Preclinical atherosclerosis may represent a risk factor for venous thromboembolism (VTE). In longitudinal study we followed longitudinally 96 patients (32 men) with thrombophilias with (n=51) and without (n=45) history of VTE. In both groups we studied the changes of preclinical atherosclerosis at peripherally located arteries detected by ultrasound. In addition, we assessed changes in selected risk factors of atherosclerosis. During the mean follow-up of 56.0±7.62 months we did not find significant change in preclinical atherosclerosis defined as Belcaro score in either group (-3 % in the VTE group vs 0 % in non VTE group). Significant increase in body mass index (1.03±1.98 kg*m-2, resp. 1.21±1.67 kg*m-2, p<0.01) and non-significant increase in systolic blood pressure were detected in both groups. Waist circumference increased significantly only in patients without VTE (4.11±7.84 cm, p<0.05). No differences in changes of risk factors under study between both groups were detected. In summary, patients with thrombophilia and history of VTE showed no evidence of greater progression of atherosclerosis or increase in traditional risk factors of atherosclerosis than patients with thrombophilia without history of VTE. Unfavorable changes of body mass index, waist circumference and systolic blood pressure were detected in both groups during study period., O. Auzký, R. Dembovská, J. Mrázková, Š. Nováková, L. Pagáčová, J. Piťha., and Obsahuje bibliografii
Using non-cholesterol sterols investigation several authors postulated a hypothesis that in the metabolic syndrome cholesterol endogenous synthesis is increased and its absorption decreased. Our study is the first attempt to evaluate the direct relation of cholesterol metabolism to the principal pathogenetic phenomenon of the metabolic syndrome – namely to insulin resistance. We have measured insulin sensitivity by two methods – Quicki (Quantitative Sensitivity Check Index) and intravenous insulin tolerance test (Kitt) and 3 indirect markers - fasting insulin level, fasting C-peptide level and SHBG (sex hormone binding globulin). The investigation was performed in three groups of subjects with a different prevalence of insulin resistance: 72 non-diabetics with ischemic heart disease, 117 young blood donors and 63 type 2 diabetics on diet therapy only. Analyzing altogether 60 relationships – between four sterols (lathosterol, squalene, sitosterol and campesterol) and five markers of insulin resistance in three groups of subjects – we have found only six significant relations between cholesterol synthesis and absorption and insulin resistance in all groups of patients. Our results indicate that there exists a significant relationship between insulin sensitivity and indices of either increased cholesterol synthesis or decreased cholesterol absorption. Insulin resistance explains only a part of both abnormalities mentioned above., A. Šmahelová, R. Hypšler, T. Haas., and Obsahuje bibliografii a bibliografické odkazy
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 ex-periments 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 measure-ments were performed during normal ventilation (17 animals) and hypoventilation (10 animals). The HR was re-corded immediately before the rise of ventricular arrhy-thmias. Results are expressed as arithmetic means ± S.D. and differences are considered significant when p<0.05. The basic pe-riodic 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., P. Švorc, I. Bračoková, I. Podlubný., and Obsahuje bibliografii
Arterial wall stiffness is considered an independent cardiovascular risk factor. Aim of this study was to evaluate relationship between clinical, 24-hour, average day-time and night-time blood pressure (BP) and measures of arterial stiffness assessed by pulse wave velocity (PWV) (using SphygmoCor applanation tonometer) in essential hypertension (severe-resistant (RH, n=29) and moderate hypertension (EH, n=35)) and in normotensive control subjects (n-29) (NCS) matched by age. After multiple regression analysis, PWV remains significantly correlated mainly with night-time pulse pressure and to a lesser extent with age. PWV was significantly higher in RH compared to moderate EH and NCS., J. Rosa, B. Štrauch, O. Petrák, T. Pikus, R. Holaj, T. Zelinka, D. Wichterle, J. Widimský Jr., and Obsahuje bibliografii a bibliografické odkazy
Inactive forearm muscle oxygenation has been reported to begin decreasing from the respiratory compensation point (RCP) during ramp leg cycling. From the RCP, hyperventilation occurs with a decrease in arterial CO2 pressure (PaCO2). The aim of this study was to determine which of these two factors, hyperventilation or decrease in PaCO2, is related to a decrease in inactive biceps brachii muscle oxygenation during leg cycling. Each subject (n = 7) performed a 6-min two-step leg cycling. The exercise intensity in the first step (3 min) was halfway between the ventilatory threshold and RCP (170±21 watts), while that in the second step (3 min) was halfway between the RCP and peak oxygen uptake (240±28 watts). The amount of hyperventilation and PaCO2 were calculated from gas parameters. The average cross correlation function in seven subjects between inactive muscle oxygenation and amount of hyperventilation showed a negative peak at the time shift of zero (r = -0.72, p<0.001), while that between inactive muscle oxygenation and calculated PaCO2 showed no peak near the time shift of zero. Thus, we concluded that decrease in oxygenation in inactive arm muscle is closely coupled with increase in the amount of hyperventilation., H. Ogata, T. Arimitsu, R. Matsuura, T. Yunoki, M. Horiuchi, T. Yano., and Obsahuje bibliografii a bibliografické odkazy
Our main objective was to test whether chronic orthostatic body position induces network changes in the saphenous vein superficial tributary system of the rat. Fourteen male Sprague-Dawley rats were kept in tilted tube cages (45º head-up position) for two weeks to induce chronic gravitational load to their leg veins. Ten animals housed in normal cages and four animals kept in horizontally positioned tube cages served as controls. The whole superficial network of the left saphenous vein was microprepared surgically under anesthesia, superfused with saline and observed under a videomicroscope, while normal flow and pressure were maintained in the lumen. Branching angles, lengths of venous segments and their diameters were measured offline from digitized images using special image-analyzing software. Several branching angles at the popliteal confluence were significantly reduced by 12.5-15.8 %. The in vivo diameter of the main branch (936±34 vs. 805±44 µm) and of one of the popliteal tributaries (776±38 vs. 635±36 µm) increased (p<0.05), comparing vessels from tilted animals with those from normal controls. Maintaining the animals in horizontal tube cages did not induce the above alterations. The increased diameters and reduced branching angles of the saphenous vein network observed are adaptive responses of the venous network to a long-term gravitational load., M. Lóránt, G. L. Nádasy, G. Raffai, E. Monos., and Obsahuje bibliografii
Remote ischemic preconditioning (RIP)-induced protection of myocardial energetics was well documented on the level of tissue, but data concerning the involvement of mitochondria were missing. We aimed at the identification of changes in membrane properties and respiratory functions induced in rat heart mitochondria by RIP. Experiments were performed on 46 male Wistar rats divided into control and RIP-treated groups of 21 animals each. Blood flow in the occluded area was recorded by MRI angiography in four animals. RIP protocol comprised of three successive 5-min occlusions each followed by 5-min reperfusions of descending branches of the right hind limb femoral artery. The efficacy of RIP was evaluated as the extent of RIP-induced protection against damage to the functions of mitochondria isolated by differential centrifugation after 30-min global ischemia followed by 40-min reperfusion of the hearts in Langendorff mode. Assessments: mitochondrial membrane fluidity with a fluorescent probe DPH, CoQ9 and CoQ10 with HPLC, mitochondrial respiration with the Oxygraph-2k (Oroboros). Results revealed that RIP was affecting the mitochondria. The immediate protection conferred by RIP involves beneficial and prognostically significant effects: a total elimination of ischemia/reperfusion-induced depression of mitochondrial membrane fluidity and a trend for better preservation of mitochondrial state 3 respiration., M. Ferko, I. Kancirová, M. Jašová, S. Čarnická, M. Muráriková, I. Waczulíková, Z. Sumbalová, J. Kucharská, O. uličná, T. Ravingerová, A. Ziegelhöffer., and Obsahuje bibliografii
Remote ischemic preconditioning (RIPC) is a novel strategy of protection against ischemia-reperfusion (IR) injury in the heart (and/or other organs) by brief episodes of non-lethal IR in a distant organ/tissue. Importantly, RIPC can be induced noninvasively by limitation of blood flow in the extremity implying the applicability of this method in clinical situations. RIPC (and its delayed phase) is a form of relatively short-term adaptation to ischemia, similar to ischemic PC, and likely they both share triggering mechanisms, whereas mediators and end-effectors may differ. It is hypothesized that communication between the signals triggered in the remote organs and protection in the target organ may be mediated through substances released from the preconditioned organ and transported via the circulation (humoral pathways), by neural pathways and/or via systemic anti-inflammatory and antiapoptotic response to short ischemic bouts. Identification of molecules involved in RIPC cascades may have therapeutic and diagnostic implications in the management of myocardial ischemia. Elucidation of the mechanisms of endogenous cardioprotection triggered in the remote organ could lead to the development of diverse pharmacological RIPC mimetics. In the present article, the authors provide a short overview of RIPC-induced protection, proposed underlying mechanisms and factors modulating RIPC as a promising cardioprotective strategy., T. Ravingerova, V. Farkasova, L. Griecsova, S. Carnicka, M. Murarikova, E. Barlaka, F. Kolar, M. Bartekova, L. Lonek, J. Slezak, A. Lazou., and Obsahuje bibliografii
Akt kinase regulates numerous cell functions including glucose metabolism, cell growth, survival, protein synthesis, and control of local hemodynamics. mTOR is one of down-stream effectors of Akt involved in the initiation of protein translation. However, renal Akt signaling in Type 1 diabetes (DM) in vivo, in particular under the conditions reflecting differences in metabolic control, has received less attention. Renal cortical activity and expression of Akt and mTOR (kinase assay, western blotting) were determined in streptozotocin-diabetic rats (D) with different levels of glycemic control (blood glucose 22.0± 1.0, 13.4±1.5, 8.1±0.4 mmol/l, p<0.05 between the groups), achieved by varying insulin treatment (0,4 and 12 IU/day), and in control rats with (C4) or without (C) chronic insulin administration. Renal Akt activity was reduced in D rats without insulin treatment and severe hyperglycemia (D-0, -62 %, p<0.01 vs. C), partially restored in moderately hypergly cemic rats (D-4, -30 %, p<0.05 vs. C), and normalized in D rats with intensive insulin and tight metabolic control (D-12). Expression of active mTOR paralleled Akt activity in D-0 (-51 %, p<0.01 vs. C), but not in D-4 and D- 12 that demonstrated increases in active mTOR (+55 %, +80 % resp., p<0.05) as compared to C. Moreover, insulin activated renal Akt (+82 %, p<0.01), but not mTOR in C4. In conclusion, glycemic control and intensity of insulin treatment are important modulators of renal Akt and mTOR activity in diabetes. While Akt activity is reversible by tight metabolic control, combination of hyperglycemia and insulin treatment resulted in enhancement of mTOR activity. In addition to Akt, other signaling pathways likely contribute to regulation of renal mTOR activity in diabetes., J. Ždychová, J. Veselá, L. Kazdová, R. Komers., and Obsahuje bibliografii a bibliografické odkazy
Previous investigations revealed that most of the fluid regulating hormones showed no consistent relationship to the hypoxic diuretic response (HDR). In this study we examined if adrenomedullin (AM), a hypoxia-mediated diuretic/natriuretic peptide is connected to HDR. Thirty-three persons were examined at low altitude (LA), on the third exposure day at 3440 m (medium altitude, MA) and on the fourteenth day at 5050 m (high altitude, HA). Nocturnal diuresis rose from 460 ml [interquartile range 302 ml] at LA to 560 [660] ml at MA to 1015 [750] ml at HA (p<0.005). Sodium excretion was similar at LA and MA (41.8 [27.0] vs. 41.4 [28.4] mM) and increased to 80.2 [29.1] mM at HA (p<0.005). Urinary AM excretion was 7.9 [3.9] at LA, 7.5 [5.7] pM at MA, and increased to 10.5 [5.1] pM (p<0.05) at HA. Urinary AM excretion was correlated to diuresis (r=0.72, p<0.005) and sodium excretion (r=0.57, p<0.005). Plasma AM concentration rose from 16.4 [3.1] to 18.8 [4.9] pM/l at MA (p<0.005) and to 18.3 [4.3] pM/l at HA (p<0.005). Plasma AM concentration and urinary AM excretion were not correlated, neither were plasma AM concentration and diuresis or natriuresis. Our data suggest the involvement of increased renal AM production in the pathophysiology of high altitude fluid and sodium loss., B. Haditsch, A. Roessler, H. G. Hinghofer-Szalkay., and Obsahuje bibliografii a bibliografické odkazy