BACKGROUND: Aim of the study was to compare metabolic response of leg skeletal muscle during functional electrical stimulation-driven unloaded cycling (FES) to that seen during volitional supine cycling. METHODS: Fourteen healthy volunteers were exposed in random order to supine cycling, either volitional (10-25-50 W, 10 min) or FES assisted (unloaded, 10 min) in a crossover design. Whole body and leg muscle metabolism were assessed by indirect calorimetry with concomitant repeated measurements of femoral venous-arterial differences of blood gases, glucose, lactate and amino acids. RESULTS: Unloaded FES cycling, but not volitional exercise, led to a significant increase in across-leg lactate production (from -1.1±2.1 to 5.5±7.4 mmol/min, p<0.001) and mild elevation of arterial lactate (from 1.8±0.7 to 2.5±0.8 mM). This occurred without widening of across-leg veno-arterial (VA) O2 and CO2 gaps. Femoral SvO2 difference was directly proportional to VA difference of lactate (R2 = 0.60, p = 0.002). Across-leg glucose uptake did not change with either type of exercise. Systemic oxygen consumption increased with FES cycling to similarly to 25W volitional exercise (138±29% resp. 124±23% of baseline). There was a net uptake of branched-chain amino acids and net release of Alanine from skeletal muscle, which were unaltered by either type of exercise. CONCLUSIONS: Unloaded FES cycling, but not volitional exercise causes significant lactate production without hypoxia in skeletal muscle. This phenomenon can be significant in vulnerable patients' groups.
- MeSH
- aminokyseliny metabolismus MeSH
- arteria femoralis metabolismus MeSH
- bérec MeSH
- cyklistika fyziologie MeSH
- dospělí MeSH
- elektrická stimulace MeSH
- klinické křížové studie MeSH
- kosterní svaly metabolismus MeSH
- kyselina mléčná biosyntéza krev MeSH
- kyslík krev MeSH
- lidé MeSH
- mladý dospělý MeSH
- nepřímá kalorimetrie MeSH
- oxid uhličitý krev MeSH
- spotřeba kyslíku MeSH
- supinační poloha fyziologie MeSH
- terapie cvičením metody MeSH
- vena femoralis metabolismus MeSH
- zdraví dobrovolníci pro lékařské studie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Venoarterial extracorporeal membrane oxygenation (VA ECMO) is widely used in treatment of decompensated heart failure. Our aim was to investigate its effects on regional perfusion and tissue oxygenation with respect to extracorporeal blood flow (EBF). In five swine, decompensated low-output chronic heart failure was induced by long-term rapid ventricular pacing. Subsequently, VA ECMO was introduced and left ventricular (LV) volume, aortic blood pressure, regional arterial flow and tissue oxygenation were continuously recorded at different levels of EBF. With increasing EBF from minimal to 5 l/min, mean arterial pressure increased from 47+/-22 to 84+/-12 mm Hg (P<0.001) and arterial blood flow increased in carotid artery from 211+/-72 to 479+/-58 ml/min (P<0.01) and in subclavian artery from 103+/-49 to 296+/-54 ml/min (P<0.001). Corresponding brain and brachial tissue oxygenation increased promptly from 57+/-6 to 74+/-3 % and from 37+/-6 to 77+/-6 %, respectively (both P<0.01). Presented results confirm that VA ECMO is a capable form of heart support. Regional arterial flow and tissue oxygenation suggest that partial circulatory support may be sufficient to supply brain and peripheral tissue by oxygen.
- MeSH
- arteria femoralis metabolismus MeSH
- arteria subclavia metabolismus MeSH
- arteriae carotides metabolismus MeSH
- chronická nemoc MeSH
- koronární cévy metabolismus MeSH
- mimotělní membránová oxygenace metody MeSH
- oxymetrie metody MeSH
- prasata MeSH
- rychlost toku krve fyziologie MeSH
- srdeční selhání metabolismus terapie MeSH
- vena femoralis metabolismus MeSH
- výsledek terapie MeSH
- zvířata MeSH
- Check Tag
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
The activation of Ca(2+)-dependent Cl(-) channels during norepinephrine-induced contraction of vascular smooth muscle was suggested to depolarize cell membrane and to increase Ca(2+) entry. Hypertension and ageing are associated with altered Ca(2+) handling including possible activation of Ca(2+)-dependent Cl(-) channels. Our study was aimed to determine Ca(2+)-dependent Cl(-) channels contribution to norepinephrine-induced contraction during hypertension and ageing. Norepinephrine-induced concentration-response curves of femoral arteries from 6- and 12-month-old spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats were recorded using wire myograph. Pretreatment with Ca(2+)-dependent Cl- channel inhibitor indanyloxyacetic acid 94 [R(+)-IAA-94](IAA) attenuated norepinephrine-induced contraction in all groups, but relatively more in WKY than SHR arteries. The attenuation of norepinephrine-induced contraction after Ca(2+)-dependent Cl(-) channels blockade was partially reduced in 12-month-old WKY rats, but substantially diminished in 12-month-old SHR. IAA effect was enhanced after NO synthase inhibition but decreased by ageing. In 20-month-old WKY rats norepinephrine-induced contraction was not affected by IAA but was almost abolished after cyclooxygenase inhibition by indomethacin or niflumic acid. In conclusion, contribution of Ca(2+)-dependent Cl(-) channels to norepinephrine-induced contraction diminished with age, hypertension development, and/or NO synthesis inhibition. Ca(2+)-dependent Cl(-) channels are important for maintenance of normal vascular tone while their inactivation/closing might be a pathological mechanism.
- MeSH
- arteria femoralis účinky léků metabolismus fyziologie MeSH
- chloridové kanály metabolismus MeSH
- endoteliny metabolismus MeSH
- hypertenze metabolismus MeSH
- krevní tlak účinky léků fyziologie MeSH
- krysa rodu rattus MeSH
- noradrenalin farmakologie MeSH
- oxidy dusíku metabolismus MeSH
- potkani inbrední SHR MeSH
- potkani inbrední WKY MeSH
- stárnutí účinky léků metabolismus MeSH
- svaly hladké cévní účinky léků metabolismus fyziologie MeSH
- vápník metabolismus MeSH
- vazokonstrikce účinky léků fyziologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Anthracyclines are one of the most effective anticancer drugs ever developed, but their clinical use has been hampered by the risk of severe cardiotoxicity. In this study, we investigated whether rabbits exposed to a different cumulative dose of anthracycline suffer from immunohistochemically detectable vascular toxicity and endothelial dysfunction. Daunorubicin (3 mg/kg, i.e. 50 mg/m²) was administered i.v. to rabbits once weekly for 1-10 weeks to reach different cumulative doses of the drug (50-500 mg/m²), while control rabbits received saline. The rabbits were sacrificed either 24 hours or 7 days after reaching each particular cumulative dose, and aortas and right femoral arteries were collected for immunohistochemical analysis. Immunohistochemical analysis showed ICAM-1 staining in many aortas from both saline and daunorubicin-treated rabbits without any relationship to the anthracycline treatment. On the contrary, unlike in the lipopolysaccharide-treated or hypercholesterolemic rabbits, no distinct immunoreactivity for other markers of inflammation, oxidative and nitrosative stress (VCAM-1, 4-HNE, iNOS and nitrotyrosine) were detected in aortas and femoral arteries from either control or daunorubicin-treated animals. No relationship to the cumulative dose of the drug or post-expose set up of harvesting was found. In this study, we have demonstrated that daunorubicin does not induce gross histopathological changes in the studied arteries and it fails to induce immunohistochemically detectable endothelial dysfunction. Thus, we propose that endothelial cells are much less susceptible to anthracycline toxicity than cardiac myocytes. In addition, our data suggest that vascular toxicity of anthracyclines plays rather a minor role in the cardiovascular complications of anthracycline chemotherapy.
- MeSH
- antibiotika antitumorózní farmakologie MeSH
- antigeny CD31 metabolismus MeSH
- antracykliny farmakologie MeSH
- aorta účinky léků metabolismus MeSH
- apoptóza MeSH
- arteria femoralis metabolismus MeSH
- daunomycin farmakologie MeSH
- endoteliální buňky cytologie MeSH
- imunohistochemie metody MeSH
- kardiomyocyty účinky léků MeSH
- králíci MeSH
- mezibuněčná adhezivní molekula-1 metabolismus MeSH
- nemoci cév chemicky indukované MeSH
- P-selektin metabolismus MeSH
- zvířata MeSH
- Check Tag
- králíci MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Endothelium-dependent contraction elicited by high concentrations of acetylcholine was described in hypertensive as well as in aged normotensive rats. The contribution of endothelium-derived constricting factor (EDCF) to norepinephrine-induced contraction is still unknown. We aimed to compare EDCF participation to norepinephrine-induced arterial contraction in spontaneously hypertensive rats (SHR) and aged normotensive Wistar-Kyoto (WKY) rats. Femoral arteries from either adult (7-months-old) or aged (14-months-old) animals were placed in myograph and norepinephrine-induced concentration-response curves were recorded under control conditions and in the presence of indomethacin (cyclooxygenase inhibitor, 10(-5) mol/l) or L-NNA (NO synthase inhibitor, 10(-4) mol/l) or both. Norepinephrine-induced concentration-response curve was enhanced in SHR compared to WKY rats, but concentration-response curve of aged WKY rats was similar to those of adult SHR. Cyclooxygenase inhibition largely attenuated concentration-response curves in all groups. However, this effect was greater in aged WKY rats and adult SHR compared to adult WKY rats. NO synthase inhibition augmented norepinephrine-induced contraction in arteries of adult WKY rats, but not in arteries from aged WKY rats or adult SHR. The combined administration of L-NNA and indomethacin had no additive effects on concentration-response curves. EDCF contribution to norepinephrine-induced contractions of arteries was considerably greater in adult SHR (80±3%) and aged WKY rats (86±2%) compared to adult WKY rats (35±10%). The inhibition of NO synthase augmented EDCF contribution to norepinephrine-induced contraction only in arteries from adult WKY rats (76±9%). We conclude that EDCF contribution to norepinephrine-induced contraction of conduit arteries is similarly enhanced in adult hypertensive and aged normotensive rats.
- MeSH
- acetylcholin farmakologie MeSH
- arteria femoralis účinky léků metabolismus fyziologie MeSH
- cyklooxygenasy metabolismus MeSH
- endoteliny metabolismus MeSH
- hypertenze metabolismus patofyziologie MeSH
- indomethacin farmakologie MeSH
- inhibitory cyklooxygenasy farmakologie MeSH
- krysa rodu rattus MeSH
- noradrenalin farmakologie MeSH
- stárnutí metabolismus fyziologie MeSH
- synthasa oxidu dusnatého antagonisté a inhibitory MeSH
- techniky in vitro MeSH
- vazokonstrikce účinky léků MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Klíčová slova
- PROVINOL,
- MeSH
- arteria femoralis fyziologie metabolismus MeSH
- cévní endotel metabolismus MeSH
- fenoly farmakologie MeSH
- finanční podpora výzkumu jako téma MeSH
- krysa rodu rattus MeSH
- oxid dusnatý fyziologie MeSH
- vazodilatace fyziologie MeSH
- víno využití MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
