Cough is a vital airway reflex that keeps the respiratory tract wisely protected. It is also a sign of many diseases of the respiratory system and it may become a disease in its own right. Even though the efficacy of antitussive compounds is extensively studied in animal models with promising results, the treatment of pathological cough in humans is insufficient at the moment. The limited translational potential of animal models used to study cough causes, mechanisms and possible therapeutic targets stems from multiple sources. First of all, cough induced in the laboratory by mechanical or chemical stimuli is far from natural cough present in human disease. The main objective of this review is to provide a comprehensive summary of animal models currently used in cough research and to address their advantages and disadvantages. We also want to encourage cough researchers to call for precision is research by addressing the sex bias which has existed in basic cough research for decades and discuss the role of specific pathogen-free (SPF) animals.
- MeSH
- kašel * MeSH
- modely nemocí na zvířatech * MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
The main aim was to find out whether long-lasting stepwise exposure to extreme hypoxia affects left ventricular (LV) geometry and systolic function. Adult male rats were exposed to intermittent hypobaric hypoxia (8 h/day) with increasing altitude in steps of 1000 m every 3 weeks up to 8000 m. While the LV cavity diastolic diameter did not change over the whole range of hypoxia, the wall thickness increased significantly at the altitude of 8000 m. LV fractional shortening ranged between 48.1 % and 50.1 % and remained unaffected even at the most severe hypoxia. At the end of experiment, haematocrit reached 83 %, mean systemic arterial pressure 120 % and relative LV weight 154 % of normoxic values while RV systolic pressure and relative RV weight doubled. Myocyte hypertrophy and myocardial fibrosis were more pronounced in RV than in LV. In conclusion, LV systolic function was preserved after chronic stepwise exposure of rats to extreme intermittent hypoxia despite moderate concentric hypertrophy and myocardial remodelling.
- MeSH
- funkce levé komory srdeční fyziologie MeSH
- funkce pravé komory srdeční fyziologie MeSH
- hypoxie krev patofyziologie MeSH
- krysa rodu rattus MeSH
- nadmořská výška * MeSH
- potkani Wistar MeSH
- remodelace komor fyziologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Respiratory sinus arrhythmia (RSA) is an index of cardiovagal regulation, emotional and cognitive processing. RSA is quantified using heart rate variability (HRV) spectral analysis at respiratory-linked high-frequency band (HF-HRV) using Fast Fourier transformation (FFT) or autoregressive (AR) method, both requiring resampling of recordings - a potential source of error. We hypothesized that rarely used HRV time-frequency analysis with Lomb-Scargle periodogram (LSP) without resampling could be more sensitive to detect neurocardiac response to posture change than FFT and AR. Orthostasis (posture change from supine to standing) evoked significant decrease of HF-HRV well detectable by FFT, AR, and LSP. In contrast, during posture change from sitting to lying, significant increase of HF-HRV and peak HF was best detected using LSP. In regression analysis, the associations between RR-interval, HF-HRV, and peak HF were best detected when evaluated using LSP. Time-frequency HRV analysis with LSP could represent an important alternative to conventional FFT and AR methods for assessment of cardiovagal regulation indexed by RSA.
- MeSH
- časové faktory MeSH
- dechová frekvence fyziologie MeSH
- elektrokardiografie MeSH
- Fourierova analýza MeSH
- lidé MeSH
- mladiství MeSH
- neparametrická statistika MeSH
- regresní analýza MeSH
- respirační sinusová arytmie fyziologie MeSH
- srdeční frekvence fyziologie MeSH
- Check Tag
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Lifesaving therapy for patients with end-stage lung disease is lung transplantation. However, there are not enough available donors. A relatively new method of transplantation from non-heart-beating donors (NHBDs) allows the treatment of the lung outside the body and could increase the number of suitable lungs. We have focused on hypercapnic ventilation, which has the possibility of reducing reactive oxygen species damage. We used four experimental and two control groups of adult rats. Each experimental group underwent the protocol of NHBD lung harvesting. The lungs were than perfused in an ex vivo model and we measured weight gain, arterial-venous difference in partial pressure of oxygen and perfusion pressure. We observed that hypercapnic ventilation during reperfusion reduces the development of pulmonary oedema and has a protective effect on the oxygen transport ability of the lungs after warm ischemia. The effect of CO2 on pulmonary oedema and on oxygen transport ability after warm ischemia could be of clinical importance for NHBD transplantation.
- MeSH
- hyperkapnie * MeSH
- krysa rodu rattus MeSH
- modely nemocí na zvířatech MeSH
- potkani Wistar MeSH
- reperfuzní poškození patofyziologie prevence a kontrola MeSH
- transplantace plic škodlivé účinky MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Two challenges in the management of Acute Respiratory Distress Syndrome are the difficulty in diagnosing cyclical atelectasis, and in individualising mechanical ventilation therapy in real-time. Commercial optical oxygen sensors can detect [Formula: see text] oscillations associated with cyclical atelectasis, but are not accurate at saturation levels below 90%, and contain a toxic fluorophore. We present a computer-controlled test rig, together with an in-house constructed ultra-rapid sensor to test the limitations of these sensors when exposed to rapidly changing [Formula: see text] in blood in vitro. We tested the sensors' responses to simulated respiratory rates between 10 and 60 breaths per minute. Our sensor was able to detect the whole amplitude of the imposed [Formula: see text] oscillations, even at the highest respiratory rate. We also examined our sensor's resistance to clot formation by continuous in vivo deployment in non-heparinised flowing animal blood for 24h, after which no adsorption of organic material on the sensor's surface was detectable by scanning electron microscopy.
- MeSH
- analýza rozptylu MeSH
- atelektáza krev MeSH
- biologické hodiny MeSH
- hemokoagulace fyziologie MeSH
- krevní tlak fyziologie MeSH
- kyslík krev MeSH
- mikroskopie elektronová rastrovací MeSH
- parciální tlak MeSH
- počítačová simulace * MeSH
- technologie optických vláken * MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- techniky in vitro MeSH
Tetrahydrobiopterin (BH4) is an essential cofactor for nitric oxide synthases (NOS). Oxidative stress oxidises BH4 to dihydrobioptein (BH2), resulting in the uncoupling of the two enzymatic domains of NOS and the production of superoxide rather than NO (NOS uncoupling). Oxidative stress is known to be increased in the early stage of chronic hypoxia. This study investigated the participation of NOS uncoupling in the early phase of hypoxia-induced pulmonary hypertension in rats. Rats were exposed to 10% O(2) for 4 days. We investigated the effect of BH4 in vitro on isolated rat lungs and isolated rat peripheral pulmonary blood vessels and in vivo on exhaled NO concentration in exhaled air. BH4 attenuated hypoxic pulmonary vasoconstriction in isolated lungs and its effect was reversed by l-NAME (NOS inhibitor). The main finding of the study is that the effect of BH4 was smaller in rats exposed to 4 days of hypoxia than in normoxic controls. The finding was similar in isolated pulmonary blood vessels. BH4 increased exhaled NO in both normoxic and hypoxic rats. This increase was blunted by l-NIL (specific iNOS inhibitor) and therefore attributable to iNOS. We conclude that BH4 increased NO production in both normoxic and hypoxic rats. The increase was, however, smaller in hypoxic lungs than in controls. We assume that the smaller increase in NO production in hypoxic lungs is due to the decreased BH4/BH2 ratio in chronic hypoxia and NOS uncoupling resulting from this condition.
- MeSH
- biopteriny analogy a deriváty metabolismus MeSH
- hypoxie metabolismus patofyziologie MeSH
- krysa rodu rattus MeSH
- oxid dusnatý biosyntéza MeSH
- plíce metabolismus patofyziologie MeSH
- plicní hypertenze metabolismus patofyziologie MeSH
- potkani Wistar MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
This review deals with the capability of the heart to adapt to chronic hypoxia in animals exposed to either natural or simulated high altitude. From the broad spectrum of related issues, we focused on the development and reversibility of both beneficial and adverse adaptive myocardial changes. Particular attention was paid to cardioprotective effects of adaptation to chronic high-altitude hypoxia and their molecular mechanisms. Moreover, interspecies and age differences in the cardiac sensitivity to hypoxia-induced effects in various experimental models were emphasized.
- MeSH
- aklimatizace fyziologie MeSH
- atmosférický tlak MeSH
- chronická nemoc MeSH
- financování organizované MeSH
- hypoxie komplikace metabolismus MeSH
- ischemie etiologie metabolismus MeSH
- kyslík krev MeSH
- myokard metabolismus MeSH
- nadmořská výška MeSH
- reperfuzní poškození myokardu etiologie metabolismus MeSH
- věkové faktory MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- přehledy MeSH
We have reviewed the role of afferent inputs and blood chemical changes to the central nervous system, and the way in which they modify the cough and expiration reflexes (CR and ER). Slowly adapting pulmonary stretch receptors (SARs) augment the CR, insofar as when their activity is abolished the CRs from the tracheobronchial (TB) tree and larynx are abolished or weakened. However, stimulation of SARs by lung inflation has an inconsistent effect on the CR. Activation of SARs strongly potentiates the ER from the vocal folds, by a reflex mechanism, and inhibition of SARs weakens the ER. Bronchopulmonary C-fibre receptors inhibit the CR, as do capsaicin-sensitive afferents from the heart and splanchnic bed, cutaneous cold receptors and those that respond to chest wall vibration. Nasal receptors responsive to the irritant agent capsaicin potentiate the reflex. Acute hypoxia also augments the CR, and the reflex is down-regulated by carotid body resection. On the other hand, the CR is inhibited by prolonged hypoxia and hyperoxia, and by hypercapnia. Thus different inputs to the cough-controlling mechanism in the brainstem have very varied effects on the CR. We conclude that the sensitivities of the CR and ER can be modified in a large variety of physiological and clinical conditions, and that there is no clear relationship between the reflexes and changes in breathing caused by the interventions.
