Based on the World Health Organization statistics, cardiovascular diseases represent the major cause of death worldwide. Although a wide range of treatment approaches and pharmaceuticals is available, the therapy is often not effective enough and therefore health risks for the patient persist. Thus, it is still essential to test new drug candidates for the treatment of various pathophysiological conditions related to cardiovascular system. In vivo models represent indispensable part of preclinical testing of such substances. Anesthetized guinea pig as a whole-body model allows to evaluate complex reactions of cardiovascular system to tested substance. Moreover, action potential of guinea pig cardiomyocyte is quite comparable to that of human. Hence, the results from this model are then quite well translatable to clinical medicine. Aim of this paper was to summarize the methodology of this model, including its advantages and/or limitations and risks, based on the effects of two substances with adrenergic activity on the ECG parameters. The model of anesthetized guinea pig proved to be valuable and suitable for testing of drugs with cardiovascular effects.
- MeSH
- elektrokardiografie * MeSH
- kardiovaskulární systém * účinky léků MeSH
- kontrakce myokardu * účinky léků fyziologie MeSH
- krevní tlak účinky léků MeSH
- lidé MeSH
- modely nemocí na zvířatech MeSH
- morčata MeSH
- preklinické hodnocení léčiv * MeSH
- srdce účinky léků fyziologie MeSH
- srdeční frekvence MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- morčata MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
In the prevention and treatment of cardiovascular disease, in addition to the already proven effective treatment of dyslipidemia, hypertension and diabetes mellitus, omega-3 polyunsaturated fatty acids (n-3 PUFAs) are considered as substances with additive effects on cardiovascular health. N-3 PUFAs combine their indirect effects on metabolic, inflammatory and thrombogenic parameters with direct effects on the cellular level. Eicosapentaenoic acid (EPA) seems to be more efficient than docosahexaenoic acid (DHA) in the favorable mitigation of atherothrombosis due to its specific molecular properties. The inferred mechanism is a more favorable effect on the cell membrane. In addition, the anti-fibrotic effects of n-3 PUFA were described, with potential impacts on heart failure with a preserved ejection fraction. Furthermore, n-3 PUFA can modify ion channels, with a favorable impact on arrhythmias. However, despite recent evidence in the prevention of cardiovascular disease by a relatively high dose of icosapent ethyl (EPA derivative), there is still a paucity of data describing the exact mechanisms of n-3 PUFAs, including the role of their particular metabolites. The purpose of this review is to discuss the effects of n-3 PUFAs at several levels of the cardiovascular system, including controversies.
- Klíčová slova
- cardiovascular disease, docosahexaenoic acid, eicosapentaenoic acid, omega-3 polyunsaturated fatty acids,
- MeSH
- kardiovaskulární nemoci metabolismus prevence a kontrola MeSH
- kyseliny mastné omega-3 metabolismus farmakologie MeSH
- lidé MeSH
- srdce účinky léků fyziologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- kyseliny mastné omega-3 MeSH
Metabolic syndrome (MetS) belongs to the serious health complications expanding in cardiovascular diseases, obesity, insulin resistance, and hyperglycemia. In this study, hypertriacylglycerolemic rats fed a high-fat-fructose diet (HFFD) were used as an experimental model of MetS to explore the effect of tested compounds. Effects of a new prospective pyridoindole derivative coded SMe1EC2 and the natural polyphenol rutin were tested. Endothelial nitric oxide synthase (NOS3) and nuclear factor kappa B (NF-?B) expression were assessed in the left ventricle immunohistochemically and left ventricle activity was monitored in isolated perfused rat hearts. NOS3 activity in the left ventricle decreased markedly as a result of a HFFD. NOS3 expression was upregulated by both substances. NF-?B expression was increased in the MetS group in comparison to control rats and the expression further increased in the SMe1EC2 treatment. This compound significantly improved the coronary flow in comparison to the control group during reperfusion of the heart followed after ischemia. Further, it tended to increase left ventricular systolic pressure, heart product, rate of maximal contraction and relaxation, and coronary flow during baseline assessment. Moreover, the compound SMe1EC2 decreased the sensitivity of hearts to electrically induced ventricular fibrillation. Contrary to this rutin decreased coronary flow in reperfusion. Present results suggest that despite upregulation of NOS3 by both substances tested, pyridoindole SMe1EC2 rather than rutin could be suitable in treatment strategies of cardiovascular disorders in MetS-like conditions.
- MeSH
- biometrie MeSH
- fruktosa škodlivé účinky MeSH
- indoly farmakologie terapeutické užití MeSH
- krysa rodu Rattus MeSH
- metabolický syndrom farmakoterapie enzymologie etiologie MeSH
- myokard metabolismus MeSH
- NF-kappa B metabolismus MeSH
- potkani Wistar MeSH
- preklinické hodnocení léčiv MeSH
- pyridiny farmakologie terapeutické užití MeSH
- rutin farmakologie terapeutické užití MeSH
- srdce účinky léků MeSH
- synthasa oxidu dusnatého, typ III metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- fruktosa MeSH
- indoly MeSH
- NF-kappa B MeSH
- Nos3 protein, rat MeSH Prohlížeč
- pyridiny MeSH
- rutin MeSH
- SMe1EC2 MeSH Prohlížeč
- synthasa oxidu dusnatého, typ III MeSH
BACKGROUND: EXPLORER-HCM (Clinical Study to Evaluate Mavacamten [MYK-461] in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy) demonstrated that mavacamten, a cardiac myosin inhibitor, improves symptoms, exercise capacity, and left ventricular outflow tract (LVOT) obstruction in patients with obstructive hypertrophic cardiomyopathy (oHCM). OBJECTIVES: The purpose of this study was to evaluate mavacamten's effect on measures of cardiac structure and function and its association with changes in other clinical measures. METHODS: Key echocardiographic parameters from serial echocardiograms over 30 weeks from 251 symptomatic oHCM patients (mavacamten [n = 123], placebo [n = 128]) were assessed in a core laboratory. RESULTS: More patients on mavacamten (80.9%; n = 76 of 94) vs placebo (34.0%; n = 33 of 97) showed complete resolution of mitral valve systolic anterior motion after 30 weeks (difference, 46.8%; P < 0.0001). Mavacamten also improved measures of diastolic function vs placebo, including left atrial volume index (LAVI) (mean ± SD baseline: 40 ± 12 mL/m2 vs 41 ± 14 mL/m2; mean change from baseline of -7.5 mL/m2 [95% CI: -9.0 to -6.1 mL/m2] vs -0.09 mL/m2 [95% CI: -1.6 to 1.5 mL/m2]; P < 0.0001) and lateral E/e' (baseline, 15 ± 6 vs 15 ± 8; change of -3.8 [95% CI: -4.7 to -2.8] vs 0.04 [95% CI: -0.9 to 1.0]; P < 0.0001). Among mavacamten-treated patients, improvement in resting, Valsalva, and post-exercise LVOT gradients, LAVI, and lateral E/e' was associated with reduction in N-terminal pro-B-type natriuretic peptide (P ≤ 0.03 for all). Reduction in LAVI was associated with improved peak exercise oxygen consumption (P = 0.04). CONCLUSIONS: Mavacamten significantly improved measures of left ventricular diastolic function and systolic anterior motion. Improvement in LVOT obstruction, LAVI, and E/e' was associated with reduction in a biomarker of myocardial wall stress (N-terminal pro-B-type natriuretic peptide). These findings demonstrate improvement in important markers of the pathophysiology of oHCM with mavacamten. (Clinical Study to Evaluate Mavacamten [MYK-461] in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy; NCT03470545).
- Klíčová slova
- N-terminal pro–B-type natriuretic peptide, diastolic function, hypertrophic cardiomyopathy, mavacamten,
- MeSH
- benzylaminy farmakologie terapeutické užití MeSH
- biologické markery krev MeSH
- dvojitá slepá metoda MeSH
- echokardiografie MeSH
- hypertrofická kardiomyopatie krev diagnostické zobrazování farmakoterapie MeSH
- lidé středního věku MeSH
- lidé MeSH
- senioři MeSH
- srdce účinky léků MeSH
- srdeční myosiny antagonisté a inhibitory MeSH
- tolerance zátěže účinky léků MeSH
- uracil analogy a deriváty farmakologie terapeutické užití MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze III MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
- Názvy látek
- benzylaminy MeSH
- biologické markery MeSH
- MYK-461 MeSH Prohlížeč
- srdeční myosiny MeSH
- uracil MeSH
Light pollution disturbs circadian rhythm, and this can also be deleterious to the heart by increased susceptibility to arrhythmias. Herein, we investigated if rats exposed to continuous light had altered myocardial gene transcripts and/or protein expression which affects arrhythmogenesis. We then assessed if Omacor® supplementation benefitted affected rats. Male and female spontaneously hypertensive (SHR) and normotensive Wistar rats (WR) were housed under standard 12 h/12 h light/dark cycles or exposed to 6-weeks continuous 300 lux light for 24 h. Half the rats were then treated with 200 mg/100 g b.w. Omacor®. Continuous light resulted in higher male rat vulnerability to malignant ventricular fibrillation (VF). This was linked with myocardial connexin-43 (Cx43) down-regulation and deteriorated intercellular electrical coupling, due in part to increased pro-inflammatory NF-κB and iNOS transcripts and decreased sarcoplasmic reticulum Ca2+ATPase transcripts. Omacor® treatment increased the electrical threshold to induce the VF linked with amelioration of myocardial Cx43 mRNA and Cx43 protein levels and the suppression of NF-κB and iNOS. This indicates that rat exposure to continuous light results in deleterious cardiac alterations jeopardizing intercellular Cx43 channel-mediated electrical communication, thereby increasing the risk of malignant arrhythmias. The adverse effects were attenuated by treatment with Omacor®, thus supporting its potential benefit and the relevance of monitoring omega-3 index in human populations at risk.
- Klíčová slova
- NF-κB, cardiac arrhythmias, connexin-43, iNOS, light pollution, omacor, rats,
- MeSH
- fixní kombinace léků MeSH
- fyziologický stres * MeSH
- hypertenze komplikace MeSH
- konexin 43 metabolismus MeSH
- krevní tlak účinky léků MeSH
- krysa rodu Rattus MeSH
- kyselina eikosapentaenová aplikace a dávkování chemie farmakologie MeSH
- kyseliny dokosahexaenové aplikace a dávkování chemie farmakologie MeSH
- modely nemocí na zvířatech MeSH
- potkani inbrední SHR MeSH
- potkani Wistar MeSH
- potravní doplňky * MeSH
- srdce účinky léků MeSH
- srdeční arytmie komplikace patofyziologie prevence a kontrola MeSH
- světelné znečištění * MeSH
- vodní organismy MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- fixní kombinace léků MeSH
- konexin 43 MeSH
- kyselina eikosapentaenová MeSH
- kyseliny dokosahexaenové MeSH
- Omacor MeSH Prohlížeč
Metformin can reduce cardiovascular risk independent of glycemic control. The mechanisms behind its non-glycemic benefits, which include decreased energy intake, lower blood pressure and improved lipid and fatty acid metabolism, are not fully understood. In our study, metformin treatment reduced myocardial accumulation of neutral lipids-triglycerides, cholesteryl esters and the lipotoxic intermediates-diacylglycerols and lysophosphatidylcholines in a prediabetic rat model (p < 0.001). We observed an association between decreased gene expression and SCD-1 activity (p < 0.05). In addition, metformin markedly improved phospholipid fatty acid composition in the myocardium, represented by decreased SFA profiles and increased n3-PUFA profiles. Known for its cardioprotective and anti-inflammatory properties, metformin also had positive effects on arachidonic acid metabolism and CYP-derived arachidonic acid metabolites. We also found an association between increased gene expression of the cardiac isoform CYP2c with increased 14,15-EET (p < 0.05) and markedly reduced 20-HETE (p < 0.001) in the myocardium. Based on these results, we conclude that metformin treatment reduces the lipogenic enzyme SCD-1 and the accumulation of the lipotoxic intermediates diacylglycerols and lysophosphatidylcholine. Increased CYP2c gene expression and beneficial effects on CYP-derived arachidonic acid metabolites in the myocardium can also be involved in cardioprotective effect of metformin.
- Klíčová slova
- arachidonic acid, cytochrome P450, fatty acid profile, lipotoxic intermediates, metformin, myocardial function, myocardial phospholipids, stearoyl-CoA desaturase,
- MeSH
- bazální metabolismus účinky léků MeSH
- biologické markery krev MeSH
- desaturasy mastných kyselin metabolismus MeSH
- hyperlipoproteinemie typ IV farmakoterapie metabolismus MeSH
- hypoglykemika farmakologie MeSH
- kardiotonika farmakologie MeSH
- krysa rodu Rattus MeSH
- kyselina arachidonová metabolismus MeSH
- mediátory zánětu krev MeSH
- metabolismus lipidů účinky léků MeSH
- metformin farmakologie MeSH
- modely nemocí na zvířatech MeSH
- myokard metabolismus MeSH
- potkani Wistar MeSH
- prediabetes farmakoterapie metabolismus MeSH
- rizikové faktory MeSH
- srdce účinky léků MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- biologické markery MeSH
- desaturasy mastných kyselin MeSH
- hypoglykemika MeSH
- kardiotonika MeSH
- kyselina arachidonová MeSH
- mediátory zánětu MeSH
- metformin MeSH
Nicotinic receptors (NRs) play an important role in the cholinergic regulation of heart functions, and converging evidence suggests a diverse repertoire of NR subunits in the heart. A recent hypothesis about the plasticity of β NR subunits suggests that β2-subunits and β4-subunits may substitute for each other. In our study, we assessed the hypothetical β-subunit interchangeability in the heart at the level of mRNA. Using two mutant mice strains lacking β2 or β4 NR subunits, we examined the relative expression of NR subunits and other key cholinergic molecules. We investigated the physiology of isolated hearts perfused by Langendorff's method at basal conditions and after cholinergic and/or adrenergic stimulation. Lack of β2 NR subunit was accompanied with decreased relative expression of β4-subunits and α3-subunits. No other cholinergic changes were observed at the level of mRNA, except for increased M3 and decreased M4 muscarinic receptors. Isolated hearts lacking β2 NR subunit showed different dynamics in heart rate response to indirect cholinergic stimulation. In hearts lacking β4 NR subunit, increased levels of β2-subunits were observed together with decreased mRNA for acetylcholine-synthetizing enzyme and M1 and M4 muscarinic receptors. Changes in the expression levels in β4-/- hearts were associated with increased basal heart rate and impaired response to a high dose of acetylcholine upon adrenergic stimulation. In support of the proposed plasticity of cardiac NRs, our results confirmed subunit-dependent compensatory changes to missing cardiac NRs subunits with consequences on isolated heart physiology.NEW & NOTEWORTHY In the present study, we observed an increase in mRNA levels of the β2 NR subunit in β4-/- hearts but not vice versa, thus supporting the hypothesis of β NR subunit plasticity that depends on the specific type of missing β-subunit. This was accompanied with specific cholinergic adaptations. Nevertheless, isolated hearts of β4-/- mice showed increased basal heart rate and a higher sensitivity to a high dose of acetylcholine upon adrenergic stimulation.
- Klíčová slova
- cardiac cholinergic system, heart physiology, nicotinic receptor, receptor plasticity,
- MeSH
- acetylcholin farmakologie MeSH
- antagonisté muskarinových receptorů farmakologie MeSH
- atropin farmakologie MeSH
- cholinesterasové inhibitory farmakologie MeSH
- hexamethonium farmakologie MeSH
- isoprenalin farmakologie MeSH
- myokard metabolismus MeSH
- myši knockoutované MeSH
- myši MeSH
- neostigmin farmakologie MeSH
- nikotinové receptory metabolismus MeSH
- srdce účinky léků MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- acetylcholin MeSH
- antagonisté muskarinových receptorů MeSH
- atropin MeSH
- cholinesterasové inhibitory MeSH
- hexamethonium MeSH
- isoprenalin MeSH
- neostigmin MeSH
- nikotinové receptory MeSH
The normal physiologic range of QRS complex duration spans between 80 and 125 ms with known differences between females and males which cannot be explained by the anatomical variations of heart sizes. To investigate the reasons for the sex differences as well as for the wide range of normal values, a technology is proposed based on the singular value decomposition and on the separation of different orthogonal components of the QRS complex. This allows classification of the proportions of different components representing the 3-dimensional representation of the electrocardiographic signal as well as classification of components that go beyond the 3-dimensional representation and that correspond to the degree of intricate convolutions of the depolarisation sequence. The technology was applied to 382,019 individual 10-s ECG samples recorded in 639 healthy subjects (311 females and 328 males) aged 33.8 ± 9.4 years. The analyses showed that QRS duration was mainly influenced by the proportions of the first two orthogonal components of the QRS complex. The first component demonstrated statistically significantly larger proportion of the total QRS power (expressed by the absolute area of the complex in all independent ECG leads) in females than in males (64.2 ± 11.6% vs 59.7 ± 11.9%, p < 0.00001-measured at resting heart rate of 60 beats per minute) while the second component demonstrated larger proportion of the QRS power in males compared to females (33.1 ± 11.9% vs 29.6 ± 11.4%, p < 0.001). The analysis also showed that the components attributable to localised depolarisation sequence abnormalities were significantly larger in males compared to females (2.85 ± 1.08% vs 2.42 ± 0.87%, p < 0.00001). In addition to the demonstration of the technology, the study concludes that the detailed convolution of the depolarisation waveform is individual, and that smoother and less intricate depolarisation propagation is the mechanism likely responsible for shorter QRS duration in females.
- MeSH
- algoritmy MeSH
- analýza dat MeSH
- biologická variabilita populace MeSH
- dospělí MeSH
- elektrofyziologické jevy * účinky léků MeSH
- elektrokardiografie * metody MeSH
- lidé středního věku MeSH
- lidé MeSH
- sexuální faktory MeSH
- srdce účinky léků fyziologie MeSH
- výpočetní biologie metody MeSH
- zdraví dobrovolníci pro lékařské studie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The mechanisms behind the cardiovascular and renal benefits of empagliflozin is not fully understood. The positive impact of the medication on cardiovascular mortality can not be solely attributed to its antidiabetic effect, with a metabolic mechanism possibly involved. To investigate the metabolic effects of empagliflozin treatment (10 mg/kg/day for 6 weeks), we used an adult male rat model with serious vascular complications associated with metabolic syndrome and prediabetes. Impaired glucose tolerance, severe albuminuria and impaired insulin sensitivity were induced by intragastric administration of methylglyoxal and high sucrose diet feeding for four months. Although empagliflozin decreased body weight, non-fasting glucose and insulin, glucagon levels remained unchanged. In addition, empagliflozin increased adiponectin levels (+40%; p < 0.01) and improved skeletal muscle insulin sensitivity. Increased non-esterified fatty acids (NEFA) in empagliflozin-treated rats is understood to generate ketone bodies. Empagliflozin increased β-hydroxybutyrate levels in serum (+66%; p < 0.05) and the myocardium (30%; p < 0.01), suggesting its possible involvement as an alternative substrate for metabolism. Empagliflozin switched substrate utilisation in the myocardium, diverting glucose oxidation to fatty acid oxidation. Representing another favorable effect, empagliflozin also contributed to decreased uric acid plasma levels (-19%; p < 0.05). In the kidney cortex, empagliflozin improved oxidative and dicarbonyl stress parameters and increased gene expression of β-hydroxybutyrate dehydrogenase, an enzyme involved in ketone body utilisation. In addition, empagliflozin decreased microalbuminuria (-27%; p < 0.01) and urinary neutrophil gelatinase-associated lipocalin (NGAL) excretion (-29%; p < 0.01). Our results reveal the important systemic metabolic effect of empagliflozin on alterations in substrate utilisation and on increased ketone body use in prediabetic rats. Improved oxidative and dicarbonyl stress and decreased uric acid are also possibly involved in the cardio- and reno-protective effects of empagliflozin.
- MeSH
- benzhydrylové sloučeniny farmakologie MeSH
- glukosa metabolismus MeSH
- glukosidy farmakologie MeSH
- inzulinová rezistence MeSH
- ketolátky metabolismus MeSH
- krysa rodu Rattus MeSH
- ledviny účinky léků metabolismus MeSH
- modely nemocí na zvířatech MeSH
- ochranné látky farmakologie MeSH
- oxidační stres účinky léků MeSH
- potkani Wistar MeSH
- prediabetes farmakoterapie metabolismus MeSH
- srdce účinky léků MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- benzhydrylové sloučeniny MeSH
- empagliflozin MeSH Prohlížeč
- glukosa MeSH
- glukosidy MeSH
- ketolátky MeSH
- ochranné látky MeSH
Acute excessive ethyl alcohol (ethanol) consumption alters cardiac electrophysiology and can evoke cardiac arrhythmias, e.g., in 'holiday heart syndrome'. Ethanol acutely modulates numerous targets in cardiomyocytes, including ion channels, Ca2+-handling proteins and gap junctions. However, the mechanisms underlying ethanol-induced arrhythmogenesis remain incompletely understood and difficult to study experimentally due to the multiple electrophysiological targets involved and their potential interactions with preexisting electrophysiological or structural substrates. Here, we employed cellular- and tissue-level in-silico analyses to characterize the acute effects of ethanol on cardiac electrophysiology and arrhythmogenesis. Acute electrophysiological effects of ethanol were incorporated into human atrial and ventricular cardiomyocyte computer models: reduced INa, ICa,L, Ito, IKr and IKur, dual effects on IK1 and IK,ACh (inhibition at low and augmentation at high concentrations), and increased INCX and SR Ca2+ leak. Multiscale simulations in the absence or presence of preexistent atrial fibrillation or heart-failure-related remodeling demonstrated that low ethanol concentrations prolonged atrial action-potential duration (APD) without effects on ventricular APD. Conversely, high ethanol concentrations abbreviated atrial APD and prolonged ventricular APD. High ethanol concentrations promoted reentry in tissue simulations, but the extent of reentry promotion was dependent on the presence of altered intercellular coupling, and the degree, type, and pattern of fibrosis. Taken together, these data provide novel mechanistic insight into the potential proarrhythmic interactions between a preexisting substrate and acute changes in cardiac electrophysiology. In particular, acute ethanol exposure has concentration-dependent electrophysiological effects that differ between atria and ventricles, and between healthy and diseased hearts. Low concentrations of ethanol can have anti-fibrillatory effects in atria, whereas high concentrations promote the inducibility and maintenance of reentrant atrial and ventricular arrhythmias, supporting a role for limiting alcohol intake as part of cardiac arrhythmia management.
- Klíčová slova
- Arrhythmia, Atrial fibrillation, Cardiac electrophysiology, Computational modeling, Ethanol,
- MeSH
- akční potenciály účinky léků MeSH
- elektrofyziologické jevy účinky léků MeSH
- ethanol škodlivé účinky MeSH
- fibróza MeSH
- iontové kanály metabolismus MeSH
- kardiomyocyty účinky léků metabolismus MeSH
- lidé MeSH
- mezerový spoj účinky léků metabolismus MeSH
- počítačová simulace MeSH
- remodelace cév účinky léků MeSH
- srdce účinky léků patofyziologie MeSH
- srdeční arytmie patologie patofyziologie MeSH
- srdeční síně účinky léků patologie patofyziologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- Názvy látek
- ethanol MeSH
- iontové kanály MeSH