Various types of mechanosensitive ion channels, including cationic stretch-activated channels (SAC NS ) and stretch-activated BKca (SAKca) channels, modulate heart rhythm. Bepridil has been used as an antiarrhythmic drug with multiple pharmacological effects; however, whether it is effective for mechanically induced arrhythmia has not been well investigated. To test the effects of Bepridil on SAKca channels activity, cultured chick embryo nic ventricular myocytes were used for single - channel recordings. Bepridil significantly reduced the open probability of the SAKca channel (PO). Next, to test the effects of bepridil on stretch-induced extrasystoles (SIE), we used an isolated 2-week-old Langendorff-perfused chick heart. The left ventricle (LV) volume was rapidly changed, and the probability of SIE was calculated in the presence and absence of bepridil, and the effect of the drug was compared with that of Gadolinium (Gd3+). Bepridil decreased the probability of SIE despite its suppressive effects on SAKca channel activity. The effects of Gd3+, which blocks both SAKca and SACNS , on the probability of SIE were the same as those of bepridil. Our results suggest that bepridil blocks not only SAKc a channels but possibly also blocks SACNS , and thus decreases the stretch -induced cation influx (stabilizing membrane potential) to compensate and override the effects of the decrease in outward SAKca current (destabilizing membrane potential)., H. Jin, G. Iribe, K. Naruse., and Obsahuje bibliografii
Beta-hydroxy-beta-methylbutyrate (HMB) is a leucine metabolite with protein anabolic effects. Since HMB is synthesized in the liver, unique effects of exogenous HMB intake may be hypothesized in subjects with liver disease, in which muscle wasting is frequently found. We studied effects of HMB on the liver and soleus (SOL) and extensor digitorum longus (EDL) muscles in partially-hepatectomized (PH) rats. HMB or saline was infused using osmotic pumps to PH or sham-operated rats for 7 days. We found lower body weight and protein content in EDL of PH rats treated with saline than in sham-operated animals. These effects were insignificant in HMB treated animals. In blood plasma of PH rats treated with HMB we found lower concentrations of creatinine and higher concentrations of urea and branched-chain amino acids (BCAA; valine, leucine, and isoleucine) than in PH animals treated with saline. HMB increased BCAA concentrations in SOL and EDL of PH animals and decreased proteolysis in EDL of both sham-operated and PH animals. In the livers of PH rats treated with HMB we found higher DNA content, DNA fragmentation, and BCAA concentrations than in saline-treated animals. The results indicate that HMB affects metabolism of BCAA and has positive influence on protein balance in muscles. Further studies are needed to clarify the effect of HMB on liver regeneration., M. Holeček, M. Vodeničarovová., and Obsahuje bibliografii
The effects of exercise on mechanical hyperalgesia, joint contracture, and muscle injury resulting from immobilization are not completely understood. This study aimed to investigate the effects of cyclic stretching on these parameters in a rat model of chronic post-cast pain (CPCP). Seventeen 8-week-old Wistar rats were randomly assigned to (1) control group, (2) immobilization (CPCP) group, or (3) immobilization and stretching exercise (CPCP+STR) group. In the CPCP and CPCP+STR groups, both hindlimbs of each rat were immobilized in full plantar flexion with a plaster cast for a 4-week period. In the CPCP+STR group, cyclic stretching exercise was performed 6 days/week for 2 weeks, beginning immediately after cast removal prior to reloading. Although mechanical hyperalgesia in the plantar skin and calf muscle, ankle joint contracture, and gastrocnemius muscle injury were observed in both immobilized groups, these changes were significantly less severe in the CPCP+STR group than in the CPCP group. These results clearly demonstrate the beneficial effect of cyclic stretching exercises on widespread mechanical hyperalgesia, joint contracture, and muscle injury in a rat model of CPCP., Kazuhiro Hayashi, Saori Fukuyasu-Matsuo, Takayuki Inoue, Mitsuhiro Fujiwara, Yuji Asai, Masahiro Iwata, Shigeyuki Suzuki., and Obsahuje bibliografii
Effects of ectopic pacing on left ventricular repolarization were studied in six anesthetized open-c hest chickens. In each animal, unipolar electrograms were acquired from as many as 98 sites with 14 plunge needles (seven transmural locations between epicardium and endocardium in each needle). Activation-recovery intervals (ARIs), corrected to the cycle length, were used for estimating repolarization. At baseline, the nonuniform ARI distribution in the left ventricle resulted in the apicobasal differences being greater than the transmural gradient. Nonuniform ARI prolongation caused by ectopic pacing resulted in decreasing the transmural repolarization gradient and increasing the differences in th e apex-to-base direction. The basal, but not apical transmural differences contributed to the total left ventricular transmural gradient. The total left ventricular apicobasal gradient was contribute d by the apicobasal differences in mid-myocardial and subendoc ardial layers more than in subepicardial ones. Thus, in in situ chicken hearts, the transmural and apicobasal ARI gradients exist within the left ventricle with the shortest ARIs in the basal subepicardium and the longest ARIs in the subendocardium of th e apical and middle parts of the left ventricle. Apicobasal compar ed to transmural heterogeneity of local repolarization properties contributes more to the total left ventricular repolarization gradient., S. N. Kharin, D. N. Shmakov, N. A. Antonova., and Obsahuje bibliografii
We previously found that Endothelin-11-31 (ET-11-31) exhibited a pro-arrhythmogenic effect in isolated rat hearts. In this study, we further investigated the effects of ET-11-31 on a cell viability and observed [Ca2+]i in cultured cardiomyocytes. Cultured neonatal rat cardiomyocytes were treated with 0.1, 1, and 10 nM ET-11-31 for 24h in the presence or absence of ETA receptor antagonist (BQ123) or phosphoramidon, a NEP/ECE inhibitor. Cell injury was evaluated by supernatant lactate dehydrogenase (LDH) assay, superoxide dismutase (SOD activity, and malondialdehyde (MDA) content. Cell viability was assessed by MTT assay. [Ca2+]i was measured with Fluo-3/AM under a laser confocal microscope. 1) ET-11-31 dose-dependently increased LDH release and decreased cell viability. 2) LDH and MDA levels were significantly elevated and SOD activity decreased after administration of 1 nM ET-11-31 for 24h, and these changes were markedly attenuated by 1 uM BQ123. 3) Exposure to 10 nM ET-11-31 caused a continuous increase in [Ca2+]i to cultured beating cardiomyocytes and termination of [Ca2+]i transient within 6 min, and this change was reversed by 1 uM BQ123 and attenuated by 0.5 mM phosphoramidon. These results suggest that ET-11-31 could cause cell injury, and that the effect of ET-11-31 on [Ca2+]i transients is mainly mediated by ETA receptor and partially attributed to the conversion of ET-11-31 to ET-11-21., A.-J. Ren, X. Yuan, L. Lin, Y.-X. Pan, Y.-W. Qing, W.-J. Yuan., and Obsahuje bibliografii a bibliografické odkazy
Abnormal cholesterol metabolism, including low intestinal cholesterol absorption and elevated synthesis, is prevalent in diabetes, obesity, hyperlipidemia, and the metabolic syndrome. Diet-induced weight loss improves cholesterol absorption in these populations, but it is not known if endurance exercise training also improves cholesterol homeostasis. To examine this, we measured circulating levels of campesterol, sitosterol, and lathosterol in 65 sedentary subjects (average age 59 years; with at least one metabolic syndrome risk factor) before and after 6 months of endurance exercise training. Campesterol and sitosterol are plant sterols that correlate with intestinal cholesterol absorption, while lathosterol is a marker of whole body cholesterol synthesis. Following the intervention, plant sterol levels were increased by 10 % (p<0.05), but there was no change in plasma lathosterol. In addition, total and LDL-cholesterol were reduced by 0.16 mmol and 0.10 mmol, respectively (p<0.05), while HDL-C levels increased by 0.09 mmol (p<0.05). Furthermore, the change in plant sterols was positively correlated with the change in VO2 max (r = 0.310, p=0.004), independent of other metabolic syndrome risk factors. These data indicate that exercise training reduces plasma cholesterol despite increasing cholesterol absorption in subjects with metabolic syndrome risk factors., K. R. Wilund ... [et al.]., and Obsahuje seznam literatury
The present study was carried out to search whether organophosphate pesticides affect the mechanical properties of the thoracic aorta. Wistar fema le rats (aged 6-8 weeks) were assigned randomly to a control group and groups treated with either dichlorvos or chlorpyriphos for 90 days at a dose of 5 mg/kg/day. After that period, animals were killed and thoracic aorta strips in longitudinal direction were isolated. The stress, strain and elastic modulus were obtained from the strips. Our results showed that chronic administration of chlorpyriphos and dichlorvos caused downward shift of the stress-strain relations compared to the control curve. The elastic modulu s-stress curve revealed distinct characterist ics in the low and high stress regions. A power function was used to simulate the low stress region while a line was fit to the high stress region. Curve fitting procedure illustrated that both pesticides influenced mainly the high stress region, but they had diverse effects at the low stress region. The results also imply that chlorpyriphos and dichlorvos decrease the strength of the aorta and therefore might influence the response of the aorta to mechanical loading induced by blood pressure. and B. Guvenc Tuna ... [et al.].
The cold pressor test (CPT) triggers in healthy subjects a vascular sympathetic activation and an increase in blood pressure. The heart rate (HR) response to this test is less well defined, with a high inter-individual variability. We used traditional spectral analysis together with the non-linear detrended fluctuation analysis to study the autonomic control of HR during a 3-min CPT. 39 healthy young subjects (23.7 ± 3.2 years, height 180.4 ± 4.7 cm and weight 73.3 ± 6.4 kg) were divided into two groups according to their HR responses to CPT. Twenty subjects have a sustained increase in HR throughout the test with reciprocal autonomic interaction, i.e. increase in sympathetic activity and decrease vagal outflow. In the 19 remainders, HR decreased after an initial increase, with indication of involvement of both sympathetic and vagal outflow. Baseline evaluation of the subjects revealed no difference between the two groups. Nevertheless, a higher sympathetic activity at the skin level during CPT was present in the group with decreased HR. Further studies are needed to explain why healthy subjects react differently to the CPT and if this has potential clinical implications., L. Mourot, M. Bouhaddi, J. Regnard., and Obsahuje seznam literatury
The in vivo effects of recombinant human interleukin-1 receptor antagonist (rhIL-1Ra) administration on endogenous IL-1 levels in the circulation and conditioned media (CM) from different immunohematopoietic organ/tissues were studied in CBA mice under steady state and postirradiation conditions. In normal mice, constitutive IL-1 levels were demonstrated in the plasma, CM of peritoneal exudate cells and full-thickness skin explants with low or undetectable levels in CM of splenic and bone marrow cell suspensions. In irradiated mice (2 Gy, X rays) on day 3 post exposure a significant increase of IL-1 levels was seen in the circulation and CM of peritoneal exudate cells, with no significantly different levels in postirradiation bone marrow, spleen and skin. After rhIL-1Ra treatment of the animals (2 x 50 mg/mouse, i.p.), significantly elevated IL-1 levels were observed in the skin and CM of peritoneal exudate cells in normal mice, whereas slightly increased levels were detected in CM of splenic cells. The rhIL-1Ra administration in irradiated mice led to decreased IL-1 concentrations in the circulation, and CM of peritoneal exudate cells and skin. The results pointed out the importance of IL-1 secretion and receptor expression in the maintenance of homeostasis in steady state, as well as during recovery after irradiation. Modulatory effects of IL-1Ra on IL-1 production were dependent on basic endogenous IL-1 concentration., D. Bugarski, G. Jovčić, M. Kataranovski, Z. Ivanović, M. Petakov, N. Stojanović, P. Milenković., and Obsahuje bibliografii
This paper is devoted to yet unpublished electrode-less methods (ELM) of cell layers impedance measurement based on transformer principle. The main advantage of ELM is elimination uncertainties caused by interface between electrodes and measured electrolyte. The method of avoiding distortion caused by non-ideal transformer transfer function (“deconvolution”) and errors caused by residual voltage is described. The modification of original transformer based method allowing to measure an impedance of inserted object is proposed. Results of several calibration measurements confirming the proper function of ELM including example of transepithelial resistance of cells layer are presented. Crucial parts of measuring system and recommendation for their realization are included., J. Krůšek, S. Ďáďo., and Obsahuje bibliografii