It is known that hypertension is accompanied by increased [Na+]i. The functional properties of Na,K-ATPase, which transports the Na+ out and K+ into myocardial cells during the relaxation phase, were investigated in the left ventricle (LV), septum (SV) and the right ventricle (RV) of anesthetized dogs with moderate acute blood pressure elevation elicited by short-term (4-hour) NO synthase inhibition. The NO-insufficiency was induced by administration of an L-arginine analogue, the NG-nitro-L-arginine methyl ester (L-NAME). Concerning the function of Na,K-ATPase under the conditions of lowered NO synthesis, we focused our attention to the binding of Na+ to the enzyme molecule. Activation of the enzyme by increasing Na+ concentrations revealed significant changes in both the maximal velocity (Vmax) and the affinity for Na+ (KNa) in all investigated heart sections. The Vmax increased by 27 % in LV, by 87 % in SV and by 58 % in RV. The KNa value increased by 86 % in LV, by 105 % in SV and by 93% in RV, indicating an apparent decrease in the sensitivity of the Na+-binding site in the Na,K-ATPase molecule. This apparently decreased pump affinity for Na+ together with the increase of Vmax suggest that, during the short-term inhibition of NO synthesis, the Na,K-ATPase is capable of extruding the excessive Na+ from the myocardial cells more effectively at higher [Na+]i as compared to the Na,K-ATPase of control animals., N. Vrbjar, M. Strnisková, O. Pecháňová, M. Gerová., and Obsahuje bibliografii
a1_Statins, the inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, are most frequently used drugs in the prevention of coronary artery disease due to their cholesterol- lowering activity. However, it is not exactly known whether these effects of statins or those independent of cholesterol decrease account for the protection ag ainst myocardial ischemia- reperfusion (I/R) injury. In this study, we investigated the effect of 5-day treatment with simvastatin (10 mg/kg) in Langendorff- perfused hearts of healthy control (C) and diabetic- hypercholesterolemic (D-H; strept ozotocin + high fat-cholesterol diet, 5 days) rats subjected to 30-min global ischemia followed by 40-min reperfusion for the examination of postischemic contractile dysfunction and reperfusion-induced ventricular arrhythmias or to 30-min (left anterior descending) coronary artery occlusion and 2-h reperfusion for the infarct size determination (IS; tetrazolium stai ning). Postischemic recovery of left ventricular developed pressu re (LVDP) in animals with D-H was improved by simvastatin therapy (62.7±18.2 % of preischemic values vs. 30.3±5.7 % in the untreated D-H; P<0.05), similar to the values in the simvastatin-treated C group, which were 2.5-fold higher than those in the untreated C group. No ventricular fibrillation occurred in the simvastatin-treated C and D-H animals during reperf usion. Likewise, simvastatin shortened the duration of ventri cular tachycardia (10.2±8.1 s and 57.8±29.3 s in C and D-H vs. 143.6±28.6 s and 159.3±44.3 s in untreated C and D-H, respectively, both P<0.05). The decreased arrhythmogenesis in the simvastatin-treated groups correlated with the limitation of IS (in % of risk area) by 66 % and 62 % in C and D-H groups, respectively. However, simvastatin treatment decreased plasma cholesterol levels neither in the D-H animals nor in C., a2_The results indicate that other effects of statins (independent of cholesterol lowering) are involved in the improvement of contractile recovery and attenuation of lethal I/R injury in both, healthy and diseased individuals., A. Adameová, A. Harčárová, J. Matejíková, D. Pancza, M. Kuželová, S. Čarnická, P. Švec, M. Barteková, J. Styk, T. Ravingerová., and Obsahuje bibliografii
Inhalational anesthetic-induced preconditioning (APC) has been shown to reduce infarct size and attenuate contractile dysfunction caused by myocardial ischemia. Only a few studies have reported the effects of APC on arrhythmias during myocardial ischemia-reperfusion injury, focusing exclusively on reperfusion. Accordingly, the ai m of the present study was to examine the influence of APC on ventricular arrhythmias evoked by regional no-flow ischemia. APC was induced in adult male Wistar rats by 12-min exposures to two different concentrations (0.5 and 1.0 MAC) of isoflurane followed by 30-min wash-out periods. Ventricular arrhythmias were assessed in the isolated perfused hearts during a 45- min regional ischemia and a subsequent 15-min reperfusion. Myocardial infarct size was determined after an additional 45 min of reperfusion. The incidence, severity and duration of ventricular arrhythmias during ischemia were markedly reduced by APC. The higher concentration of isoflurane had a larger effect on the incidence of ventricular fibrillation than the lower concentration. The incidence of ventricular tachycardia and reversible ventricular fibrillation during reperfusion was also significantly reduced by APC; the same was true for myocardial infarct size. In conclusion, we have shown that preconditioning with isoflurane confers profound protection against myocardial is chemia- and reperfusion-induced arrhythmias and lethal myocardial injury., H. Říha ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
The study has been designed to characterize protein systems involved in the responses of rat hearts to chronic doxorubicin (DOX) treatment. We investigated the influence of DOX on cardiac function, mitogen-activated protein kinases (MAPKs) and heat stress proteins (HSPs). Doxorubicin was administered to rats by intraperitoneal injections over a period of 6 weeks. In control and DOX-treated hearts exposed to 20 min global ischemia and 40 min reperfusion the recovery of contractile function after ischemia/reperfusion (I/R) was determined. The levels and phosphorylation state of proteins in tissue samples were analyzed using specific antibodies. We found an activation of extracellular signal-regulated kinases (ERKs) in rat hearts exposed to DOX treatment and better recovery of contractile function after I/R. Analysis of HSPs showed that DOX induced up-regulation of the levels of HSP60 and down-regulation of HSP70 levels. The levels and/or specific phosphorylation of other studied proteins (p38-MAPK, HSP27, HSP90) were not in fluenced by DOX. The results point to the possible role of ERKs and some HSPs in mechanisms underlying the response of rat hearts to chronic DOX treatment., P. Šimončíková, T. Ravingerová, M. Barančík., and Obsahuje bibliografii a bibliografické odkazy
Factors modulating cardiac susceptibility to ischemia-reperfusion (I/R) are permannetly attracting the attention of experimental cardiology research. We investigated, whether continuous 24 h/day light exposure of rats can modify cardiac response to I/R, NO-synthase (NOS) activity and the level of oxidative load represented by conjugated dienes (CD) concentration. Two groups of male adult Wistar rats were studied: controls exposed to normal light/dark cycle (12 h/day light, 12 h/day dark) and rats exposed to continuous light for 4 weeks. Perfused isolated hearts (Langendorff technique) were exposed to 25 min global ischemia and subsequent 30 min reperfusion. The recovery of functional parameters (coronary flow, left ventricular developed pressure, contractility and relaxation index) during reperfusion as well as the incidence, severity and duration of arrhythmias during first 10 min of reperfusion were determined. The hearts from rats exposed to continuous light showed more rapid recovery of functional parameters but higher incidence, duration and severity of reperfusion arrhythmias compared to controls. In the left ventricle, the NOS activity was attenuated, but the CD concentration was not significantly changed. We conclude that the exposure of rats to continuous light modified cardiac response to I/R. This effect could be at least partially mediated by attenuated NO production., R. Važan, P. Janega, S. Hojná, J. Zicha, F. Šimko, O. Pecháňová, J. Styk, L'. Paulis., and Obsahuje bibliografii
Thyroid hormones (TH) are powerful modulators of heart function, but their arrhythmogenic effects are less elucidated. We have examined both acute and long-term action of TH on the heart susceptibility to the ventricular fibrillation (VF) and on the heart ability to terminate VF and restore a sinus rhythm. Triiodothyronine (T3) was applied in the range of 10-9-10-6 mol/l in acute experiments using isolated perfused aged (14-month-old) guinea pig hearts. L-thyroxine (T4) was applied in the dose of 50 μg/100g/day to young (3-month-old) and aged (20-month-old) rats for 2 weeks. The T4 treatment resulted in an increased susceptibility of young, but not adult rat hearts to a hypokalemia induced VF and facilitated a spontaneous sinus rhythm (SSR) restoration in the latter group. The acute T3 administration in the range of 10-9-10-7 mol/l significantly decreased the susceptibility of an isolated heart to an electrically induced VF and also facilitated the sinus rhythm restoration. The SSR restoration was, however, not affected by 10-6 mol/l concentration of T3, which also led to an increased VF susceptibility. Results indicate that TH can affect the susceptibility of the heart to VF and its ability to restore the sinus rhythm via acute (non-genomic) and long-term (genomic) actions. Furthermore, an anti- and pro-arrhythmic potential of TH appears to be age- and dose-dependent., V. Knezl, T. Soukup, Ľ. Okruhlicová, J. Slezák, N. Tribulová., and Obsahuje bibliografii a bibliografické odkazy
Vasoactive intestinal peptide (VIP) is a neuropeptide released from the autonomic nerves exerting multiple antiinflammatory effects. The aim of the present study was to investigate the impact of severe sepsis and hemofiltration in two settings on plasma and tissue concentrations of VIP in a porcine model of sepsis. Thirty-two pigs were di vided into 5 groups: 1) control group; 2) control group with conventional hemofiltration; 3) septic group; 4) septic group with conventional hemofiltration; 5) septic group with high-volume hemofiltration. Sepsis induced by faecal peritonitis continued for 22 hours. Hemofiltration was applied for the last 10 hours. Hemodynamic, inflammatory and oxidative stress parameters (heart rate, mean arterial pressure, cardiac output, systemic vascular resistance, plasma concentrations of tumor necrosis factor- α , interleukin-6, thiobarbituric acid reactive species, nitrate + nitrite, asymmetric dimethylarginine) and the systemic VIP concentrations were measured before faeces inoculation and at 12 and 22 hours of peritonitis. VIP tissue levels were determined in the left ventricle, mesenteric and coronary arteries. Sepsis induced significant increases in VIP concentrations in the plasma and mesenteric artery, but it decreased peptide levels in the coronary artery. Hemofiltration in both settings reduced concentrations of VIP in the mesenteric artery. In severe sepsis, VIP seems to be rapidly depleted from the coronary artery and, on the other hand, upregulated in the mesenteric artery. Hemofiltration in both settings has a tendency to drain away these upregulated tissue stores which could result in the limited secretory capacity of the peptide., J. Kuncová ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Hypertrophied hearts are known for increased risk of arrhythmias and are linked with reduced ischemic tolerance. However, still little is known about state characterized only by increased left ventricle (LV) mass fraction. Seventeen isolated rabbit hearts with various LV mass were divided into two groups according to LV weight/heart weight ratio (LVW/HW ratio), namely group H and L (with higher and lower LVW/HW ratio, respectively) and underwent three short cycles of global ischemia and reperfusion. The differences in electrogram (heart rate, QRSmax, mean number, onset and dominant form of ventricular premature beats) and in biochemical markers of myocardial injury (creatine kinase, lactate dehydrogenase - LDH) and lipid peroxidation (4-hydroxy-2-nonenal - 4-HNE) were studied. As compared to group L, hearts in group H exhibited lower tolerance to ischemia expressed as higher incidence and severity of arrhythmias in the first ischemic period as well as increase of LDH and 4-HNE after the first reperfusion. In the third cycle of ischemia-reperfusion, the preconditioning effect was observed in both electrophysiological parameters and LDH release in group H. Our results showed consistent trends when comparing changes in electrograms and biochemical markers. Moreover, 4-HNE seems to be good potential parameter of moderate membrane alteration following ischemia-reperfusion injury., M. Hlaváčová, V. Olejníčková, M. Ronzhina, T. Stračina, O. Janoušek, M. Nováková, P. Babula, J. Kolářová, I. Provazník, H. Paulová., and Obsahuje bibliografii
The effects of transient and sustained hyperthyroidism on vasoactive intestinal polypeptide-like immunoreactivity (VIP-LI) levels were studied in the heart atria of developing and adult rats. Newborn rats were divided into 5 groups. Neo-T animals were treated with thyroxine (T4) during postnatal days 1-8 and sacrificed at the age of 60 days. Neo-S rats were treated with T4 during postnatal days 1-60 and sacrificed one day later. Adult-1 and Adult-2 animals received T4 during days 52-60 and were sacrificed 5-6 days and 1 day later, respectively. Control animals were injected with saline. VIP-LI concentrations were determined in extracts from the left and right atria separately. In Neo-S and Adult-2 rats, spontaneous heart rate, the weight of both atria and total T4 serum levels were significantly enhanced, while their body weight was decreased. The ratio atria weight to body weight was significantly increased in all groups except for Adult-1 animals. Hyperthyroidism led to a significant decrease in VIP-LI levels in both atria of Neo-S and Neo-T rats. Hyperthyroidism induced in adult rats also decreased VIP-LI levels in both atria. However, this change was only transient. In conclusion, our data have provided new evidence that hyperthyroidism induced during the early neonatal period interferes with the development of VIP-ergic innervation in rat atria. The period of the first few postnatal days seems to be essential for this effect, since VIP-LI concentrations in 60-day-old animals did not significantly differ between Neo-S and Neo-T atria., J. Kuncová, J. Slavíková., and Obsahuje bibliografii
Ventricular assist devices (VAD ) have recently established themselves as an irreplaceable th erapeutic modality of terminal heart failure. Because of the worldwide shortage of donors, ventricular assist devices play a key role in modern heart failure therapy. Some clinical data have revealed the possibility of cardiac recovery during VAD applic ation. On the other hand, both clinical and experiment al studies indicate the risk of the cardiac atrophy development, especially after prolonged mechanical unloading. Little is known about the specific mechanisms governing the unloading-induced cardiac atrophy and about the exact ultrastructural changes in cardiomyocytes, and even less is known about the ways in which possible therapeutical interventions may affect heart at rophy. One aim of this review was to present important aspects of the development of VAD- related cardiac atrophy in humans and we also review the most significant observations linking clinical data and those derived from studies using experimental mo dels. The focus of this article was to review current methods applied to alleviate cardiac atrophy which follows mechanical unloading of the heart. Out of many pharmacological agents studied, only the selective beta2 agonist clenbuterol has been proved to have a significantly beneficial effect on unloading-induced atrophy. Mechanical means of atrophy alleviation also seem to be effective and promising., M. Pokorný ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy