To test whether macrophages can play any role in hypoxic pulmonary vasoconstriction, we tested the in vitro response of rings from small pulmonary arteries to the activation of macrophages by FMLP, a substance stimulating predominantly membrane-bound NADPH oxidase. A small vessel myograph was used to measure the responses of rings from small pulmonary arteries (300-400 μ m) isolated from rat lungs. Rings from 5 rats were placed into both chambers of the myograph. The vessels were stabilized for 40 min and then normalized by automatic stretching to a wall tension equivalent to the intravascular pressure 30 mm Hg. At the start of each experiment, vessels were exposed to 80 mM K + to obtain maximal contractile response, which was used to normalize subsequent contractile responses. 2x10 6 viable macrophages, obtained by peritoneal lavage, were added into one chamber, then 5 μ M FMLP was administrated to both chambers and the tension measurement was started. The hydrogen peroxide concentration produced by stimulated macrophages was measured luminometrically. The concentrations of H 2 O 2 in specimens from chambers containing activated macrophages rose from 3.5±1.5 nM to 110±28 nM within 25 min of stimulation, while FMLP itself didn’t increase the H 2 O 2 concentration from the baseline value (4.5±3 nM) in samples from control chambers. After FMLP administration, the tension of the vessel rings in the presence of macrophages reached 0.23±0.07 of maximal contractile response, it did not change in controls. The additi on of ROS scavenger 4-hydroxy- TEMPO blocked the contractile response to the activation of macrophages. We conclude that the activation of macrophages stimulates the contraction of small pulmonary arteries and that this contraction is probably mediated by reactive oxygen species., M. Žaloudíková, J. Herget, M. Vízek., and Obsahuje bibliografii a bibliografické odkazy
The aim of the present study was to determine the optimal initial tension, i.e. initial stretch for rat coronary artery when using the multi-wire myograph system. We used the normalization procedure to mimic physiological conditions and to stretch the coronary arterial segments to normalized internal circumference (IC 1 ). It is determined the internal circumference when the vessel relaxed under a transmural pressure of 100 mm Hg (IC 100 ), and the IC 1 is calculated by multiplying the IC 100 by a factor k. The impact of different factor k on the initial stretch and agonist- induced tension of coronary arteries were investigated. The results showed that the maximal agonist-induced tension was achieved at the factor k value of 0.90 and the initial stretch tension was given 1.16±0.04 mN/mm. The most appropriate factor k value was 0.90-0.95 and the most appropriate initial tension was 1.16-1.52 mN/mm. Th e equilibration time of the coronary artery segments should be at least 1.0 h. In the same optimal initial tension, the agonist-induced tension increased as equilibration time lengthened., N.-N. Ping ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
a1_Diabetes mellitus is not just a simple metabolic disorder, however, it is considered to be a cardiovascular disease of a metabolic origin. This is apparent especially when speaking about type 2 diabetes (DM II). The objective of our study was to determine whether a comprehensive spa treatment (procedures and drinking cure) may affect the level of the sympathetic tone of patients suffering from DM II. As an indicator of the sympathetic tone, selected electrocardiographic parameters derived from the heart rate variability and microwave alternans were chosen. There were 96 patients enrolled in our study: 38 patients with poorly controlled DM II and two control groups: 9 patients with compensated DM II and 49 patients, average age without diabetes or other disorders of the glucose metabolism. All received an identical spa treatment and continued their medical therapy. The electrophysiological examination of patients was performed before and after a three-week spa treatment using the KARDiVAR system. Parameters derived from the analysis of heart rate variability (HRV), microvolt T-wave alternans, and microvolt R-wave alternans were analyzed in order to evaluate the tones of the autonomic nervous system (ANS). The control group showed a slight increase of parameter the index of activity of regulatory systems (IRSA) (4.4±1.3 vs. 3.8±1.4; p=0.006) after the spa treatment, while increased heart rate (80.9±11.0 vs. 74.6±9.6; p=0.028), reduced index of centralization (IC) (1.3±0.6 vs. 2.9±1.4; p=0.027) and reduced index of myocardium (IM) (9.9±7.4 vs. 18.0±6.3; p=0.041) were found in patients with a compensated DM II. Patients with a poorly compensated DM II showed a decreased IM (10.9±8.6 vs. 16.9±5.2; p=0.001) and also a reduced IRSA (4.1±3.5 vs. 6.3±1.9; p=0.001)., a2_The results proved favorable changes in ANS cardiovascular control of patients with DM II after a spa treatment, especially in terms of reducing the sympathoadrenal system activity (decreased IRSA), improving electrical stability of the myocardium and increasing centrally controlled heart rate variability without overloading the cardiovascular system (drop of IM)., E. Fialová, O. Kittnar., and Obsahuje bibliografii
The mitochondrial DNA (mtDNA) amount in cells as the basis for mitochondrial energy generating system, which produces ATP, plays an important role in the fetal development and postnatal morbidity. Isolated human cord blood leukocytes (HCBL) contribute very little to the overall metabolic turnover, but they may serve as easily available marker cells for the study of the mtDNA amount changes in cord blood during fetal development. The aim of our study was to analyze the mtDNA amount in HCBL. HCBL were isolated from cord blood samples of 107 neonates born between the 25th and 41st week of gestation. The mtDNA amount was analyzed by the real-time PCR method. The significant negative correlations were found between the relative mtDNA amount in HCBL and gestational age (r = -0.54, p<0.01) and birth weight (r = -0.43, p<0.01), respectively. The results revealed that the mtDNA content per cell decreases in HCBL with progressing fetal development. This may be explained by gradual shift of the hematopoiesis from fetal liver to bone marrow during the second half of pregnancy presumably accompanied by decreasing cell volume of HCBL as it was shown similarly in red blood cells., M. Pejznochová, M. Tesařová, T. Honzík, H. Hansíková, M. Magner, J. Zeman., and Obsahuje bibliografii a bibliografické odkazy
Drugs interfering with the renin-angiotensin-aldosterone system (RAAS) improved the prognosis in patients with hypertension, heart failure, diabetes and chronic kidney disease. However, combining different drugs brought no further benefit while increasing the risk of hyperkalemia, hypotension and acute renal failure. This was so with combining angiotensin converting enzyme inhibitors (ACEi) and angiotensin II receptors type 1 antagonists (ARB). Dissimilarly, in animal disease models this dual therapy proved clearly superior to single drug treatment and became the optimal standard regime for comparison with other treatments. This review analyzes the causes of the discrepancy of effects of the dual therapy between animal experiments versus clinical studies, and is focused on the outcomes in chronic kidney disease. Discussed is the role of species differences in RAAS, of the variability of the disease features in humans versus relative stability in animals, of the genetic uniformity in the animals but not in humans, and of the biased publication habits of experimental versus clinical studies. We attempt to understand the causes and reconcile the discordant findings and suggest to what extent dual RAAS inhibition should be continued in animal experiments and why its application in the clinics should be limited to strictly selected groups of patients., V. Čertíková Chábová, L. Červenka., and Obsahuje bibliografii
Increased colonic Cl - secretion was supposed to be a causative factor of diarrhea in inflammatory bowel diseases. Surprisingly, hyporesponsiveness to Cl - secretagogues was later described in inflamed colon. Our aim was to evaluate changes in secretory responses to cholinergic agonist ca rbachol in distal and proximal colon during colitis development, regarding secretory activity of enteric nervous system (ENS) and prostaglandins. Increased responsiveness to carbachol was observed in both distal and proximal colon after 3 days of 2 % dextran sodium sulfate (DSS) administration. It was measured in the presence of mucosal Ba2+ to emphasize Cl - secretion. The described increase was abolished by combined inhibitory effect of tetrodotoxin (TTX) and indomethacin. Indomethacin al so significantly reduced TTX- sensitive current. On the 7 th day of colitis development responsiveness to carbachol decreased in distal colon (compared to untreated mice), but did not change in proximal colon. TTX- sensitive current did not change during colitis development, but indomethacin-sensitive current was significantly increased the 7 th day. Decreased and deformed current responses to serosal Ba 2+ were observed during colitis induct ion, but only in proximal colon. We conclude that besides inhibitory effect of DSS on distal colon responsiveness, there is an early stimulatory effect that manifests in both distal and proximal colon., M. Hock ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Attention has recently been focused on endothelial function after a single high-fat meal, i.e. on the anticipated direct atherogenic effect of triglyceride-rich lipoproteins. Our study was designed to investigate the effect of a low-fat diet given for four weeks followed by a high-fat diet for another four weeks. At the end of each dietary period, a non-invasive ultrasound investigation of endothelial function of the brachial artery was performed along with laboratory tests. Endothelial function was measured immediately before the dietary load and after three and six hours in 11 healthy volunteers. The results were expressed as percentage of the changes in artery diameter at rest and during hyperemia; the data were processed using computer technology. When compared to the low-fat regimen, the total cholesterol content rose after the high-fat diet from 4.28 mmol/l to 5.15 mmol/l (p<0.05) in the whole group of volunteers. There was no difference between both dietary regimens in baseline triglycerides. The brachial artery dilatation under basal conditions was 5.26±2.88 mm after the high-fat diet compared with the value of 3.13±3.01 mm (p<0.05) after the low-fat diet. When measured individually endothelial function in the whole group of volunteers in the course of the day, the degree of arterial dilatation after one month on low-fat diet was 3.13±3.0 %, 3.88±2.5 % and 5.23±3.3 % at single measurement. When comparing arterial dilatation at two closest measurements, a non-significant trend, p>0.05 was seen in either case. The following values were obtained after one month on the high-fat diet: 5.26±2.9 %, 4.47±1.7 %, and 6.2±3.6 %; again showing a non-significant trend of p>0.05. In this study, a single high-fat meal at the different dietary regimen did not significantly influence the vasoreactivity of the brachial artery in young volunteers., T. Šejda, J. Kovář, J. Piťha, R. Cífková, E. Švandová, R. Poledne., and Obsahuje bibliografii
Sudden death is a possible occurrence for newborns younger than 1 year with severe aortic coarctation (CoA) before surgical correction. In our previous study, we showed a significant increase of QTc-D and JTc-D in newborns with isolated severe aortic coarctation, electrocardiog raphic parameters that clinical and experimental studies have suggested could reflect the physiological variability of regional and ventricular repolarization and could provide a substrate for life-threatening ventricular arrhythmias. The aim of the current study was to evaluate the effect of surgical repair of CoA on QTc-d, JTc-d in severe aortic coarctation newborns with no associated congenital cardiac malformations. The study included 30 newborns (18M; 70±12 h old) affected by severe congenit al aortic coarct ation, without associated cardiac malformation s. All newborns underwent to classic extended end-to-end repair. Echocardiographic and electrocardiographic measurements were performed in each patient 24 h before and 24 h afte r the interventional procedure and at the end of the follow-up period, 1 month after the surgical correction. All patients at baseline, 24 h and one month after CoA surgical repair did not significantly differ in terms of heart rate, weight, height, and echocardiographic parameters. There were no statistically significant differences in QTc-D (111.7±47.4 vs 111.9±63.8 ms vs 108.5±55.4 ms; P =0.4) and JTc-D (98.1±41.3 vs 111.4±47.5 vs 105.1±33.4 ms; P =0.3) before, 24 h and 1 month after CoA surgical correction. In conclusions, our study did not show a statistically signif icant decrease in QTc-D and JTc- D, suggesting the hypothesis that the acute left ventricular afterload reduction, related to successful CoA surgical correction, may not reduce the ventricular electrical instability in the short- term follow-up., G. Nigro ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Two different isolated skeletal muscles of Japanese quail were used. The influence of branched chain amino acids on the fractional rate of protein synthesis (FSR) was evaluated using 14C-tyrosine. The addition of 0.5 mM valine, leucine or isoleucine to the incubation medium significantly decreased (P<0.05) the value of FSR in extensor metacarpalis radialis. In the ambiens muscle only the application of leucine increased the FSR significantly while valine and isoleucine were without any effect., J. Antalíková, J. Jankela, M. Baranovská., and Obsahuje bibliografii
The increase of radical forms of mitochondrial respiratory chain compounds (MRCC) is an indicator of an increased risk of the formation of oxygen radicals. Using electron paramagnetic resonance (EPR), we found an increase of signals corresponding to ubisemichinone radical (·QH) and ironsulfur proteins radical forms (·FeS) of these respiratory chain compounds during ischemia in the isolated perfused rat heart (·QH increased from 1.51 to 3.08, ·FeS1 from 1.14 to 2.65 arbitrary units). During the 5-min reperfusion, the signals returned to normoxic levels. In isolated mitochondria exposed to anoxia and reoxygenation the radical forms of ·QH and ·FeS2 changed in a similar manner as in the intact heart. A combination of in vivo captopril treatment and in vitro L-arginine administration significantly decreased the levels of MRCC radicals in the isolated myocardium (·QH from 2.61 to 1.72 and ·FeS1 from 1.82 to 0.46 under normoxia; ·QH from 4.35 to 2.66 and ·FeS1 from 1.93 to 1.35 during ischemia). This decrease in MRCC radical forms was associated with increased NO levels in the perfusate, determined as NO2-/ NO3-, as well as tissue NO levels determined using EPR as the dinitrosyl iron complex (DNIC). These results provide new information about the cardioprotective effects of ACE inhibitors and L-arginine., H. Vavřínková, M. Tutterová, P. Stopka, J. Divišová, L. Kazdová, Z. Drahota., and Obsahuje bibliografii