Increased parasympathetic tone achieved with endurance training may provide cardioprotection after menopause. To compare heart rate variability (HRV) from rest through maximal exercise and recovery in trained postmenopausal women. Thirtysix postmenopausal women who self-reported training at either moderate (MOD; 3-5.9 METS; 58.9±4.4 year) or vigorous (VIG; >6 METS; 59.7±5.2 year) intensities participated. HRV was measured for 5 min in the supine position, in the last minute of the VO2max test and after 2 min of active recovery. HRV in MOD and VIG was compared using a factorial ANOVA with repeated measures on time. MOD and VIG responded similarly over the three time periods for root mean square of sequential deviations (rMSSD), and high (HF) and low frequency (LF) power (p>0.05). Maximal exercise lowered rMSSD (3.3±0.08 vs. 1.2±0.06) and lnLF (4.1±0.05 vs. 3.3±0.13) and increased lnHF (3.3±0.14 vs. 4.0±0.10; p<0.01) from resting. However, active recovery restored lnHF (3.3±0.11) and lnLF (4.1±0.08) from maximal values (p<0.01). Our findings suggest that moderate and vigorous exercise training may enhance HRV recovery following one bout of maximal exercise in older women., J. C. Orri, E. M. Hughes, D. G. Mistry, A. Scala., and Obsahuje bibliografii
Induction of the inducible form of nitric oxide synthase (iNOS) in the vascular and cardiac tissue by several inflammatory stimuli may result in the production of large amounts of nitric oxide (NO) for a sustained period. Recent data obtained in the rat aorta in which iNOS was induced by lipopolysaccharide (LPS) have demonstrated that adventitial cells represent the main site of NO production. Adventitial-derived NO can exert an immediate down-regulatory effect on smooth muscle contraction (via activation of the cyclic GMP pathway) but may also initiate longer lasting effects through the formation of NO stores within the medial layer. One candidate for such NO stores are dinitrosyl non-heme iron complexes. Low molecular weight thiols interact with preformed NO stores and promote vasorelaxation by a cyclic GMP-independent mechanism involving the activation of potassium channels. In the heart, the induction of iNOS is involved in delayed protection against ischemia-reperfusion-induced functional damages. Recent data obtained with monophosphoryl lipid A, a non-toxin derivative of LPS, strongly suggest that iNOS-derived NO in the rat heart does not act as an immediate mediator of the cardioprotection but rather as a trigger of long-term protective mechanisms. Thus, the present data reveal the important role of adventitial cells as a site of iNOS expression and activity in intact blood vessels. The induction of adaptive mechanisms in the heart and the formation of releasable NO stores in blood vessels are examples of long-term consequences of iNOS induction. These new information are relevant for a better understanding of the circumstances in which NO overproduction by iNOS may play either a beneficial or deleterious role in these tissues., B. Muller, A. L. Kleschyov, K. Gyorgy, J.-C. Stoclet., and Obsahuje bibliografii
Continuous normobaric hypoxia (CNH) renders the heart more tolerant to acute ischemia/reperfusion injury. Protein kinase C (PKC) is an important component of the protective signaling pathway, but the contribution of individual PKC isoforms under different hypoxic conditions is poorly understood. The aim of this study was to analyze the expression of PKCε after the adaptation to CNH and to clarify its role in increased cardiac ischemic tolerance with the use of PKCε inhibitory peptide KP-1633. Adult male Wistar rats were exposed to CNH (10 % O2, 3 weeks) or kept under normoxic conditions. The protein level of PKCε and its phosphorylated form was analyzed by Western blot in homogenate, cytosolic and particulate fractions; the expression of PKCε mRNA was measured by RT-PCR. The effect of KP-1633 on cell viability and lactate dehydrogenase (LDH) release was analyzed after 25-min metabolic inhibition followed by 30-min reenergization in freshly isolated left ventricular myocytes. Adaptation to CNH increased myocardial PKCε at protein and mRNA levels. The application of KP-1633 blunted the hypoxiainduced salutary effects on cell viability and LDH release, while control peptide KP-1723 had no effect. This study indicates that PKCε is involved in the cardioprotective mechanism induced by CNH., K. Holzerová, M. Hlaváčková, J. Žurmanová, G. Borchert, J. Neckář, F. Kolář, F. Novák, O. Nováková., and Obsahuje bibliografii
Chronic intermittent hypoxia (CIH ) is associated with increased production of reactive oxygen species that contributes to the adaptive mechanism underlying the improved myocardial ischemic tolerance. The aim was to find out whether the antioxidative enzyme manganese superoxide dismutase (MnSOD) can play a role in CIH-induced cardioprotection. Adult male Wistar rats were exposed to intermittent hypobaric hypoxia (7000 m, 8 h/day, 25 exposures) (n=14) or kept at normoxia (n=14). Half of the animals from each group received N-acetylcysteine (NAC, 100 mg/kg) daily before the hypoxic exposure. The activity and expression of MnSOD were increased by 66 % and 23 %, respectively, in the mitochondrial fraction of CIH hearts as compared with th e normoxic group; these effects were suppressed by NAC treatment. The negative correlation between MnSOD activity and myoc ardial infarct size suggests that MnSOD can contribute to the improved ischemic tolerance of CIH hearts., P. Balková ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Hypoventilation, as one of ventilatory disorders, decreases the electrical stability of the heart similarly as ischemia. If preconditioning by short cycles of ischemia has a cardioprotective effect against harmful influences of a prolonged ischemic period, then preconditioning by hypoventilation (HPC) can also have a similar effect. Anesthetized rats (ketamine 100 mg/kg + xylasine 15 mg/kg i.m., open chest experiments) were subjected to 20 min of hypoventilation followed by 20 min of reoxygenation (control group). The preconditioning (PC) was induced by one (1PC), two (2PC) or three (3PC) cycles of 5-min hypoventilation followed by 5-min reoxygenation. The electrical stability of the heart was measured by a ventricular arrhythmia threshold (VAT) tested by electrical stimulation of the right ventricle. Twenty-minute hypoventilation significantly decreased the VAT in the control and 1PC groups (p<0.05) and non-significantly in 2PC vs. the initial values. Reoxygenation reversed the VAT values to the initial level only in the control group. In 3PC, the VAT was increased from 2.32±0.69 mA to 4.25±1.31 mA. during hypoventilation (p<0.001) and to 4.37±1.99 mA during reoxygenation (p<0.001). It is concluded that cardioprotection against the hypoventilation/ reoxygenation-induced decrease of VAT proved to be effective only after three cycles of HPC., P. Švorc, I. Bračoková., and Obsahuje bibliografii
Gap junction connexin channels are important determinants of myocardial conduction and synchronization that is crucial for coordinated heart function. One of the main risk factors for cardiovascular events that results in heart attack, congestive heart failure, stroke as well as sudden arrhythmic death is hypertension. Mislocalization and/or dysfunction of specific connexin-43 channels due to hypertension-induced myocardial remodeling have been implicated in the occurrence of lifethreatening arrhythmias and heart failure in both, humans as well as experimental animals. Recent studies suggest that downregulation of myocardial connexin-43, its abnormal distribution and/or phosphorylation might be implicated in this process. On the other hand, treatment of hypertensive animals with cardioprotective drugs (e.g. statins) or supplementation with non-pharmacological compounds, such as melatonin, omega-3 fatty acids and red palm oil protects from lethal arrhythmias. The antiarrhythmic effects are attributed to the attenuation of myocardial connexin-43 abnormalities associated with preservation of myocardial architecture and improvement of cardiac conduction. Findings uncover novel mechanisms of cardioprotective (antihypertensive and antiarrhythmic) effects of compounds that are used in clinical settings. Well-designed trials are needed to explore the antiarrhythmic potential of these compounds in patients suffering from hypertension., T. Egan Benova, B. Szeiffova Bacova, C. Viczenczova, E. Diez, M. Barancik, N. Tribulova., and Obsahuje bibliografii
Remifentanil is a commonly used opioid in anesthesia with cardioprotective effect in ischemia-reperfused (I/R) heart. We evaluated the influence of remifentanil on myocardial infarct size and expressions of proteins involved in apoptosis in I/R rat heart following various time protocols of remifentanil administration. Artificially ventilated anesthetized Sprague-Dawley rats were subjected to a 30 min of left anterior descending coronary artery occlusion followed by 2 h of reperfusion. Rats were randomly assigned to one of five groups; Sham, I/R only, remifentanil preconditioning, postconditioning and continuous infusion group. Myocardial infarct size, the phosphorylation of ERK1/2, Bcl2, Bax and cytochrome c and the expression of genes influencing Ca2+ homeostasis were assessed. In remifentanil-administered rat hearts, regardless of the timing and duration of administration, infarct size was consistently reduced compared to I/R only rats. Remifentanil improved expression of ERK 1/2 and anti-apoptotic protein Bcl2, and expression of sarcoplasmic reticulum genes which were significantly reduced in the I/R rats only. Remifentanil reduced expression of pro-apoptotic protein, Bax and cytochrome c. These suggested that remifentanil produced cardioprotective effect by preserving the expression of proteins involved in anti-apoptotic pathways, and the expression of sarcoplasmic reticulum genes in I/R rat heart, regardless of the timing of administration., H. S. Kim ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
It has been suggested that increase in acute nitric oxide (NO) or cyclic guanosine monophosphate production may be involved in cardioprotection induced by chronic hypoxia (CH). We studied the effect of NO donor molsi domine and phosphodiesterase type 5 inhibitor sildenafil on myocardial ischemia/reperfusion (I/R) injury in rats adapted to CH. Male Wistar rats were exposed to continuous hypoxia in a normobaric chamber (10 % O 2 , 4 weeks). Rats received either saline, mol sidomine (10 mg/kg body weight, i.v.) or sildenafil (0.7 mg/kg body weight, i.v.) 30 min before ischemia. Control rats were kept under normoxia and treated in a corresponding manner. Adaptation to CH increased the myocardial ischemic tolerance. Acute treat ment with either molsidomine or sildenafil significantly reduced infarct size in normoxic rats and further enhanced cardioprotection induced by CH. However, the cardioprotective effect of CH on I/R injury was not additive to the cardioprotection provided b y the drugs., P. Alánová, F. Kolář, B. Ošťádal, J. Neckář., and Obsahuje bibliografii
Although physical exercise is known to reduce size of infarction,
incidence of ventricular arrhythmias, and to improve heart
function, molecular mechanisms of this protection are not fully
elucidated. We explored the hypothesis that voluntary running,
similar to adaptive interventions, such as ischemic or remote
preconditioning, may activate components of pro-survival (RISK)
pathway and potentially modify cell proliferation. Sprague-Dawley
adult male rats freely exercised for 23 days in cages equipped
with running wheels, while sedentary controls were housed in
standard cages. After 23 days, left ventricular (LV) myocardial
tissue samples were collected for the detection of expression and
activation of RISK proteins (WB). The day before, a marker of
cell proliferation 5-bromo-2'-deoxyuridine (BrdU) was given to all
animals to detect its incorporation into DNA of the LV cells
(ELISA). Running increased phosphorylation (activation) of Akt,
as well as the levels of PKCε and phospho-ERK1/2, whereas BrdU
incorporation into DNA was unchanged. In contrast, exercise
promoted pro-apoptotic signaling - enhanced Bax/Bcl-2 ratio and
activation of GSK-3β kinase. Results suggest that in the rat
myocardium adapted to physical load, natural cardioprotective
processes associated with physiological hypertrophy are
stimulated, while cell proliferation is not modified. Up-regulation
of pro-apoptotic markers indicates potential induction of cell
death mechanisms that might lead to maladaptation in the longterm.