High frequency oscillatory ventilation (HFOV), contrary to conventional ventilation, enables a safe increase in tidal volume (VT) without endangering alveoli by volutrauma or barotrauma. The aim of the study is to introduce the concept of normocapnic high frequency oscillatory hyperventilation and to assess its effect upon oxygen gain under experiment al conditions. Laboratory pigs (n=9) were investigated under total intravenous anesthesia in three phases. Phase 1: Initial volume controlled HFOV period. Phase 2 : Hyperventilation - VT was increased by (46 ± 12) % when compared to normocapnic VT during phase 1. All other ventilatory parameters were unchanged. A significant increase in PaO 2 (by 3.75 ± 0.52 kPa, p<0.001) and decrease in PaCO 2 (by -2.05 ± 0.31 kPa, p<0.001) were obtained. Phase 3: Normocapnia during hyperventilation was achiev ed by an iterative increase in the CO 2 fraction in the inspiratory gas by a CO2 admixture. All ventilatory parameters were unchanged. A significant increase in PaO2 (by 3.79 ± 0.73 kPa, p<0.001), similar to that which was observed in phase 2, was preserved in phase 3 whereas normocapnia was fully re-established. The concept of high frequency normocapnic hyperventilation offers a lung protective strategy that significantly improves oxygenation whilst preserving normocapnia., K. Roubík, J. Pachl, V. Zábrodský., and Obsahuje bibliografii a bibliografické odkazy
Cardiac fibroblast-myofibroblast transformation (CMT) is a critical event in the initiation of myocardial fibrosis. Notch signaling has been shown to regulate myofibroblast transformation from other kinds of cells. However, whether Notch signaling is also involved in CMT remains unclear. In the present study, expressions of Notch receptors in cardiac fibroblasts (CFs) were examined, effects of Notch signaling inhibi tor N-[N-(3,5-difluorophenacetyl)- l-alanyl]-S-phenylglycine t-butyl ester (DAPT) and transforming growth factor-β1 (TGF-β1) on CMT were determined by increasing alpha-smooth muscle actin (α-SMA) expression and collagen synthesis, and Notch signaling was examined by analyzing expressions of Notch receptors. The results showed that: (1) Notch receptor 1, 2, 3 and 4 were all expressed in CFs; (2) DAPT promoted CMT in a time -dependent manner; (3) During the period of CMT induced by TGF-β1, expressions of Notch receptor 1, 3 and 4 in CFs were down-regulated, whereas there was no change for Notch receptor 2. Moreover, the downtrends of Notch 1, 3 and 4 were corresponding to the trend growth of α-SMA expression and collagen synthesis. These results suggested that inhibiting of Notch signaling might promote CMT. The down-regulations of Notch receptor 1, 3 and 4 induced by TGF-β1 may facilitate CMT. In conclusion, inhibition of Notch signaling might be a novel mech anism of CMT in myocardial fibrosis., Y.-H. Fan ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Fyziologický ústav AV ČR (FGÚ), význačná česká výzkumná instituce v oblasti fyziologie a patofyziologie živočichů a člověka, si v roce 2014 připomíná 60. výročí svého založení. Motto oslav „Od mozku přes srdce až po tkáňové náhrady“ vyjadřuje historický vývoj hlavních směrů výzkumu v ústavu. Již po 60 let zdejší vědci svými objevy prohlubují teoretické základy medicíny a objasňují podstatu mnoha závažných onemocnění člověka. Mezi nejvýznamnější akce k jubileu FGÚ patří nový cyklus přednášek pojmenovaný na počest slavného neurofyziologa dr. Jana Bureše. Odborné veřejnosti se tak představují významné osobnosti světové fyziologie, z nichž mnohé v minulosti s ústavem spolupracovaly nebo stále spolupracují. and Petr Zouhar, Olga Zimmermannová.
Olfaction enables most mammalian species to detect and discriminate vast numbers of chemical structures called odorants and pheromones. The perception of such chemical compounds is mediated via two major olfactory systems, the main olfactory system and the vomeronasal system, as well as minor systems, such as the septal organ and the Grueneberg ganglion. Distinct differences exist not only among species but also among individuals in terms of their olfactory sensitivity; however, little is known about the mechanisms that determine these differences. In research on the olfactory sensitivity of mammals, scientists thus depend in most cases on behavioral testing. In this article, we reviewed scientific studies performed on various mammalian species using different methodologies and target chemical substances. Human and non-human primates as well as rodents and dogs are the most frequently studied species. Olfactory threshold studies on other species do not exist with the exception of domestic pigs. Olfactory testing performed on seals, elephants, and bats focused more on discriminative abilities than on sensitivity. An overview of olfactory sensitivity studies as well as olfactory detection ability in most studied mammalian species is presented here, focusing on comparable olfactory detection thresholds. The basics of olfactory perception and olfactory sensitivity factors are also described., M. Wackermannová, L. Pinc, L. Jebavý., and Obsahuje bibliografii
Mitral allografts are still used only exceptionally in the mitral or tricuspid position. The main indication remains infectious endocarditis of atrioventricular valves for its flexibility and low risk of infection. The aim of our study was to evaluate 1-year results of mitral allografts transplantation into the tricuspid position in a sheep model. Mitral allografts were processed, cryopreserved, a nd transplanted into the tricuspid position anatomically (Group I - 11 animals) or antianatomically (Group II - 8 animals). All survivors (4 from Group I, and 3 from Group II) were checked at 3, 6, and 12 months by echocardiography with the exception of one survivor from Group II (which was examinated only visually). Examination throughout follow-up included for mitral allograft regurgitation and annuli dilatation. At postmortem, the papillary muscles were healed and firmly anchored to the right ventricular wall in all subjects. Transventricular fixation of the papillary muscles with buttressed sutures was proven to be a stable, reproducible, and safe method for anchoring mitral allograft leaflets. There were no significant differences between the two implan tation methods. Annulus support of mitral allografts might be very useful in this type of operation and could prevent annular dilatation., A. Mokracek, J. Canadyova, Z. Simunkova, R. Fiala, M. Hmirak, M. Sulda, J. Burkert, J. Tintera, P. Kobylka, J. Spatenka., and Obsahuje bibliografii
This study sought to evaluate whether consumption of polyphenol extract from Cognac (CPC) modulates platelet activation and cardiovascular reactivity in rats. Male Wistar rats were treated daily for 4 weeks by intra-gastric gavage receiving CPC at 80 mg/kg/day or vehicle (5 % glucose). Platelet adhesion and aggregation in response to different activators were assessed. Cardiac and vascular reactivity in response to various agonists as well as NO measurement by electron paramagnetic resonance technique were investigated in isolated heart and thoracic aorta. Oral administration of CPC decreased platelet aggregation induced by ADP but not by collagen. CPC did not affect adhesion to collagen. The chronotropic but not the inotropic response to isoprenaline was reduced without alteration of NO production in hearts from CPC-treated rats. CPC treatment did not affect ex vivo relaxation to acetylcholine nor NO content of rat aorta. CPC did not significantly alter the response to phenylephrine in aorta despite the participation of endothelial vasoconstrictor products. In summary, chronic treatment with CPC has no impact on ex vivo vascular and cardiac reactivity; however, it reduced heart work and platelet aggregation. These data suggest the existence of compounds in Cognac that may decrease the risk of coronary thrombosis and protect against some cardiac diseases., N. Carusio, R. Wangensteen, A. Filippelli, R. Andriantsitohaina., and Obsahuje bibliiografii a bibliografické odkazy
Orexins (orexin A and B) are initially known to be a hypothalamic peptide critical for feeding and normal wakefulness. In addition, emerging evidence from behavioral tests suggests that orexins are also involved in the regulation of nociceptive processing, suggesting a novel potential therapeutic approach for pain treatment. Both spinal and supraspinal mechanisms appear to contribute to the role of orexin in nociception. In the spinal cord, dorsal root ganglion (DRG) neurons are primary afferent neurons that transmit peripheral stimuli to the pain-processing areas. Morphological results show that both orexin A and orexin-1 receptor are distributed in DRG neurons. Moreover, by using whole-cell patch-clamp recordings and calcium imaging measurements we found that orexin A induced excitability and intracellular calcium concentration elevation in the isolated rat DRG neurons, which was mainly dependent on the activation of spinal orexin-1 receptor. Based on these findings, we propose a hypothesis that the direct effect of orexin A on DRG neurons would represent a possible mechanism for the orexinergic modulation of spinal nociceptive transmission., J.-A. Yan, L. Ge, W. Huang, B. Song, X.-W. Chen, Z.-P. Yu., and Obsahuje bibliografii a bibliografické odkazy
The microcirculation plays a crucial role in the interaction between blood and tissues both in physiological and pathophysiological states. Despite its critical role in numer ous diseases including diabetes, hypertension, sepsis or multiple organ failure, methods for direct visualization and quantitative assessm ent of human microcirculation at the bedside are limited. Orthogonal polarization spectral (OPS) imaging is a relatively new noninvasive method for assessment of human microcirculation without using fluorescent dyes. Recent clinical studies using OPS imaging in various pathological states have shown a wide spectrum of different clinical applications with evident impact on the diagnosis, treatment or prognosis assessment. Thus, there is a great effort to validate OPS imaging for various clinical purposes. The principles of OPS imaging, validation studies, its advantages, limitations, methods of quantitative assessment and current experience in clinical practice are discussed., V. Černý, Z. Turek, R. Pařízková., and Obsahuje bibliografii a bibliografické odkazy
Muscarinc receptor-mediated signaling takes part in many physiological functions ranging from complex higher nervous activity to vegetative responses. Specificity of action of the natural muscarinic agon ist acetylcholine is effected by action on five muscarinic receptor subtypes with particular tissue and cellular localization, and coupling preference with different G-proteins and their signalin g pathways. In addition to physiological roles it is also implicated in pathologic events like promotion of carcinoma cells growth, early pathogenesis of neurodegenerative diseases in th e central nervous system like Alzheimer's disease and Parkinson's disease, schizophrenia, intoxications resulting in drug addiction, or overactive bladder in the periphery. All of these disturbances demonstrate involvement of specific muscarinic receptor subtypes and point to the importance to develop selective pharmacotherapeutic interventions. Because of the high homology of the orthosteric binding site of muscarinic receptor subtypes there is virtually no subtype selective agonist that binds to this site. Activation of specific receptor subtypes may be achieved by developing allosteric modulators of acetylcholine binding, since ectopic binding domains on the receptor are less conserved compared to the orthosteric site. Potentiation of the effects of acetylcholine by allosteric modulators would be beneficial in cases where acetylcholine release is reduced due to pathological conditions. When presynaptic function is severly compromised, the utilization of ectopic agonists can be a thinkable solution., J. Jakubík ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy