27833156

  6. The effects of autonomous and controlled regulation of performance-approach goals on well-being: a process model.

    PubMed

    Gillet, Nicolas; Lafrenière, Marc-André K; Vallerand, Robert J; Huart, Isabelle; Fouquereau, Evelyne

    2014-03-01

    The main purpose of the present research was to propose and test a motivational model linking achievement goal approach and self-determination theory. First, the effects of performance-approach goals and the autonomous and controlling reasons underlying their pursuit on well-being were investigated. Second, the mediating variables (i.e., effort, goal attainment, need satisfaction, and thwarting) at play in these relationships were examined based on the self-concordance model (Sheldon & Elliot, 1999). The model was tested in two studies in educational and work settings using cross sectional (Study 1) and prospective designs (Study 2). The present results revealed that considering autonomous and controlled regulations underlying performance-approach goals predicted well-being above and beyond the strength of performance-approach goals. Moreover, the mediational sequence based on the self-concordance model was supported in both studies. Theoretical implications and directions for future research are discussed.

  7. Transcriptional Pathways and Potential Therapeutic Targets in the Regulation of Ncx1 Expression in Cardiac Hypertrophy and Failure

    PubMed Central

    Li, Mona S.; Chernysh, Olga; Renaud, Ludivine; Kimbrough, Denise; Kasiganesan, Harinath; Mani, Santhosh K.

    2013-01-01

    Changes in cardiac gene expression contribute to the progression of heart failure by affecting cardiomyocyte growth, function, and survival. The Na+ -Ca2+ exchanger gene (Ncx1) is upregulated in hypertrophy and is often found elevated in end-stage heart failure. Studies have shown that the change in its expression contributes to contractile dysfunction. Several transcriptional pathways mediate Ncx1 expression in pathological cardiac remodeling. Both α-adrenergic receptor (α-AR) and β-adrenergic receptor (β-AR) signaling can play a role in the regulation of calcium homeostasis in the cardiomyocyte, but chronic activation in periods of cardiac stress contributes to heart failure by mechanisms which include Ncx1 upregulation. Our studies have even demonstrated that NCX1 can directly act as a regulator of “activity-dependent signal transduction” mediating changes in its own expression. Finally, we present evidence that histone deacetylases (HDACs) and histone acetyltransferases (HATs) act as master regulators of Ncx1 expression. We show that many of the transcription factors regulating Ncx1 expression are important in cardiac development and also in the regulation of many other genes in the so-called fetal gene program, which are activated by pathological stimuli. Importantly, studies have revealed that the transcriptional network regulating Ncx1 expression is also mediating many of the other changes in genetic remodeling contributing to the development of cardiac dysfunction and revealed potential therapeutic targets for the treatment of hypertrophy and failure. PMID:23224875

  8. Regulation of cardiac myocyte contractility by phospholemman: Na+/Ca2+ exchange versus Na+ -K+ -ATPase.

    PubMed

    Song, Jianliang; Zhang, Xue-Qian; Wang, JuFang; Cheskis, Ellina; Chan, Tung O; Feldman, Arthur M; Tucker, Amy L; Cheung, Joseph Y

    2008-10-01

    Phospholemman (PLM) regulates cardiac Na(+)/Ca(2+) exchanger (NCX1) and Na(+)-K(+)-ATPase in cardiac myocytes. PLM, when phosphorylated at Ser(68), disinhibits Na(+)-K(+)-ATPase but inhibits NCX1. PLM regulates cardiac contractility by modulating Na(+)-K(+)-ATPase and/or NCX1. In this study, we first demonstrated that adult mouse cardiac myocytes cultured for 48 h had normal surface membrane areas, t-tubules, and NCX1 and sarco(endo)plasmic reticulum Ca(2+)-ATPase levels, and retained near normal contractility, but alpha(1)-subunit of Na(+)-K(+)-ATPase was slightly decreased. Differences in contractility between myocytes isolated from wild-type (WT) and PLM knockout (KO) hearts were preserved after 48 h of culture. Infection with adenovirus expressing green fluorescent protein (GFP) did not affect contractility at 48 h. When WT PLM was overexpressed in PLM KO myocytes, contractility and cytosolic Ca(2+) concentration ([Ca(2+)](i)) transients reverted back to those observed in cultured WT myocytes. Both Na(+)-K(+)-ATPase current (I(pump)) and Na(+)/Ca(2+) exchange current (I(NaCa)) in PLM KO myocytes rescued with WT PLM were depressed compared with PLM KO myocytes. Overexpressing the PLMS68E mutant (phosphomimetic) in PLM KO myocytes resulted in the suppression of I(NaCa) but had no effect on I(pump). Contractility, [Ca(2+)](i) transient amplitudes, and sarcoplasmic reticulum Ca(2+) contents in PLM KO myocytes overexpressing the PLMS68E mutant were depressed compared with PLM KO myocytes overexpressing GFP. Overexpressing the PLMS68A mutant (mimicking unphosphorylated PLM) in PLM KO myocytes had no effect on I(NaCa) but decreased I(pump). Contractility, [Ca(2+)](i) transient amplitudes, and sarcoplasmic reticulum Ca(2+) contents in PLM KO myocytes overexpressing the S68A mutant were similar to PLM KO myocytes overexpressing GFP. We conclude that at the single-myocyte level, PLM affects cardiac contractility and [Ca(2+)](i) homeostasis primarily by its direct

  9. Regulation of pyruvate dehydrogenase activity and citric acid cycle intermediates during high cardiac power generation.

    PubMed

    Sharma, Naveen; Okere, Isidore C; Brunengraber, Daniel Z; McElfresh, Tracy A; King, Kristen L; Sterk, Joseph P; Huang, Hazel; Chandler, Margaret P; Stanley, William C

    2005-01-15

    A high rate of cardiac work increases citric acid cycle (CAC) turnover and flux through pyruvate dehydrogenase (PDH); however, the mechanisms for these effects are poorly understood. We tested the hypotheses that an increase in cardiac energy expenditure: (1) activates PDH and reduces the product/substrate ratios ([NADH]/[NAD(+)] and [acetyl-CoA]/[CoA-SH]); and (2) increases the content of CAC intermediates. Measurements were made in anaesthetized pigs under control conditions and during 15 min of a high cardiac workload induced by dobutamine (Dob). A third group was made hyperglycaemic (14 mm) to stimulate flux through PDH during the high work state (Dob + Glu). Glucose and fatty acid oxidation were measured with (14)C-glucose and (3)H-oleate. Compared with control, the high workload groups had a similar increase in myocardial oxygen consumption ( and cardiac power. Dob increased PDH activity and glucose oxidation above control, but did not reduce the [NADH]/[NAD(+)] and [acetyl-CoA]/[CoA-SH] ratios, and there were no differences between the Dob and Dob + Glu groups. An additional group was treated with Dob + Glu and oxfenicine (Oxf) to inhibit fatty acid oxidation: this increased [CoA-SH] and glucose oxidation compared with Dob; however, there was no further activation of PDH or decrease in the [NADH]/[NAD(+)] ratio. Content of the 4-carbon CAC intermediates succinate, fumarate and malate increased 3-fold with Dob, but there was no change in citrate content, and the Dob + Glu and Dob + Glu + Oxf groups were not different from Dob. In conclusion, compared with normal conditions, at high myocardial energy expenditure (1) the increase in flux through PDH is regulated by activation of the enzyme complex and continues to be partially controlled through inhibition by fatty acid oxidation, and (2) there is expansion of the CAC pool size at the level of 4-carbon intermediates that is largely independent of myocardial fatty acid oxidation.

  10. A cardiac mitochondrial cAMP signaling pathway regulates calcium accumulation, permeability transition and cell death

    PubMed Central

    Wang, Z; Liu, D; Varin, A; Nicolas, V; Courilleau, D; Mateo, P; Caubere, C; Rouet, P; Gomez, A-M; Vandecasteele, G; Fischmeister, R; Brenner, C

    2016-01-01

    Although cardiac cytosolic cyclic 3′,5′-adenosine monophosphate (cAMP) regulates multiple processes, such as beating, contractility, metabolism and apoptosis, little is known yet on the role of this second messenger within cardiac mitochondria. Using cellular and subcellular approaches, we demonstrate here the local expression of several actors of cAMP signaling within cardiac mitochondria, namely a truncated form of soluble AC (sACt) and the exchange protein directly activated by cAMP 1 (Epac1), and show a protective role for sACt against cell death, apoptosis as well as necrosis in primary cardiomyocytes. Upon stimulation with bicarbonate (HCO3−) and Ca2+, sACt produces cAMP, which in turn stimulates oxygen consumption, increases the mitochondrial membrane potential (ΔΨm) and ATP production. cAMP is rate limiting for matrix Ca2+ entry via Epac1 and the mitochondrial calcium uniporter and, as a consequence, prevents mitochondrial permeability transition (MPT). The mitochondrial cAMP effects involve neither protein kinase A, Epac2 nor the mitochondrial Na+/Ca2+ exchanger. In addition, in mitochondria isolated from failing rat hearts, stimulation of the mitochondrial cAMP pathway by HCO3− rescued the sensitization of mitochondria to Ca2+-induced MPT. Thus, our study identifies a link between mitochondrial cAMP, mitochondrial metabolism and cell death in the heart, which is independent of cytosolic cAMP signaling. Our results might have implications for therapeutic prevention of cell death in cardiac pathologies. PMID:27100892

  11. Cardiac calcium signalling pathologies associated with defective calmodulin regulation of type 2 ryanodine receptor

    PubMed Central

    Arnáiz-Cot, Juan José; Damon, Brooke James; Zhang, Xiao-Hua; Cleemann, Lars; Yamaguchi, Naohiro; Meissner, Gerhard; Morad, Martin

    2013-01-01

    Cardiac ryanodine receptor (RyR2) is a homotetramer of 560 kDa polypeptides regulated by calmodulin (CaM), which decreases its open probability at diastolic and systolic Ca2+ concentrations. Point mutations in the CaM-binding domain of RyR2 (W3587A/L3591D/F3603A, RyR2ADA) in mice result in severe cardiac hypertrophy, poor left ventricle contraction and death by postnatal day 16, suggesting that CaM inhibition of RyR2 is required for normal cardiac function. Here, we report on Ca2+ signalling properties of enzymatically isolated, Fluo-4 dialysed whole cell clamped cardiac myocytes from 10–15-day-old wild-type (WT) and homozygous Ryr2ADA/ADA mice. Spontaneously occurring Ca2+ spark frequency, measured at −80 mV, was 14-fold lower in mutant compared to WT myocytes. ICa, though significantly smaller in mutant myocytes, triggered Ca2+ transients that were of comparable size to those of WT myocytes, but with slower activation and decay kinetics. Caffeine-triggered Ca2+ transients were about three times larger in mutant myocytes, generating three- to four-fold bigger Na+-Ca2+ exchanger NCX currents (INCX). Mutant myocytes often exhibited Ca2+ transients of variable size and duration that were accompanied by similarly alternating and slowly activating INCX. The data suggest that RyR2ADA mutation produces significant reduction in ICa density and ICa-triggered Ca2+ release gain, longer but infrequently occurring Ca2+ sparks, larger sarcoplasmic reticulum Ca2+ loads, and spontaneous Ca2+ releases accompanied by activation of large and potentially arrhythmogenic inward INCX. PMID:23836685

  12. SHP-2 acts via ROCK to regulate the cardiac actin cytoskeleton.

    PubMed

    Langdon, Yvette; Tandon, Panna; Paden, Erika; Duddy, Jennifer; Taylor, Joan M; Conlon, Frank L

    2012-03-01

    Noonan syndrome is one of the most common causes of human congenital heart disease and is frequently associated with missense mutations in the protein phosphatase SHP-2. Interestingly, patients with acute myelogenous leukemia (AML), acute lymphoblastic leukemia (ALL), juvenile myelomonocytic leukemia (JMML) and LEOPARD syndrome frequently carry a second, somatically introduced subset of missense mutations in SHP-2. To determine the cellular and molecular mechanisms by which SHP-2 regulates heart development and, thus, understand how Noonan-associated mutations affect cardiogenesis, we introduced SHP-2 encoding the most prevalent Noonan syndrome and JMML mutations into Xenopus embryos. Resulting embryos show a direct relationship between a Noonan SHP-2 mutation and its ability to cause cardiac defects in Xenopus; embryos expressing Noonan SHP-2 mutations exhibit morphologically abnormal hearts, whereas those expressing an SHP-2 JMML-associated mutation do not. Our studies indicate that the cardiac defects associated with the introduction of the Noonan-associated SHP-2 mutations are coupled with a delay or arrest of the cardiac cell cycle in M-phase and a failure of cardiomyocyte progenitors to incorporate into the developing heart. We show that these defects are a result of an underlying malformation in the formation and polarity of cardiac actin fibers and F-actin deposition. We show that these defects can be rescued in culture and in embryos through the inhibition of the Rho-associated, coiled-coil-containing protein kinase 1 (ROCK), thus demonstrating a direct relationship between SHP-2(N308D) and ROCK activation in the developing heart.

  13. Insignificant effects of plasma catecholamines on dynamic heart rate regulation by the cardiac sympathetic nerve.

    PubMed

    Kawada, T; Inagaki, M; Zheng, C; Li, M; Sunagawa, K; Sugimachi, M

    2005-01-01

    Although plasma catecholamines such as norepinephrine (NE) and epinephrine (Epi) increase during severe exercise, the effects of high levels of plasma catecholamines on dynamic heart rate (HR) regulation by the cardiac sympathetic nerve remains unknown. The aim of the present study was to examine the effects of plasma catecholamines on the transfer function from sympathetic nerve stimulation to HR. In anesthetized rabbits, we randomly stimulated the right cardiac sympathetic nerve according to a binary white noise signal while measuring HR. The effects of intravenous NE administration at 1 and 10 mugmiddotkg-1middoth-1 were examined in 6 rabbits. The effects of intravenous Epi administration at 1 and 10 mugmiddotkg-1middoth-1 were examined in different 6 rabbits. Although plasma NE increased 10 times as high as the baseline level during the NE administration at mugmiddotkg-1middoth-1 , dynamic gain of the transfer function was not changed significantly (7.1plusmn1.2, 6.9plusmn1.1, and 7.7plusmn1.1 beatsmiddotmin-1middotHz-1). Similarly, although plasma Epi increased 10 times as high as the baseline level during the Epi administration at 10 mugmiddotkg-1middoth-1, dynamic gain of the transfer function was not changed significantly (7.5plusmn0.8, 7.9plusmn0.8, and 7.6plusmn1.2 beatsmiddotmin-1middotHz-1). In conclusion, plasma catecholamines of physiologically-relevant high concentrations did not interfere with the dynamic HR regulation by the cardiac sympathetic nerve.

  14. Noninvasive evaluation of cardiac autonomic modulation in children with primary Raynaud’s phenomenon: a controlled study.

    PubMed

    Oflaz, Mehmet Burhan; Ece, İbrahim; Kibar, Ayşe Esin; Ballı, Şevket; Alaygut, Demet; Guven, Ahmet Sami; Bolat, Fatih; Duksal, Fatma; Cevit, Ömer

    2014-01-01

    This study aimed to objectively evaluate autonomic nervous function in children with primary Raynaud’s phenomenon (PRP). Thirty-two children with PRP and 30 healthy subjects were included in the study. We analyzed heart rate variability (HRV) in the time domain by the following six standard time-domain measures: standard deviation of all normal R-R intervals during 24 h (SDNN), standard deviation of all normal R-R intervals for all 5-min segments (SDNNi), standard deviation of the average normal R-R intervals for all 5-min segments (SDANN), root mean square of the successive normal R-R interval difference, percentage of successive normal R-R intervals longer than 50 ms, and triangular index (integral of the density distribution of NN intervals divided by the maximum of the density distribution). The mean heart rate throughout 24 h was significantly higher in the PRP group than in the control group (p = 0.001). Although heart rate during the activity period was not significantly different from that during the night period, it was higher in the PRP group than in the control group (p = 0.002). In children with PRP, HRV analysis showed significantly lower values of SDNN (p = 0.01), SDNNi (p = 0.005), SDANN (p = 0.02), and HRV triangular index (p = 0.02) compared with the control group. HRV analysis for sympathovagal balance demonstrated a preponderance for the sympathetic component in patients with PRP. We conclude that all time-domain parameters evaluated in HRV analysis are significantly lower in children with PRP than in healthy subjects.

  15. miR-300 mediates Bmi1 function and regulates differentiation in primitive cardiac progenitors.

    PubMed

    Cruz, F M; Tomé, M; Bernal, J A; Bernad, A

    2015-10-29

    B lymphoma Mo-MLV insertion region 1 (Bmi1) is a polycomb-family transcriptional factor critical for self-renewal in many adult stem cells and human neoplasia. We sought to identify microRNAs regulated by Bmi1 that could play a role in multipotent cardiac progenitor cell (CPC) decisions. We found that miR-300, a poorly characterized microRNA mapping in the Dlk1-Dio3 microRNA cluster, was positively regulated by Bmi1 in CPCs. Forced expression of miR-300 in CPCs promoted an improved stemness signature with a significant increase in Oct4 levels, a reduction in senescence progression and an enhanced proliferative status via p19 activation and inhibition of p16 accumulation. Endothelial and cardiogenic differentiation were clearly compromised by sustained miR-300 expression. Additionally, RNA and protein analysis revealed a significant reduction in key cardiac transcription factors, including Nkx2.5 and Tbx5. Collectively, these results suggest that some functions attributed to Bmi1 are due to induction of miR-300, which decreases the cardiogenic differentiation potential of multipotent CPCs in vitro and promotes self-renewal.

  16. Does visual fatigue from 3D displays affect autonomic regulation and heart rhythm?

    PubMed

    Park, S; Won, M J; Mun, S; Lee, E C; Whang, M

    2014-02-15

    Most investigations into the negative effects of viewing stereoscopic 3D content on human health have addressed 3D visual fatigue and visually induced motion sickness (VIMS). Very few, however, have looked into changes in autonomic balance and heart rhythm, which are homeostatic factors that ought to be taken into consideration when assessing the overall impact of 3D video viewing on human health. In this study, 30 participants were randomly assigned to two groups: one group watching a 2D video, (2D-group) and the other watching a 3D video (3D-group). The subjects in the 3D-group showed significantly increased heart rates (HR), indicating arousal, and an increased VLF/HF (Very Low Frequency/High Frequency) ratio (a measure of autonomic balance), compared to those in the 2D-group, indicating that autonomic balance was not stable in the 3D-group. Additionally, a more disordered heart rhythm pattern and increasing heart rate (as determined by the R-peak to R-peak (RR) interval) was observed among subjects in the 3D-group compared to subjects in the 2D-group, further indicating that 3D viewing induces lasting activation of the sympathetic nervous system and interrupts autonomic balance.

  17. The Role of Parents in Facilitating Autonomous Self-Regulation for Education

    ERIC Educational Resources Information Center

    Grolnick, Wendy S.

    2009-01-01

    Self-determination theory identifies three dimensions of parenting--autonomy support versus control, involvement, and structure--as facilitating children's autonomous motivation in school. Research involving children of a range of ages--one-year-olds through adolescents--and from a variety of research labs supports this theory. This work is…

  18. The relationship between cardiac autonomic function and maximal oxygen uptake response to high-intensity intermittent-exercise training.

    PubMed

    Boutcher, Stephen H; Park, Young; Dunn, Sarah Louise; Boutcher, Yati N

    2013-01-01

    Major individual differences in the maximal oxygen uptake response to aerobic training have been documented. Vagal influence on the heart has been shown to contribute to changes in aerobic fitness. Whether vagal influence on the heart also predicts maximal oxygen uptake response to interval-sprinting training, however, is undetermined. Thus, the relationship between baseline vagal activity and the maximal oxygen uptake response to interval-sprinting training was examined. Exercisers (n = 16) exercised three times a week for 12 weeks, whereas controls did no exercise (n = 16). Interval-sprinting consisted of 20 min of intermittent sprinting on a cycle ergometer (8 s sprint, 12 s recovery). Maximal oxygen uptake was assessed using open-circuit spirometry. Vagal influence was assessed through frequency analysis of heart rate variability. Participants were aged 22 ± 4.5 years and had a body mass of 72.7 ± 18.9 kg, a body mass index of 26.9 ± 3.9 kg · m(-2), and a maximal oxygen uptake of 28 ± 7.4 ml · kg(-1) · min(-1). Overall increase in maximal oxygen uptake after the training programme, despite being anaerobic in nature, was 19 ± 1.2%. Change in maximal oxygen uptake was correlated with initial baseline heart rate variability high-frequency power in normalised units (r = 0.58; P < 0.05). Thus, cardiac vagal modulation of heart rate was associated with the aerobic training response after 12 weeks of high-intensity intermittent-exercise. The mechanisms underlying the relationship between the aerobic training response and resting heart rate variability need to be established before practical implications can be identified.

  19. Noninvasive evaluation of the cardiac autonomic nervous system. Final progress report, December 24, 1993--February 28, 1994

    SciTech Connect

    Not Available

    1994-12-31

    During the first year of funding, C-11 hydroxyephedrine has been introduced as the first clinically usable norepinephrine analogue. Studies in normal volunteers and patients with various cardiac disorders indicated the feasibility of this tracer for further evaluation. Simultaneously, animal studies have been used to assess the use of these radiopharmaceuticals in ischemic injury in order to define neuronal damage. Current research focuses on the comparison of C-11 hydroxyephedrine with other neurotransmitters such as C-11 epinephrine and C-11 threo-hydroxyephedrine. Epinephrine is primarily stored in vesicles of the nerve terminal, while threo-hydroxyephedrine is only substrate to uptake I mechanism. Such a combination of radiotracers may allow the dissection of uptake I mechanism as well as vesicular storage. In parallel to the refinement of presynaptic tracers for the sympathetic nervous system, the authors are developing radiopharmaceuticals to delineate the adrenergic receptors in the heart. The combined evaluation of pre- and postsynaptic nerve function will improve their ability to identify abnormalities. They are currently developing a new radiosynthesis of the hydrophilic adrenergic receptor antagonist C-11 CGP-12177 which has been used by others for the visualization of adrenergic receptors in the heart. In addition, they are participating in the development of radiopharmaceuticals for the delineation of presynaptic cholinergic nerve terminals. Derivatives of benzovesamicol have been labeled in their institution and are currently under investigation. The most promising agent is F-18 benzovesamicol (FEBOBV) which allows the visualization of parasympathetic nerve terminals in the canine heart as demonstrated by preliminary PET data. A compilation of all publications funded by this grant is presented in this report.

  20. Abelson Family Tyrosine Kinases Regulate the Function of Nicotinic Acetylcholine Receptors and Nicotinic Synapses on Autonomic NeuronsS⃞

    PubMed Central

    Jayakar, Selwyn S.

    2011-01-01

    Abelson family kinases (AFKs; Abl1, Abl2) are non-receptor tyrosine kinases (NRTKs) implicated in cancer, but they also have important physiological roles that include regulating synaptic structure and function. Recent studies using Abl-deficient mice and the antileukemia drug STI571 [imatinib mesylate (Gleevec); Novartis], which potently and selectively blocks Abl kinase activity, implicate AFKs in regulating presynaptic neurotransmitter release in hippocampus and postsynaptic clustering of nicotinic acetylcholine receptors (nAChRs) in muscle. Here, we tested whether AFKs are relevant for regulating nAChRs and nAChR-mediated synapses on autonomic neurons. AFK immunoreactivity was detected in ciliary ganglion (CG) lysates and neurons, and STI571 application blocked endogenous Abl tyrosine kinase activity. With similar potency, STI571 specifically reduced whole-cell current responses generated by both nicotinic receptor subtypes present on CG neurons (α3*- and α7-nAChRs) and lowered the frequency and amplitude of α3*-nAChR-mediated excitatory postsynaptic currents. Quantal analysis indicated that the synaptic perturbations were postsynaptic in origin, and confocal imaging experiments revealed they were unaccompanied by changes in nAChR clustering or alignment with presynaptic terminals. The results indicate that in autonomic neurons, Abl kinase activity normally supports postsynaptic nAChR function to sustain nAChR-mediated neurotransmission. Such consequences contrast with the influence of Abl kinase activity on presynaptic function and synaptic structure in hippocampus and muscle, respectively, demonstrating a cell-specific mechanism of action. Finally, because STI571 potently inhibits Abl kinase activity, the autonomic dysfunction side effects associated with its use as a chemotherapeutic agent may result from perturbed α3*- and/or α7-nAChR function. PMID:21502378

  1. Non-Cell-Autonomous Regulation of Retrograde Motoneuronal Axonal Transport in an SBMA Mouse Model

    PubMed Central

    Halievski, Katherine; Kemp, Michael Q.; Breedlove, S. Marc; Miller, Kyle E.

    2016-01-01

    Abstract Defects in axonal transport are seen in motoneuronal diseases, but how that impairment comes about is not well understood. In spinal bulbar muscular atrophy (SBMA), a disorder linked to a CAG/polyglutamine repeat expansion in the androgen receptor (AR) gene, the disease-causing AR disrupts axonal transport by acting in both a cell-autonomous fashion in the motoneurons themselves, and in a non-cell-autonomous fashion in muscle. The non-cell-autonomous mechanism is suggested by data from a unique “myogenic” transgenic (TG) mouse model in which an AR transgene expressed exclusively in skeletal muscle fibers triggers an androgen-dependent SBMA phenotype, including defects in retrograde transport. However, motoneurons in this TG model retain the endogenous AR gene, leaving open the possibility that impairments in transport in this model also depend on ARs in the motoneurons themselves. To test whether non-cell-autonomous mechanisms alone can perturb retrograde transport, we generated male TG mice in which the endogenous AR allele has the testicular feminization mutation (Tfm) and, consequently, is nonfunctional. Males carrying the Tfm allele alone show no deficits in motor function or axonal transport, with or without testosterone treatment. However, when Tfm males carrying the myogenic transgene (Tfm/TG) are treated with testosterone, they develop impaired motor function and defects in retrograde transport, having fewer retrogradely labeled motoneurons and deficits in endosomal flux based on time-lapse video microscopy of living axons. These findings demonstrate that non-cell-autonomous disease mechanisms originating in muscle are sufficient to induce defects in retrograde transport in motoneurons. PMID:27517091

  2. Non-Cell-Autonomous Regulation of Retrograde Motoneuronal Axonal Transport in an SBMA Mouse Model.

    PubMed

    Halievski, Katherine; Kemp, Michael Q; Breedlove, S Marc; Miller, Kyle E; Jordan, Cynthia L

    2016-01-01

    Defects in axonal transport are seen in motoneuronal diseases, but how that impairment comes about is not well understood. In spinal bulbar muscular atrophy (SBMA), a disorder linked to a CAG/polyglutamine repeat expansion in the androgen receptor (AR) gene, the disease-causing AR disrupts axonal transport by acting in both a cell-autonomous fashion in the motoneurons themselves, and in a non-cell-autonomous fashion in muscle. The non-cell-autonomous mechanism is suggested by data from a unique "myogenic" transgenic (TG) mouse model in which an AR transgene expressed exclusively in skeletal muscle fibers triggers an androgen-dependent SBMA phenotype, including defects in retrograde transport. However, motoneurons in this TG model retain the endogenous AR gene, leaving open the possibility that impairments in transport in this model also depend on ARs in the motoneurons themselves. To test whether non-cell-autonomous mechanisms alone can perturb retrograde transport, we generated male TG mice in which the endogenous AR allele has the testicular feminization mutation (Tfm) and, consequently, is nonfunctional. Males carrying the Tfm allele alone show no deficits in motor function or axonal transport, with or without testosterone treatment. However, when Tfm males carrying the myogenic transgene (Tfm/TG) are treated with testosterone, they develop impaired motor function and defects in retrograde transport, having fewer retrogradely labeled motoneurons and deficits in endosomal flux based on time-lapse video microscopy of living axons. These findings demonstrate that non-cell-autonomous disease mechanisms originating in muscle are sufficient to induce defects in retrograde transport in motoneurons.

  3. Regulation of Cardiac Calcium Channels in the Fight-or-Flight Response.

    PubMed

    Catterall, William A

    2015-01-01

    Intracellular calcium transients generated by activation of voltage-gated calcium (CaV) channels generate local signals, which initiate physiological processes such as secretion, synaptic transmission, and excitation-contraction coupling. Regulation of calcium entry through CaV channels is crucial for control of these physiological processes. In this article, I review experimental results that have emerged over several years showing that cardiac CaV1.2 channels form a local signaling complex, in which their proteolytically processed distal C-terminal domain, an A-Kinase Anchoring Protein, and cyclic AMP-dependent protein kinase (PKA) interact directly with the transmembrane core of the ion channel through the proximal C-terminal domain. This signaling complex is the substrate for β-adrenergic up-regulation of the CaV1.2 channel in the heart during the fight-or-flight response. Protein phosphorylation of two sites at the interface between the distal and proximal C-terminal domains contributes importantly to control of basal CaV1.2 channel activity, and phosphorylation of Ser1700 by PKA at that interface up-regulates CaV1.2 activity in response to β-adrenergic signaling. Thus, the intracellular C-terminal domain of CaV1.2 channels serves as a signaling platform, mediating beat-to-beat physiological regulation of channel activity and up-regulation by β-adrenergic signaling in the fight-or-flight response.

  4. Nkx2-5 regulates cardiac growth through modulation of Wnt signaling by R-spondin3.

    PubMed

    Cambier, Linda; Plate, Markus; Sucov, Henry M; Pashmforoush, Mohammad

    2014-08-01

    A complex regulatory network of morphogens and transcription factors is essential for normal cardiac development. Nkx2-5 is among the earliest known markers of cardiac mesoderm that is central to the regulatory pathways mediating second heart field (SHF) development. Here, we have examined the specific requirements for Nkx2-5 in the SHF progenitors. We show that Nkx2-5 potentiates Wnt signaling by regulating the expression of the R-spondin3 (Rspo3) gene during cardiogenesis. R-spondins are secreted factors and potent Wnt agonists that in part regulate stem cell proliferation. Our data show that Rspo3 is markedly downregulated in Nkx2-5 mutants and that Rspo3 expression is regulated by Nkx2-5. Conditional inactivation of Rspo3 in the Isl1 lineage resulted in embryonic lethality secondary to impaired development of SHF. More importantly, we find that Wnt signaling is significantly attenuated in Nkx2-5 mutants and that enhancing Wnt/β-catenin signaling by pharmacological treatment or by transgenic expression of Rspo3 rescues the SHF defects in the conditional Nkx2-5(+/-) mutants. We have identified a previously unrecognized genetic link between Nkx2-5 and Wnt signaling that supports continued cardiac growth and proliferation during development. Identification of Rspo3 in cardiac development provides a new paradigm in temporal regulation of Wnt signaling by cardiac-specific transcription factors.

  5. Parent Emotion Socialization Practices and Child Self-regulation as Predictors of Child Anxiety: The Mediating Role of Cardiac Variability.

    PubMed

    Williams, Sarah R; Woodruff-Borden, Janet

    2015-08-01

    The importance of the parent-child relationship in emotional development is well supported. The parental role of facilitating a child's self-regulation may provide a more focused approach for examining the role of parenting in child anxiety. The current study hypothesized that parent emotion socialization practices would predict a child's abilities in self-regulation. Given that physiological arousal has been implicated in emotional development, this was hypothesized to mediate the relationship between parental emotion socialization and child emotion regulation to predict child anxiety. Eighty-five parent and child dyads participated in the study. Parents reporting higher degrees of unsupportive emotion socialization were more likely to have children with fewer abilities in emotion regulation. Cardiac responsiveness mediated the relationship between unsupportive emotion socialization and child emotion regulation. The model of cardiac responsiveness mediating the relationship between unsupportive emotion socialization and child emotion regulation failed to reach statistical significance in predicting child anxiety symptoms.

  6. Apocynin improving cardiac remodeling in chronic renal failure disease is associated with up-regulation of epoxyeicosatrienoic acids.

    PubMed

    Zhang, Kun; Liu, Yu; Liu, Xiaoqiang; Chen, Jie; Cai, Qingqing; Wang, Jingfeng; Huang, Hui

    2015-09-22

    Cardiac remodeling is one of the most common cardiac abnormalities and associated with a high mortality in chronic renal failure (CRF) patients. Apocynin, a nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase inhibitor, has been showed cardio-protective effects. However, whether apocynin can improve cardiac remodeling in CRF and what is the underlying mechanism are unclear. In the present study, we enrolled 94 participants. In addition, we used 5/6 nephrectomized rats to mimic cardiac remodeling in CRF. Serum levels of epoxyeicosatrienoic acids (EETs) and its mainly metabolic enzyme-soluble epoxide hydrolase (sEH) were measured. The results showed that the serum levels of EETs were significantly decreased in renocardiac syndrome participants (P < 0.05). In 5/6 nephrectomized CRF model, the ratio of left ventricular weight / body weight, left ventricular posterior wall thickness, and cardiac interstitial fibrosis were significantly increased while ejection fraction significantly decreased (P < 0.05). All these effects could partly be reversed by apocynin. Meanwhile, we found during the process of cardiac remodeling in CRF, apocynin significantly increased the reduced serum levels of EETs and decreased the mRNA and protein expressions of sEH in the heart (P < 0.05). Our findings indicated that the protective effect of apocynin on cardiac remodeling in CRF was associated with the up-regulation of EETs. EETs may be a new mediator for the injury of kidney-heart interactions.

  7. Cardiac Autonomic Dysfunction: Particulate Air Pollution Effects Are Modulated by Epigenetic Immunoregulation of Toll‐like Receptor 2 and Dietary Flavonoid Intake

    PubMed Central

    Zhong, Jia; Colicino, Elena; Lin, Xinyi; Mehta, Amar; Kloog, Itai; Zanobetti, Antonella; Byun, Hyang‐Min; Bind, Marie‐Abèle; Cantone, Laura; Prada, Diddier; Tarantini, Letizia; Trevisi, Letizia; Sparrow, David; Vokonas, Pantel; Schwartz, Joel; Baccarelli, Andrea A.

    2015-01-01

    Background Short‐term fine particles (PM2.5) exposure is associated with reduced heart rate variability, a strong predictor of cardiac mortality among older people. Identifying modifiable factors that confer susceptibility is essential for intervention. We evaluated whether Toll‐like receptor 2 (TLR2) methylation, a reversible immune‐epigenetic process, and its dietary modulation by flavonoids and methyl nutrients, modify susceptibility to heart rate variability effects following PM2.5 exposure. Methods and Results We measured heart rate variability and PM2.5 repeatedly over 11 years (1275 total observations) among 573 elderly men from the Normative Aging Study. Blood TLR2 methylation was analyzed using pyrosequencing. Daily flavonoid and methyl nutrients intakes were assessed through the Food Frequency Questionnaire (FFQ). Every 10 μg/m3 increase in 48‐hour PM2.5 moving average was associated with 7.74% (95% CI: −1.21% to 15.90%; P=0.09), 7.46% (95% CI: 0.99% to 13.50%; P=0.02), 14.18% (95% CI: 1.14% to 25.49%; P=0.03), and 12.94% (95% CI: −2.36% to 25.96%; P=0.09) reductions in root mean square of successive differences, standard deviation of normal‐to‐normal intervals, low‐frequency power, and high‐frequency power, respectively. Higher TLR2 methylation exacerbated the root mean square of successive differences, standard deviation of normal‐to‐normal intervals, low‐frequency, and high‐frequency reductions associated with heightened PM2.5 (Pinteraction=0.006, 0.03, 0.05, 0.04, respectively). Every interquartile‐range increase in flavonoid intake was associated with 5.09% reduction in mean TLR2 methylation (95% CI: 0.12% to 10.06%; P=0.05) and counteracted the effects of PM2.5 on low frequency (Pinteraction=0.05). No significant effect of methyl nutrients on TLR2 methylation was observed. Conclusions Higher TLR2 methylation may confer susceptibility to adverse cardiac autonomic effects of PM2.5 exposure in older individuals. Higher

  8. Biotelemetric investigation of the regulation of the cardiac frequency in animals with use of telestimulation. Model examinations in the neat.

    PubMed

    Börnert, D; Börnert, G

    1975-01-01

    A method for the assessment of behaviour of the cardiac frequency regulation in freely moving animals by means of telestimulation and biotelemetry is described. The results of the examinations allow, in spite of individual variability, a classification of the animals into different types of regulation by consideration of the biorhythm. The assessment of the individual type of regulation in correlation to the biorhythmic structure of the organism is of basic significance for the evaluation of its capacity of performance and adapation.

  9. Cardiomyogenesis in the Developing Heart Is Regulated by c-kit-Positive Cardiac Stem Cells

    PubMed Central

    Ferreira-Martins, João; Ogórek, Barbara; Cappetta, Donato; Matsuda, Alex; Signore, Sergio; D'Amario, Domenico; Kostyla, James; Steadman, Elisabeth; Ide-Iwata, Noriko; Sanada, Fumihiro; Iaffaldano, Grazia; Ottolenghi, Sergio; Hosoda, Toru; Leri, Annarosa; Kajstura, Jan; Anversa, Piero; Rota, Marcello

    2012-01-01

    Rationale Embryonic and fetal myocardial growth is characterized by a dramatic increase in myocyte number, but whether the expansion of the myocyte compartment is dictated by activation and commitment of resident cardiac stem cells (CSCs), division of immature myocytes or both is currently unknown. Objectives In this study, we tested whether prenatal cardiac development is controlled by activation and differentiation of CSCs and whether division of c-kit-positive CSCs in the mouse heart is triggered by spontaneous Ca2+ oscillations. Results We report that embryonic-fetal c-kit-positive CSCs are self-renewing, clonogenic and multipotent in vitro and in vivo. The growth and commitment of c-kit-positive CSCs is responsible for the generation of the myocyte progeny of the developing heart. The close correspondence between values computed by mathematical modeling and direct measurements of myocyte number at E9, E14, E19 and one day after birth strongly suggests that the organogenesis of the embryonic heart is dependent on a hierarchical model of cell differentiation regulated by resident CSCs. The growth promoting effects of c-kit-positive CSCs are triggered by spontaneous oscillations in intracellular Ca2+, mediated by IP3 receptor activation, which condition asymmetric stem cell division and myocyte lineage specification. Conclusions Myocyte formation derived from CSC differentiation is the major determinant of cardiac growth during development. Division of c-kit-positive CSCs in the mouse is promoted by spontaneous Ca2+ spikes, which dictate the pattern of stem cell replication and the generation of a myocyte progeny at all phases of prenatal life and up to one day after birth. PMID:22275487

  10. Intrinsic Cardiac Autonomic Ganglionated Plexi within Epicardial Fats Modulate the Atrial Substrate Remodeling: Experiences with Atrial Fibrillation Patients Receiving Catheter Ablation

    PubMed Central

    Singhal, Rahul; Lo, Li-Wei; Lin, Yenn-Jiang Lin; Chang, Shih-Lin; Hu, Yu-Feng; Chao, Tze-Fan; Chung, Fa-Po; Chiou, Cheun-Wang; Tsao, Hsuan-Ming; Chen, Shih-Ann

    2016-01-01

    Background A recent study reported the close relationship between high dominant frequent (DF) sites [atrial fibrillation (AF) nest] and the intrinsic cardiac autonomic nervous system. The aim of this study was to investigate the correlation between the regional distribution of epicardial fat and the properties of the biatrial substrates in AF patients. Methods We studied 32 patients with paroxysmal (n = 23) and persistent (n = 9) AF. The epicardial fat volume around the left atrium (LA) was evaluated using 64-slice multidetector computed tomography and the topographic distribution of the fat volume was assessed. The biatrial DFs, voltages, and total activation times (TATs) were obtained during sinus rhythm. Results Out of the 8 divided LA regions, a significant linear correlation existed between the LA fat and mean DF values in the right upper anterior LA, left upper anterior LA, right lower anterior LA, right upper posterior LA, left upper posterior LA, and left lower posterior LA. There was no significant correlation between the regional LA fat distribution and regional LA peak-to-peak bipolar voltage and TAT. During a mean follow-up of 17 ± 8 months, 22 of the 32 (69%) patients were free of AF. In the multivariate analysis, only the mean LA DF was found to be a significant predictor of recurrence. Conclusions There was a close association between the regional distribution of the LA epicardial fat and the atrial substrate manifesting high frequency during sinus rhythm (AF nest). Those nests were related to ablation outcome. Hence, epicardial fat may play a significant role in atrial substrate remodeling and thereby in the pathogenesis and maintenance of AF. PMID:27122948

  11. Metabolomics-assisted proteomics identifies succinylation and SIRT5 as important regulators of cardiac function

    PubMed Central

    Sadhukhan, Sushabhan; Liu, Xiaojing; Ryu, Dongryeol; Nelson, Ornella D.; Stupinski, John A.; Li, Zhi; Chen, Wei; Zhang, Sheng; Weiss, Robert S.; Auwerx, Johan; Lin, Hening

    2016-01-01

    Cellular metabolites, such as acyl-CoA, can modify proteins, leading to protein posttranslational modifications (PTMs). One such PTM is lysine succinylation, which is regulated by sirtuin 5 (SIRT5). Although numerous proteins are modified by lysine succinylation, the physiological significance of lysine succinylation and SIRT5 remains elusive. Here, by profiling acyl-CoA molecules in various mouse tissues, we have discovered that different tissues have different acyl-CoA profiles and that succinyl-CoA is the most abundant acyl-CoA molecule in the heart. This interesting observation has prompted us to examine protein lysine succinylation in different mouse tissues in the presence and absence of SIRT5. Protein lysine succinylation predominantly accumulates in the heart when Sirt5 is deleted. Using proteomic studies, we have identified many cardiac proteins regulated by SIRT5. Our data suggest that ECHA, a protein involved in fatty acid oxidation, is a major enzyme that is regulated by SIRT5 and affects heart function. Sirt5 knockout (KO) mice have lower ECHA activity, increased long-chain acyl-CoAs, and decreased ATP in the heart under fasting conditions. Sirt5 KO mice develop hypertrophic cardiomyopathy, as evident from the increased heart weight relative to body weight, as well as reduced shortening and ejection fractions. These findings establish that regulating heart metabolism and function is a major physiological function of lysine succinylation and SIRT5. PMID:27051063

  12. Autonomous regulation mode moderates the effect of actual physical activity on affective states: an ambulant assessment approach to the role of self-determination.

    PubMed

    Kanning, Martina; Ebner-Priemer, Ulrich; Brand, Ralf

    2012-04-01

    Studies have shown that physical activity influences affective states. However, studies have seldom depicted these associations in ongoing real-life situations, and there is no investigation showing that motivational states (i.e., more or less autonomously regulated) would moderate these effects in situ. To investigate the interaction of autonomous regulation and actual physical activity (aPA) with affective states, we use an ambulatory assessment approach. The participants were 44 university students (mean age: 26.2 ± 3.2 years). We assessed aPA through 24-hr accelerometry and affective states and autonomous regulation via electronic diaries. Palmtop devices prompted subjects every 45 min during a 14-hr daytime period. We performed hierarchical multilevel analyses. Both aPA and autonomous regulation significantly influenced affective states. The interaction was significant for two affects. The higher the volume of aPA and thereby the more autonomously regulated the preceding bout of aPA was, the more our participants felt energized (r = .16) but agitated (r = -.18).

  13. HIF-1α regulates the response of primary sarcomas to radiation therapy through a cell autonomous mechanism

    PubMed Central

    Zhang, Minsi; Qiu, Qiong; Li, Zhizhong; Sachdeva, Mohit; Min, Hooney; Cardona, Diana M.; DeLaney, Thomas F.; Han, Tracy; Ma, Yan; Luo, Lixia; Ilkayeva, Olga R.; Lui, Ki; Nichols, Amanda G.; Newgard, Christopher B.; Kastan, Michael B.; Rathmell, Jeffrey C.; Dewhirst, Mark W.; Kirsch, David G.

    2016-01-01

    Hypoxia is a major cause of radiation resistance, which may predispose to local recurrence after radiation therapy (RT). While hypoxia increases tumor cell survival after RT because there is less oxygen to oxidize damaged DNA, whether signaling pathways triggered by hypoxia contribute to radiation resistance is poorly understood. For example, intratumoral hypoxia can increase hypoxia inducible factor 1 alpha (HIF-1α), which may regulate pathways that contribute to radiation sensitization or radiation resistance. To clarify the role of HIF-1α in regulating tumor response to radiation therapy, we generated a novel genetically engineered mouse model of soft tissue sarcoma with an intact or deleted HIF-1α. Deletion of HIF-1α sensitized primary sarcomas to RT in vivo. Moreover, cell lines derived from primary sarcomas lacking HIF-1α, or in which HIF-1α was knocked down, had decreased clonogenic survival in vitro, demonstrating that HIF-1α can promote radiation resistance in a cell autonomous manner. In HIF-1α intact and deleted sarcoma cells, radiation-induced reactive oxygen species (ROS), DNA damage repair, and activation of autophagy were similar. However, sarcoma cells lacking HIF-1α had impaired mitochondrial biogenesis and metabolic response after radiation which might contribute to radiation resistance. These results show that HIF-1α promotes radiation resistance in a cell autonomous manner. PMID:25973951

  14. A logical molecular circuit for programmable and autonomous regulation of protein activity using DNA aptamer-protein interactions.

    PubMed

    Han, Da; Zhu, Zhi; Wu, Cuichen; Peng, Lu; Zhou, Leiji; Gulbakan, Basri; Zhu, Guizhi; Williams, Kathryn R; Tan, Weihong

    2012-12-26

    Researchers increasingly envision an important role for artificial biochemical circuits in biological engineering, much like electrical circuits in electrical engineering. Similar to electrical circuits, which control electromechanical devices, biochemical circuits could be utilized as a type of servomechanism to control nanodevices in vitro, monitor chemical reactions in situ, or regulate gene expressions in vivo. (1) As a consequence of their relative robustness and potential applicability for controlling a wide range of in vitro chemistries, synthetic cell-free biochemical circuits promise to be useful in manipulating the functions of biological molecules. Here, we describe the first logical circuit based on DNA-protein interactions with accurate threshold control, enabling autonomous, self-sustained and programmable manipulation of protein activity in vitro. Similar circuits made previously were based primarily on DNA hybridization and strand displacement reactions. This new design uses the diverse nucleic acid interactions with proteins. The circuit can precisely sense the local enzymatic environment, such as the concentration of thrombin, and when it is excessively high, a coagulation inhibitor is automatically released by a concentration-adjusted circuit module. To demonstrate the programmable and autonomous modulation, a molecular circuit with different threshold concentrations of thrombin was tested as a proof of principle. In the future, owing to tunable regulation, design modularity and target specificity, this prototype could lead to the development of novel DNA biochemical circuits to control the delivery of aptamer-based drugs in smart and personalized medicine, providing a more efficient and safer therapeutic strategy.

  15. New evidence on an old question: is the "fight or flight" stage present in the cardiac and respiratory regulation of decapod crustaceans?

    PubMed

    Canero, Eliana M; Hermitte, Gabriela

    2014-01-01

    The ability to stay alert to subtle changes in the environment and to freeze, fight or flight in the presence of predators requires integrating sensory information as well as triggering motor output to target tissues, both of which are associated with the autonomic nervous system. These reactions, which are commonly related to vertebrates, are the fundamental physiological responses that allow an animal to survive danger. The circulatory activity in vertebrates changes in opposite phases. The stage where circulatory activity is high is termed the "fight or flight stage", while the stage where circulatory activity slows down is termed the "rest and digest stage". It may be assumed that highly evolved invertebrates possess a comparable response system as they also require rapid cardiovascular and respiratory regulation to be primed when necessary. However, in invertebrates, the body plan may have developed such a system very differently. Since this topic is insufficiently studied, it is necessary to extend studies for a comparative analysis. In the present review, we use our own experimental results obtained in the crab Neohelice granulata and both older and newer findings obtained by other authors in decapod crustaceans as well as in other invertebrates, to compare the pattern of change in circulatory activity, especially in the "fight or flight" stage. We conclude that the main features of neuroautonomic regulation of the cardiac function were already present early in evolution, at least in highly evolved invertebrates, although conspicuous differences are also evident.

  16. Circulatory response and autonomic nervous activity during gum chewing.

    PubMed

    Hasegawa, Yoko; Sakagami, Joe; Ono, Takahiro; Hori, Kazuhiro; Zhang, Min; Maeda, Yoshinobu

    2009-08-01

    Mastication has been proven to enhance the systemic circulation, with circulatory responses seeming to be largely regulated by autonomic nervous activity via a more complex regulatory system than those of other activities. However, few studies have examined the relationships between changes in autonomic nervous activity and the systemic circulation that are induced by masticatory movement. We investigated changes in the systemic circulation and autonomic nervous activity during gum chewing to clarify the influence of mastication. Electrocardiograms, arterial blood pressure, and masseter electromyograms were taken while chewing gum continuously as indicators of systemic circulation in 10 healthy subjects with normal dentition. Cardiac sympathetic activity and vagus nervous activity, as well as vasomotor sympathetic nervous activity, were evaluated by fluctuation analysis of heart rate and blood pressure. Repeated analysis of variance and multiple comparisons were performed to determine chronological changes in each indicator during gum chewing. Gum chewing increased the heart rate and the mean arterial pressure. Although cardiac sympathetic activity and vagus nervous activity showed significant changes, vasomotor sympathetic nervous activity did not. These results suggest that changes in the autonomic nervous activity of the heart are mainly involved in the enhancement of systemic circulation with gum chewing. This explains some characteristics of autonomic nervous regulation in masticatory movement.

  17. Regulation of cardiac autophagy by insulin-like growth factor 1.

    PubMed

    Troncoso, Rodrigo; Díaz-Elizondo, Jessica; Espinoza, Sandra P; Navarro-Marquez, Mario F; Oyarzún, Alejandra P; Riquelme, Jaime A; Garcia-Carvajal, Ivonne; Díaz-Araya, Guillermo; García, Lorena; Hill, Joseph A; Lavandero, Sergio

    2013-07-01

    Insulin-like growth factor-1 (IGF-1) signaling is a key pathway in the control of cell growth and survival. Three critical nodes in the IGF-1 signaling pathway have been described in cardiomyocytes: protein kinase Akt/mammalian target of rapamycin (mTOR), Ras/Raf/extracellular signal-regulated kinase (ERK), and phospholipase C (PLC)/inositol 1,4,5-triphosphate (InsP3 )/Ca(2+) . The Akt/mTOR and Ras/Raf/ERK signaling arms govern survival in the settings of cardiac stress and hypertrophic growth. By contrast, PLC/InsP3 /Ca(2+) functions to regulate metabolic adaptability and gene transcription. Autophagy is a catabolic process involved in protein degradation, organelle turnover, and nonselective breakdown of cytoplasmic components during nutrient starvation or stress. In the heart, autophagy is observed in a variety of human pathologies, where it can be either adaptive or maladaptive, depending on the context. We proposed the hypothesis that IGF-1 protects the heart by rescuing the mitochondrial metabolism and the energetics state, reducing cell death and controls the potentially exacerbate autophagic response to nutritional stress. In light of the importance of IGF-1 and autophagy in the heart, we review here IGF-1 signaling and autophagy regulation in the context of cardiomyocyte nutritional stress.

  18. Functional coupling as a basic mechanism of feedback regulation of cardiac energy metabolism.

    PubMed

    Saks, V A; Kuznetsov, A V; Vendelin, M; Guerrero, K; Kay, L; Seppet, E K

    2004-01-01

    In this review we analyze the concepts and the experimental data on the mechanisms of the regulation of energy metabolism in muscle cells. Muscular energetics is based on the force-length relationship, which in the whole heart is expressed as a Frank-Starling law, by which the alterations of left ventricle diastolic volume change linearly both the cardiac work and oxygen consumption. The second basic characteristics of the heart is the metabolic stability--almost constant levels of high energy phosphates, ATP and phosphocreatine, which are practically independent of the workload and the rate of oxygen consumption, in contrast to the fast-twitch skeletal muscle with no metabolic stability and rapid fatigue. Analysis of the literature shows that an increase in the rate of oxygen consumption by order of magnitude, due to Frank-Starling law, is observed without any significant changes in the intracellular calcium transients. Therefore, parallel activation of contraction and mitochondrial respiration by calcium ions may play only a minor role in regulation of respiration in the cells. The effective regulation of the respiration under the effect of Frank-Starling law and metabolic stability of the heart are explained by the mechanisms of functional coupling within supramolecular complexes in mitochondria, and at the subcellular level within the intracellular energetic units. Such a complex structural and functional organisation of heart energy metabolism can be described quantitatively by mathematical models.

  19. The Role of c-SKI in Regulation of TGFβ-induced Human Cardiac Fibroblast Proliferation and ECM Protein Expression.

    PubMed

    Wang, Juan; Guo, Liping; Shen, Difei; Xu, Xiao; Wang, Jiaping; Han, Suxia; He, Wen

    2017-02-18

    Cardiac fibrosis is characterized by over-deposition of extracellular matrix (ECM) proteins and over-proliferation of cardiac fibroblast, and contributes to both systolic and diastolic dysfunction in many cardiac pathophysiologic conditions. Transforming growth factor β 1 (TGFβ1) is as an essential inducing factor of cardiac fibrosis. C-Ski protein has been identified as an inhibitory regulator of TGFβ signaling. In the present study, we revealed the repressive effect of c-Ski on TGFβ1-induced human cardiac fibroblast (HCFB) proliferation and ECM protein increase (Collagen I and α-SMA). Moreover, miR-155 and miR-17 could inhibit SKI mRNA expression by direct binding to the 3'UTR of SKI, so as to reduce c-Ski protein level. Either miR-155 inhibition or miR-17 inhibition could reverse TGFβ1-induced HCFB proliferation and ECM protein increase. Taken together, we provided a potential therapy to treat cardiac fibrosis by inhibiting miR-155/miR-17 so as to restore the repressive effect of c-Ski on TGFβ1 signaling. This article is protected by copyright. All rights reserved.

  20. HIF-1alpha regulates epithelial inflammation by cell autonomous NFkappaB activation and paracrine stromal remodeling.

    PubMed

    Scortegagna, Marzia; Cataisson, Christophe; Martin, Rebecca J; Hicklin, Daniel J; Schreiber, Robert D; Yuspa, Stuart H; Arbeit, Jeffrey M

    2008-04-01

    Hypoxia inducible factor-1 (HIF-1) is a master regulatory transcription factor controlling multiple cell-autonomous and non-cell-autonomous processes, such as metabolism, angiogenesis, matrix invasion, and cancer metastasis. Here we used a new line of transgenic mice with constitutive gain of HIF-1 function in basal keratinocytes and demonstrated a signaling pathway from HIF-1 to nuclear factor kappa B (NFkappaB) activation to enhanced epithelial chemokine and cytokine elaboration. This pathway was responsible for a phenotypically silent accumulation of stromal inflammatory cells and a marked inflammatory hypersensitivity to a single 12-O-tetradecanoylphorbol-13-acetate (TPA) challenge. HIF-1-induced NFkappaB activation was composed of 2 elements, IkappaB hyperphosphorylation and phosphorylation of Ser276 on p65, enhancing p65 nuclear localization and transcriptional activity, respectively. NFkappaB transcriptional targets macrophage inflammatory protein-2 (MIP-2/CXCL2/3), keratinocyte chemokine (KC/CXCL1), and tumor necrosis factor [alfa] (TNFalpha) were constitutively up-regulated and further increased after TPA challenge both in cultured keratinocytes and in transgenic mice. Whole animal KC, MIP-2, or TNFalpha immunodepletion each abrogated TPA-induced inflammation, whereas blockade of either VEGF or placenta growth factor (PlGF) signaling did not affect transgenic inflammatory hyper-responsiveness. Thus, epithelial HIF-1 gain of function remodels the local environment by cell-autonomous NFkappaB-mediated chemokine and cytokine secretion, which may be another mechanism by which HIF-1 facilitates either inflammatory diseases or malignant progression.

  1. The Ski-Zeb2-Meox2 pathway provides a novel mechanism for regulation of the cardiac myofibroblast phenotype.

    PubMed

    Cunnington, Ryan H; Northcott, Josette M; Ghavami, Saeid; Filomeno, Krista L; Jahan, Fahmida; Kavosh, Morvarid S; Davies, Jared J L; Wigle, Jeffrey T; Dixon, Ian M C

    2014-01-01

    Cardiac fibrosis is linked to fibroblast-to-myofibroblast phenoconversion and proliferation but the mechanisms underlying this are poorly understood. Ski is a negative regulator of TGF-β-Smad signaling in myofibroblasts, and might redirect the myofibroblast phenotype back to fibroblasts. Meox2 could alter TGF-β-mediated cellular processes and is repressed by Zeb2. Here, we investigated whether Ski diminishes the myofibroblast phenotype by de-repressing Meox2 expression and function through repression of Zeb2 expression. We show that expression of Meox1 and Meox2 mRNA and Meox2 protein is reduced during phenoconversion of fibroblasts to myofibroblasts. Overexpression of Meox2 shifts the myofibroblasts into fibroblasts, whereas the Meox2 DNA-binding mutant has no effect on myofibroblast phenotype. Overexpression of Ski partially restores Meox2 mRNA expression levels to those in cardiac fibroblasts. Expression of Zeb2 increased during phenoconversion and Ski overexpression reduces Zeb2 expression in first-passage myofibroblasts. Furthermore, expression of Meox2 is decreased in scar following myocardial infarction, whereas Zeb2 protein expression increases in the infarct scar. Thus Ski modulates the cardiac myofibroblast phenotype and function through suppression of Zeb2 by upregulating the expression of Meox2. This cascade might regulate cardiac myofibroblast phenotype and presents therapeutic options for treatment of cardiac fibrosis.

  2. The autonomic laboratory

    NASA Technical Reports Server (NTRS)

    Low, P. A.; Opfer-Gehrking, T. L.

    1999-01-01

    The autonomic nervous system can now be studied quantitatively, noninvasively, and reproducibly in a clinical autonomic laboratory. The approach at the Mayo Clinic is to study the postganglionic sympathetic nerve fibers of peripheral nerve (using the quantitative sudomotor axon reflex test [QSART]), the parasympathetic nerves to the heart (cardiovagal tests), and the regulation of blood pressure by the baroreflexes (adrenergic tests). Patient preparation is extremely important, since the state of the patient influences the results of autonomic function tests. The autonomic technologist in this evolving field needs to have a solid core of knowledge of autonomic physiology and autonomic function tests, followed by training in the performance of these tests in a standardized fashion. The range and utilization of tests of autonomic function will likely continue to evolve.

  3. Differential regulation of collagen secretion by kinin receptors in cardiac fibroblast and myofibroblast

    SciTech Connect

    Catalán, Mabel; Smolic, Christian; Contreras, Ariel; Ayala, Pedro; Olmedo, Ivonne; Copaja, Miguel; Boza, Pía; Vivar, Raúl; Avalos, Yennifer; Lavandero, Sergio; Velarde, Victoria; Díaz-Araya, Guillermo

    2012-06-15

    regulated differentially by kinin receptor agonists in cultured CF and CMF. -- Highlights: ► B1 and B2 kinin receptors modulates collagen secretion in cardiac myofibroblast. ► TGF-β1 increases B1 kinin receptor expression levels in cardiac myofibroblast. ► B1 kinin receptor through COX-2 decreases collagen synthesis in cardiac myofibroblast.

  4. Reciprocal repression between Fgf8 and miR-133 regulates cardiac induction through Bmp2 signaling.

    PubMed

    Lopez-Sanchez, Carmen; Franco, Diego; Bonet, Fernando; Garcia-Lopez, Virginio; Aranega, Amelia; Garcia-Martinez, Virginio

    2015-12-01

    This data article contains complementary figures and results related to the research article entitled "Negative Fgf8-Bmp2 feed-back is controlled by miR-130 during early cardiac specification" [15], which reveals what specific role miR-130 plays during the cardiac induction process. This study evidenced miR-130 a putative microRNA that targets Erk1/2 (Mapk1) 3'UTR- as a necessary linkage in the control of Fgf8 signaling, mediated by Bmp2. Thus, miR-130 regulates a negative Fgf8-Bmp2 feed-back loop responsible to achieve early cardiac specification. A significant aspect supporting our conclusions is given by the expression pattern of miR-130 during early cardiac specification, as well as by those results obtained after the designed experimental procedures. The data presented here reveal that miR-133 is also expressed within the precardiac areas during early cardiogenesis, pattern which is comparable to that of FGFR1, receptor involved in the Fgf8/ERK signaling pathway. Interestingly, our miR-133 overexpression experiments resulted in a decrease of Fgf8 expression, whereas we observed an increase of Bmp2 and subsequently of cardiac specific markers Nkx-2.5 and Gata4. Additionally, our loss-of-function experiments -through Fgf8 siRNA electroporation- showed an increase of miR-133 expression. Finally, after our Bmp2 experiments, we observed that miR-133 is upstream-regulated by Bmp2. All those results suggest that miR-133 also constitutes a crucial linkage in the crosstalk between Fgf8 and Bmp2 signaling by regulating the Fgf8/ERK pathway during cardiac induction.

  5. Camkii-Dependent Phosphorylation of Cardiac Ryanodine Receptors Regulates Cell Death In Cardiac Ischemia/Reperfusion Injury

    PubMed Central

    Di Carlo, Mariano N.; Said, Matilde; Ling, Haiyun; Valverde, Carlos A.; De Giusti, Verónica; Sommese, Leandro; Palomeque, Julieta; Aiello, Alejandro E.; Skapura, Darlene G.; Rinaldi, Gustavo; Respress, Jonathan L.; Brown, Joan Heller; Wehrens, Xander H.T.; Salas, Margarita A.; Mattiazzi, Alicia

    2014-01-01

    Ca2+-Calmodulin kinase II (CaMKII) activation is deleterious in cardiac ischemia/reperfusion (I/R). Moreover, inhibition of CaMKII-dependent phosphorylations at the sarcoplasmic reticulum (SR) prevents CaMKII-induced I/R damage. However, the downstream targets of CaMKII at the SR level, responsible for this detrimental effect, remain unclear. In the present study we aimed to dissect the role of the two main substrates of CaMKII at the SR level, phospholamban (PLN) and ryanodine receptors (RyR2), in CaMKII-dependent I/R injury. In mouse hearts subjected to global I/R (45/120 min), phosphorylation of the primary CaMKII sites, S2814 on cardiac RyR2 and of T17 on PLN, significantly increased at the onset of reperfusion whereas PKA-dependent phosphorylation of RyR2 and PLN did not change. Similar results were obtained in vivo, in mice subjected to regional myocardial I/R (1/24 hrs). Knock-in mice with an inactivated serine 2814 phosphorylation site on RyR2 (S2814A), significantly improved post-ischemic mechanical recovery, reduced infarct size and decreased apoptosis. Conversely, knock-in mice, in which CaMKII site of RyR2 is constitutively activated (S2814D), significantly increased infarct size and exacerbated apoptosis. In S2814A and S2814D mice subjected to regional myocardial ischemia, infarct size was also decreased and increased respectively. Transgenic mice with double-mutant non-phosphorylatable PLN (S16A/T17A) in the PLN knockout background (PLNDM) also showed significantly increased post-ischemic cardiac damage. This effect cannot be attributed to PKA-dependent PLN phosphorylation and was not due to the enhanced L-type Ca2+ current, present in these mice. Our results reveal a major role for the phosphorylation of S2814 site on RyR2 in CaMKII-dependent I/R cardiac damage. In contrast, they showed that CaMKII-dependent increase in PLN phosphorylation during reperfusion opposes rather than contributes to I/R damage. PMID:24949568

  6. Regulation of cardiac function during a cold pressor test in athletes and untrained subjects.

    PubMed

    Ifuku, Hirotoshi; Moriyama, Kayo; Arai, Kuniko; Shiraishi-Hichiwa, Yumiko

    2007-09-01

    By using (dP/dt)/P of carotid artery pulse, a non-invasive index of cardiac contractility, we examined the regulatory mechanism of cardiac function during a cold pressor test in athletes and untrained subjects. Twenty-four healthy subjects (9 athletes, 8 untrained subjects, and 7 hyperreactors of 4 athletes and 3 untrained subjects with a rise of 15 mmHg or greater in systolic and/or diastolic blood pressure) underwent the cold pressor test according to Hines and Brown (Am Heart J 11:1-9, 1936): immersion of the right hand in 4 degrees C water for 1 min. Although mean blood pressure increased during the cold stress in all the groups, cardiac function differed. In athletes, heart rate and cardiac contractility caused cardiac output to increase while total peripheral resistance (TPR) did not change. In untrained subjects, however, heart rate and cardiac contractility tended to decrease cardiac output and thus TPR increased. In hyperreactors, heart rate and cardiac contractility increased during cold stress, and also TPR increased. After the end of the test, heart rate and cardiac contractility decreased only in untrained group. The findings that during a cold pressor test heart rate and cardiac contractility are enhanced in athletes but depressed in untrained subjects indicate that the state of physical training influences cardiac sympathetic neural reactivity to cold stress, except for hyperreactors.

  7. Components of the interleukin-33/ST2 system are differentially expressed and regulated in human cardiac cells and in cells of the cardiac vasculature.

    PubMed

    Demyanets, Svitlana; Kaun, Christoph; Pentz, Richard; Krychtiuk, Konstantin A; Rauscher, Sabine; Pfaffenberger, Stefan; Zuckermann, Andreas; Aliabadi, Arezu; Gröger, Marion; Maurer, Gerald; Huber, Kurt; Wojta, Johann

    2013-07-01

    Interleukin-33 (IL-33) is a recently described member of the IL-1 family of cytokines, which was identified as a ligand for the ST2 receptor. Components of the IL-33/ST2 system were shown to be expressed in normal and pressure overloaded human myocardium, and soluble ST2 (sST2) has emerged as a prognostic biomarker in myocardial infarction and heart failure. However, expression and regulation of IL-33 in human adult cardiac myocytes and fibroblasts was not tested before. In this study we found that primary human adult cardiac fibroblasts (HACF) and human adult cardiac myocytes (HACM) constitutively express nuclear IL-33 that is released during cell necrosis. Tumor necrosis factor (TNF)-α, interferon (IFN)-γ and IL-1β significantly increased both IL-33 protein and IL-33 mRNA expression in HACF and HACM as well as in human coronary artery smooth muscle cells (HCASMC). The nuclear factor-κB (NF-κB) inhibitor dimethylfumarate inhibited TNF-α- and IL-1β-induced IL-33 production as well as nuclear translocation of p50 and p65 NF-κB subunits in these cells. Mitogen-activated protein/extracellular signal-regulated kinase inhibitor U0126 abrogated TNF-α-, IFN-γ-, and IL-1β-induced and Janus-activated kinase inhibitor I reduced IFN-γ-induced IL-33 production. We detected IL-33 mRNA in human myocardial tissue from patients undergoing heart transplantation (n=27) where IL-33 mRNA levels statistically significant correlated with IFN-γ (r=0.591, p=0.001) and TNF-α (r=0.408, p=0.035) mRNA expression. Endothelial cells in human heart expressed IL-33 as well as ST2 protein. We also reveal that human cardiac and vascular cells have different distribution patterns of ST2 isoforms (sST2 and transmembrane ST2L) mRNA expression and produce different amounts of sST2 protein. Both human macrovascular (aortic and coronary artery) and heart microvascular endothelial cells express specific mRNA for both ST2 isoforms (ST2L and sST2) and are a source for sST2 protein, whereas

  8. A sympathetic neuron autonomous role for Egr3-mediated gene regulation in dendrite morphogenesis and target tissue innervation.

    PubMed

    Quach, David H; Oliveira-Fernandes, Michelle; Gruner, Katherine A; Tourtellotte, Warren G

    2013-03-06

    Egr3 is a nerve growth factor (NGF)-induced transcriptional regulator that is essential for normal sympathetic nervous system development. Mice lacking Egr3 in the germline have sympathetic target tissue innervation abnormalities and physiologic sympathetic dysfunction similar to humans with dysautonomia. However, since Egr3 is widely expressed and has pleiotropic function, it has not been clear whether it has a role within sympathetic neurons and if so, what target genes it regulates to facilitate target tissue innervation. Here, we show that Egr3 expression within sympathetic neurons is required for their normal innervation since isolated sympathetic neurons lacking Egr3 have neurite outgrowth abnormalities when treated with NGF and mice with sympathetic neuron-restricted Egr3 ablation have target tissue innervation abnormalities similar to mice lacking Egr3 in all tissues. Microarray analysis performed on sympathetic neurons identified many target genes deregulated in the absence of Egr3, with some of the most significantly deregulated genes having roles in axonogenesis, dendritogenesis, and axon guidance. Using a novel genetic technique to visualize axons and dendrites in a subpopulation of randomly labeled sympathetic neurons, we found that Egr3 has an essential role in regulating sympathetic neuron dendrite morphology and terminal axon branching, but not in regulating sympathetic axon guidance to their targets. Together, these results indicate that Egr3 has a sympathetic neuron autonomous role in sympathetic nervous system development that involves modulating downstream target genes affecting the outgrowth and branching of sympathetic neuron dendrites and axons.

  9. Regulation of intracellular calcium by bupivacaine isomers in cardiac myocytes from Wistar rats.

    PubMed

    Chedid, Núbia G B; Sudo, Roberto T; Aguiar, Marli I S; Trachez, Margarete M; Masuda, Masako O; Zapata-Sudo, Gisele

    2006-03-01

    In this study we investigated the effects of a racemic mixture of bupivacaine (RS(+/-)bupivacaine) and its isomers (S(-)bupivacaine and R(+)bupivacaine) on the Ca2+ handling by ventricular myocytes from Wistar rats. Single ventricular myocytes were enzymatically isolated and loaded with the fluorescent Ca2+ indicator fura 2-am to estimate intracellular Ca2+ concentration during contraction and relaxation cycles. S(-)bupivacaine (10 muM) significantly increased peak amplitude and the rate of increase of Ca2+ transients in 155% +/- 54% (P < 0.05) and 194% +/- 94% (P < 0.01) of control. However, exposure to R(+)bupivacaine had no effect on either peak amplitude or rate of increase at any concentration tested. Saponin-skinned ventricular fibers were used to investigate the effect of bupivacaine on the intracellular Ca2+ regulation by sarcoplasmic reticulum (SR) and on the Ca2+ sensitivity of contractile system. S(-), R(+), and RS(+/-)bupivacaine induced Ca2+ release from SR (P < 0.01). In SR-disrupted skinned ventricular cells, bupivacaine and its isomers (5 mM) increased the sensitivity of contractile system to Ca(2+). S(-), RS(+/-), and R(+)bupivacaine significantly increased pCa50 from 5.8 +/- 0.1, 5.8 +/- 0.1, and 5.8 +/- 0.1, to 6.1 +/- 0.1 (P < 0.05), 6.0 +/- 0.1 (P < 0.05), and 6.1 +/- 0.1 (P < 0.05). Ca2+ release from SR through RyR2 activation could explain the increase of Ca2+ transients in cardiac cells. Increased intracellular Ca2+ in cardiac myocytes display a stereoselectivity to S(-)bupivacaine.

  10. Reconstitution and regulation of cation-selective channels from cardiac sarcoplasmic reticulum.

    PubMed

    Rousseau, E; Chabot, H; Beaudry, C; Muller, B

    1992-09-08

    In order to study the conductances of the Sarcoplasmic Reticulum (SR) membrane, microsomal fractions from cardiac SR were isolated by differential and sucrose gradient centrifugations and fused into planar lipid bilayers (PLB) made of phospholipids. Using either KCl or K-gluconate solutions, a large conducting K+ selective channel was characterized by its ohmic conductance (152 pS in 150 mM K+), and the presence of short and long lasting subconducting states. Its open probability Po increased with depolarizing voltages, thus supporting the idea that this channel might allow counter-charge movements of monovalent cations during rapid SR Ca2+ release. An heterogeneity in the kinetic behavior of this channel would suggest that the cardiac SR K+ channels might be regulated by cytoplasmic, luminal, or intra SR membrane biochemical mechanisms. Since the behavior was not modified by variations of [Ca2+] nor by the addition of soluble metabolites such as ATP, GTP, cAMP, cGMP, nor by phosphorylation conditions on both sides of the PLB, a specific interaction with a SR membrane component is postulated. Another cation selective channel was studied in asymmetric Ca2+, Ba2+ or Mg(2+)-HEPES buffers. This channel displayed large conductance values for the above divalent cations 90, 100, and 40 pS, respectively. This channel was activated by microM Ca2+ while its Ca2+ sensitivity was potentiated by millimolar ATP. However Mg2+ and calmodulin modulated its gating behavior. Ca2+ releasing drugs such as caffeine and ryanodine increased its Po. All these features are characteristics of the SR Ca2+ release channel. The ryanodine receptor which has been purified and reconstituted into PLB, may form a cation selective pathway.(ABSTRACT TRUNCATED AT 250 WORDS)

  11. β-Adrenergic Regulation of Cardiac Progenitor Cell Death Versus Survival and Proliferation

    PubMed Central

    Khan, Mohsin; Mohsin, Sadia; Avitabile, Daniele; Siddiqi, Sailay; Nguyen, Jonathan; Wallach, Kathleen; Quijada, Pearl; McGregor, Michael; Gude, Natalie; Alvarez, Roberto; Tilley, Douglas G.; Koch, Walter J.; Sussman, Mark A.

    2013-01-01

    Rationale Short-term β-adrenergic stimulation promotes contractility in response to stress but is ultimately detrimental in the failing heart because of accrual of cardiomyocyte death. Endogenous cardiac progenitor cell (CPC) activation may partially offset cardiomyocyte losses, but consequences of long-term β-adrenergic drive on CPC survival and proliferation are unknown. Objective We sought to determine the relationship between β-adrenergic activity and regulation of CPC function. Methods and Results Mouse and human CPCs express only β2 adrenergic receptor (β2-AR) in conjunction with stem cell marker c-kit. Activation of β2-AR signaling promotes proliferation associated with increased AKT, extracellular signal-regulated kinase 1/2, and endothelial NO synthase phosphorylation, upregulation of cyclin D1, and decreased levels of G protein–coupled receptor kinase 2. Conversely, silencing of β2-AR expression or treatment with β2-antagonist ICI 118, 551 impairs CPC proliferation and survival. β1-AR expression in CPC is induced by differentiation stimuli, sensitizing CPC to isoproterenol-induced cell death that is abrogated by metoprolol. Efficacy of β1-AR blockade by metoprolol to increase CPC survival and proliferation was confirmed in vivo by adoptive transfer of CPC into failing mouse myocardium. Conclusions β-adrenergic stimulation promotes expansion and survival of CPCs through β2-AR, but acquisition of β1-AR on commitment to the myocyte lineage results in loss of CPCs and early myocyte precursors. PMID:23243208

  12. Glucose oxidation positively regulates glucose uptake and improves cardiac function recovery after myocardial reperfusion.

    PubMed

    Li, Tingting; Xu, Jie; Qin, Xinghua; Hou, Zuoxu; Guo, Yongzheng; Liu, Zhenhua; Wu, Jianjiang; Zheng, Hong; Zhang, Xing; Gao, Feng

    2017-03-21

    Myocardial reperfusion decreases glucose oxidation and uncouples glucose oxidation from glycolysis. Therapies that increase glucose oxidation lessen myocardial ischemia/reperfusion injury. However, the regulation of glucose uptake during reperfusion remains poorly understood. Here we found that glucose uptake was remarkably diminished in myocardium following reperfusion in Sprague-Dawley rats as detected by 18F-labeled and fluorescent-labeled glucose analogs, even though GLUT1 was upregulated by 3 folds and GLUT4 translocation remained unchanged compared with those of sham rats. The decreased glucose uptake was accompanied by suppressed glucose oxidation. Interestingly, stimulating glucose oxidation by inhibition of pyruvate dehydrogenase kinase 4 (PDK4), a rate-limiting enzyme for glucose oxidation, increased glucose uptake and alleviated ischemia/reperfusion injury. In vitro data in neonatal myocytes showed that PDK4 overexpression decreased glucose uptake, while its knockdown increased glucose uptake, suggesting a role of PDK4 in regulating glucose uptake. Moreover, inhibition of PDK4 increased myocardial glucose uptake with concomitant enhancement of cardiac insulin sensitivity following myocardial ischemia/reperfusion. These results showed that the suppressed glucose oxidation mediated by PDK4 contributes to the reduced glucose uptake in myocardium following reperfusion, and enhancement of glucose uptake exerts cardioprotection. The findings suggest that stimulating glucose oxidation via PDK4 could be an efficient approach to improve recovery from myocardial ischemia/reperfusion injury.

  13. Machine learning classification of cell-specific cardiac enhancers uncovers developmental subnetworks regulating progenitor cell division and cell fate specification.

    PubMed

    Ahmad, Shaad M; Busser, Brian W; Huang, Di; Cozart, Elizabeth J; Michaud, Sébastien; Zhu, Xianmin; Jeffries, Neal; Aboukhalil, Anton; Bulyk, Martha L; Ovcharenko, Ivan; Michelson, Alan M

    2014-02-01

    The Drosophila heart is composed of two distinct cell types, the contractile cardial cells (CCs) and the surrounding non-muscle pericardial cells (PCs), development of which is regulated by a network of conserved signaling molecules and transcription factors (TFs). Here, we used machine learning with array-based chromatin immunoprecipitation (ChIP) data and TF sequence motifs to computationally classify cell type-specific cardiac enhancers. Extensive testing of predicted enhancers at single-cell resolution revealed the added value of ChIP data for modeling cell type-specific activities. Furthermore, clustering the top-scoring classifier sequence features identified novel cardiac and cell type-specific regulatory motifs. For example, we found that the Myb motif learned by the classifier is crucial for CC activity, and the Myb TF acts in concert with two forkhead domain TFs and Polo kinase to regulate cardiac progenitor cell divisions. In addition, differential motif enrichment and cis-trans genetic studies revealed that the Notch signaling pathway TF Suppressor of Hairless [Su(H)] discriminates PC from CC enhancer activities. Collectively, these studies elucidate molecular pathways used in the regulatory decisions for proliferation and differentiation of cardiac progenitor cells, implicate Su(H) in regulating cell fate decisions of these progenitors, and document the utility of enhancer modeling in uncovering developmental regulatory subnetworks.

  14. Machine learning classification of cell-specific cardiac enhancers uncovers developmental subnetworks regulating progenitor cell division and cell fate specification

    PubMed Central

    Ahmad, Shaad M.; Busser, Brian W.; Huang, Di; Cozart, Elizabeth J.; Michaud, Sébastien; Zhu, Xianmin; Jeffries, Neal; Aboukhalil, Anton; Bulyk, Martha L.; Ovcharenko, Ivan; Michelson, Alan M.

    2014-01-01

    The Drosophila heart is composed of two distinct cell types, the contractile cardial cells (CCs) and the surrounding non-muscle pericardial cells (PCs), development of which is regulated by a network of conserved signaling molecules and transcription factors (TFs). Here, we used machine learning with array-based chromatin immunoprecipitation (ChIP) data and TF sequence motifs to computationally classify cell type-specific cardiac enhancers. Extensive testing of predicted enhancers at single-cell resolution revealed the added value of ChIP data for modeling cell type-specific activities. Furthermore, clustering the top-scoring classifier sequence features identified novel cardiac and cell type-specific regulatory motifs. For example, we found that the Myb motif learned by the classifier is crucial for CC activity, and the Myb TF acts in concert with two forkhead domain TFs and Polo kinase to regulate cardiac progenitor cell divisions. In addition, differential motif enrichment and cis-trans genetic studies revealed that the Notch signaling pathway TF Suppressor of Hairless [Su(H)] discriminates PC from CC enhancer activities. Collectively, these studies elucidate molecular pathways used in the regulatory decisions for proliferation and differentiation of cardiac progenitor cells, implicate Su(H) in regulating cell fate decisions of these progenitors, and document the utility of enhancer modeling in uncovering developmental regulatory subnetworks. PMID:24496624

  15. Direct non-cell autonomous Pax6 activity regulates eye development in the zebrafish

    PubMed Central

    Lesaffre, Brigitte; Joliot, Alain; Prochiantz, Alain; Volovitch, Michel

    2007-01-01

    Background Modifications in Pax6 homeogene expression produce strong eye phenotypes. This suggested to us that eye development might be an appropriate model to verify if homeoprotein intercellular passage has important functions in early development. Similar to other homeoproteins, Pax6 has two domains that enable secretion and internalization by live cells and, thus, intercellular passage. In principle, a straightforward way to test the hypothesis would be to mutate one of the two sequences to produce a 'cell autonomous only' Pax6. However, this was not possible because these sequences are in the homeodomain and their modification would affect Pax6 transcriptional properties. We have thus developed an approach aimed at blocking Pax6 only in the extracellular milieu of developing zebrafish embryos. Results A first strategy was to inject a one-cell embryo with a mRNA encoding a secreted single-chain anti-Pax6 antibody. A second, complementary, strategy was to inject a Pax6 antibody in the blastula extracellular milieu. In both cases, 'dissymmetric eyes', 'one eye only' and 'no eye' phenotypes were produced. In most cases, lens phenotypes paralleled retina malformations. Although eye phenotypes were analyzed 30 hours post-fertilization, there was a strong correlation between early eye field asymmetry, early asymmetry in Pax6 expression and later-occurring eye malformations. Several controls were introduced, demonstrating that the effect is specific to Pax6 and cannot be explained by intracellular antibody activities. Conclusion This study supports the hypothesis that the Pax6 transcription factor is also a signaling molecule with direct non-cell autonomous activity. PMID:17229313

  16. Cardiovascular autonomic regulation in subjects with normal blood pressure, high-normal blood pressure and recent-onset hypertension.

    PubMed

    Prakash, E Sankaranarayanan; Madanmohan; Sethuraman, K Raman; Narayan, Sunil K

    2005-01-01

    1. In the present study, we tested the hypothesis that heart rate variability (HRV) is reduced in recent-onset hypertension and that pressor responses to standard autonomic reflex tests are not any different in hypertensives compared with normotensives. We also hypothesized that subjects with high-normal blood pressure (BP) would be distinguishable from normotensives on the basis of short-term HRV indices. 2. Three groups of subjects, each consisting of 15 men and 10 women, were examined. The first group consisted of subjects with recent-onset hypertension who were not taking antihypertensive medication (mean (+/-SD) age 50 +/- 12 years; BP >/= 140/90 mmHg), the second group consisted of subjects with high-normal BP (mean age 46 +/- 13 years; BP 130-139/85-89 mmHg) and the third group consisted of subjects with normal BP (mean age 48 +/- 12 years; BP < 120/80 mmHg). The aim was to characterize the autonomic state in each group. 3. Blood pressure, heart rate (HR), indices of short-term HRV during supine rest and quiet standing, HR variation during timed deep breathing (HRVdb) and pressor responses to the cold pressor test and sustained isometric handgrip were compared between the groups. 4. Although the three groups were comparable (P > 0.1) in terms of mean HR and low-frequency (LF) power expressed in normalized units at rest and during quiet standing, the standard deviation of normal-to-normal RR intervals (SDNN) during supine rest, LF and high-frequency spectral powers during supine rest and HRVdb were lowest in hypertensives (P cardiac vagal effects in hypertensives, the rate-pressure product provides a simple measure of overall HRV in hypertensives

  17. The influence of environmental factors on heart rate chronostructure depending on the individual characteristics of autonomic regulation. Results of long-term medical-ecological studies.

    NASA Astrophysics Data System (ADS)

    Isaeva, Olga; Zenchenko, Tatiana; Breus, Tamara; Chernikova, Anna; Baevsky, Roman

    It was previously shown [Baevsky, Petrov, 1998] that during space flight under influence of geomagnetic disturbances there are both specific response of the autonomic regulation system in the form of vasomotor cardiovascular center activation (LF spectral components) and non-specific stress response, which depends on the actual autonomic balance [Breus, Baevsky, 2002]. Within the project "Mars-500" the parallel medical-ecological studies were conducted in 10 groups (10-16 people), that lived in different regions of the world under the influence of various environmental factors - climatic, geographic, industrial, social and other. It allowed us to obtain a sufficiently large number of variants of adaptive reactions caused by differences in external impacts. The main research method was the heart rate variability (HRV) analysis in short ECG samples (5 minutes) for assessing heart rate chronostructure and functional status of autonomic regulation. Results of studies have demonstrated that environmental loads on the regulatory mechanisms is higher in the northern and north-eastern regions of Russia - Magadan and Syktyvkar. Stress-index of regulatory systems and adaptive risk indicator is significantly higher in these groups [Baevsky, Berseneva, 2013]. The preliminary search of weather factors (atmospheric pressure, air temperature, humidity and magnetic index Kp) influence on the autonomic regulation of heart rate showed that there are no any significant changes and relationships in the entire group of participants. We have assumed that the character of adaptive responses, including responses to changing weather and geomagnetic conditions, is associated with the individual characteristics and the initial functional state of autonomic regulation. To test this hypothesis, we have identified two groups of subjects with different autonomic balance. The first group included individuals with a pronounced predominance of sympathetic regulation (n = 127), the second - with a

  18. Effect of Shensong Yangxin on the Progression of Paroxysmal Atrial Fibrillation is Correlated with Regulation of Autonomic Nerve Activity

    PubMed Central

    Zhao, Hong-Yi; Zhang, Shu-Di; Zhang, Kai; Wang, Xi; Zhao, Qing-Yan; Zhang, Shu-Juan; Dai, Zi-Xuan; Qian, Yong-Sheng; Zhang, You-Jing; Wei, Hao-Tian; Tang, Yan-Hong; Huang, Cong-Xin

    2017-01-01

    Background: Shensong Yangxin (SSYX), a traditional Chinese herbal medicine, has long been used clinically to treat arrhythmias in China. However, the mechanism of SSYX on atrial fibrillation (AF) is unknown. In this study, we tested the hypothesis that the effect of SSYX on the progression of paroxysmal AF is correlated with the regulation of autonomic nerve activity. Methods: Eighteen mongrel dogs were randomly divided into control group (n = 6), pacing group (n = 6), and pacing + SSYX group (n = 6). The control group was implanted with pacemakers without pacing; the pacing group was implanted with pacemakers with long-term intermittent atrial pacing; the pacing + SSYX group underwent long-term intermittent atrial pacing and SSYX oral administration. Results: Compared to the pacing group, the parameters of heart rate variability were lower after 8 weeks in the pacing + SSYX group (low-frequency [LF] component: 20.85 ± 3.14 vs. 15.3 ± 1.89 ms2, P = 0.004; LF component/high-frequency component: 1.34 ± 0.33 vs. 0.77 ± 0.15, P < 0.001). The atrial effective refractory period (AERP) was shorter and the dispersion of the AERP was higher after 8 weeks in the pacing group, while the changes were suppressed by SSYX intake. The dogs in the pacing group had more episodes and longer durations of AF than that in the pacing + SSYX group. SSYX markedly inhibited the increase in sympathetic nerves and upregulation of tumor necrosis factor-alpha and interleukin-6 expression in the pacing + SSYX group. Furthermore, SSYX suppressed the decrease of acetylcholine and α7 nicotinic acetylcholine receptor protein induced by long-term intermittent atrial pacing. Conclusions: SSYX substantially prevents atrial electrical remodeling and the progression of AF. These effects of SSYX may have association with regulating the imbalance of autonomic nerve activity and the cholinergic anti-inflammatory pathway. PMID:28091409

  19. Na/K-ATPase signaling regulates collagen synthesis through microRNA-29b-3p in cardiac fibroblasts.

    PubMed

    Drummond, Christopher A; Hill, Michael C; Shi, Huilin; Fan, Xiaoming; Xie, Jeffrey X; Haller, Steven T; Kennedy, David J; Liu, Jiang; Garrett, Michael R; Xie, Zijian; Cooper, Christopher J; Shapiro, Joseph I; Tian, Jiang

    2016-03-01

    Chronic kidney disease (CKD) is accompanied by cardiac fibrosis, hypertrophy, and dysfunction, which are commonly referred to as uremic cardiomyopathy. Our previous studies found that Na/K-ATPase ligands or 5/6th partial nephrectomy (PNx) induces cardiac fibrosis in rats and mice. The current study used in vitro and in vivo models to explore novel roles for microRNA in this mechanism of cardiac fibrosis formation. To accomplish this, we performed microRNA profiling with RT-qPCR based arrays on cardiac tissue from rats subjected to marinobufagenin (MBG) infusion or PNx. The analysis showed that a series of fibrosis-related microRNAs were dysregulated. Among the dysregulated microRNAs, microRNA (miR)-29b-3p, which directly targets mRNA of collagen, was consistently reduced in both PNx and MBG-infused animals. In vitro experiments demonstrated that treatment of primary cultures of adult rat cardiac fibroblasts with Na/K-ATPase ligands induced significant increases in the fibrosis marker, collagen protein, and mRNA expression compared with controls, whereas miR-29b-3p expression decreased >50%. Transfection of miR-29b-3p mimics into cardiac fibroblasts inhibited cardiotonic steroids-induced collagen synthesis. Moreover, a specific Na/K-ATPase signaling antagonist, pNaKtide, prevented ouabain-induced increases in collagen synthesis and decreases in miR-29b-3p expression in these cells. In conclusion, these data are the first to indicate that signaling through Na/K-ATPase regulates miRNAs and specifically, miR-29b-3p expression both in vivo and in vitro. Additionally, these data indicate that miR-29b-3p expression plays an important role in the formation of cardiac fibrosis in CKD.

  20. Negative Fgf8-Bmp2 feed-back is regulated by miR-130 during early cardiac specification.

    PubMed

    Lopez-Sanchez, Carmen; Franco, Diego; Bonet, Fernando; Garcia-Lopez, Virginio; Aranega, Amelia; Garcia-Martinez, Virginio

    2015-10-01

    It is known that secreted proteins from the anterior lateral endoderm, FGF8 and BMP2, are involved in mesodermal cardiac differentiation, which determines the first cardiac field, defined by the expression of the earliest specific cardiac markers Nkx-2.5 and Gata4. However, the molecular mechanisms responsible for early cardiac development still remain unclear. At present, microRNAs represent a novel layer of complexity in the regulatory networks controlling gene expression during cardiovascular development. This paper aims to study the role of miR130 during early cardiac specification. Our model is focused on developing chick at gastrula stages. In order to identify those regulatory factors which are involved in cardiac specification, we conducted gain- and loss-of-function experiments in precardiac cells by administration of Fgf8, Bmp2 and miR130, through in vitro electroporation technique and soaked beads application. Embryos were subjected to in situ hybridization, immunohistochemistry and qPCR procedures. Our results reveal that Fgf8 suppresses, while Bmp2 induces, the expression of Nkx-2.5 and Gata4. They also show that Fgf8 suppresses Bmp2, and vice versa. Additionally, we observed that Bmp2 regulates miR-130 -a putative microRNA that targets Erk1/2 (Mapk1) 3'UTR, recognizing its expression in precardiac cells which overlap with Erk1/2 pattern. Finally, we evidence that miR-130 is capable to inhibit Erk1/2 and Fgf8, resulting in an increase of Bmp2, Nkx-2.5 and Gata4. Our data present miR-130 as a necessary linkage in the control of Fgf8 signaling, mediated by Bmp2, establishing a negative feed-back loop responsible to achieve early cardiac specification.

  1. Autonomous and Autonomic Swarms

    NASA Technical Reports Server (NTRS)

    Hinchey, Michael G.; Rash, James L.; Truszkowski, Walter F.; Rouff, Christopher A.; Sterritt, Roy

    2005-01-01

    A watershed in systems engineering is represented by the advent of swarm-based systems that accomplish missions through cooperative action by a (large) group of autonomous individuals each having simple capabilities and no global knowledge of the group s objective. Such systems, with individuals capable of surviving in hostile environments, pose unprecedented challenges to system developers. Design and testing and verification at much higher levels will be required, together with the corresponding tools, to bring such systems to fruition. Concepts for possible future NASA space exploration missions include autonomous, autonomic swarms. Engineering swarm-based missions begins with understanding autonomy and autonomicity and how to design, test, and verify systems that have those properties and, simultaneously, the capability to accomplish prescribed mission goals. Formal methods-based technologies, both projected and in development, are described in terms of their potential utility to swarm-based system developers.

  2. Identification of two nuclear factor-binding domains on the chicken cardiac actin promoter: implications for regulation of the gene.

    PubMed Central

    Quitschke, W W; DePonti-Zilli, L; Lin, Z Y; Paterson, B M

    1989-01-01

    The cis-acting regions that appear to be involved in negative regulation of the chicken alpha-cardiac actin promoter both in vivo and in vitro have been identified. A nuclear factor(s) binding to the proximal region mapped over the TATA element between nucleotides -50 and -25. In the distal region, binding spanned nucleotides -136 to -112, a region that included a second CArG box (CArG2) 5' to the more familiar CCAAT-box (CArG1) consensus sequence. Nuclear factors binding to these different domains were found in both muscle and nonmuscle preparations but were detectable at considerably lower levels in tissues expressing the alpha-cardiac actin gene. In contrast, concentrations of the beta-actin CCAAT-box binding activity were similar in all extracts tested. The role of these factor-binding domains on the activity of the cardiac actin promoter in vivo and in vitro and the prevalence of the binding factors in nonmuscle extracts are consistent with the idea that these binding domains and their associated factors are involved in the tissue-restricted expression of cardiac actin through both positive and negative regulatory mechanisms. In the absence of negative regulatory factors, these same binding domains act synergistically, via other factors, to activate the cardiac actin promoter during myogenesis. Images PMID:2552286

  3. Vagal tone regulates cardiac shunts during activity and at low temperatures in the South American rattlesnake, Crotalus durissus.

    PubMed

    Filogonio, Renato; Wang, Tobias; Taylor, Edwin W; Abe, Augusto S; Leite, Cléo A C

    2016-12-01

    The undivided ventricle of non-crocodilian reptiles allows for intracardiac admixture of oxygen-poor and oxygen-rich blood returning via the atria from the systemic circuit and the lungs. The distribution of blood flow between the systemic and pulmonary circuits may vary, based on differences between systemic and pulmonary vascular conductances. The South American rattlesnake, Crotalus durissus, has a single pulmonary artery, innervated by the left vagus. Activity in this nerve controls pulmonary conductance so that left vagotomy abolishes this control. Experimental left vagotomy to abolish cardiac shunting had no effect on long-term survival and failed to identify a functional role in determining metabolic rate, growth or resistance to food deprivation. Accordingly, the present investigation sought to evaluate the extent to which cardiac shunt patterns are actively controlled during changes in body temperature and activity levels. We compared hemodynamic parameters between intact and left-vagotomized rattlesnakes held at different temperatures and subjected to enforced physical activity. Increased temperature and enforced activity raised heart rate, cardiac output, pulmonary and systemic blood flow in both groups, but net cardiac shunt was reversed in the vagotomized group at lower temperatures. We conclude that vagal control of pulmonary conductance is an active mechanism regulating cardiac shunts in C. durissus.

  4. Relationship of disease-associated gene expression to cardiac phenotype is buffered by genetic diversity and chromatin regulation.

    PubMed

    Karbassi, Elaheh; Monte, Emma; Chapski, Douglas J; Lopez, Rachel; Rosa Garrido, Manuel; Kim, Joseph; Wisniewski, Nicholas; Rau, Christoph D; Wang, Jessica J; Weiss, James N; Wang, Yibin; Lusis, Aldons J; Vondriska, Thomas M

    2016-08-01

    Expression of a cohort of disease-associated genes, some of which are active in fetal myocardium, is considered a hallmark of transcriptional change in cardiac hypertrophy models. How this transcriptome remodeling is affected by the common genetic variation present in populations is unknown. We examined the role of genetics, as well as contributions of chromatin proteins, to regulate cardiac gene expression and heart failure susceptibility. We examined gene expression in 84 genetically distinct inbred strains of control and isoproterenol-treated mice, which exhibited varying degrees of disease. Unexpectedly, fetal gene expression was not correlated with hypertrophic phenotypes. Unbiased modeling identified 74 predictors of heart mass after isoproterenol-induced stress, but these predictors did not enrich for any cardiac pathways. However, expanded analysis of fetal genes and chromatin remodelers as groups correlated significantly with individual systemic phenotypes. Yet, cardiac transcription factors and genes shown by gain-/loss-of-function studies to contribute to hypertrophic signaling did not correlate with cardiac mass or function in disease. Because the relationship between gene expression and phenotype was strain specific, we examined genetic contribution to expression. Strikingly, strains with similar transcriptomes in the basal heart did not cluster together in the isoproterenol state, providing comprehensive evidence that there are different genetic contributors to physiological and pathological gene expression. Furthermore, the divergence in transcriptome similarity versus genetic similarity between strains is organ specific and genome-wide, suggesting chromatin is a critical buffer between genetics and gene expression.

  5. Regulation of L-type calcium channel by phospholemman in cardiac myocytes.

    PubMed

    Zhang, Xue-Qian; Wang, JuFang; Song, Jianliang; Rabinowitz, Joseph; Chen, Xiongwen; Houser, Steven R; Peterson, Blaise Z; Tucker, Amy L; Feldman, Arthur M; Cheung, Joseph Y

    2015-07-01

    We evaluated whether phospholemman (PLM) regulates L-type Ca(2+) current (ICa) in mouse ventricular myocytes. Expression of α1-subunit of L-type Ca(2+) channels between wild-type (WT) and PLM knockout (KO) hearts was similar. Compared to WT myocytes, peak ICa (at -10 mV) from KO myocytes was ~41% larger, the inactivation time constant (τ(inact)) of ICa was ~39% longer, but deactivation time constant (τ(deact)) was similar. In the presence of isoproterenol (1 μM), peak ICa was ~48% larger and τ(inact) was ~144% higher in KO myocytes. With Ba(2+) as the permeant ion, PLM enhanced voltage-dependent inactivation but had no effect on τ(deact). To dissect the molecular determinants by which PLM regulated ICa, we expressed PLM mutants by adenovirus-mediated gene transfer in cultured KO myocytes. After 24h in culture, KO myocytes expressing green fluorescent protein (GFP) had significantly larger peak ICa and longer τ(inact) than KO myocytes expressing WT PLM; thereby independently confirming the observations in freshly isolated myocytes. Compared to KO myocytes expressing GFP, KO myocytes expressing the cytoplasmic domain truncation mutant (TM43), the non-phosphorylatable S68A mutant, the phosphomimetic S68E mutant, and the signature PFXYD to alanine (ALL5) mutant all resulted in lower peak ICa. Expressing PLM mutants did not alter expression of α1-subunit of L-type Ca(2+) channels in cultured KO myocytes. Our results suggested that both the extracellular PFXYD motif and the transmembrane domain of PLM but not the cytoplasmic tail were necessary for regulation of peak ICa amplitude. We conclude that PLM limits Ca(2+) influx in cardiac myocytes by reducing maximal ICa and accelerating voltage-dependent inactivation.

  6. Emotion Regulation via the Autonomic Nervous System in Children with Attention-Deficit/Hyperactivity Disorder (ADHD)

    ERIC Educational Resources Information Center

    Musser, Erica D.; Backs, Richard W.; Schmitt, Colleen F.; Ablow, Jennifer C.; Measelle, Jeffery R.; Nigg, Joel T.

    2011-01-01

    Despite growing interest in conceptualizing ADHD as involving disrupted emotion regulation, few studies have examined the physiological mechanisms related to emotion regulation in children with this disorder. This study examined parasympathetic and sympathetic nervous system reactivity via measures of respiratory sinus arrhythmia (RSA) and cardiac…

  7. Roles of phosphodiesterases in the regulation of the cardiac cyclic nucleotide cross-talk signaling network.

    PubMed

    Zhao, Claire Y; Greenstein, Joseph L; Winslow, Raimond L

    2016-02-01

    The balanced signaling between the two cyclic nucleotides (cNs) cAMP and cGMP plays a critical role in regulating cardiac contractility. Their degradation is controlled by distinctly regulated phosphodiesterase isoenzymes (PDEs), which in turn are also regulated by these cNs. As a result, PDEs facilitate communication between the β-adrenergic and Nitric Oxide (NO)/cGMP/Protein Kinase G (PKG) signaling pathways, which regulate the synthesis of cAMP and cGMP respectively. The phenomena in which the cAMP and cGMP pathways influence the dynamics of each other are collectively referred to as cN cross-talk. However, the cross-talk response and the individual roles of each PDE isoenzyme in shaping this response remain to be fully characterized. We have developed a computational model of the cN cross-talk network that mechanistically integrates the β-adrenergic and NO/cGMP/PKG pathways via regulation of PDEs by both cNs. The individual model components and the integrated network model replicate experimentally observed activation-response relationships and temporal dynamics. The model predicts that, due to compensatory interactions between PDEs, NO stimulation in the presence of sub-maximal β-adrenergic stimulation results in an increase in cytosolic cAMP accumulation and corresponding increases in PKA-I and PKA-II activation; however, the potentiation is small in magnitude compared to that of NO activation of the NO/cGMP/PKG pathway. In a reciprocal manner, β-adrenergic stimulation in the presence of sub-maximal NO stimulation results in modest cGMP elevation and corresponding increase in PKG activation. In addition, we demonstrate that PDE2 hydrolyzes increasing amounts of cAMP with increasing levels of β-adrenergic stimulation, and hydrolyzes increasing amounts of cGMP with decreasing levels of NO stimulation. Finally, we show that PDE2 compensates for inhibition of PDE5 both in terms of cGMP and cAMP dynamics, leading to cGMP elevation and increased PKG activation

  8. Up-regulation of cardiac nitric oxide synthase 1-derived nitric oxide after myocardial infarction in senescent rats.

    PubMed

    Damy, Thibaud; Ratajczak, Philippe; Robidel, Estelle; Bendall, Jennifer K; Oliviéro, Patricia; Boczkowski, Jorge; Ebrahimian, Talin; Marotte, Françoise; Samuel, Jane-Lise; Heymes, Christophe

    2003-10-01

    Nitric oxide (NO) has been implicated in the development of heart failure, although the source, significance, and functional role of the different NO synthase (NOS) isoforms in this pathology are controversial. The presence of a neuronal-type NOS isoform (NOS1) in the cardiac sarcoplasmic reticulum has been recently discovered, leading to the hypothesis that NOS1-derived NO may notably alter myocardial inotropy. However, the regulation and role(s) of NOS1 in cardiac diseases remain to be determined. Using an experimental model of myocardial infarction (MI) in senescent rats, we demonstrated a significant increase in cardiac NOS1 expression and activity in MI, coupled with the translocation of this enzyme to the sarcolemma through interactions with caveolin-3. The enhanced NOS1 activity counteracts the decrease in cardiac NOS3 expression and activity observed in heart failure. We demonstrated an increased interaction between NOS1 and its regulatory protein HSP90 in post-MI hearts, a potential mechanism for the higher NOS1 activity in this setting. Finally, preferential in vivo inhibition of NOS1 activity enhanced basal post-MI left ventricular dysfunction in senescent rats. These results provide the first evidence that increased NOS1-derived NO production may play a significant role in the autocrine regulation of myocardial contractility after MI in aging rats.

  9. Counterregulation of insulin by leptin as key component of autonomic regulation of body weight

    PubMed Central

    Borer, Katarina T

    2014-01-01

    A re-examination of the mechanism controlling eating, locomotion, and metabolism prompts formulation of a new explanatory model containing five features: a coordinating joint role of the (1) autonomic nervous system (ANS); (2) the suprachiasmatic (SCN) master clock in counterbalancing parasympathetic digestive and absorptive functions and feeding with sympathetic locomotor and thermogenic energy expenditure within a circadian framework; (3) interaction of the ANS/SCN command with brain substrates of reward encompassing dopaminergic projections to ventral striatum and limbic and cortical forebrain. These drive the nonhomeostatic feeding and locomotor motivated behaviors in interaction with circulating ghrelin and lateral hypothalamic neurons signaling through melanin concentrating hormone and orexin-hypocretin peptides; (4) counterregulation of insulin by leptin of both gastric and adipose tissue origin through: potentiation by leptin of cholecystokinin-mediated satiation, inhibition of insulin secretion, suppression of insulin lipogenesis by leptin lipolysis, and modulation of peripheral tissue and brain sensitivity to insulin action. Thus weight-loss induced hypoleptimia raises insulin sensitivity and promotes its parasympathetic anabolic actions while obesity-induced hyperleptinemia supresses insulin lipogenic action; and (5) inhibition by leptin of bone mineral accrual suggesting that leptin may contribute to the maintenance of stability of skeletal, lean-body, as well as adipose tissue masses. PMID:25317239

  10. Regulation of energy consumption in cardiac muscle: analysis of isometric contractions.

    PubMed

    Landesberg, A; Sideman, S

    1999-03-01

    The well-known linear relationship between oxygen consumption and force-length area or the force-time integral is analyzed here for isometric contractions. The analysis, which is based on a biochemical model that couples calcium kinetics with cross-bridge cycling, indicates that the change in the number of force-generating cross bridges with the change in the sarcomere length depends on the force generated by the cross bridges. This positive-feedback phenomenon is consistent with our reported cooperativity mechanism, whereby the affinity of the troponin for calcium and, hence, cross-bridge recruitment depends on the number of force-generating cross bridges. Moreover, it is demonstrated that a model that does not include a feedback mechanism cannot describe the dependence of energy consumption on the loading conditions. The cooperativity mechanism, which has been shown to determine the force-length relationship and the related Frank-Starling law, is shown here to provide the basis for the regulation of energy consumption in the cardiac muscle.

  11. A flatness-based control approach to drug infusion for cardiac function regulation

    NASA Astrophysics Data System (ADS)

    Rigatos, Gerasimos; Zervos, Nikolaos; Melkikh, Alexey

    2016-12-01

    A new control method based on differential flatness theory is developed in this article, aiming at solving the problem of regulation of haemodynamic parameters, Actually control of the cardiac output (volume of blood pumped out by heart per unit of time) and of the arterial blood pressure is achieved through the administered infusion of cardiovascular drugs, such as dopamine and sodium nitroprusside. Time delays between the control inputs and the system's outputs are taken into account. Using the principle of dynamic extension, which means that by considering certain control inputs and their derivatives as additional state variables, a state-space description for the heart's function is obtained. It is proven that the dynamic model of the heart is a differentially flat one. This enables its transformation into a linear canonical and decoupled form, for which the design of a stabilizing feedback controller becomes possible. The proposed feedback controller is of proven stability and assures fast and accurate tracking of the reference setpoints by the outputs of the heart's dynamic model. Moreover, by using a Kalman Filter-based disturbances' estimator, it becomes possible to estimate in real-time and compensate for the model uncertainty and external perturbation inputs that affect the heart's model.

  12. Nrac, a Novel Nutritionally-Regulated Adipose and Cardiac-Enriched Gene

    PubMed Central

    Zhang, Ren; Yao, Fayi; Gao, Feng; Abou-Samra, Abdul B.

    2012-01-01

    Obesity increases the risk of multiple diseases, such as type 2 diabetes and coronary heart diseases, and therefore the current obesity epidemic poses a major public health issue. Therapeutic approaches are urgently needed to treat obesity as well as its complications. Plasma-membrane proteins with restricted tissue distributions are attractive drug targets, because of their accessibility to various drug delivery mechanisms and potentially alleviated side effects. To identify genes involved in metabolism, we performed RNA-Seq on fat in mice treated with a high-fat diet or fasting. Here we show that the gene A530016L24Rik (human ortholog C14orf180), named Nrac, is a novel nutritionally-regulated adipose and cardiac-enriched gene. Nrac is expressed specifically and abundantly in fat and the heart. Both fasting and obesity reduced Nrac expression in white adipose tissue, and fasting reduced its expression in brown fat. Nrac is localized to the plasma membrane, and highly induced during adipocyte differentiation. Nrac is therefore a novel adipocyte marker and has potential functions in metabolism. PMID:23029450

  13. Role of the basement membrane in regulation of cardiac electrical properties.

    PubMed

    Yang, Huaxiao; Borg, Thomas K; Wang, Zhonghai; Ma, Zhen; Gao, Bruce Z

    2014-06-01

    In the heart muscle, each adult cardiomyocyte is enclosed by a basement membrane (BM). This innermost extracellular matrix is a layered assembly of laminin, collagen IV, glycoproteins, and proteoglycans. In this study, the role of the BM network in regulation of the electrical properties of neonatal cardiomyocytes (NCMs) cultured on an aligned collagen I gel was investigated using a multielectrode array (MEA). A laminin antibody was added to the culture medium for 48-120 h to conjugate newly secreted laminin. Then, morphology of the NCMs on an MEA was monitored using a phase contrast microscope, and the BM network that was immunocytostained for laminin was imaged using a fluorescence microscope. When the BM laminin was absent in this culture model, dramatic changes in NCM morphology were observed. Simultaneously, the MEA-recorded cardiac field potential showed changes compared to that from the control groups: The period of contraction shortened to 1/2 of that from the control groups, and the waveform of the calcium influx shifted from a flat plateau to a peak-like waveform, indicating that the electrical properties of the NCMs were closely related to the components and distribution of the BM network.

  14. Rem-GTPase regulates cardiac myocyte L-type calcium current

    PubMed Central

    Magyar, Janos; Kiper, Carmen E.; Sievert, Gail; Cai, Weikang; Shi, Geng-Xian; Crump, Shawn M.; Li, Liren; Niederer, Steven; Smith, Nic; Andres, Douglas A.; Satin, Jonathan

    2012-01-01

    Rationale: The L-type calcium channels (LTCC) are critical for maintaining Ca2+-homeostasis. In heterologous expression studies, the RGK-class of Ras-related G-proteins regulates LTCC function; however, the physiological relevance of RGK–LTCC interactions is untested. Objective: In this report we test the hypothesis that the RGK protein, Rem, modulates native Ca2+ current (ICa,L) via LTCC in murine cardiomyocytes. Methods and Results: Rem knockout mice (Rem−/−) were engineered, and ICa,L and Ca2+-handling properties were assessed. Rem−/− ventricular cardiomyocytes displayed increased ICa,L density. ICa,L activation was shifted positive on the voltage axis, and β-adrenergic stimulation normalized this shift compared with wild-type ICa,L. Current kinetics, steady-state inactivation, and facilitation was unaffected by Rem−/−. Cell shortening was not significantly different. Increased ICa,L density in the absence of frank phenotypic differences motivated us to explore putative compensatory mechanisms. Despite the larger ICa,L density, Rem−/− cardiomyocyte Ca2+ twitch transient amplitude was significantly less than that compared with wild type. Computer simulations and immunoblot analysis suggests that relative dephosphorylation of Rem−/− LTCC can account for the paradoxical decrease of Ca2+ transients. Conclusions: This is the first demonstration that loss of an RGK protein influences ICa,L in vivo in cardiac myocytes. PMID:22854599

  15. Keap1 redox-dependent regulation of doxorubicin-induced oxidative stress response in cardiac myoblasts

    SciTech Connect

    Nordgren, Kendra K.S. Wallace, Kendall B.

    2014-01-01

    Doxorubicin (DOX) is a widely prescribed treatment for a broad scope of cancers, but clinical utility is limited by the cumulative, dose-dependent cardiomyopathy that occurs with repeated administration. DOX-induced cardiotoxicity is associated with the production of reactive oxygen species (ROS) and oxidation of lipids, DNA and proteins. A major cellular defense mechanism against such oxidative stress is activation of the Keap1/Nrf2-antioxidant response element (ARE) signaling pathway, which transcriptionally regulates expression of antioxidant genes such as Nqo1 and Gstp1. In the present study, we address the hypothesis that an initial event associated with DOX-induced oxidative stress is activation of the Keap1/Nrf2-dependent expression of antioxidant genes and that this is regulated through drug-induced changes in redox status of the Keap1 protein. Incubation of H9c2 rat cardiac myoblasts with DOX resulted in a time- and dose-dependent decrease in non-protein sulfhydryl groups. Associated with this was a near 2-fold increase in Nrf2 protein content and enhanced transcription of several of the Nrf2-regulated down-stream genes, including Gstp1, Ugt1a1, and Nqo1; the expression of Nfe2l2 (Nrf2) itself was unaltered. Furthermore, both the redox status and the total amount of Keap1 protein were significantly decreased by DOX, with the loss of Keap1 being due to both inhibited gene expression and increased autophagic, but not proteasomal, degradation. These findings identify the Keap1/Nrf2 pathway as a potentially important initial response to acute DOX-induced oxidative injury, with the primary regulatory events being the oxidation and autophagic degradation of the redox sensor Keap1 protein. - Highlights: • DOX caused a ∼2-fold increase in Nrf2 protein content. • DOX enhanced transcription of several Nrf2-regulated down-stream genes. • Redox status and total amount of Keap1 protein were significantly decreased by DOX. • Loss of Keap1 protein was due to

  16. Autonomic dysfunction in multiple sclerosis.

    PubMed

    Racosta, Juan Manuel; Kimpinski, Kurt; Morrow, Sarah Anne; Kremenchutzky, Marcelo

    2015-12-01

    Autonomic dysfunction is a prevalent and significant cause of disability among patients with multiple sclerosis. Autonomic dysfunction in multiple sclerosis is usually explained by lesions within central nervous system regions responsible for autonomic regulation, but novel evidence suggests that other factors may be involved as well. Additionally, the interactions between the autonomic nervous system and the immune system have generated increased interest about the role of autonomic dysfunction in the pathogenesis of multiple sclerosis. In this paper we analyze systematically the most relevant signs and symptoms of autonomic dysfunction in MS, considering separately their potential causes and implications.

  17. Cell-Autonomous Regulation of Dendritic Spine Density by PirB.

    PubMed

    Vidal, George S; Djurisic, Maja; Brown, Kiana; Sapp, Richard W; Shatz, Carla J

    2016-01-01

    Synapse density on cortical pyramidal neurons is modulated by experience. This process is highest during developmental critical periods, when mechanisms of synaptic plasticity are fully engaged. In mouse visual cortex, the critical period for ocular dominance (OD) plasticity coincides with the developmental pruning of synapses. At this time, mice lacking paired Ig-like receptor B (PirB) have excess numbers of dendritic spines on L5 neurons; these spines persist and are thought to underlie the juvenile-like OD plasticity observed in adulthood. Here we examine whether PirB is required specifically in excitatory neurons to exert its effect on dendritic spine and synapse density during the critical period. In mice with a conditional allele of PirB (PirB(fl/fl)), PirB was deleted only from L2/3 cortical pyramidal neurons in vivo by timed in utero electroporation of Cre recombinase. Sparse mosaic expression of Cre produced neurons lacking PirB in a sea of wild-type neurons and glia. These neurons had significantly elevated dendritic spine density, as well as increased frequency of miniature EPSCs, suggesting that they receive a greater number of synaptic inputs relative to Cre(-) neighbors. The effect of cell-specific PirB deletion on dendritic spine density was not accompanied by changes in dendritic branching complexity or axonal bouton density. Together, results imply a neuron-specific, cell-autonomous action of PirB on synaptic density in L2/3 pyramidal cells of visual cortex. Moreover, they are consistent with the idea that PirB functions normally to corepress spine density and synaptic plasticity, thereby maintaining headroom for cells to encode ongoing experience-dependent structural change throughout life.

  18. Pejvakin, a Candidate Stereociliary Rootlet Protein, Regulates Hair Cell Function in a Cell-Autonomous Manner.

    PubMed

    Kazmierczak, Marcin; Kazmierczak, Piotr; Peng, Anthony W; Harris, Suzan L; Shah, Prahar; Puel, Jean-Luc; Lenoir, Marc; Franco, Santos J; Schwander, Martin

    2017-03-29

    Mutations in the Pejvakin (PJVK) gene are thought to cause auditory neuropathy and hearing loss of cochlear origin by affecting noise-induced peroxisome proliferation in auditory hair cells and neurons. Here we demonstrate that loss of pejvakin in hair cells, but not in neurons, causes profound hearing loss and outer hair cell degeneration in mice. Pejvakin binds to and colocalizes with the rootlet component TRIOBP at the base of stereocilia in injectoporated hair cells, a pattern that is disrupted by deafness-associated PJVK mutations. Hair cells of pejvakin-deficient mice develop normal rootlets, but hair bundle morphology and mechanotransduction are affected before the onset of hearing. Some mechanotransducing shorter row stereocilia are missing, whereas the remaining ones exhibit overextended tips and a greater variability in height and width. Unlike previous studies of Pjvk alleles with neuronal dysfunction, our findings reveal a cell-autonomous role of pejvakin in maintaining stereocilia architecture that is critical for hair cell function.SIGNIFICANCE STATEMENT Two missense mutations in the Pejvakin (PJVK or DFNB59) gene were first identified in patients with audiological hallmarks of auditory neuropathy spectrum disorder, whereas all other PJVK alleles cause hearing loss of cochlear origin. These findings suggest that complex pathogenetic mechanisms underlie human deafness DFNB59. In contrast to recent studies, we demonstrate that pejvakin in auditory neurons is not essential for normal hearing in mice. Moreover, pejvakin localizes to stereociliary rootlets in hair cells and is required for stereocilia maintenance and mechanosensory function of the hair bundle. Delineating the site of the lesion and the mechanisms underlying DFNB59 will allow clinicians to predict the efficacy of different therapeutic approaches, such as determining compatibility for cochlear implants.

  19. Cell-Autonomous Regulation of Dendritic Spine Density by PirB

    PubMed Central

    2016-01-01

    Synapse density on cortical pyramidal neurons is modulated by experience. This process is highest during developmental critical periods, when mechanisms of synaptic plasticity are fully engaged. In mouse visual cortex, the critical period for ocular dominance (OD) plasticity coincides with the developmental pruning of synapses. At this time, mice lacking paired Ig-like receptor B (PirB) have excess numbers of dendritic spines on L5 neurons; these spines persist and are thought to underlie the juvenile-like OD plasticity observed in adulthood. Here we examine whether PirB is required specifically in excitatory neurons to exert its effect on dendritic spine and synapse density during the critical period. In mice with a conditional allele of PirB (PirBfl/fl), PirB was deleted only from L2/3 cortical pyramidal neurons in vivo by timed in utero electroporation of Cre recombinase. Sparse mosaic expression of Cre produced neurons lacking PirB in a sea of wild-type neurons and glia. These neurons had significantly elevated dendritic spine density, as well as increased frequency of miniature EPSCs, suggesting that they receive a greater number of synaptic inputs relative to Cre– neighbors. The effect of cell-specific PirB deletion on dendritic spine density was not accompanied by changes in dendritic branching complexity or axonal bouton density. Together, results imply a neuron-specific, cell-autonomous action of PirB on synaptic density in L2/3 pyramidal cells of visual cortex. Moreover, they are consistent with the idea that PirB functions normally to corepress spine density and synaptic plasticity, thereby maintaining headroom for cells to encode ongoing experience-dependent structural change throughout life. PMID:27752542

  20. Cardiac glycosides induce autophagy in human non-small cell lung cancer cells through regulation of dual signaling pathways.

    PubMed

    Wang, Yan; Qiu, Qiang; Shen, Jia-Jia; Li, Dian-Dong; Jiang, Xue-Jun; Si, Shu-Yi; Shao, Rong-Guang; Wang, Zhen

    2012-11-01

    Na(+)/K(+)-ATPase targeted cancer therapy has attracted increasing interests of oncologists in lung cancer field. Although multiple anti-cancer mechanisms of cardiac glycosides as Na(+)/K(+)-ATPase inhibitors are revealed, the role of autophagy and related molecular signaling pathway for the class of compounds in human non-small cell lung cancer (NSCLC) cells has not been systematically examined. We herein investigated the anti-cancer effects of two representative cardiac glycosides, digoxin and ouabain, in A549 and H460 cell lines. Both agents caused significant growth inhibition at nanomolar level. The cardiac glycosides were found to induce moderate G(2)/M arrest but not apoptosis at IC(50) level in the NSCLC cell lines. Moreover, autophagy was markedly induced by both agents, as evidenced by the time- and dose-dependent increase of LC3-II, up-regulation of Atg5 and Beclin1, as well as by the observations through acridine orange staining, transmission electron microscopy and quantification of GFP-LC3 fluorescence. Importantly, AMP-activated protein kinase (AMPK) pathway was activated, resulting in mammalian target of rapamycin (mTOR) deactivation during autophagy induction. Moreover, extracellular-signal-regulated kinase 1/2 (ERK1/2) activation was simultaneously found to be involved in the autophagy regulation. Co-treatment with respective inhibitors or siRNAs could either block the autophagic phenotypes and signals, or significantly increase the cellular viability, indicating the drugs-induced autophagy plays tumor-suppressing role. This work provides first evidence showing that the cardiac glycosides induce autophagy in human NSCLC cells through regulation of both mTOR and ERK1/2 signaling pathways. The autophagy may at least partially account for the growth inhibitory effects of the compounds in human NSCLC cells.

  1. Cell-autonomous FGF signaling regulates anteroposterior patterning and neuronal differentiation in the mesodiencephalic dopaminergic progenitor domain.

    PubMed

    Lahti, Laura; Peltopuro, Paula; Piepponen, T Petteri; Partanen, Juha

    2012-03-01

    The structure and projection patterns of adult mesodiencephalic dopaminergic (DA) neurons are one of the best characterized systems in the vertebrate brain. However, the early organization and development of these nuclei remain poorly understood. The induction of midbrain DA neurons requires sonic hedgehog (Shh) from the floor plate and fibroblast growth factor 8 (FGF8) from the isthmic organizer, but the way in which FGF8 regulates DA neuron development is unclear. We show that, during early embryogenesis, mesodiencephalic neurons consist of two distinct populations: a diencephalic domain, which is probably independent of isthmic FGFs; and a midbrain domain, which is dependent on FGFs. Within these domains, DA progenitors and precursors use partly different genetic programs. Furthermore, the diencephalic DA domain forms a distinct cell population, which also contains non-DA Pou4f1(+) cells. FGF signaling operates in proliferative midbrain DA progenitors, but is absent in postmitotic DA precursors. The loss of FGFR1/2-mediated signaling results in a maturation failure of the midbrain DA neurons and altered patterning of the midbrain floor. In FGFR mutants, the DA domain adopts characteristics that are typical for embryonic diencephalon, including the presence of Pou4f1(+) cells among TH(+) cells, and downregulation of genes typical of midbrain DA precursors. Finally, analyses of chimeric embryos indicate that FGF signaling regulates the development of the ventral midbrain cell autonomously.

  2. Regulation of the Cardiac Sodium/Bicarbonate Cotransporter by Angiotensin II: Potential Contribution to Structural, Ionic and Electrophysiological Myocardial Remodelling

    PubMed Central

    Aiello, Ernesto Alejandro; Giusti, Verónica Celeste De

    2013-01-01

    The sodium/ bicarbonate cotransporter (NBC) is, with the Na+/H+ exchanger (NHE), an important alkalinizing mechanism that maintains cellular intracellular pH (pHi). In the heart exists at least three isoforms of NBC, one that promotes the co-influx of 1 molecule of Na+ per 1molecule of HCO3-(electroneutral isoform; nNBC) and two others that generates the co-influx of 1 molecule of Na+ per 2 molecules of HCO3- (electrogenic isoforms; eNBC). In addition, the eNBC generates an anionic repolarizing current that modulate the cardiac action potential (CAP), adding to such isoforms the relevance to modulate the electrophysiological function of the heart. Angiotensin II (Ang II) is one of the main hormones that regulate cardiac physiology. The alkalinizing mechanisms (NHE and NBC) are stimulated by Ang II, increasing pHi and intracellular Na+ concentration, which indirectly, due to the stimulation of the Na+/Ca2+ exchanger (NCX) operating in the reverse form, leads to an increase in the intracellular Ca2+ concentration. Interestingly, it has been shown that Ang II exhibits an opposite effect on NBC isoforms: it activates the nNBC and inhibits the eNBC. This inhibition generates a CAP prolongation, which could directly increase the intracellular Ca2+ concentration. The regulation of the intracellular Na+ and Ca2+ concentrations is crucial for the cardiac cellular physiology, but these ions are also involved in the development of cardiac hypertrophy and the damage produced by ischemia-reperfusion, suggesting a potential role of NBC in cardiac diseases. PMID:23116057

  3. Class I HDACs Regulate Angiotensin II-Dependent Cardiac Fibrosis via Fibroblasts and Circulating Fibrocytes

    PubMed Central

    Williams, Sarah M.; Golden-Mason, Lucy; Ferguson, Bradley S.; Douglas, Katherine B.; Cavasin, Maria A.; Demos-Davies, Kim; Yeager, Michael E.; Stenmark, Kurt R.; McKinsey, Timothy A.

    2014-01-01

    Fibrosis, which is defined as excessive accumulation of fibrous connective tissue, contributes to the pathogenesis of numerous diseases involving diverse organ systems. Cardiac fibrosis predisposes individuals to myocardial ischemia, arrhythmias and sudden death, and is commonly associated with diastolic dysfunction. Histone deacetylase (HDAC) inhibitors block cardiac fibrosis in pre-clinical models of heart failure. However, which HDAC isoforms govern cardiac fibrosis, and the mechanisms by which they do so, remains unclear. Here, we show that selective inhibition of class I HDACs potently suppresses angiotensin II (Ang II)-mediated cardiac fibrosis by targeting two key effector cell populations, cardiac fibroblasts and bone marrow-derived fibrocytes. Class I HDAC inhibition blocks cardiac fibroblast cell cycle progression through derepression of the genes encoding the cyclin-dependent kinase (CDK) inhibitors, p15 and p57. In contrast, class I HDAC inhibitors block agonist-dependent differentiation of fibrocytes through a mechanism involving repression of ERK1/2 signaling. These findings define novel roles for class I HDACs in the control of pathological cardiac fibrosis. Furthermore, since fibrocytes have been implicated in the pathogenesis of a variety of human diseases, including heart, lung and kidney failure, our results suggest broad utility for isoform-selective HDAC inhibitors as anti-fibrotic agents that function, in part, by targeting these circulating mesenchymal cells. PMID:24374140

  4. Calcium-mediated dual-mode regulation of cardiac sodium channel gating.

    PubMed

    Biswas, Subrata; DiSilvestre, Deborah; Tian, Yanli; Halperin, Victoria L; Tomaselli, Gordon F

    2009-04-10

    Intracellular Ca(2+) ([Ca(2+)](i)) can trigger dual-mode regulation of the voltage gated cardiac sodium channel (Na(V)1.5). The channel components of the Ca(2+) regulatory system are the calmodulin (CaM)-binding IQ motif and the Ca(2+) sensing EF hand-like (EFL) motif in the carboxyl terminus of the channel. Mutations in either motif have been associated with arrhythmogenic changes in expressed Na(V)1.5 currents. Increases in [Ca(2+)](i) shift the steady-state inactivation of Na(V)1.5 in the depolarizing direction and slow entry into inactivated states. Mutation of the EFL (Na(V)1.5(4X)) shifts inactivation in the hyperpolarizing direction compared with the wild-type channel and eliminates the Ca(2+) sensitivity of inactivation gating. Modulation of the steady-state availability of Na(V)1.5 by [Ca(2+)](i) is more pronounced after the truncation of the carboxyl terminus proximal to the IQ motif (Na(V)1.5(Delta1885)), which retains the EFL. Mutating the EFL (Na(V)1.5(4X)) unmasks CaM-mediated regulation of the kinetics and voltage dependence of inactivation. This latent CaM modulation of inactivation is eliminated by mutation of the IQ motif (Na(V)1.5(4X-IQ/AA)). The LQT3 EFL mutant channel Na(V)1.5(D1790G) exhibits Ca(2+) insensitivity and unmasking of CaM regulation of inactivation gating. The enhanced effect of CaM on Na(V)1.5(4X) gating is associated with significantly greater fluorescence resonance energy transfer between enhanced cyan fluorescent protein-CaM and Na(V)1.5(4X) channels than is observed with wild-type Na(V)1.5. Unlike other isoforms of the Na channel, the IQ-CaM interaction in the carboxyl terminus of Na(V)1.5 is latent under physiological conditions but may become manifest in the presence of disease causing mutations in the CT of Na(V)1.5 (particularly in the EFL), contributing to the production of potentially lethal ventricular arrhythmias.

  5. Cardiac catheterization

    MedlinePlus

    Catheterization - cardiac; Heart catheterization; Angina - cardiac catheterization; CAD - cardiac catheterization; Coronary artery disease - cardiac catheterization; Heart valve - cardiac catheterization; Heart failure - ...

  6. Autonomic adjustments to exercise in humans.

    PubMed

    Fisher, James P; Young, Colin N; Fadel, Paul J

    2015-04-01

    Autonomic nervous system adjustments to the heart and blood vessels are necessary for mediating the cardiovascular responses required to meet the metabolic demands of working skeletal muscle during exercise. These demands are met by precise exercise intensity-dependent alterations in sympathetic and parasympathetic nerve activity. The purpose of this review is to examine the contributions of the sympathetic and parasympathetic nervous systems in mediating specific cardiovascular and hemodynamic responses to exercise. These changes in autonomic outflow are regulated by several neural mechanisms working in concert, including central command (a feed forward mechanism originating from higher brain centers), the exercise pressor reflex (a feed-back mechanism originating from skeletal muscle), the arterial baroreflex (a negative feed-back mechanism originating from the carotid sinus and aortic arch), and cardiopulmonary baroreceptors (a feed-back mechanism from stretch receptors located in the heart and lungs). In addition, arterial chemoreceptors and phrenic afferents from respiratory muscles (i.e., respiratory metaboreflex) are also capable of modulating the autonomic responses to exercise. Our goal is to provide a detailed review of the parasympathetic and sympathetic changes that occur with exercise distinguishing between the onset of exercise and steady-state conditions, when appropriate. In addition, studies demonstrating the contributions of each of the aforementioned neural mechanisms to the autonomic changes and ensuing cardiac and/or vascular responses will be covered.

  7. Cardiac gene expression data and in silico analysis provide novel insights into human and mouse taste receptor gene regulation.

    PubMed

    Foster, Simon R; Porrello, Enzo R; Stefani, Maurizio; Smith, Nicola J; Molenaar, Peter; dos Remedios, Cristobal G; Thomas, Walter G; Ramialison, Mirana

    2015-10-01

    G protein-coupled receptors are the principal mediators of the sweet, umami, bitter, and fat taste qualities in mammals. Intriguingly, the taste receptors are also expressed outside of the oral cavity, including in the gut, airways, brain, and heart, where they have additional functions and contribute to disease. However, there is little known about the mechanisms governing the transcriptional regulation of taste receptor genes. Following our recent delineation of taste receptors in the heart, we investigated the genomic loci encoding for taste receptors to gain insight into the regulatory mechanisms that drive their expression in the heart. Gene expression analyses of healthy and diseased human and mouse hearts showed coordinated expression for a subset of chromosomally clustered taste receptors. This chromosomal clustering mirrored the cardiac expression profile, suggesting that a common gene regulatory block may control the taste receptor locus. We identified unique domains with strong regulatory potential in the vicinity of taste receptor genes. We also performed de novo motif enrichment in the proximal promoter regions and found several overrepresented DNA motifs in cardiac taste receptor gene promoters corresponding to ubiquitous and cardiac-specific transcription factor binding sites. Thus, combining cardiac gene expression data with bioinformatic analyses, this study has provided insights into the noncoding regulatory landscape for taste GPCRs. These findings also have broader relevance for the study of taste GPCRs outside of the classical gustatory system, where understanding the mechanisms controlling the expression of these receptors may have implications for future therapeutic development.

  8. Particles Alter Diesel Exhaust Gases-Induced Hypotension, Cardiac Arrhythmia,Conduction Disturbance, and Autonomic Imbalance in Heart Failure-Prone Rats

    EPA Science Inventory

    Epidemiologic studies indicate that acute exposures to vehicular traffic and particulate matter (PM) air pollution are key causes of fatal cardiac arrhythmia, especially in those with preexisting cardiovascular disease. Researchers point to electrophysiologic dysfunction and auto...

  9. Cell autonomous regulation of herpes and influenza virus infection by the circadian clock

    PubMed Central

    Edgar, Rachel S.; Stangherlin, Alessandra; Nagy, Andras D.; Nicoll, Michael P.; Efstathiou, Stacey; O’Neill, John S.; Reddy, Akhilesh B.

    2016-01-01

    Viruses are intracellular pathogens that hijack host cell machinery and resources to replicate. Rather than being constant, host physiology is rhythmic, undergoing circadian (∼24 h) oscillations in many virus-relevant pathways, but whether daily rhythms impact on viral replication is unknown. We find that the time of day of host infection regulates virus progression in live mice and individual cells. Furthermore, we demonstrate that herpes and influenza A virus infections are enhanced when host circadian rhythms are abolished by disrupting the key clock gene transcription factor Bmal1. Intracellular trafficking, biosynthetic processes, protein synthesis, and chromatin assembly all contribute to circadian regulation of virus infection. Moreover, herpesviruses differentially target components of the molecular circadian clockwork. Our work demonstrates that viruses exploit the clockwork for their own gain and that the clock represents a novel target for modulating viral replication that extends beyond any single family of these ubiquitous pathogens. PMID:27528682

  10. [The role of the autonomic nervous system in regulating the hydrodynamics of the intact eye].

    PubMed

    Kibiakov, A V; Razumovskiĭ, M I; Shutko, A N

    1976-05-01

    In cats, the low-molecular indicator: radioactive phosphorus, and the tonography revealed that the local application of acetylcholine accelerates the fluid exchange in the intact eye, considerably facilitating the outflow. Noradrenaline and the threshold stimulation of the cervical sympathetic nerve slow down the intraeye fluid exchange, decreasing the outflow. The data obtained suggest that the neural regulation of the eye hydrodynamics involves, mainly, a direct effect of the vegetative innervation on the eye drainage system.

  11. Doxorubicin Regulates Autophagy Signals via Accumulation of Cytosolic Ca2+ in Human Cardiac Progenitor Cells

    PubMed Central

    Park, Ji Hye; Choi, Sung Hyun; Kim, Hyungtae; Ji, Seung Taek; Jang, Woong Bi; Kim, Jae Ho; Baek, Sang Hong; Kwon, Sang Mo

    2016-01-01

    Doxorubicin (DOXO) is widely used to treat solid tumors. However, its clinical use is limited by side effects including serious cardiotoxicity due to cardiomyocyte damage. Resident cardiac progenitor cells (hCPCs) act as key regulators of homeostasis in myocardial cells. However, little is known about the function of hCPCs in DOXO-induced cardiotoxicity. In this study, we found that DOXO-mediated hCPC toxicity is closely related to calcium-related autophagy signaling and was significantly attenuated by blocking mTOR signaling in human hCPCs. DOXO induced hCPC apoptosis with reduction of SMP30 (regucalcin) and autophagosome marker LC3, as well as remarkable induction of the autophagy-related markers, Beclin-1, APG7, and P62/SQSTM1 and induction of calcium-related molecules, CaM (Calmodulin) and CaMKII (Calmodulin kinase II). The results of an LC3 puncta assay further indicated that DOXO reduced autophagosome formation via accumulation of cytosolic Ca2+. Additionally, DOXO significantly induced mTOR expression in hCPCs, and inhibition of mTOR signaling by rapamycin, a specific inhibitor, rescued DOXO-mediated autophagosome depletion in hCPCs with significant reduction of DOXO-mediated cytosolic Ca2+ accumulation in hCPCs, and restored SMP30 and mTOR expression. Thus, DOXO-mediated hCPC toxicity is linked to Ca2+-related autophagy signaling, and inhibition of mTOR signaling may provide a cardio-protective effect against DOXO-mediated hCPC toxicity. PMID:27735842

  12. Estradiol regulates human QT-interval: acceleration of cardiac repolarization by enhanced KCNH2 membrane trafficking

    PubMed Central

    Anneken, Lars; Baumann, Stefan; Vigneault, Patrick; Biliczki, Peter; Friedrich, Corinna; Xiao, Ling; Girmatsion, Zenawit; Takac, Ina; Brandes, Ralf P.; Kissler, Stefan; Wiegratz, Inka; Zumhagen, Sven; Stallmeyer, Birgit; Hohnloser, Stefan H.; Klingenheben, Thomas; Schulze-Bahr, Eric; Nattel, Stanley; Ehrlich, Joachim R.

    2016-01-01

    Background Modulation of cardiac repolarization by sexual hormones is controversial and hormonal effects on ion channels remain largely unknown. In the present translational study, we therefore assessed the relationship between QTc duration and gonadal hormones and studied underlying mechanisms. Methods and results We measured hormone levels and QTc intervals in women during clomiphene stimulation for infertility and women before, during, and after pregnancy. Three heterozygous LQT-2 patients (KCNH2-p.Arg752Pro missense mutation) and two unaffected family members additionally were studied during their menstrual cycles. A comprehensive cellular and molecular analysis was done to identify the mechanisms of hormonal QT-interval regulation. High estradiol levels, but neither progesterone nor estradiol/progesterone ratio, inversely correlated with QTc. Consistent with clinical data, in vitro estradiol stimulation (60 pmol/L, 48 h) enhanced IKCNH2. This increase was mediated by estradiol receptor-α-dependent promotion of KCNH2-channel trafficking to the cell membrane. To study the underlying mechanism, we focused on heat-shock proteins. The heat-shock protein-90 (Hsp90) inhibitor geldanamycin abolished estradiol-induced increase in IKCNH2. Geldanamycin had no effect on KCNH2 transcription or translation; nor did it affect expression of estradiol receptors and chaperones. Estradiol enhanced the physical interaction of KCNH2-channel subunits with heat-shock proteins and augmented ion-channel trafficking to the membrane. Conclusion Elevated estradiol levels were associated with shorter QTc intervals in healthy women and female LQT-2 patients. Estradiol acts on KCNH2 channels via enhanced estradiol-receptor-α-mediated Hsp90 interaction, augments membrane trafficking and thereby increases repolarizing current. These results provide mechanistic insights into hormonal control of human ventricular repolarization and open novel therapeutic avenues. PMID:26271031

  13. EHD3-Dependent Endosome Pathway Regulates Cardiac Membrane Excitability and Physiology

    PubMed Central

    Curran, Jerry; Makara, Michael A.; Little, Sean C.; Musa, Hassan; Liu, Bin; Wu, Xiangqiong; Polina, Iuliia; Alecusan, Joe; Wright, Patrick; Li, Jingdong; Billman, George E.; Boyden, Penelope A.; Gyorke, Sandor; Band, Hamid; Hund, Thomas J.; Mohler, Peter J.

    2014-01-01

    Rationale Cardiac function is dependent on the coordinate activities of membrane ion channels, transporters, pumps, and hormone receptors to dynamically tune the membrane electrochemical gradient in response to acute and chronic stress. While our knowledge of membrane proteins has rapidly advanced over the past decade, our understanding of the subcellular pathways governing the trafficking and localization of integral membrane proteins is limited, and essentially unstudied in vivo. In heart, to our knowledge, there are no in vivo mechanistic studies that directly link endosome-based machinery with cardiac physiology. Objective Define the in vivo roles of endosome-based cellular machinery for cardiac membrane protein trafficking, myocyte excitability, and cardiac physiology. Methods and Results We identify the endosome-based EHD3 pathway as essential for cardiac physiology. EHD3−/− hearts display structural and functional defects including bradycardia and rate variability, conduction block, and blunted response to adrenergic stimulation. Mechanistically, EHD3 is critical for membrane protein trafficking, as EHD3−/− myocytes display reduced expression/localization of Na/Ca exchanger and Cav1.2 with a parallel reduction in INCX and ICa,L. Functionally, EHD3−/− myocytes show increased sarcoplasmic reticulum [Ca], increased spark frequency, and reduced expression/localization of ankyrin-B, a binding partner for EHD3 and Na/Ca exchanger. Finally, we show that in vivo EHD3−/− defects are due to cardiac-specific roles of EHD3 as mice with cardiac-selective EHD3 deficiency demonstrate both structural and electrical phenotypes. Conclusions These data provide new insight into the critical role of endosome-based pathways in membrane protein targeting and cardiac physiology. EHD3 is a critical component of protein trafficking in heart and is essential for the proper membrane targeting of select cellular proteins that maintain excitability. PMID:24759929

  14. Homocysteine induces cardiac hypertrophy by up-regulating ATP7a expression

    PubMed Central

    Cao, Zhanwei; Zhang, Yanzhou; Sun, Tongwen; Zhang, Shuguang; Yu, Weiya; Zhu, Jie

    2015-01-01

    Aims: The aim of the study is to investigate the molecular mechanism by which homocysteine (Hcy) induces cardiac hypertrophy. Methods: Primary cardiomyocytes were obtained from baby Sprague-Dawley rats within 3 days after birth. Flow cytometry was used to measure cell sizes. Quantitative real-time polymerase chain reaction was performed to measure the expression of β-myosin heavy chain and atrial natriuretic peptide genes. Western blotting assay was employed to determine ATP7a protein expression. Cytochrome C oxidase (COX) activity test was used to evaluate the activity of COX. Atomic absorption spectroscopy was performed to determine copper content. siRNAs were used to target-silence the expression of ATP7a. Results: Hcy induced cardiac hypertrophy and increased the expression of cardiac hypertrophy-related genes. ATP7a was a key factor in cardiac hypertrophy induced by Hcy. Reduced ATP7a expression inhibited cardiac hypertrophy induced by Hcy. Elevated ATP7a expression induced by Hcy inhibited COX activity. Enhanced ATP7a expression inhibited COX activity by lowering intracellular copper content. Conclusions: Hcy elevates ATP7a protein expression, reduces copper content, and lowers COX activity, finally leading to cardiac hypertrophy. PMID:26722473

  15. Phospholemman regulates cardiac Na+/Ca2+ exchanger by interacting with the exchanger's proximal linker domain.

    PubMed

    Zhang, Xue-Qian; Wang, Jufang; Carl, Lois L; Song, Jianliang; Ahlers, Belinda A; Cheung, Joseph Y

    2009-04-01

    Phospholemman (PLM) belongs to the FXYD family of small ion transport regulators. When phosphorylated at Ser(68), PLM inhibits cardiac Na(+)/Ca(2+) exchanger (NCX1). We previously demonstrated that the cytoplasmic tail of PLM interacts with the proximal intracellular loop (residues 218-358), but not the transmembrane (residues 1-217 and 765-938) or Ca(2+)-binding (residues 371-508) domains, of NCX1. In this study, we used intact Na(+)/Ca(2+) exchanger with various deletions in the intracellular loop to map the interaction sites with PLM. We first demonstrated by Western blotting and confocal immunofluorescence microscopy that wild-type (WT) NCX1 and its deletion mutants were expressed in transfected HEK-293 cells. Cotransfection with PLM and NCX1 (or its deletion mutants) in HEK-293 cells did not decrease expression of NCX1 (or its deletion mutants). Coexpression of PLM with WT NCX1 inhibited NCX1 current (I(NaCa)). Deletion of residues 240-679, 265-373, 250-300, or 300-373 from WT NCX1 resulted in loss of inhibition of I(NaCa) by PLM. Inhibition of I(NaCa) by PLM was preserved when residues 229-237, 270-300, 328-330, or 330-373 were deleted from the intracellular loop of NCX1. These results suggest that PLM mediated inhibition of I(NaCa) by interacting with two distinct regions (residues 238-270 and 300-328) of NCX1. Indeed, I(NaCa) measured in mutants lacking residues 238-270, 300-328, or 238-270 + 300-328 was not affected by PLM. Glutathione S-transferase pull-down assays confirmed that PLM bound to fragments corresponding to residues 218-371, 218-320, 218-270, 238-371, and 300-373, but not to fragments encompassing residues 250-300 and 371-508 of NCX1, indicating that residues 218-270 and 300-373 physically associated with PLM. Finally, acute regulation of I(NaCa) by PLM phosphorylation observed with WT NCX1 was absent in 250-300 deletion mutant but preserved in 229-237 deletion mutant. We conclude that PLM mediates its inhibition of NCX1 by interacting with

  16. A novel conditional mouse model for Nkx2-5 reveals transcriptional regulation of cardiac ion channels.

    PubMed

    Furtado, Milena B; Wilmanns, Julia C; Chandran, Anjana; Tonta, Mary; Biben, Christine; Eichenlaub, Michael; Coleman, Harold A; Berger, Silke; Bouveret, Romaric; Singh, Reena; Harvey, Richard P; Ramialison, Mirana; Pearson, James T; Parkington, Helena C; Rosenthal, Nadia A; Costa, Mauro W

    2016-01-01

    Nkx2-5 is one of the master regulators of cardiac development, homeostasis and disease. This transcription factor has been previously associated with a suite of cardiac congenital malformations and impairment of electrical activity. When disease causative mutations in transcription factors are considered, NKX2-5 gene dysfunction is the most common abnormality found in patients. Here we describe a novel mouse model and subsequent implications of Nkx2-5 loss for aspects of myocardial electrical activity. In this work we have engineered a new Nkx2-5 conditional knockout mouse in which flox sites flank the entire Nkx2-5 locus, and validated this line for the study of heart development, differentiation and disease using a full deletion strategy. While our homozygous knockout mice show typical embryonic malformations previously described for the lack of the Nkx2-5 gene, hearts of heterozygous adult mice show moderate morphological and functional abnormalities that are sufficient to sustain blood supply demands under homeostatic conditions. This study further reveals intriguing aspects of Nkx2-5 function in the control of cardiac electrical activity. Using a combination of mouse genetics, biochemistry, molecular and cell biology, we demonstrate that Nkx2-5 regulates the gene encoding Kcnh2 channel and others, shedding light on potential mechanisms generating electrical abnormalities observed in patients bearing NKX2-5 dysfunction and opening opportunities to the study of novel therapeutic targets for anti-arrhythmogenic therapies.

  17. Does self-regulation and autonomic regulation have an influence on survival in breast and colon carcinoma patients? results of a prospective outcome study

    PubMed Central

    2011-01-01

    Background Cancer Related Fatigue (CRF) and circadian rhythm have a great impact on the quality of life (HRQL) of patients with breast (BC) and colon cancer (CRC). Other patient related outcomes in oncology are measured by new instruments focusing on adaptive characteristics such as sense of coherence or self-regulation, which could be more appropriate as a prognostic tool than classical HRQL. The aim of this study was to assess the association of autonomic regulation (aR) and self-regulation (SR) with survival. Methods 146 cancer patients and 120 healthy controls took part in an initial evaluation in 2000/2001. At a median follow up of 5.9 years later, 62 of 95 BC, 17 of 51 CRC patients, and 85 of 117 healthy controls took part in the follow-up study. 41 participants had died. For the follow-up evaluation, participants were requested to complete the standardized aR and SR questionnaires. Results On average, cancer patients had survived for 10.1 years with the disease. Using a Cox proportional hazard regression with stepwise variables such as age, diagnosis group, Charlson co-morbidity index, body mass index (BMI)) aR and SR. SR were identified as independent parameters with potential prognostic relevance on survival While aR did not significantly influence survival, SR showed a positive and independent impact on survival (OR = 0.589; 95%-CI: 0.354 - 0.979). This positive effect persisted significantly in the sensitivity analysis of the subgroup of tumour patients and in the subscale 'Achieve satisfaction and well-being' and by tendency in the UICC stages nested for the different diagnoses groups. Conclusions Self-regulation might be an independent prognostic factor for the survival of breast and colon carcinoma patients and merits further prospective studies. PMID:21961625

  18. Insulin signaling in Caenorhabditis elegans regulates both endocrine-like and cell-autonomous outputs.

    PubMed

    Iser, Wendy B; Gami, Minaxi S; Wolkow, Catherine A

    2007-03-15

    In C. elegans, insulin signaling affects development, lifespan and stress resistance. Several studies have shown that insulin signaling affects lifespan in an endocrine-like manner from different cells, while the major downstream target of insulin, the FOXO transcription factor encoded by daf-16, may act preferentially in intestinal cells to prolong lifespan. This discrepancy raised the possibility that insulin may have both endocrine and cell-intrinsic outputs. Here, we further investigated the types of cells capable of producing endocrine outputs of insulin and also identified a new cell-intrinsic insulin output. We found that insulin signaling within groups of neurons promoted wildtype lifespan, showing that the endocrine outputs of insulin were not restricted to specific cells. In contrast, DAF-16 appeared to have a greater effect on lifespan when expressed in a combination of tissues. These results suggest that insulin signaling may regulate DAF-16 through cell-intrinsic and endocrine pathways. We also found that an insulin-dependent response to fasting in intestinal cells was preferentially regulated by intestinal insulin signaling and was less responsive to insulin signaling from non-intestinal cells. Together, these results show that C. elegans insulin signaling has endocrine as well as tissue-specific outputs which could influence lifespan in a combinatorial fashion.

  19. Circumventricular organs: definition and role in the regulation of endocrine and autonomic function.

    PubMed

    Ganong, W F

    2000-01-01

    1. The circumventricular organs (CVO) are structures that permit polypeptide hypothalamic hormones to leave the brain without disrupting the blood-brain barrier (BBB) and permit substances that do not cross the BBB to trigger changes in brain function. 2. In mammals, CVO include only the median eminence and adjacent neurohypophysis, organum vasculosum lamina terminalis, subfornical organ and the area postrema. 3. The CVO are characterized by their small size, high permeability and fenestrated capillaries. The subcommissural organ is not highly permeable and does not have fenestrated capillaries, but new evidence indicates that it may be involved in the hypertension produced by aldosterone acting on the brain. 4. Feedback control of corticotropin-releasing hormone (CRH) secretion is exerted by free steroids diffusing into the brain, but substances such as cytokines and angiotensin II act on CVO to produce increases in CRH secretion. Gonadal steroids also diffuse into the brain to regulate gonadotrophin-releasing hormone secretion. Thyrotropin-releasing hormone secretion is regulated by thyroid hormones transported across cerebral capillaries. However, CVO may be involved in the negative feedback control of growth hormone and prolactin secretion.

  20. Cell non-autonomous regulation of hepatic IGF-1 and neonatal growth by Kinase Suppressor of Ras 2 (KSR2)

    PubMed Central

    Guo, Lili; Costanzo-Garvey, Diane L.; Smith, Deandra R.; Zavorka, Megan E.; Venable-Kang, Megan; MacDonald, Richard G.; Lewis, Robert E.

    2016-01-01

    Individuals with poor postnatal growth are at risk for cardiovascular and metabolic problems as adults. Here we show that disruption of the molecular scaffold Kinase Suppressor of Ras 2 (KSR2) causes selective inhibition of hepatic GH signaling in neonatal mice with impaired expression of IGF-1 and IGFBP3. ksr2−/− mice are normal size at birth but show a marked increase in FGF21 accompanied by reduced body mass, shortened body length, and reduced bone mineral density (BMD) and content (BMC) first evident during postnatal development. However, disrupting FGF21 in ksr2−/− mice does not normalize mass, length, or bone density and content in fgf21−/−ksr2−/− mice. Body length, BMC and BMD, but not body mass, are rescued by infection of two-day-old ksr2−/− mice with a recombinant adenovirus encoding human IGF-1. Relative to wild-type mice, GH injections reveal a significant reduction in JAK2 and STAT5 phosphorylation in liver, but not in skeletal muscle, of ksr2−/− mice. However, primary hepatocytes isolated from ksr2−/− mice show no reduction in GH-stimulated STAT5 phosphorylation. These data indicate that KSR2 functions in a cell non-autonomous fashion to regulate GH-stimulated IGF-1 expression in the liver of neonatal mice, which plays a key role in the development of body length. PMID:27561547