RESUMEN
A regular heartbeat is essential to vertebrate life. In the mature heart, this function is driven by an anatomically localized pacemaker. By contrast, pacemaking capability is broadly distributed in the early embryonic heart1-3, raising the question of how tissue-scale activity is first established and then maintained during embryonic development. The initial transition of the heart from silent to beating has never been characterized at the timescale of individual electrical events, and the structure in space and time of the early heartbeats remains poorly understood. Using all-optical electrophysiology, we captured the very first heartbeat of a zebrafish and analysed the development of cardiac excitability and conduction around this singular event. The first few beats appeared suddenly, had irregular interbeat intervals, propagated coherently across the primordial heart and emanated from loci that varied between animals and over time. The bioelectrical dynamics were well described by a noisy saddle-node on invariant circle bifurcation with action potential upstroke driven by CaV1.2. Our work shows how gradual and largely asynchronous development of single-cell bioelectrical properties produces a stereotyped and robust tissue-scale transition from quiescence to coordinated beating.
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Desarrollo Embrionario , Frecuencia Cardíaca , Corazón , Pez Cebra , Animales , Potenciales de Acción , Corazón/embriología , Corazón/inervación , Corazón/fisiología , Frecuencia Cardíaca/fisiología , Pez Cebra/embriología , Pez Cebra/fisiología , Electrofisiología , Análisis de la Célula IndividualRESUMEN
The heart is vital for biological function in almost all chordates, including humans. It beats continually throughout our life, supplying the body with oxygen and nutrients while removing waste products. If it stops, so does life. The heartbeat involves precise coordination of the activity of billions of individual cells, as well as their swift and well-coordinated adaption to changes in physiological demand. Much of the vital control of cardiac function occurs at the level of individual cardiac muscle cells, including acute beat-by-beat feedback from the local mechanical environment to electrical activity (as opposed to longer term changes in gene expression and functional or structural remodeling). This process is known as mechano-electric coupling (MEC). In the current review, we present evidence for, and implications of, MEC in health and disease in human; summarize our understanding of MEC effects gained from whole animal, organ, tissue, and cell studies; identify potential molecular mediators of MEC responses; and demonstrate the power of computational modeling in developing a more comprehensive understanding of ?what makes the heart tick.Ë®.
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Frecuencia Cardíaca/fisiología , Corazón/fisiología , Estimulación Física , Animales , Arritmias Cardíacas/fisiopatología , Relojes Biológicos , Humanos , Miocardio/citología , Miocitos Cardíacos/fisiologíaRESUMEN
Groups often outperform individuals in problem-solving. Nevertheless, failure to critically evaluate ideas risks suboptimal outcomes through so-called groupthink. Prior studies have shown that people who hold shared goals, perspectives, or understanding of the environment show similar patterns of brain activity, which itself can be enhanced by consensus-building discussions. Whether shared arousal alone can predict collective decision-making outcomes, however, remains unknown. To address this gap, we computed interpersonal heart rate synchrony, a peripheral index of shared arousal associated with joint attention, empathic accuracy, and group cohesion, in 44 groups (n = 204) performing a collective decision-making task. The task required critical examination of all available information to override inferior, default options and make the right choice. Using multidimensional recurrence quantification analysis (MdRQA) and machine learning, we found that heart rate synchrony predicted the probability of groups reaching the correct consensus decision with >70% cross-validation accuracy-significantly higher than that predicted by the duration of discussions, subjective assessment of team function or baseline heart rates alone. We propose that heart rate synchrony during group discussion provides a biomarker of interpersonal engagement that facilitates adaptive learning and effective information sharing during collective decision-making.
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Toma de Decisiones , Frecuencia Cardíaca , Humanos , Frecuencia Cardíaca/fisiología , Toma de Decisiones/fisiología , Masculino , Femenino , Adulto , Relaciones Interpersonales , Procesos de Grupo , Adulto JovenRESUMEN
The heart beats approximately 100,000 times per day in humans, imposing substantial energetic demands on cardiac muscle. Adenosine triphosphate (ATP) is an essential energy source for normal function of cardiac muscle during each beat, as it powers ion transport, intracellular Ca2+ handling, and actin-myosin cross-bridge cycling. Despite this, the impact of excitation-contraction coupling on the intracellular ATP concentration ([ATP]i) in myocytes is poorly understood. Here, we conducted real-time measurements of [ATP]i in ventricular myocytes using a genetically encoded ATP fluorescent reporter. Our data reveal rapid beat-to-beat variations in [ATP]i. Notably, diastolic [ATP]i was <1 mM, which is eightfold to 10-fold lower than previously estimated. Accordingly, ATP-sensitive K+ (KATP) channels were active at physiological [ATP]i. Cells exhibited two distinct types of ATP fluctuations during an action potential: net increases (Mode 1) or decreases (Mode 2) in [ATP]i. Mode 1 [ATP]i increases necessitated Ca2+ entry and release from the sarcoplasmic reticulum (SR) and were associated with increases in mitochondrial Ca2+. By contrast, decreases in mitochondrial Ca2+ accompanied Mode 2 [ATP]i decreases. Down-regulation of the protein mitofusin 2 reduced the magnitude of [ATP]i fluctuations, indicating that SR-mitochondrial coupling plays a crucial role in the dynamic control of ATP levels. Activation of ß-adrenergic receptors decreased [ATP]i, underscoring the energetic impact of this signaling pathway. Finally, our work suggests that cross-bridge cycling is the largest consumer of ATP in a ventricular myocyte during an action potential. These findings provide insights into the energetic demands of EC coupling and highlight the dynamic nature of ATP concentrations in cardiac muscle.
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Adenosina Trifosfato , Calcio , Acoplamiento Excitación-Contracción , Ventrículos Cardíacos , Miocitos Cardíacos , Miocitos Cardíacos/metabolismo , Adenosina Trifosfato/metabolismo , Acoplamiento Excitación-Contracción/fisiología , Animales , Calcio/metabolismo , Ventrículos Cardíacos/metabolismo , Ventrículos Cardíacos/citología , Potenciales de Acción/fisiología , Retículo Sarcoplasmático/metabolismo , Frecuencia Cardíaca/fisiología , Humanos , Canales KATP/metabolismo , Contracción Miocárdica/fisiología , RatonesRESUMEN
The parasympathetic nervous system via the vagus nerve exerts profound influence over the heart. Together with the sympathetic nervous system, the parasympathetic nervous system is responsible for fine-tuned regulation of all aspects of cardiovascular function, including heart rate, rhythm, contractility, and blood pressure. In this review, we highlight vagal efferent and afferent innervation of the heart, with a focus on insights from comparative biology and advances in understanding the molecular and genetic diversity of vagal neurons, as well as interoception, parasympathetic dysfunction in heart disease, and the therapeutic potential of targeting the parasympathetic nervous system in cardiovascular disease.
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Medicina Clínica , Cardiopatías , Humanos , Nervio Vago/fisiología , Corazón , Frecuencia Cardíaca/fisiologíaRESUMEN
The dorsal anterior cingulate cortex (dACC) is a critical brain area for pain and autonomic processing, making it a promising noninvasive therapeutic target. We leverage the high spatial resolution and deep focal lengths of low-intensity focused ultrasound (LIFU) to noninvasively modulate the dACC for effects on behavioral and cardiac autonomic responses using transient heat pain stimuli. A N = 16 healthy human volunteers (6â M/10â F) received transient contact heat pain during either LIFU to the dACC or Sham stimulation. Continuous electroencephalogram (EEG), electrocardiogram (ECG), and electrodermal response (EDR) were recorded. Outcome measures included pain ratings, heart rate variability, EDR response, blood pressure, and the amplitude of the contact heat-evoked potential (CHEP).LIFU reduced pain ratings by 1.09 ± 0.20 points relative to Sham. LIFU increased heart rate variability indexed by the standard deviation of normal sinus beats (SDNN), low-frequency (LF) power, and the low-frequency/high-frequency (LF/HF) ratio. There were no effects on the blood pressure or EDR. LIFU resulted in a 38.1% reduction in the P2 CHEP amplitude. Results demonstrate LIFU to the dACC reduces pain and alters autonomic responses to acute heat pain stimuli. This has implications for the causal understanding of human pain and autonomic processing in the dACC and potential future therapeutic options for pain relief and modulation of homeostatic signals.
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Dolor Agudo , Giro del Cíngulo , Humanos , Giro del Cíngulo/diagnóstico por imagen , Sistema Nervioso Autónomo , Corazón , Frecuencia Cardíaca/fisiología , Percepción del DolorRESUMEN
SignificanceAmbient nighttime light exposure is implicated as a risk factor for adverse health outcomes, including cardiometabolic disease. However, the effects of nighttime light exposure during sleep on cardiometabolic outcomes and the related mechanisms are unclear. This laboratory study shows that, in healthy adults, one night of moderate (100 lx) light exposure during sleep increases nighttime heart rate, decreases heart rate variability (higher sympathovagal balance), and increases next-morning insulin resistance when compared to sleep in a dimly lit (<3 lx) environment. Moreover, a positive relationship between higher sympathovagal balance and insulin levels suggests that sympathetic activation may play a role in the observed light-induced changes in insulin sensitivity.
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Enfermedades Cardiovasculares , Resistencia a la Insulina , Adulto , Enfermedades Cardiovasculares/etiología , Ritmo Circadiano/fisiología , Frecuencia Cardíaca/fisiología , Humanos , Resistencia a la Insulina/fisiología , Sueño/fisiologíaRESUMEN
A century-long debate on bodily states and emotions persists. While the involvement of bodily activity in emotion physiology is widely recognized, the specificity and causal role of such activity related to brain dynamics has not yet been demonstrated. We hypothesize that the peripheral neural control on cardiovascular activity prompts and sustains brain dynamics during an emotional experience, so these afferent inputs are processed by the brain by triggering a concurrent efferent information transfer to the body. To this end, we investigated the functional brainheart interplay under emotion elicitation in publicly available data from 62 healthy subjects using a computational model based on synthetic data generation of electroencephalography and electrocardiography signals. Our findings show that sympathovagal activity plays a leading and causal role in initiating the emotional response, in which ascending modulations from vagal activity precede neural dynamics and correlate to the reported level of arousal. The subsequent dynamic interplay observed between the central and autonomic nervous systems sustains the processing of emotional arousal. These findings should be particularly revealing for the psychophysiology and neuroscience of emotions.
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Nivel de Alerta , Encéfalo , Electroencefalografía , Corazón , Nervio Vago , Nivel de Alerta/fisiología , Encéfalo/fisiología , Emociones/fisiología , Corazón/inervación , Frecuencia Cardíaca/fisiología , Humanos , Nervio Vago/fisiologíaRESUMEN
BACKGROUND: Heat extremes are associated with greater risk for cardiovascular death. The pathophysiologic mechanisms mediating this association are unknown. OBJECTIVE: To quantify the myocardial blood flow (MBF) requirements of heat exposure. DESIGN: Experimental study. (ClinicalTrials.gov: NCT04549974). SETTING: Laboratory-based. PARTICIPANTS: 61 participants, comprising 20 healthy young adults (mean age, 28 years), 21 healthy older adults (mean age, 67 years), and 20 older adults with coronary artery disease (CAD) (mean age, 70 years). INTERVENTION: Participants were heated until their core temperature increased 1.5 °C; MBF was measured before heat exposure and at every increase of 0.5 °C in core temperature. MEASUREMENTS: The primary outcome was MBF measured by positron emission tomography-computed tomography. Secondary outcomes included heart rate, blood pressure, and body weight change. RESULTS: At a core temperature increase of 1.5 °C, MBF increased in healthy young adults (change, 0.8 mL/min/g [95% CI, 0.5 to 1.0 mL/min/g]), healthy older adults (change, 0.7 mL/min/g [CI, 0.5 to 0.9 mL/min/g]), and older adults with CAD (change, 0.6 mL/min/g [CI, 0.3 to 0.8 mL/min/g]). This represented a 2.08-fold (CI, 1.75- to 2.41-fold), 1.79-fold (CI, 1.59- to 1.98-fold), and 1.64-fold (CI, 1.41- to 1.87-fold) change, respectively, from preexposure values. Imaging evidence of asymptomatic heat-induced myocardial ischemia was seen in 7 adults with CAD (35%) in post hoc analyses. LIMITATIONS: In this laboratory-based study, heating was limited to about 100 minutes and participants were restricted in movement and fluid intake. Participants refrained from strenuous exercise and smoking; stopped alcohol and caffeine intake; and withheld ß-blockers, calcium-channel blockers, and nitroglycerin before heating. CONCLUSION: Heat exposure that increases core temperature by 1.5 °C nearly doubles MBF. Changes in MBF did not differ by age or presence of CAD, but some older adults with CAD may experience asymptomatic myocardial ischemia. PRIMARY FUNDING SOURCE: Canadian Institutes of Health Research.
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Enfermedad de la Arteria Coronaria , Circulación Coronaria , Calor , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Presión Sanguínea/fisiología , Enfermedad de la Arteria Coronaria/fisiopatología , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Circulación Coronaria/fisiología , Frecuencia Cardíaca/fisiología , Calor/efectos adversos , Tomografía Computarizada por Tomografía de Emisión de PositronesRESUMEN
Adults with type 1 diabetes (T1D) have an elevated risk for cardiovascular disease (CVD) compared with the general population. HbA1c is the primary modifiable risk factor for CVD in T1D. Fewer than 1% of patients achieve euglycemia (<5.7% HbA1c). Ketogenic diets (KD; ≤50 g carbohydrate/day) may improve glycemia and downstream vascular dysfunction in T1D by reducing HbA1c and insulin load. However, there are concerns regarding the long-term CVD risk from a KD. Therefore, we compared data collected in a 60-day window in an adult with T1D on exogenous insulin who consumed a KD for 10 years versus normative values in those with T1D (T1D norms). The participant achieved euglycemia with an HbA1c of 5.5%, mean glucose of 98 [5] mg/dL (median [interquartile range]), 90 [11]% time-in-range 70-180 mg/dL (T1D norms: 1st percentile for all), and low insulin requirements of 0.38 ± 0.03 IU/kg/day (T1D norms: 8th percentile). Seated systolic blood pressure (SBP) was 113 mmHg (T1D norms: 18th percentile), while ambulatory awake SBP was 132 ± 15 mmHg (T1D target: <130 mmHg), blood triglycerides were 69 mg/dL (T1D norms: 34th percentile), low-density lipoprotein was 129 mg/dL (T1D norms: 60th percentile), heart rate was 56 beats/min (T1D norms: >1SD below the mean), carotid-femoral pulse wave velocity was 7.17 m/s (T1D norms: lowest quartile of risk), flow-mediated dilation was 12.8% (T1D norms: >1SD above mean), and cardiac vagal baroreflex gain was 23.5 ms/mmHg (T1D norms: >1SD above mean). Finally, there was no indication of left ventricular diastolic dysfunction from echocardiography. Overall, these data demonstrate below-average CVD risk relative to T1D norms despite concerns regarding the long-term impact of a KD on CVD risk.NEW & NOTEWORTHY Adults with type 1 diabetes (T1D) have a 10-fold higher risk for cardiovascular disease (CVD) compared with the general population. We assessed cardiovascular health metrics in an adult with T1D who presented with a euglycemic HbA1c after following a ketogenic diet for the past 10 years. Despite concerns about the ketogenic diet increasing CVD risk, the participant exhibited below-average CVD risk relative to others with T1D when considering all outcomes together.
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Glucemia , Enfermedades Cardiovasculares , Diabetes Mellitus Tipo 1 , Dieta Cetogénica , Humanos , Diabetes Mellitus Tipo 1/dietoterapia , Diabetes Mellitus Tipo 1/fisiopatología , Diabetes Mellitus Tipo 1/sangre , Adulto , Glucemia/metabolismo , Masculino , Enfermedades Cardiovasculares/dietoterapia , Enfermedades Cardiovasculares/prevención & control , Enfermedades Cardiovasculares/fisiopatología , Femenino , Hemoglobina Glucada/metabolismo , Presión Sanguínea/fisiología , Insulina/sangre , Factores de Riesgo , Frecuencia Cardíaca/fisiologíaRESUMEN
The blood pressure-lowering effect of aerobic training is preceded by improving cardiovascular autonomic control. We previously demonstrated that aerobic training conducted in the evening (ET) induces a greater decrease in blood pressure than morning training (MT). To study whether the greater blood pressure decrease after ET occurs through better cardiovascular autonomic regulation, this study aimed to compare MT versus ET on muscle sympathetic nerve activity (MSNA) and baroreflex sensitivity (BRS) in treated patients with hypertension. Elderly patients treated for hypertension were randomly allocated into MT (n = 12, 07.00-10.00 h) or ET (n = 11, 17.00-20.00 h) groups. Both groups trained for 10 weeks, 3 times/week, cycling for 45 min at moderate intensity. Beat-to-beat blood pressure (finger photoplethysmography), heart rate (electrocardiography) and MSNA (microneurography) were assessed at the initial and final phases of the study at baseline and during sequential bolus infusions of sodium nitroprusside and phenylephrine (modified-Oxford technique) to evaluate cardiac and sympathetic BRS. Mean blood pressure decreased significantly after ET but not after MT (-9 ± 11 vs. -1 ± 8 mmHg, P = 0.042). MSNA decreased significantly only after ET with no change after MT (-12 ± 5 vs. -3 ± 7 bursts/100 heart beats, P = 0.013). Sympathetic BRS improved after ET but not after MT (-0.8 ± 0.7 vs. 0.0 ± 0.8 bursts/100 heart beats/mmHg, P = 0.052). Cardiac BRS improved similarly in both groups (ET: +1.7 ± 1.8 vs. MT: +1.4 ± 1.9 ms/mmHg, Pphase ≤ 0.001). In elderly patients treated for hypertension, only ET decreased mean blood pressure and MSNA and improved sympathetic BRS. These findings revealed that the sympathetic nervous system has a key role in ET's superiority to MT in blood pressure-lowering effect. KEY POINTS: Reducing muscle nerve sympathetic activity and increasing sympathetic baroreflex sensitivity plays a key role in promoting the greater blood pressure reduction observed with evening training. These findings indicated that simply changing the timing of exercise training may offer additional benefits beyond antihypertensive medications, such as protection against sympathetic overdrive and loss of baroreflex sensitivity, independent markers of mortality. Our new findings also suggest new avenues of investigation, such as the possibility that evening aerobic training may be beneficial in other clinical conditions with sympathetic overdrive, such as congestive heart failure and hypertrophic cardiomyopathy.
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Sistema Cardiovascular , Hipertensión , Humanos , Anciano , Barorreflejo/fisiología , Hipertensión/terapia , Presión Sanguínea/fisiología , Corazón , Sistema Nervioso Simpático/fisiología , Frecuencia Cardíaca/fisiología , Músculo EsqueléticoRESUMEN
Sympathetic transduction is the study of how impulses of sympathetic nerve activity (SNA) affect end-organ function. Recently, the transduction of resting bursts of muscle SNA (MSNA) has been investigated and shown to have a role in the maintenance of blood pressure through changes in vascular tone in humans. In the present study, we investigate whether directly recorded resting cardiac SNA (CSNA) regulates heart rate (HR), coronary blood flow (CoBF), coronary vascular conductance (CVC), cardiac output (CO) and mean arterial pressure. Instrumentation was undertaken to record CSNA and relevant vascular variables in conscious sheep. Recordings were performed at baseline, as well as after the infusion of a ß-adrenoceptor blocker (propranolol) to determine the role of ß-adrenergic signalling in sympathetic transduction in the heart. The results show that after every burst of CSNA, there was a significant effect of time on HR (n = 10, ∆: +2.1 ± 1.4 beats min-1 , P = 0.002) and CO (n = 8, ∆: +100 ± 150 mL min-1 , P = 0.002) was elevated, followed by an increase in CoBF (n = 9, ∆: +0.76 mL min-1 , P = 0.001) and CVC (n = 8, ∆: +0.0038 mL min-1 mmHg-1 , P = 0.0028). The changes in HR were graded depending on the size and pattern of CSNA bursts. The HR response was significantly attenuated after the infusion of propranolol. Our study is the first to explore resting sympathetic transduction in the heart, suggesting that CSNA can dynamically change HR mediated by an action on ß-adrenoceptors. KEY POINTS: Sympathetic transduction is the study of how impulses of sympathetic nerve activity (SNA) affect end-organ function. Previous studies have examined sympathetic transduction primarily in the skeletal muscle and shown that bursts of muscle SNA alter blood flow to skeletal muscle and mean arterial pressure, although this has not been examined in the heart. We investigated sympathetic transduction in the heart and show that, in the conscious condition, the size of bursts of SNA to the heart can result in incremental increases in heart rate and coronary blood flow mediated by ß-adrenoceptors. The pattern of bursts of SNA to the heart also resulted in incremental increases in heart rate mediated by ß-adrenoceptors. This is the first study to explore the transduction of bursts of SNA to the heart.
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Corazón , Propranolol , Humanos , Ovinos , Animales , Propranolol/farmacología , Corazón/inervación , Presión Arterial , Presión Sanguínea/fisiología , Frecuencia Cardíaca/fisiología , Sistema Nervioso Simpático/fisiología , Receptores AdrenérgicosRESUMEN
The present study investigated the impact of central α2-adrenergic mechanisms on sympathetic action potential (AP) discharge, recruitment and latency strategies. We used the microneurographic technique to record muscle sympathetic nerve activity and a continuous wavelet transform to investigate postganglionic sympathetic AP firing during a baseline condition and an infusion of a α2-adrenergic receptor agonist, dexmedetomidine (10 min loading infusion of 0.225 µg kg-1; maintenance infusion of 0.1-0.5 µg kg h-1) in eight healthy individuals (28 ± 7 years, five females). Dexmedetomidine reduced mean pressure (92 ± 7 to 80 ± 8 mmHg, P < 0.001) but did not alter heart rate (61 ± 13 to 60 ± 14 bpm; P = 0.748). Dexmedetomidine reduced sympathetic AP discharge (126 ± 73 to 27 ± 24 AP 100 beats-1, P = 0.003) most strongly for medium-sized APs (normalized cluster 2: 21 ± 10 to 5 ± 5 AP 100 beats-1; P < 0.001). Dexmedetomidine progressively de-recruited sympathetic APs beginning with the largest AP clusters (12 ± 3 to 7 ± 2 clusters, P = 0.002). Despite de-recruiting large AP clusters with shorter latencies, dexmedetomidine reduced AP latency across remaining clusters (1.18 ± 0.12 to 1.13 ± 0.13 s, P = 0.002). A subset of six participants performed a Valsalva manoeuvre (20 s, 40 mmHg) during baseline and the dexmedetomidine infusion. Compared to baseline, AP discharge (Δ 361 ± 292 to Δ 113 ± 155 AP 100 beats-1, P = 0.011) and AP cluster recruitment elicited by the Valsalva manoeuvre were lower during dexmedetomidine (Δ 2 ± 1 to Δ 0 ± 2 AP clusters, P = 0.041). The reduction in sympathetic AP latency elicited by the Valsalva manoeuvre was not affected by dexmedetomidine (Δ -0.09 ± 0.07 to Δ -0.07 ± 0.14 s, P = 0.606). Dexmedetomidine reduced baroreflex gain, most strongly for medium-sized APs (normalized cluster 2: -6.0 ± 5 to -1.6 ± 2 % mmHg-1; P = 0.008). These data suggest that α2-adrenergic mechanisms within the central nervous system modulate sympathetic postganglionic neuronal discharge, recruitment and latency strategies in humans. KEY POINTS: Sympathetic postganglionic neuronal subpopulations innervating the human circulation exhibit complex patterns of discharge, recruitment and latency. However, the central neural mechanisms governing sympathetic postganglionic discharge remain unclear. This microneurographic study investigated the impact of a dexmedetomidine infusion (α2-adrenergic receptor agonist) on muscle sympathetic postganglionic action potential (AP) discharge, recruitment and latency patterns. Dexmedetomidine infusion inhibited the recruitment of large and fast conducting sympathetic APs and attenuated the discharge of medium sized sympathetic APs that fired during resting conditions and the Valsalva manoeuvre. Dexmedetomidine infusion elicited shorter sympathetic AP latencies during resting conditions but did not affect the reductions in latency that occurred during the Valsalva manoeuvre. These data suggest that α2-adrenergic mechanisms within the central nervous system modulate sympathetic postganglionic neuronal discharge, recruitment and latency strategies in humans.
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Potenciales de Acción , Agonistas de Receptores Adrenérgicos alfa 2 , Dexmedetomidina , Sistema Nervioso Simpático , Humanos , Dexmedetomidina/farmacología , Femenino , Adulto , Masculino , Agonistas de Receptores Adrenérgicos alfa 2/farmacología , Sistema Nervioso Simpático/fisiología , Sistema Nervioso Simpático/efectos de los fármacos , Potenciales de Acción/efectos de los fármacos , Potenciales de Acción/fisiología , Adulto Joven , Frecuencia Cardíaca/efectos de los fármacos , Frecuencia Cardíaca/fisiología , Presión Sanguínea/fisiología , Presión Sanguínea/efectos de los fármacos , Músculo Esquelético/fisiología , Músculo Esquelético/inervación , Músculo Esquelético/efectos de los fármacos , Receptores Adrenérgicos alfa 2/fisiología , Receptores Adrenérgicos alfa 2/metabolismoRESUMEN
BACKGROUND: The circuit boundaries for reentrant ventricular tachycardia (VT) have been historically conceptualized within a 2-dimensional (2D) construct, with their fixed or functional nature unresolved. This study aimed to examine the correlation between localized lines of conduction block (LOB) evident during baseline rhythm with lateral isthmus boundaries that 3-dimensionally constrain the VT isthmus as a hyperboloid structure. METHODS: A total of 175 VT activation maps were correlated with isochronal late activation maps during baseline rhythm in 106 patients who underwent catheter ablation for scar-related VT from 3 centers (42% nonischemic cardiomyopathy). An overt LOB was defined by a deceleration zone with split potentials (≥20 ms isoelectric segment) during baseline rhythm. A novel application of pacing within deceleration zone (≥600 ms) was implemented to unmask a concealed LOB not evident during baseline rhythm. LOB identified during baseline rhythm or pacing were correlated with isthmus boundaries during VT. RESULTS: Among 202 deceleration zones analyzed during baseline rhythm, an overt LOB was evident in 47%. When differential pacing was performed in 38 deceleration zones without overt LOB, an underlying concealed LOB was exposed in 84%. In 152 VT activation maps (2D=53, 3-dimensional [3D]=99), 69% of lateral boundaries colocalized with an LOB in 2D activation patterns, and the depth boundary during 3D VT colocalized with an LOB in 79%. In VT circuits with isthmus regions that colocalized with a U-shaped LOB (n=28), the boundary invariably served as both lateral boundaries in 2D and 3D. Overall, 74% of isthmus boundaries were identifiable as fixed LOB during baseline rhythm or differential pacing. CONCLUSIONS: The majority of VT circuit boundaries can be identified as fixed LOB from intrinsic or paced activation during sinus rhythm. Analysis of activation while pacing within the scar substrate is a novel technique that may unmask concealed LOB, previously interpreted to be functional in nature. An LOB from the perspective of a myocardial surface is frequently associated with intramural conduction, supporting the existence of a 3D hyperboloid VT circuit structure. Catheter ablation may be simplified to targeting both sides around an identified LOB during sinus rhythm.
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Ablación por Catéter , Taquicardia Ventricular , Humanos , Cicatriz , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/cirugía , Arritmias Cardíacas , Frecuencia Cardíaca/fisiología , Bloqueo CardíacoRESUMEN
Sudden changes in pacing cycle length are frequently associated with repolarization abnormalities initiating cardiac arrhythmias, and physiologists have long been interested in measuring the likelihood of these events before their manifestation. A marker of repolarization stability has been found in the electrical restitution (ER), the response of the ventricular action potential duration to a pre- or post-mature stimulation, graphically represented by the so-called ER curve. According to the restitution hypothesis (ERH), the slope of this curve provides a quantitative discrimination between stable repolarization and proneness to arrhythmias. ER has been studied at the body surface, whole organ, and tissue level, and ERH has soon become a key reference point in theoretical, clinical, and pharmacological studies concerning arrhythmia development, and, despite criticisms, it is still widely adopted. The ionic mechanism of ER and cellular applications of ERH are covered in the present review. The main criticism on ERH concerns its dependence from the way ER is measured. Over the years, in fact, several different experimental protocols have been established to measure ER, which are also described in this article. In reviewing the state-of-the art on cardiac cellular ER, I have introduced a notation specifying protocols and graphical representations, with the aim of unifying a sometime confusing nomenclature, and providing a physiological tool, better defined in its scope and limitations, to meet the growing expectations of clinical and pharmacological research.
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Ventrículos Cardíacos , Corazón , Humanos , Potenciales de Acción/fisiología , Corazón/fisiología , Arritmias Cardíacas , Frecuencia Cardíaca/fisiologíaRESUMEN
Autonomic control of heart rate is well known in adult subjects, but limited data are available on the development of the heart rate control during childhood and adolescence. Continuous 12-lead electrocardiograms were recorded in 1045 healthy children and adolescents (550 females) aged 4 to 19 years during postural manoeuvres involving repeated 10-min supine, unsupported sitting, and unsupported standing positions. In each position, heart rate was measured, and heart rate variability indices were evaluated (SDNN, RMSSD, and high (HF) and low (LF) frequency components were obtained). Quasi-normalized HF frequency components were defined as qnHF = HF/(HF + LF). These measurements were, among others, related to age using linear regressions. In supine position, heart rate decreases per year of age were significant in both sexes but lower in females than in males. In standing position, these decreases per year of age were substantially lowered. RMSSD and qnHF indices were independent of age in supine position but significantly decreased with age in sitting and standing positions. Correspondingly, LF/HF proportions showed steep increases with age in sitting and standing positions but not in the supine position. The study suggests that baseline supine parasympathetic influence shows little developmental changes during childhood and adolescence but that in young children, sympathetic branch is less responsive to vagal influence. While vagal influences modulate cardiac periods in young and older children equally, they are less able to suppress the sympathetic influence in younger children.
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Sistema Nervioso Autónomo , Frecuencia Cardíaca , Humanos , Frecuencia Cardíaca/fisiología , Adolescente , Femenino , Masculino , Niño , Preescolar , Sistema Nervioso Autónomo/fisiología , Adulto Joven , Posición Supina , Electrocardiografía/métodos , Postura/fisiología , AdultoRESUMEN
Studies have reported enhanced thermoregulatory function as pregnancy progresses; however, it is unclear if differences in thermoregulation are attributed to weight gain or other physiological changes. This study aimed to determine if total body weight will influence thermoregulation (heat production (Hprod)), heart rate, and perceptual measurements in response to weight-bearing exercise during early to late pregnancy. A cross-sectional design of healthy pregnant women at different pregnancy time points (early, T1; middle, T2; late, T3) performed a 7-stage weight-bearing incremental exercise protocol. Measurements of Hprod, HR, and RPE were examined. Two experimental groups were studied: (1) weight matched and (2) non-weight matched, in T1, T2, and T3. During exercise, equivalent Hprod at T1 (326 ± 88 kJ), T2 (330 ± 43 kJ), and T3 (352 ± 52 kJ) (p = 0.504); HR (p = 0.830); and RPE (p = 0.195) were observed in the WM group at each time point. In the NWM group, Hprod (from stages 1-6 of the exercise) increased across pregnancy time points, T1 (291 ± 76 kJ) to T2 (347 ± 41 kJ) and T3 (385 ± 47 kJ) (p < 0.001). HR increased from T1 to T3 in the warm-up to stage 6 (p = 0.009). RPE did not change as pregnancy time point progressed (p = 0.309). Total body weight, irrespective of pregnancy time point, modulates Hprod and HR during exercise. Therefore, accounting for total body weight is crucial when comparing thermoregulatory function during exercise across pregnancy.
Asunto(s)
Peso Corporal , Ejercicio Físico , Femenino , Humanos , Embarazo , Ejercicio Físico/fisiología , Adulto , Peso Corporal/fisiología , Frecuencia Cardíaca/fisiología , Regulación de la Temperatura Corporal/fisiología , Termogénesis/fisiología , Estudios TransversalesRESUMEN
Phasic cardiac vagal activity (CVA), reflecting ongoing, moment-to-moment psychophysiological adaptations to environmental changes, can serve as a predictor of individual difference in executive function, particularly executive performance. However, the relationship between phasic CVA and executive function demands requires further validation because of previous inconsistent findings. Moreover, it remains unclear what types of phasic changes of CVA may be adaptive in response to heightened executive demands. This study used the standard N-back task to induce different levels of working memory (WM) load and combined functional Near-Infrared Spectroscopy (fNIRS) with a multipurpose polygraph to investigate the variations of CVA and its interactions with cognitive and prefrontal responses as executive demands increased in fifty-two healthy young subjects. Our results showed phasic decreases in CVA as WM load increased (t (51) = -3.758, p < 0.001, Cohen's d = 0.526). Furthermore, phasic changes of CVA elicited by increased executive demands moderated the association of cognitive and cerebral hemodynamic variations in the prefrontal cortex (B = 0.038, SE = 0.014, p < 0.05). Specifically, as executive demands increased, individuals with larger phasic CVA withdrawal showed a positive relationship between cognitive and hemodynamic variations in the prefrontal cortex (ß = 0.281, p = 0.031). No such significant relationship was observed in individuals with smaller phasic CVA withdrawal. The current findings demonstrate a decrease in CVA with increasing executive demands and provide empirical support for the notion that a larger phasic CVA withdrawal can be considered adaptive in situations requiring high executive function demands.
Asunto(s)
Función Ejecutiva , Memoria a Corto Plazo , Corteza Prefrontal , Espectroscopía Infrarroja Corta , Nervio Vago , Humanos , Corteza Prefrontal/fisiología , Corteza Prefrontal/diagnóstico por imagen , Masculino , Femenino , Adulto Joven , Nervio Vago/fisiología , Adulto , Función Ejecutiva/fisiología , Memoria a Corto Plazo/fisiología , Cognición/fisiología , Hemodinámica/fisiología , Frecuencia Cardíaca/fisiología , Circulación Cerebrovascular/fisiologíaRESUMEN
Insulin resistance (IR) is a risk factor for the development of several major metabolic diseases. Muscle fiber composition is established early in life and is associated with insulin sensitivity. Hence, muscle fiber composition was used to identify early defects in the development of IR in healthy young individuals in the absence of clinical manifestations. Biopsies were obtained from the thigh muscle, followed by an intravenous glucose tolerance test. Indices of insulin action were calculated and cardiovascular measurements, analyses of blood and muscle were performed. Whole body insulin sensitivity (SIgalvin) was positively related to expression of type I muscle fibers (r = 0.49; P < 0.001) and negatively related to resting heart rate (HR, r = -0.39; P < 0.001), which was also negatively related to expression of type I muscle fibers (r = -0.41; P < 0.001). Muscle protein expression of endothelial nitric oxide synthase (eNOS), whose activation results in vasodilation, was measured in two subsets of subjects expressing a high percentage of type I fibers (59 ± 6%; HR = 57 ± 9 beats/min; SIgalvin = 1.8 ± 0.7 units) or low percentage of type I fibers (30 ± 6%; HR = 71 ± 11; SIgalvin = 0.8 ± 0.3 units; P < 0.001 for all variables vs. first group). eNOS expression was 1) higher in subjects with high type I expression; 2) almost twofold higher in pools of type I versus II fibers; 3) only detected in capillaries surrounding muscle fibers; and 4) linearly associated with SIgalvin. These data demonstrate that an altered function of the autonomic nervous system and a compromised capacity for vasodilation in the microvasculature occur early in the development of IR.NEW & NOTEWORTHY Insulin resistance (IR) is a risk factor for the development of several metabolic diseases. In healthy young individuals, an elevated heart rate (HR) correlates with low insulin sensitivity and high expression of type II skeletal muscle fibers, which express low levels of endothelial nitric oxide synthase (eNOS) and, hence, a limited capacity to induce vasodilation in response to insulin. Early targeting of the autonomic nervous system and microvasculature may attenuate development of diseases stemming from insulin resistance.
Asunto(s)
Frecuencia Cardíaca , Resistencia a la Insulina , Músculo Esquelético , Óxido Nítrico Sintasa de Tipo III , Humanos , Resistencia a la Insulina/fisiología , Óxido Nítrico Sintasa de Tipo III/metabolismo , Masculino , Frecuencia Cardíaca/fisiología , Adulto Joven , Músculo Esquelético/metabolismo , Femenino , Adulto , Prueba de Tolerancia a la Glucosa , Fibras Musculares de Contracción Lenta/metabolismo , Insulina/metabolismo , Insulina/sangreRESUMEN
Electroacupuncture at Neiguan point (PC6) effectively ameliorates tachycardia. However, very little is known about the neural pathway mechanism underlying the effect of electroacupuncture at PC6 in stress-induced tachycardia. Here, we investigate whether there exists a dorsomedial hypothalamus (DMH)-raphe pallidus (RP)-heart pathway to mediate the effect of electroacupuncture at PC6. The virus tracing results show that the heart is innervated by the neurons in DMH and RP, and the neurons of DMH project to RP. Chemogenetic inhibition of RP projecting DMH neurons reverses the cardiac autonomic imbalance and tachycardia induced by stress. Of note, immunofluorescence results show that the neural activity of DMH and RP is inhibited by electroacupuncture at PC6 accompanied with improved cardiac autonomic imbalance and tachycardia under stress. Moreover, chemogenetic inhibition of RP projecting DMH neurons cannot affect autonomic nervous activity and heart rate of stress rats after administrating electroacupuncture at PC6.NEW & NOTEWORTHY Our study suggests that this dorsomedial hypothalamus (DMH)-raphe pallidus (RP)-cardiac sympathetic pathway involves in the improvement of cardiac dysfunction associated with stress by administrating electroacupuncture at PC6, thus providing beneficial information for the development of therapeutic strategies to prevent stress-induced cardiovascular diseases, and insight into neural pathway basis for electroacupuncture at PC6 intervention of cardiac dysfunction.