Úvod Obštrukčné spánkové apnoe (OSA) predstavuje komplexné ochorenie prepojené s demografickými, antropometrickými a kardiometabolickými faktormi. Elektrická aurikulárna stimulácia (EAS) predstavuje doplnkový neuromodulačný prístup, ktorý môže ovplyvniť autonómnu reguláciu, svalový tonus horných dýchacích ciest a niektoré hemodynamické parametre. Cieľom práce bolo analyzovať zmeny vo vzájomných vzťahoch medzi demografickými a antropometrickými ukazovateľmi u pacientov s OSA pred a po aurikulárnej stimulácii. Materiál a Metodika Celkovo 68 nocí zahŕňalo 27 diagnostických polysomnografických (PSG) vyšetrení (výsledky predstavovali referenčné hodnoty) a 41 stimulačných PSG vyšetrení metódou EAS. Výsledky Bivariantnou Spearmanovou korelačnou analýzou sme zistili signifikantné vzťahy medzi jednotlivými vzájomnými demografickými a antropometrickými parametrami kohorty. Z čoho vyplýva, že EAS liečba pri znížení počtu apnoickohypopnoických epizód ich trvaní, znížení desaturačného indexu a prebúdzacích reakcií by znížila index telesnej hmotnosti a antropometrické parametre (obvod pása a bokov). Záver Výsledky poukazujú na potenciál aurikulárnej stimulácie ako doplnkovej intervencie v manažmente OSA, pričom sú potrebné rozsiahlejšie klinické štúdie.

Úvod Poruchy pľúcnej ventilácie prispievajú k rozvoju kardiovaskulárnych ochorení. Animálne štúdie avšak často opomínajú mnohé faktory ovplyvňujúce validitu získaných výsledkov. Cieľ Cieľom práce bolo preskúmať vplyv pohlavia a cyklu svetlo/tma na srdcovú frekvenciu Wistar potkanov v tiletamínzolazepamovej anestézii počas apnoe a reoxygenácie. Materiál a metodika Wistar potkany boli rozdelené do štyroch skupín (n = 20/skupina) podľa pohlavia a periódy cyklu svetlo/tma. Po podaní Zoletilu 50 (30 mg/kg; i.p.) sa monitorovala srdcová frekvencia: u spontánne dýchajúcich zvierat, po tracheotómii, počas umelej pľúcnej ventilácie, po 120 s apnoe a po 20 min. reoxygenácie. Výsledky Závislosť srdcovej frekvencie na cykle svetlo/tma sa po 60 s apnoe eliminovala a po reoxygenácii čiastočne obnovila (u samcov po 10 min., u samíc po 15 min.). Apnoe vyvolalo pokles srdcovej frekvencie vo všetkých skupinách s výraznou individuálnou variabilitou. Reoxygenácia neviedla vo všetkých skupinách k návratu srdcovej frekvencie na východiskové hodnoty. Záver Pohlavie a cyklus svetlo/tma sú významné faktory, ktoré je potrebné zohľadniť v in vivo štúdiách s potkanmi v tiletamín-zolazepamovej anestézii.

INTRODUCTION:General anaesthesia is essential in surgical interventions because it reduces stress and restricts the animal's movement. However, it can interfere with the circadian clock and, consequently, with several physiological functions, including the cardiovascular system. A combination of tiletamine and zolazepam is rarely used in rat studies; therefore, its effect on cardiovascular function in the context of sex and the light/dark cycle remains unknown. AIM:This study analysed the effect of sex and the light/dark cycle on electrocardiographic parameters in Wistar rats anaesthetised with tiletamine-zolazepam. METHODS:Experiments were performed on spontaneously breathing Wistar rats of both sexes following a 4-week adaptation to a light/dark (12h/12h) cycle. After intraperitoneal administration of Zoletil 50 (30 mg/kg; Virbac; France), electrocardiographic parameters were measured in lead II using LabChart 8 (ID Instruments). RESULTS:Regarding the effect of the light/dark cycle on electrocardiographic parameters, males showed a higher heart rate and a shorter PR interval during the dark period, whereas females exhibited a longer QRS interval and a higher R wave amplitude in the dark period than in the light period. Sexual dimorphism was present during the light period, with males showing a longer QT interval and females displaying a higher T wave amplitude. In the dark period, sex differences were observed only in the PR interval, which was shorter in males. CONCLUSION:The obtained results indicate a significant effect of sex and light/dark cycle on cardiovascular parameters in rats under tiletamine-zolazepam.

Rats are frequently used in laboratory experiments and are suitable animal models for physiology, pharmacology, pathophysiology, or behavioral studies. Since rats are also used in experimental surgery, adequate anesthesia and analgesia must be ensured to comply with the principle of refinement within the "3R" rules. This study evaluated all available numerical blood pressure (BP) values reported in studies identified through a comprehensive search using PubMed, Web of Science, Scopus, ScienceDirect, and Google Scholar between 2021 and 2024 to examine whether control (baseline) BP values differ at the beginning of the experiment between various anesthetics and the site of invasive BP measurement in normotensive and hypertensive rats. Statistical analysis in normotensive male rats focused on conscious animals and those under the most commonly used anesthetics, with individual agents and their combinations categorized into four groups: urethane, ketamine, barbital, and isoflurane. No statistical comparison could be performed in hypertensive rats due to the insufficient number of data extracted. Our results suggest that the choice among these anesthetics is probably not a consistent determinant of control baseline BP values in normotensive rats when considering only the carotid and femoral arteries, which are the two most frequent sites of invasive measurement. These findings should be interpreted with caution because of several limitations, including the small number of extracted data in some groups, their uneven distribution, underpowered data in hypertensive rats, and variability related to experimental conditions, e.g., circadian rhythms, animal handling, omission of females, among others. However, we propose that most anesthetics may cause a slight initial decrease in control baseline BP at the beginning of the experiment compared to conscious rats, which warrants further investigation particularly concerning the invasive measurement site and aforementioned limitations.

AbstractExperiments should always be based on control values. This assumption fully applies to cardiovascular parameters, such as heart rate (HR) and blood pressure (BP), which are highly sensitive to various external and internal stimuli and can already be significantly altered when an experiment begins. Therefore, it is necessary to determine which values are defined as a starting point (i.e., control and baseline) or compare them with valid reference values if the goal is to evaluate the changes after experimental intervention. A generally accepted principle is a reciprocal relationship between BP and HR, in which one parameter affects the other and vice versa. BP can be measured using two methods—noninvasively (tail‐cuff) and invasively (telemetry, direct measurements of BP after introducing the sensor directly into the artery), and HR directly or by extrapolation from BP recordings. This study does not aim to evaluate the results of individual studies, but to review whether there are differences in control (baseline) BP values in normotensive and hypertensive male rats using invasive versus noninvasive methods, and to investigate whether there is a causal relationship between BP and HR in in vivo experiments with male rats.

In patients with obstructive sleep apnea (OSA) during obstructive events, episodes of hypoxia and hypercapnia may modulate the autonomic nervous system (ANS) by increasing sympathetic tone and irritability, which contributes to sympathovagal imbalance and ultimately dysautonomia. Because OSA can alter ANS function through biochemical changes, we can assume that heart rate variability (HRV) will be altered in patients with OSA. Most studies show that in both the time and frequency domains, patients with OSA have higher sympathetic components and lower parasympathetic dominance than healthy controls. These results confirm autonomic dysfunction in these patients, but also provide new therapeutic directions. Respiratory methods that modulate ANS, e.g., cardiorespiratory biofeedback, could be beneficial for these patients. Heart rate variability assessment can be used as a tool to evaluate the effectiveness of OSA treatment due to its association with autonomic impairment.

AbstractHeart rate variability (HRV) is commonly used in experimental studies to assess sympathetic and parasympathetic activities. The belief that HRV in rodents reflects similar cardiovascular regulations in humans is supported by evidence, and HRV in rats appears to be at least analogous to that in humans, although the degree of influence of the parasympathetic division of the autonomic nervous system (ANS) may be greater in rats than in humans. Experimental studies are based on control or baseline values, on the basis of which the change in ANS activity after a given experimental intervention is assessed, but it is known that the ANS in rats is very sensitive to various stress interventions, such as the manipulation itself, and ANS activity can also differ depending on sex, the time of measurement, and whether the animals are under general anaesthesia. Thus, for correct assessment, changes in ANS activity and their relationship to the observed parameter should be based on whether ANS activity does or does not change but also to what extent the activity is already changed at the start of the experiment. Since rats are considered to be the most suitable model animal for basic cardiovascular research, in this review we point out existing differences in individual HRV frequency parameters at the start of experiments (control, baseline values), taking into account sex in relation to time of measurement and anaesthesia.

The cardiovascular system is primarily controlled by the autonomic nervous system, and any changes in sympathetic or parasympathetic activity also have an impact on myocardial activity. Heart rate variability (HRV) is a readily available metric used to assess heart rate control by the autonomic nervous system. HRV can provide information about neural (parasympathetic, sympathetic, reflex) and humoral (hormones, thermoregulation) control of myocardial activity. Because there are no relevant reference values for HRV parameters in rats in the scientific literature, all experimental results are only interpreted on the basis of changes from currently measured control or baseline HRV values, which are, however, significantly different in individual studies. Considering the significant variability of published HRV data, the present study focused primarily on comparing control or baseline HRV values under different conditions in in vivo experiments involving rats. The aim of the study was therefore to assess whether there are differences in the starting values before the experiment itself.

Background: The aim of the study was to compare the continuous glucose monitoring (CGM)-determined glycaemic variability (GV) of pregnant women with gestational diabetes mellitus (GDM) and without GDM (CG; control group). The secondary aim was to evaluate the association between risk factors of diabetes in pregnancy and parameters of glyceamic control. Methods: Demographic, biometric and biochemical parameters were obtained for pregnant women (20–38 years old) who after an oral glucose tolerance test were examined by 7-day continuous glucose monitoring using a iPro®2 Professional CGM. Results: The differences in GV between women with GDM and CG compared by total area under glucose curve (total AUC, (mmol·day/L) was statistically significant (p = 0.006). Other parameters of glycaemic control such as mean glucose, standard deviation, coefficient of variation, J-index, % time-above target range 7.8 mmol/L (%TAR), % time-in range 3.5–7.8 mmol/L (%TIR), time-below target range 3.5 mmol/L (%TBR), glycated haemoglobin were not significantly different in the study groups. Risk factors (a family history of diabetes, pre-pregnancy BMI, higher weight gain and age) correlated with parameters of glycaemic control. Conclusions: We found a significant difference in GV of women with and without GDM by total AUC determined from CGM. TIR metrics were close to significance. Our work points at an increased GV in relation to the risk factors of GDM. Pregnant women with risk factors have higher probability of severe GV with its consequences on maternal and fetal health state.

It is well known that in patients with obstructive sleep apnea syndrome (OSAS) the apnea-hypopnea index (AHI) is significantly decreased during slow wave sleep (SWS). It used to be explained by the ability of SWS to stabilize the upper airways against collapse. Another explanation, which is the focus of the current study, is that it is just a result of high instability of SWS to obstructive apnea exposure, i.e. high susceptibility of SWS to transition into lighter sleep stages during exposure to obstructive apneas. A retrospective chart review was performed on 560 males who underwent an overnight polysomnography. Two hundred and eighty-seven patients were eligible for the study. They were divided into 3 groups according to different AHI level. All three groups had a higher SWS occurrence in the lateral position than in the supine position. A special fourth group of patients was created with severe OSAS in the supine position but with very mild OSAS in the lateral position. This group had, in the lateral position, (A) higher AHI in NREM sleep (4.1+/-3.1/h vs. 0.7+/-1.2/h, p<0.001) as well as (B) higher SWS occurrence (27.7+/-15.0 % vs. 21.4+/-16.2 % of NREM sleep, p<0.05), than the group with the lowest AHI in the study, i.e. AHI<5/h in NREM sleep. These data suggest that strong coincidence between SWS and low AHI is the result of the high instability of SWS to obstructive apnea exposure. The data also support the presence of SWS-rebound in OSAS patients in the lateral body position.

OBJECTIVE:Obstructive sleep apnoea syndrome (OSAS) associated with daytime sleepiness (DS) contributes to a higher incidence of motor vehicle accidents. Validation of fitness to drive in driving license applicants, with special concern regarding OSAS accompanied by excessive DS, became mandatory under new EU legislation in January 2016. The aim of the study was to translate and validate the recommended questionnaire to screen for OSAS (Q-OSAS) in the Slovak population. No data on any Q-OSAS validation has previously been published. METHODS:The translated Q-OSAS was administered to 311 Slovak patients prior to a planned overnight polysomnography. The diagnostic accuracy of the Q-OSAS in OSAS with an apnoea-hypopnoea index of 15 or more/h of sleep was evaluated by calculating the area under the ROC curve. RESULTS:The sensitivity and specificity of the cut-off at 10 points for the Q-OSAS was 57% and 67%, respectively, with an increase of sensitivity and a decrease of specificity with a lowering of the cut-off values. Excluding the Epworth Sleepiness Scale (ESS) score from the final statistics yielded the best sensitivity (77%), specificity (50%), and an area under the ROC curve (0.637) for the cut-off value of 8 points (an equivalent of 10 points with the full version of the Q-OSAS). CONCLUSION:The Q-OSAS is an appropriate screening tool to facilitate the screening of subjects potentially at risk from moderate and severe OSAS. A modified two-step interpretation of the Q-OSAS in Slovakia yielded the best sensitivity, and in the future could promote evaluation of sleepiness in sleep and wake disorders other than OSAS for fitness to drive.

The design and development of experimental, in vivo chronobiological animal models may help reveal some of the relationships between circadian rhythms and biological function, which can be very difficult to study in humans. To perform ethically acceptable cardiovascular research involving animals, the use of general anaesthesia is often necessary. However, the agents used for general anaesthesia exert a variety of effects on the cardiovascular system that may significantly impact haemodynamic data and the incidence of arrhythmias (Grund et al. 2004). All anaesthetic drugs alter normal physiology in some way and may confound the results of physiological studies. There is strong evidence from animal model and epidemiological studies showing that disruption of circadian rhythms is a significant risk factor for many cardiovascular diseases and, furthermore, that the emergence of cardiovascular diseases may be a time-dependent process (Culic 2014, Chen & Yang 2015). Given that heart rhythm disorders are also associated with changes in electrophysiological parameters of the myocardium, knowledge of the initial state of these parameters can significantly affect interpretation of the final results. Because some electrophysiological properties of the heart depend on the time of day experiments are performed, it is critically important to identify the causes of various types of ventricular arrhythmias. Problem remains fact that fluctuations in several endogenous functions, which depend on external environmental periodicities, are not often considered in experimental animal models. Unfortunately, there are no consistent methodological data regarding the daytime dependence on, or the synchronization of animals to, the light-dark cycle (12 h light : 12 h dark), because most in vivo experiments involving rats have typically been performed during the non-active (i.e. light) part of the day. Therefore, in addition to the vital importance of circadian timing, the impact of anaesthesia on this timing should also be a major consideration in experimental design. Numerous studies have referred to the impact of general anaesthesia on measurable parameters of different systems; however, relatively few have addressed the effect of general anaesthesia on the circadian variation of biological functions, particularly cardiovascular functions. Although chronobiological studies investigating interactions between general anaesthesia and circadian rhythms are sparse, all suggest that general anaesthetics have a significant effect on circadian rhythms (Dispersyn et al. 2008). Pentobarbital, ketamine/xylazine and zoletil are the most commonly used agents for general anaesthesia in experimental studies using animal models. Table 1 summarizes the results of our chronobiological studies investigating the impact of anaesthesia on cardiac electrophysiology in rats. The results clearly show differences among three types of anaesthetics and their effects on the circadian rhythmicity of myocardial electrophysiological parameters in an in vivo rat model, presented in our studies as ‘light-dark differences’. Although studies from other groups (Ohno et al. 2009, Mihara et al. 2012) have reported moderate or, alternatively, no effects of pentobarbital on the circadian rhythm of locomotor activity and the secretion of specific hormones in mice and rats, the disruptive effect of pentobarbital on circadian oscillations in electrophysiological parameters of the rat heart was evident in our study. Results regarding the effect of ketamine/xylazine anaesthesia on myocardial electrophysiology in rats are supported by the work of Pelissier et al. (1998), who also described the disruptive effect of ketamine on circadian rhythms of locomotor activity, heart rate and body temperature. The effect of ketamine was associated only with modifications, but no loss of circadian rhythms. However, to date, there is no literature evidence addressing the effect of zoletil anaesthesia on the circadian rhythms of vital functions. To conclude, we emphasize that investigators need to understand how animals are affected by anaesthetic drugs when designing and developing anaesthetic protocols, so as to minimize impact on data acquisition and analysis. Therefore, appropriate anaesthesia should be selected not only according to its particular effect on the organism, but also to factors that may be circadian dependent. The authors declare no conflict of interest.

Zoletil anaesthesia does not affect vital functions; however, there is no literature evidence regarding the effect of zoletil anaesthesia on the circadian rhythm(s) of vital functions. The aims of this study, with respect to dependence on the light-dark (LD) cycle under in vivo conditions in spontaneously breathing zoletil-anaesthetized rats, were to assess ECG parameters that may to predict development of ventricular arrhythmias and to assess arterial acid-base balance, which have the direct impact on the heart electrophysiology. The experiment was performed using zoletil-anaesthetized (30mg/kg, i.p) female Wistar rats after adaptation to LD cycle (12h:12h). LD differences were found in heart rate, rectal temperature, electrophysiological myocardial parameters and acid-base balance. Animals were in systemic acidosis, hypoxia and hypercapnia in the both lighted periods of the regimen day. These results suggest that zoletil can be used in chronobiological studies investigating in vivo electrophysiological myocardial properties in rat models.

General anaesthesia appears to disrupt cardiovascular stability by causing changes in cardiac function.The assessement of the chronobiological aspects of the pentobarbital anaesthesia impact on myocardial electrophysiology, acid-base balance and ion concentrations in a rat model was the aim of present study.The study was performed using pentobarbital-anaesthetized (40 mg/kg, intraperitoneal) female Wistar rats after adaptation to a 12h light : 12h dark (LD) cycle.Heart rate, rectal temperature, PQ interval, QT interval, QRS complex, QTc interval, and P, R and T wave amplitudes, acid-base balance and arterial concentrations of Na + , K + , Ca 2+ and Cl -were evaluated for their dependence on the LD cycle.LD differences were found in heart rate and rectal temperature measured before administration of the anaesthetic agent.Pentobarbital anaesthesia, however, eliminated LD differences in all electrophysiological parameters, parameters of acid-base balance and ion concentrations.LD differences with borderline statistical significance were found only for Na + levels, with a higher level in the light (ie, nonactive) period.Results of the present study suggest that pentobarbital is probably not the most suitable anaesthetic agent for chronobiological myocardial electrophysiological studies in rat models.

The specific aim of the present study, with respect to dependence on the light-dark (LD) cycle under in vivo conditions in spontaneously breathing rats was to review initial state in electrophysiological parameters that may predict the development of heart rhythm disorders in pentobarbital (40mg/kg), ketamine-xylazine (100+15mg/kg) and zoletil (30mg/kg) anaesthetized animals. The study was performed using female Wistar rats that were adaptated to anLD cycle (12h:12h). Heart rate, PQ and QT intervals were evaluated for their dependence on the LD cycle. The longest PQ interval duration is under zoletil anaesthesia in the light period and the longest QT interval duration is under ketamine-xylazine anaesthesia in both light periods. We concluded that the most significant predisposition toward the development of ventricular arrhythmias originating from disorders of impulse production and conduction occurred under zoletil anaesthesia in the light period; those resulting from disorders in the dispersion of refractory periods occurred under ketamine-xylazine anaesthesia in both the light periods.

Administration of anaesthesia may influence specific aspects of in vivo animal experiments and is an especially important consideration for experiments conducted during the daytime. Although chronobiological studies investigating interactions between general anaesthesia and circadian rhythms are sparse, all suggest that general anaesthetic agents have a significant effect on circadian rhythms. To assess the suitability of pentobarbital anaesthesia in chronobiological studies, this study was performed using pentobarbital-anaesthetized (40 mg/kg, intraperitoneal) female Wistar rats after adaptation to a light–dark (LD) cycle (12 h:12 h). Heart rate, rectal temperature (RT), electrocardiographic parameters, autonomic nervous system activity, acid–base balance and plasma concentrations of Na+, K+, Ca2+ and Cl- were evaluated for their dependence on the LD cycle. LD differences were found in heart rate and RT, measured before the administration of the anaesthetic agent. Pentobarbital anaesthesia eliminated LD differences in all electrophysiological parameters, parameters of heart rate variability (except RR intervals) and parameters of acid–base balance and ion concentrations. LD differences with borderline statistical significance were found only for Na+ levels, with a higher level in the light period (i.e. nonactive) of the rat regimen day. During pentobarbital anaesthesia, parasympathetic tone predominates and sympathetic activity is depressed. Spontaneously breathing rats under pentobarbital anaesthesia are in an asphyxic state independent of the LD cycle in in vivo experiments. Results of this study suggest that pentobarbital anaesthesia is not suitable for chronobiological studies. However, it is suitable for cardiovascular research that is done regardless of the circadian rhythmicity, because it does not cause significant changes in heart activity.