Nocturnal Heart Rate Variability Might Help in Predicting Severe Obstructive Sleep-Disordered Breathing

Obstructive sleep apnea (OSA) can have long-term cardiovascular and metabolic effects. The identification of OSA-related impairments would provide diagnostic and prognostic value. Heart rate variability (HRV) as a measure of cardiac autonomic regulation is a promising candidate marker of OSA and OSA-related conditions. We took advantage of the Physionet Apnea-ECG database for two purposes. First, we performed time- and frequency-domain analysis of nocturnal HRV on each recording of this database to evaluate the cardiac autonomic regulation in patients with nighttime sleep breathing disorders. Second, we conducted a logistic regression analysis (backward stepwise) to identify the HRV indices able to predict the apnea-hypopnea index (AHI) categories (i.e., "Severe OSA", AHI ≥ 30; "Moderate-Mild OSA", 5 ≥ AHI < 30; and "Normal", AHI < 5). Compared to the "Normal", the "Severe OSA" group showed lower high-frequency power in normalized units (HFnu) and higher low-frequency power in normalized units (LFnu). The standard deviation of normal R-R intervals (SDNN) and the root mean square of successive R-R interval differences (RMSSD) were independently associated with sleep-disordered breathing. Our findings suggest altered cardiac autonomic regulation with a reduced parasympathetic component in OSA patients and suggest a role of nighttime HRV in the characterization and identification of sleep breathing disorders

Bionic for Training: Smart Framework Design for Multisensor Mechatronic Platform Validation

: Home monitoring supports the continuous improvement of the therapy by sharing data with healthcare professionals. It is required when life-threatening events can still occur after hospital discharge such as neonatal apnea. However, multiple sources of external noise could affect data quality and/or increase the misdetection rate. In this study, we developed a mechatronic platform for sensor characterizations and a framework to manage data in the context of neonatal apnea. The platform can simulate the movement of the abdomen in different plausible newborn positions by merging data acquired simultaneously from three-axis accelerometers and infrared sensors. We simulated nine apnea conditions combining three different linear displacements and body postures in the presence of self-generated external noise, showing how it is possible to reduce errors near to zero in phenomena detection. Finally, the development of a smart 8Ws-based software and a customizable mobile application were proposed to facilitate data management and interpretation, classifying the alerts to guarantee the correct information sharing without specialized skills

Bifidobacterial transfer from mother to child as examined by an animal model

Bifidobacteria commonly constitute the most abundant group of microorganisms in the healthy infant gut. Their intestinal establishment is believed to be maternally driven, and their acquisition has even been postulated to occur during pregnancy. In the current study, we evaluated bifidobacterial mother-to infant transmission events in a rat model by means of quantitative PCR (qPCR), as well as by Internally Transcribed Spacer (ITS) bifidobacterial profiling. The occurrence of strains supplied by mothers during pregnancy to their corresponding newborns was observed and identified by analysis immediately following C-section delivery. These findings provide intriguing support for the existence of an unknown route to facilitate bifidobacterial transfer during the very early stages of life

Valutazione della regolazione neurovegetativa cardiaca mediante analisi della variabilità della frequenza cardiaca: studi preclinici e clinici

Cervello e cuore sono intimamente interconnessi, tuttavia, solo nelle ultime decadi crescente attenzione è stata dedicata alla regolazione nervosa dell’attività cardiaca e a come essa si modifica ed adatta alle diverse esigenze ambientali e in risposta a stimoli di varia natura. L’analisi della variabilità della frequenza cardiaca (HRV) come strumento di indagine dell’input neurovegetativo al cuore ed espressione della funzione e dello stato del cosiddetto “Brain-Heart axis” è al centro della trattazione della presente tesi, nell’ambito della quale sono presentati quattro studi sperimentali. La possibile presenza di disfunzioni autonomiche è stata infatti indagata in modelli animali di stress ed in una condizione clinica neonatale. Il primo studio ha previsto l’uso di un modello di topo Knockout (KO) condizionale per il recettore Y1 del neuropeptide Y, nel quale, grazie alla combinazione del sistema Cre-loxP e di quello tet-off, la delezione post-natale del gene Npy1r risultava ristretta a livello limbico. Tale approccio è stato usato per indagare il ruolo del recettore Y1 a livello ippocampale nella regolazione neurovegetativa dell’attività cardiaca a riposo, durante un challenge farmacologico di manipolazione del sistema nervoso autonomo ed in risposta ad uno stress sociale acuto e cronico. I topi KO mostravano una diminuita modulazione vagale e ridotta HRV in condizioni basali. Inoltre una ridotta espressione del gene Npy1r portava ad una diminuita reattività ad uno stress acuto ma non sembrava modificare la risposta al protocollo di stress psicosociale cronico attuato in questo studio. Nel secondo studio ratti, selezionati sulla base del loro tempo di latenza all’attacco verso un conspecifico estraneo nell’ambito del “resident-intruder” test, sono stati selezionati e classificati per aggressività come “High-aggressive” (HA) e “Non-aggressive” (NA). Tali animali sono successivamente stati sottoposti ad un challenge immunitario (somministrazione intraperitoneale di lipopolisaccaride, LPS). Sonno, temperatura corticale (risposta febbrile) e regolazione autonomica dell’attività cardiaca sono quindi stati valutati in entrambi i gruppi. In risposta all’LPS, solo i ratti HA mostravano un prolungato aumento del tempo speso nella fase di sonno NREM, accompagnato da una prolungata febbre. Mentre entrambi i gruppi mostravano inibizione del sonno REM ed una riduzione della HRV e della modulazione parasimpatica. Il terzo studio è stato disegnato per valutare l’insorgenza di segni fisiologici e comportamentali caratterizzanti uno stato simil-depressivo in seguito ad isolamento sociale cronico in femmine di ratto e determinare se tali sintomi siano associati o meno ad alterazioni cardiovascolari e della regolazione autonomica della frequenza cardiaca. Inoltre, è stato valutato il coinvolgimento della segnalazione endocannabinoide anche in prospettiva della successiva valutazione degli effetti del potenziamento farmacologico della stessa mediante l’inibizione dell’attività dell’enzima FAAH. Femmine di ratto wild type dopo 6 settimane di isolamento sociale sviluppavano vari segni fisiologici e comportamentali riconducibili all’instaurarsi di una condizione simil-depressiva (aumentata immobilità nel test di nuoto forzato; lieve stato anedonico; riduzione dell’attività motoria durante la fase attiva del ciclo luce/buio; iperattività dell’asse ipotalamo-ipofisi-surrene (HPA); ridotta espressione di BDNF ippocampale). Inoltre l’isolamento produceva alterazioni del ritmo circadiano della frequenza cardiaca ed ipertrofia cardiaca. Tuttavia, non sono state ritrovate drammatiche alterazioni nei parametri della HRV. L’osservata riduzione dell’endocannabinoide anandamide (AEA) nello striato e nell’ippocampo suggeriva un possibile ruolo per il sistema di neuromodulazione in questione che incentiva l’esecuzione della fase successiva (valutazione effetti dell’inibitore FAAH, URB694). Nell’ultimo studio è stata valutata la regolazione autonomica cardiaca in neonati (pre-termine e termine) presentanti convulsioni per valutare la possibile utilità dell’analisi della HRV per rilevamento/predizione e gestione delle convulsioni neonatali. I risultati suggerivano alterazioni della regolazione neurovegetativa della funzione cardiaca a riposo nei pazienti presentanti convulsioni. Un aumento della HRV è stato invece osservato durante gli episodi convulsivi soltanto tra i nati a termine, suggerendo un possibile meccanismo protettivo di natura vagale. Tuttavia la validazione dell’uso degli indici della HRV per l’identificazione/predizione delle convulsioni neonatali necessita di ulteriori studi. In conclusione, oltre ai singoli obiettivi perseguiti da ciascuno studio e all’importanza dell’utilizzo di modelli animali nella ricerca preclinica, dalla presente trattazione emergono l’importanza e la necessità di utilizzare un efficace strumento, come l’analisi della HRV, per valutare attività, adattamenti e possibili disfunzioni del sistema nervoso autonomo in diverse condizioni sia fisiologiche che patologiche in ambito preclinico e clinico

The Utility of Rodent Models of Stress for Disentangling Individual Vulnerability to Depression and Cardiovascular Comorbidity

Purpose of Review: This review offers a perspective of the utility of rodent models of stress for identifying sources of individual vulnerability to depression and cardiovascular disease comorbidity. Recent Findings: Differential stress susceptibility is found in rodents exposed to repeated social defeat as a function of their coping style. Specifically, passive coping rodents show an increase in inflammatory processes within the brain that favour the development of depressive-like symptoms and cardiovascular abnormalities. Similarly, only a sub-group of rats develops depressive-like symptoms following chronic mild stress exposure. Cardiovascular changes differ depending on individual stress susceptibility and may be related to an imbalance in the autonomic regulation of cardiac function in stress vulnerable subjects. Summary: Rodent models of stress that take into account individual phenotypic variations are useful for a better understanding of the role of neuroinflammatory and autonomic processes in the development of comorbid depression and cardiovascular disease under stressful conditions

Resting Heart Rate Variability Predicts Vulnerability to Pharmacologically-Induced Ventricular Arrhythmias in Male Rats

The electrical stability of the myocardium is dependent on the dynamic balance between sympathetic and parasympathetic influences on the heart, which is reflected by heart rate variability (HRV). Reduced HRV is a proposed predictor of sudden death caused by ventricular tachyarrhythmias in cardiac patients. However, the link between individual differences in HRV and ventricular tachyarrhythmic risk in populations without known pre-existing cardiac conditions is less well explored. In this study we investigated the extent to which individual differences in resting state HRV predict susceptibility to spontaneous and pharmacologically-induced ventricular arrhythmias in healthy rats. Radiotelemetric transmitters were implanted in 42 adult male Wild-type Groningen rats. ECG signals were recorded during 24-h resting conditions and under β-adrenoceptor pharmacological stimulation with isoproterenol and analyzed by means of time- and frequency-domain indexes of HRV. No significant association was found between individual differences in resting measures of HRV and spontaneous incidence of ventricular arrhythmias. However, lower resting values of HRV predicted a higher number of ventricular ectopic beats following β-adrenergic pharmacological stimulation with isoproterenol (0.02 mg/kg). Moreover, after isoproterenol administration, one rat with low resting HRV developed sustained ventricular tachycardia that led to death. The present results might be indicative of the potential utility of HRV measures of resting cardiac autonomic function for the prediction of ventricular arrhythmias, particularly during conditions of strong sympathetic activation, in populations without known cardiac disease

Heart rate variability in neonatal patients with seizures

Objective: Seizures are frequently observed in neurological conditions affecting newborns. Since autonomic alterations are commonly associated with neonatal seizures (NS), we investigated the utility of heart rate variability (HRV) indexes of cardiac autonomic regulation for NS detection. Methods: HRV analysis was conducted on ECG tracings recorded during video-EEG monitoring in newborns with NS and matched-controls. The effects of gestational age on HRV were also evaluated. Results: Newborns with NS showed lower resting state HRV compared to controls. Moreover, seizure episodes were characterized by a short-lasting increase in vagal indexes of HRV. Pre-term newborns with NS had a lower HRV than full-term at rest. In pre-term newborns, no changes in HRV were observed before and during NS. On the contrary, full-term newborns showed significantly higher HRV before and during NS compared to the respective baseline values. Conclusion: Our data point to resting autonomic impairment in newborns with NS. In addition, an increment in HRV has been observed during NS only in full term newborns. Significance: Although these findings do not allow validation of HRV measures for NS prediction and detection, they suggest that a putative protective vagal mechanism might be adopted when an advanced maturation of autonomic nervous system is achieved

Heart rate variability in neonatal seizures: Investigation and implications for management

: Many factors acting during the neonatal period can affect neurological development of the infant. Neonatal seizures (NS) that frequently occur in the immature brain may influence autonomic maturation and lead to detectable cardiovascular signs. These autonomic manifestations can also have significant diagnostic and prognostic value. The analysis of Heart Rate Variability (HRV) represents the most used and feasible method to evaluate cardiac autonomic regulation. This narrative review summarizes studies investigating HRV dynamics in newborns with seizures, with the aim of highlighting the potential utility of HRV measures for seizure detection and management. While HRV analysis in critically ill newborns is influenced by many potential confounders, we suggest that it can enhance the ability to better diagnose seizures in the clinical setting. We present potential applications of the analysis of HRV, which could have a useful future role, beyond the research setting

Sex differences in heart rate and heart rate variability in rats: Implications for translational research.

The present study aimed to investigate sex differences in measures of cardiac chronotropy and heart rate variability (HRV) in 132 young adult wild-type Groningen rats (n = 45 females). Electrocardiographic signals were recorded for 48 h in freely moving rats to quantify heart rate (HR) and inter-beat interval (IBI) as measures of cardiac chronotropy, and time- and frequency-domain HRV parameters as physiological readouts of cardiac vagal modulation. Females showed greater vagally-mediated HRV despite having higher HR and shorter IBI than males during undisturbed conditions. Such differences were evident i) at any given level of HRV, and ii) both during the 12-h light/inactive and 12-h dark/active phase of the daily cycle. These findings replicate the paradoxical cardiac chronotropic control reported by human meta-analytic findings, since one would expect greater vagally-mediated HRV to be associated with lower HR and longer IBI. Lastly, the association between some HRV measures and HR was stronger in female than male rats. Overall, the current study in young adult rats provides data illustrating a sex-dependent association between vagally-mediated HRV and indexes of cardiac chronotropy. The current results i) are in line with human findings, ii) suggest to always consider biological sex in the analysis and interpretation of HRV data in rats, and iii) warrant the use of rats for investigating the neuro-hormonal basis and temporal evolution of the impact of sex on the association between vagally-mediated HRV and cardiac chronotropy, which could inform the human condition