An Obstructive Sleep Apnea - A Novel Public Health Threat.

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.

General anesthesia and electrocardiographic parameters in in vivo experiments involving rats.

In in vivo cardiovascular or toxicological studies involving rat models, changes in selected electrocardiographic (ECG) parameters are monitored after various interventions to assess the origin and development of heart rhythm disorders. Each ECG parameter has diagnostic significance; as such, commonly evaluated ECG parameters, including heart rate, PR interval, P wave duration, P wave amplitude, QRS complex, QT and QTc interval duration, R wave and T wave amplitude, of rats under various types of general anesthesia were the focus of this study. Studies that performed in vivo cardiovascular or toxicological experiments in rats were retrieved from a search of the Web of Science database for articles published mainly between 2000 and 2021. In total, the search retrieved 123 articles. ECG parameters that were reported as baseline or control values were summarized and averages with ranges were calculated. It is important to be cautious when interpreting results and, in discussions addressing the mechanisms underlying a given type of arrhythmia, acknowledge that initial ECG parameters may already be affected to some extent by the general anesthesia as well as by sex and the time of day the experiments were performed.

Arterial pH and blood gas values in rats under three types of general anesthesia: a chronobiological study.

The aim of study was to review the status of arterial pH, pO(2) and pCO(2) under general anesthesias in dependence on the light-dark (LD) cycle in spontaneously breathing rats. The experiments were performed using three- to four-month-old pentobarbital(P)-, ketamine/xylazine(K/X)- and zoletil(Z)-anesthetized female Wistar rats after a four-week adaptation to an LD cycle (12 h light:12 h dark). The animals were divided into three experimental groups according to the anesthetic agent used: P (light n=11; dark n=8); K/X (light n=13; dark n=11); and Z (light n=18; dark n=26). pH and blood gases from arterial blood were analyzed. In P anesthesia, LD differences in pH, pO(2), and pCO(2) were eliminated. In K/X anesthesia, parameters showed significant LD differences. In Z anesthesia, LD differences were detected for pH and pO(2) only. Acidosis, hypoxia, and hypercapnia have been reported for all types of anesthesia during the light period. In the dark period, except for P anesthesia, the environment was more stable and values fluctuated within normal ranges. From a chronobiological perspective, P anesthesia was not the most appropriate type of anesthesia in these rat experiments. It eliminated LD differences, and also produced a more acidic environment and more pronounced hypercapnia than K/X and Z anesthesias.

Effect of reoxygenation on the electrical stability of the rat heart in vivo: a chronobiological study.

Reoxygenation following hypoxic episodes can increase the risk for the development of ventricular arrhythmias, which, in addition to circadian aspects of reoxygenation arrhythmias has not been studied extensively. The aim of the present study was to evaluate circadian changes in the electrical stability of the rat heart during reoxygenation following a hypoventilatory episode. The electrical stability of the heart, defined in the present study as the ventricular arrhythmia threshold (VAT), was measured at 3 h intervals at clock times 09:00, 12:00, 15:00, 18:00, 21:00, 24:00, 03:00, 06:00 and 09:00 during 20 min hypoventilation (20 breaths/min, tidal volume = 0.5 ml/100 g body weight [n=17]) and subsequent 20 min reoxygenation (50 breaths/min, tidal volume = 1 ml/100 g body weight [n=4]) intervals. The experiments were performed using pentobarbital-anesthetized (40 mg/kg intraperitoneally) female Wistar rats that first underwent a four-week adaptation to a 12 h light:12 h dark regimen. Detailed analysis showed that circadian VATs changed to biphasic rhythms at 10 min of hypoventilation. The VAT circadian rhythms were observed immediately following the commencement of reoxygenation, with the highest values measured between 12:00 and 15:00, and the lowest values between 24:00 and 03:00. These results suggest that myocardial vulnerability is dependent on the light:dark cycle and characteristics of pulmonary ventilation.

Autonomic nervous system under ketamine/ xylazine and pentobarbital anaesthesia in a Wistar rat model: a chronobiological view.

The aim of the present study was to determine the effect of ketamine/ xylazine and pentobarbital anaesthesia on heart rate variability as a marker of autonomic nervous system activity. The experiments were performed in ketamine/ xylazine (10 mg/kg/15 mg/kg) and pentobarbital (40 mg/kg, i.p.) anaesthetized female Wistar rats, after adaptation to a light-dark cycle of 12 hours light: 12 hours dark. Heart rate variability parameters (RR interval, power VLF (very low frequency), power LF (low frequency), power HF (high frequency) and relative powers) were evaluated during spontaneous breathing as a function of the light-dark cycle (LD cycle). Significant LD differences were found in the duration of RR intervals in ketamine/xylazine compared with pentobarbital-anaesthetized rats. Correlation analysis revealed moderate dependency between the RR interval duration and HF and LF power parameters in ketamine/xylazine anaesthesia in both light and dark parts of the cycle. In pentobarbital-anaesthetized rats, correlation analysis demonstrated a moderate dependence between RR interval duration and HF and VLF power parameters, but only in the dark part of the LD cycle. Ketamine/xylazine anaesthesia increased parasympathetic activity, and suppressed sympathetic and baroreceptor activity independently of the light-dark cycle. LD differences in RR interval duration were not eliminated. Pentobarbital anaesthesia increased parasympathetic activity, decreased sympathetic and baroreceptor activity, and eliminated LD differences in RR interval duration.

Chronophysiologic aspects of ECG changes during a systemic asphyxic episode and subsequent reoxygenation in an experimental rat model.

The aim of the study was to evaluate the effect of ventilatory manoeuvres on some ECG parameters as a function of the light-dark (LD) cycle in in vivo conditions. The PQ and QT intervals were measured in ketamine/xylazine-anaesthetized female Wistar rats (100 mg/15 mg/kg, i.m.) after adaptation to an LD cycle (12:12 h). The animals were exposed to a 2 min apneic episode and subsequent 20 min period of reoxygenation. Significant LD differences were found in the duration of the PQ interval (p < 0.001) after 30 and 60 sec., and in the QT interval after 90 (p < 0.01) and 120 sec. (p < 0.001), apneic episode. Reoxygenation restored the PQ and QT intervals with the preservation of LD differences from the pre-asphyxic period. It is concluded that although long-term asphyxia probably minimized LD differences in the duration of the PQ interval, the dispersion of refractory periods increases by the manner depending on LD cycle. Reoxygenation did not act proarrhythmogenicly and the followed parameters were recovered to the pre-asphyxic level (Fig. 5, Ref. 43).

Hemorheology and circulation.

The main functions of the blood are the transport, and delivery of oxygen and nutrients, removal of carbon dioxide and waste products of metabolism, distribution of heat and signals of immune system. They are provided by circulation due to the driving force of the heart. Circulation of the blood depends on its rheological properties of the blood as well as on characteristics of the vessels through which the blood passes. The blood flow resistance is influenced by the complicated architecture of the vascular network and flow behaviour of blood components - blood cells and plasma. The obtained data based on analysis of influences on blood flow are differentiated in the dependence on place and level of investigation. At a macroscopic level the blood appears to be a liquid material, but at a microscopic level the blood appears to be a material with microscopic solid particles of varying size - various blood cells. From this point of view, we have to consider the blood flow in large vessels, and also on the level of microvessels. This division of facts of hemorheology is somewhat simplistic, but is very useful from the point of view of explanation and comprehension.

[Chronobiology and practical medicine]. / Chronobiológia a praktická medicína.

In present time, to classify the healthy as potencional possibility of the organism to accept variable environment influences without the break of the biological important functions is not satisfactory. Examples from the different field of the clinical medicine refer to importance of the knowledge's of the circadian rhythmicity concerning many diseases, symptoms or significant remissions. Therefore, clinical trials considering the biological variability differ from the convectional studies by assumption that biology of patient is dynamic, that time of the diagnostic test running is significant and that drugs can influence safety and therapeutic effect in the dependence on the day-time. In paper, it is showed on some examples from the clinical practice that respection of the chronobiological principles may play the important role in the medical diagnostics as well as in therapy and may improve accuracy of the whatever functional examination. For terms, which are often used in the chronobiological texts, no suitable terms were available and therefore it was necessary to introduce the descriptive phrases, which would be accepted by specialists in the field. Many of the introduced terms are still unknown to many investigators and physicians who might benefit from the application of chronobiologic principles to their work.

Effect of systemic hypoxia and reoxygenation on electrical stability of the rat myocardium: chronophysiological study.

The aim of the study was to determine the dependence of changes in the electrical stability of the heart on the light-dark cycle (LD cycle) in disorders of pulmonary ventilation. The ventricular arrhythmia threshold (VAT) was measured in female Wistar rats (adaptation to the light regime 12:12 h, ketamine/xylazine anesthesia 100 mg/15 mg/kg, i.m., open chest experiments). The conditions of the normal artificial ventilation and reoxygenation were V(T) = 1 ml/100 g, respiratory rate 40 breaths/min, hypoventilation V(T) = 0.5 ml/100 g, respiratory rate 20 breaths/min. The animals (n=11 light group; n=19 dark group) were subjected to 20 min hypoventilation followed by 20 min reoxygenation. The control prehypoventilatory VAT differences were not found between the light (1.90+/-0.84 mA) and dark (1.88+/-0.87 mA) part of the day. Artificial hypoventilation changed the VAT values in light and dark part of the day differently. While during the light period, the average VAT values in most animals (90.9 %) were significantly decreased (1.29+/-0.59 vs. 1.90+/-0.84 mA control, p<0.05), during the dark part these values showed either significant increase (63.2 %) (2.23+/-0.77 vs. 1.48+/-0.39 mA, p<0.005) or a slight non-significant decrease (36.8 %) (2.18+/-0.89 vs. 2.54+/-0.99 mA). Reoxygenation returned the VAT values to the level before hypoventilation by an increase of the VAT (81.8 %) in the light part of day and by decrease of the VAT (68.4 %) in the dark part of the day. It is concluded that 1) in hypoventilation/reoxygenation model, the significant higher average VAT values are in the dark part of the day vs. the light one, 2) rat hearts are more resistant to systemic hypoxia and reoxygenation in the dark part of day, and 3) proarrhythmogenic effect of the systemic hypoxia is only seen in the light part of the day.

Ionic hemolysis behavior of erythrocytes in rats of both sexes.

Erythrocyte microrheology changes were measured by cation-osmotic haemolysis in Wistar albino rats of both sexes. Erythrocyte membrane biophysical properties were estimated using the method of cation-osmotic haemolysis (COH) described by Nicak and Mojzis [Comp. Haematol. Int. 2 (1992), 84-86]. COH in male rats was higher in low ionic strength medium (spectrin skeleton) but without of statistical significance. The significantly higher COH in male rats in comparison with female rats was observed in higher ionic strength media. COH and erythrocyte deformability is also discussed. We suggest that changes in biophysical state of spectrin skeleton are followed by changes in lipid bilayer properties.

Preconditioning by hypoventilation increases ventricular arrhythmia threshold in Wistar rats.

Hypoventilation, as one of ventilatory disorders, decreases the electrical stability of the heart similarly as ischemia. If preconditioning by short cycles of ischemia has a cardioprotective effect against harmful influences of a prolonged ischemic period, then preconditioning by hypoventilation (HPC) can also have a similar effect. Anesthetized rats (ketamine 100 mg/kg + xylasine 15 mg/kg i.m., open chest experiments) were subjected to 20 min of hypoventilation followed by 20 min of reoxygenation (control group). The preconditioning (PC) was induced by one (1PC), two (2PC) or three (3PC) cycles of 5-min hypoventilation followed by 5-min reoxygenation. The electrical stability of the heart was measured by a ventricular arrhythmia threshold (VAT) tested by electrical stimulation of the right ventricle. Twenty-minute hypoventilation significantly decreased the VAT in the control and 1PC groups (p<0.05) and non-significantly in 2PC vs. the initial values. Reoxygenation reversed the VAT values to the initial level only in the control group. In 3PC, the VAT was increased from 2.32+/-0.69 mA to 4.25+/-1.31 mA. during hypoventilation (p<0.001) and to 4.37+/-1.99 mA during reoxygenation (p<0.001). It is concluded that cardioprotection against the hypoventilation/ reoxygenation-induced decrease of VAT proved to be effective only after three cycles of HPC.

[An overview of the regulation of basic functions of the digestive system]. / Prehlad regulácií základných funkcií tráviaceho systému.

The gastrointestinal system is the gate through which nutritive substances, vitamins, minerals, and fluids enter the body. Proteins, fats and complex carbohydrates are broken down into absorbable units (products of the digestion) in the digestive tract and finally they are absorbed together with vitamins, minerals and water into the blood or the lymph. The digestive and absorptive functions of the gastrointestinal tract depend on the various mechanisms, which adjust the food, put it through the gastrointestinal tract and mix it together with digestive enzymes secreted by the salivary glands, stomach, pancreas, small intestine and with bile. Some of these mechanisms depend on the spontaneous activity of the smooth muscles, others involve the somatic and autonomous reflexes, paracrine effects of the chemical substances, hormones and local gastrointestinal hormones. The aim of this paper is to review the essential factors participating in the regulation of these processes (mainly motility and secretion) from the mouth cavity, stomach, duodenum, gallbladder, pancreas, small intestine and large intestine to the defecation. The basic regulatory factors are summarized in the schemes from the sources of the physiological textbooks, which are accepted in the whole world for the education of physiology in the medical faculties.

[Circadian rhythm of the ventricular fibrillation threshold in a model of hypoventilation-reoxygenation in female Wistar rats]. / Cirkadiánny rytmus prahu komorovej fibrilácie v hypoventilacno-reoxygenacnom modeli u samíc potkana kmena Wistar.

Hypoxia, similarly as myocardial ischemia, decreases the electric stability of the heart and thus produces the conditions for the genesis of ventricular arrhythmias within the 24 h period however a prompt restoration of oxygen supply or blood flow within myocardium causes serious ventricular arrhythmias. Therefore the aim of our study was to evaluate the reoxygenation impact on myocardium after hypoventilation in circadian dependence. The experiments were performed in female Wistar rats (pentobarbital anesthesia 40 mg/1 kg i.p., open chest experiments). The animals were adapted to the light regimen 12:12 hours, with the dark phase from 18.00 h to 06.00 h. Normal ventilation was used in the control group (n = 17) and in the second one (n = 4), 20 min reoxygenation followed 20 min of hypoventilation. The heart rate (HR) had been recorded just before the ventricular arrhythmias rose. Hypoventilation decreased significantly (p < 0.001) the VFT and HR when compared with the control group and changed the 24-hour rhythm of VFT to moderate bi-phase one. Reoxygenation counter changed this rhythm to inverse in the comparison with the control group. The lowest VFT values occurred when the top of VFT circadian rhythm was detected during normal ventilation. No dependence was detected between VFT and HR in both ventilation types. It is concluded that reoxygenation alternates the myocardial vulnerability to ventricular arrhythmias in dependence on alternation of light and dark and without the evident dependence on HR in the course of the whole 24-hour period. (Tab. 2, Fig. 2, Ref. 43.)

Relation of ventricular fibrillation threshold to heart rate during normal ventilation and hypoventilation in female Wistar rats: a chronophysiological study.

The aim of our study was to verify the relationship between heart rate (HR) and ventricular fibrillation threshold (VFT) during different types of ventilation in female Wistar rats from the circadian point of view. The experiments were performed under pentobarbital anesthesia (40 mg/kg i.p., adaptation to a light-dark cycle 12:12 h, open chest experiments) and the obtained results were averaged independently of the seasons. The VFT measurements were performed during normal ventilation (17 animals) and hypoventilation (10 animals). The HR was recorded immediately before the rise of ventricular arrhythmias. Results are expressed as arithmetic means -/+ S.D. and differences are considered significant when p<0.05. The basic periodic characteristics were calculated using single and population mean cosinor tests. The results from our experiments have demonstrate that 1) the VFT and HR respond identically to hypoventilation by a decrease in the light and also in the dark phases, and 2) hypoventilation changes the 24-h course of the VFT without a change in the 24-h rhythm of the HR. It is concluded that the HR and VFT behave as two independent functional systems without apparent significant circadian dependence during both types of ventilation.

24 h rhythm of the ventricular fibrillation threshold during normal and hypoventilation in female Wistar rats.

A 24 h rhythm of the ventricular fibrillation threshold (VFT) was investigated in female Wistar rats under conditions of normal ventilation (NV) (17 animals) and hypoventilation (HV) (10 animals). The animals were adapted to a daily 12:12 h light-dark cycle with the dark period from 18:00 to 06:00 under constant temperature conditions. The experiments were performed in pentobarbital anesthesia (40 mg/kg ip, open chest experiments) during the whole year, and the obtained results were averaged independently of the seasons. During NV, the VFT in female rats showed a significant 24 h rhythm (p < 0.01) with the mesor 2.59 +/- 0.53 mA, amplitude 0.33 +/- 0.11 mA, and acrophase -338 degrees (at 22:53 h) and the confidence intervals from -288 degrees to -7 degrees (from 19:12 to 00:28 h) using the population mean cosinor test. The maximal values of the VFT were measured in the active phase between 24:00 and 03:00 h. During HV, the rhythmicity of the VFT showed a more pronounced biphasic character with a smaller peak between 15:00 h and 18:00 h hours and a higher peak between 24:00 h and 03:00 h of the daily regime. Hypoventilation significantly decreased the VFT (p < 0.001) at each interval of the measurement. It is concluded that the electrical stability of the heart measured by the VFT shows a significant 24 h rhythm in female Wistar rats and that HV decreased the VFT during the whole 24 h period.

Circadian rhythm of the ventricular fibrillation threshold in female Wistar rats.

The circadian rhythm of ventricular fibrillation threshold (VFT) and its relation to the heart rate (HR) and the rectal temperature (RT) was studied in female Wistar rats. The animals were exposed to daily light-dark cycles of 12 h of light alternating with 12 h of darkness and were under pentobarbital anaesthesia (40 mg/kg i.p.). The experiments were performed on open chest animals and VFT was measured by direct stimulation of the myocardium. VFT in female rats showed a circadian rhythm with the acrophase -338 degrees (at 22.53 h), with the mesor 2.58 mA and the amplitude 0.33 mA. HR was not significantly changed during the experiments and no dependence was found between VFT and HR during the whole 24-hour period (r = 0.08). The acrophase of the circadian rhythm of HR (on -47 degrees, i.e. at 03.08 h) was shifted to the acrophase of VFT. The circadian rhythms of RT before the application of the anaesthetic agent and under general anaesthesia before the operative interventions had a very similar course with the nearly corresponding acrophases as the circadian rhythm of VFT. It is concluded that the electrical stability of the rat heart measured by VFT shows the significant circadian rhythm in a parallel with the circadian rhythm of RT and probably without dependence on the changes of HR.