•In this study, hearts from 72 male Wistar albino rats were divided into two main protocols: a 40 min ischemia group (protocol A, n = 53) and 10 min ischemia group (protocol B, n = 19). Protocol A subdivided into 2 groups as a control group (n = 10) and adrenaline group (n = 43). Protocol B is subdivided into 2 groups as control group (n = 10) and adrenaline group (n = 9). Both adrenaline groups received the same dose of adrenaline.•In protocol A, ventricular tachyarrhythmia (VTA) incidence was 0 % in controls but rose to 72 % in the adrenaline group (p < 0.01). Heart rates for the control and adrenaline groups in stabilization and reperfusion were 254±45 bpm and 247 ± 66 bpm, versus 277 ± 41 bpm and 651 ± 286 bpm, respectively.•In protocol B, VTA incidence reached 100 % in both groups during reperfusion, with heart rates of 393 ± 29 bpm and 892±227 bpm for controls and 350 ± 49 bpm and 949 ± 116 bpm for the adrenaline group.•These findings suggest that direct adrenaline administration into the heart in last 5 mins of the ischemic period and the 5 mins of in the reperfusion time increases the incidence of reperfusion-induced ventricular arrhythmias up to 72 % in protocol A. Protocol B hearts showed reperfusion-induced ventricular arrhythmias with 100 % incidence in both groups.

• Publikační typ
• časopisecké články MeSH

BACKGROUND: Diabetes mellitus (DM) causes myocardial electrical remodeling and promotes ventricular tachycardia and/or fibrillation (VT/VF). However, experimental studies have been frequently unsuccessful in developing a DM model with the expected high level of arrhythmic outcomes. The present study aims at evaluating cardiac electrophysiological properties in the rats with different Type 1 DM (T1DM) durations and identifying an electrophysiological phenotype associated with the high incidence of VT/VF. METHODS: The experiments were performed in 109 male Wistar rats (6-10 weeks old), subdivided into the groups of control, 4-weeks and 8-weeks T1DM (streptozotocin model). The animals were studied with epicardial electrophysiological mapping, whole-cell patch-clamp and histological examination. The VT/VF susceptibility was tested in ischemia/reperfusion induced in the anesthetized animals. RESULTS: In the 4-weeks T1DM group, we observed the increase in the incidence of reperfusion VT/VF, collagen deposition and dispersion of repolarization, slowed longitudinal and transverse conduction velocity, prolonged action potential duration, increased INa and ICaL currents, nonchanged Ito and IK1 currents. In the 8-weeks T1DM group, the VT/VF incidence, dispersion of repolarization, INa and Ito currents decreased. Other parameters persisted unchanged as compared to the 4-weeks T1DM group. CONCLUSIONS: Relatively early (4 weeks) diabetic electrical remodeling was proarrhythmic and included augmentation of sodium and calcium currents in the presence of fibrosis and slowed conduction and increased dispersion of repolarization. An unexpected finding was that diabetic arrhythmogenesis was associated with the increase in depolarizing transmembrane currents. Further research is warranted to elucidate molecular mechanisms and test the potential for the control of observed changes.

• MeSH
• diabetes mellitus 1. typu * komplikace   patofyziologie   MeSH
• experimentální diabetes mellitus patofyziologie   komplikace   MeSH
• fibrilace komor patofyziologie   MeSH
• komorová tachykardie patofyziologie   etiologie   MeSH
• krysa rodu rattus MeSH
• modely nemocí na zvířatech MeSH
• potkani Wistar * MeSH
• remodelace komor MeSH
• srdeční arytmie patofyziologie   etiologie   MeSH
• srdeční komory patofyziologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

The aim of the study was to examine the potential role of mitochondrial permeability transition pore (mPTP) in the cardioprotective effect of chronic continuous hypoxia (CH) against acute myocardial ischemia/reperfusion (I/R) injury. Adult male Wistar rats were adapted to CH for 3 weeks, while their controls were kept under normoxic conditions. Subsequently, they were subjected to I/R insult while being administered with mPTP inhibitor, cyclosporin A (CsA). Infarct size and incidence of ischemic and reperfusion arrhythmias were determined. Our results showed that adaptation to CH as well as CsA administration reduced myocardial infarct size in comparison to the corresponding control groups. However, administration of CsA did not amplify the beneficial effect of CH, suggesting that inhibition of mPTP opening contributes to the protective character of CH.

• MeSH
• chronická nemoc MeSH
• cyklosporin * farmakologie   MeSH
• hypoxie * metabolismus   MeSH
• infarkt myokardu metabolismus   patologie   prevence a kontrola   MeSH
• krysa rodu rattus MeSH
• potkani Wistar * MeSH
• přechodový pór mitochondriální permeability * metabolismus   MeSH
• reperfuzní poškození myokardu * metabolismus   prevence a kontrola   patologie   MeSH
• srdeční mitochondrie metabolismus   účinky léků   patologie   MeSH
• transportní proteiny mitochondriální membrány metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

While 3-N-butylphthalide (NBP) has demonstrated notable cardioprotective effects, its precise role in mitigating myocardial arrhythmia following ischemia/reperfusion (IR) injury in diabetes remains unclear. This study aimed to explore the potential mechanisms through which NBP mitigates reperfusion-induced myocardial arrhythmia in diabetic rats, with a particular focus on mitochondrial function and biogenesis, endoplasmic reticulum (ER) stress, and oxidative/inflammatory responses. Sixty Sprague-Dawley rats were divided into non-diabetic and diabetic groups, subjected to in-vivo myocardial IR injury, and treated with NBP (100 mg/kg, intraperitoneally) through different modalities: preconditioning, postconditioning, or a combination of both. Electrocardiography (ECG) was employed to assess the incidence and severity of arrhythmia. Fluorometric, Western blotting and ELISA analyses were utilized to measure the mitochondrial, ER stress, and cellular outcomes. Treatment of non-diabetic rats with NBP in preconditioned, postconditioned, and combined approaches significantly reduced cardiotroponin-I and the frequency and severity of arrhythmias induced by IR injury. However, only the combined preconditioning plus postconditioning approach of NBP had protective and antiarrhythmic effects in diabetic rats, in an additive manner. Moreover, the NBP combined approach improved mitochondrial function and upregulated the expression of PGC-1?, Sirt1, and glutathione while concurrently downregulating ER stress and oxidative and pro-inflammatory-related proteins in diabetic rats. In conclusion, the combined approach of NBP treatment was effective in mitigating myocardial arrhythmia in diabetic rats. This approach coordinates interactions within the mitochondria-endoplasmic reticulum network and inhibits oxidative and inflammatory mediators, offering a promising strategy for managing myocardial arrhythmia in diabetic patients. Key words: Myocardial Infarction, Mitochondria, Arrhythmia, Reperfusion, Diabetes, Ischemia.

• MeSH
• antiarytmika farmakologie   terapeutické užití   MeSH
• benzofurany * farmakologie   terapeutické užití   MeSH
• experimentální diabetes mellitus * metabolismus   farmakoterapie   komplikace   MeSH
• krysa rodu rattus MeSH
• oxidační stres * účinky léků   MeSH
• potkani Sprague-Dawley * MeSH
• reperfuzní poškození myokardu * metabolismus   farmakoterapie   prevence a kontrola   MeSH
• srdeční arytmie * etiologie   prevence a kontrola   metabolismus   farmakoterapie   MeSH
• srdeční mitochondrie metabolismus   účinky léků   MeSH
• stres endoplazmatického retikula * účinky léků   MeSH
• zánět metabolismus   farmakoterapie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Systémová hypertenze a hypertrofie levé komory srdeční jsou obecně považovány za významné rizikové faktory, které zhoršují ischemickou odolnost myokardu. Naproti tomu přibývá důkazů, že hypertenze může také aktivovat mechanizmy, které přechodně chrání srdce před poškozením. Navrhovaný projekt je zaměřen na studium akutního ischemicko-reperfúzního poškození myokardu během rozvoje angiotenzin II-dependentní formy hypertenze u Cyp1a1-Ren-2 transgenních potkanů. Předpokládáme, že časná fáze hypertenze bude spojena s rezistentním srdečním fenotypem, zatímco nadměrná aktivace RAS v pozdějším stádiu hypertenze vyvolá zhoršení ischemického poškození. Zaměříme se především na odhalení signálních drah, které podmiňují zvýšenou odolnost myokardu a na analýzu dějů zodpovědných za ztrátu protektivního účinku s rozvojem maligní hypertenze. Výsledky by mohly sloužit jako podklad pro vývoj nových přístupů k prevenci a léčbě ischemických stavů a jejich přenos do praxe.; Systemic hypertension and left ventricular hypertrophy have been widely considered as major risk factors that impair cardiac ischemic tolerance. However, the growing evidence suggests that hypertension may also activate mechanisms that provide temporal protection of the heart against injury. Our project aims at investigating myocardial tolerance to injury caused by acute ischemia/reperfusion during the development of angiotensin II-dependent form of hypertension in Cyp1a1-Ren-2 transgenic rats. We hypothesize that the early stage of hypertension will be associated with protected cardiac phenotype, whereas an excessive activation of RAS in the late stage of hypertension will result in an exacerbation of injury. The project will focus on delineating protective pathways that underlie the improved ischemic tolerance and analyzing processes responsible for the loss of protection with the progression of malignant hypertension. The results may provide a basis for a development of enhanced preventive and therapeutic strategies for ischemic heart and their translation to clinical practice.

• Klíčová slova
• ischemicko/reperfúzní poškození, infarkt myokardu, renin-angiotenzinový systém, kardioprotekce, hypertenze, arytmie, ischemia/reperfusion injury, myocardial infarction, renin-angiotensin system, cardioprotection, hypertension, arrhythmias,

• NLK Publikační typ
• závěrečné zprávy o řešení grantu AZV MZ ČR

Iron is an essential mineral participating in numerous biological processes in the organism under physiological conditions. However, it may be also involved in the pathological mechanisms activated in various cardiovascular diseases including myocardial ischemia/reperfusion (I/R) injury, due to its involvement in reactive oxygen species (ROS) production. Furthermore, iron has been reported to participate in the mechanisms of iron-dependent cell death defined as "ferroptosis". On the other hand, iron may be also involved in the adaptive processes of ischemic preconditioning (IPC). This study aimed to elucidate whether small amounts of iron may modify the cardiac response to I/R in isolated perfused rat hearts and their protection by IPC. Pretreatment of the hearts with iron nanoparticles 15 min prior to sustained ischemia (iron preconditioning, Fe-PC) did not attenuate post-I/R contractile dysfunction. Recovery of left ventricular developed pressure (LVDP) was significantly improved only in the group with combined pretreatment with iron and IPC. Similarly, the rates of contraction and relaxation [+/-(dP/dt)max] were almost completely restored in the group preconditioned with a combination of iron and IPC but not with iron alone. In addition, the severity of reperfusion arrhythmias was reduced only in the iron+IPC group. No changes in protein levels of "survival" kinases of the RISK pathway (Reperfusion Injury Salvage Kinase) were found except for reduced caspase 3 levels in both preconditioned groups. The results indicate that a failure to precondition rat hearts with iron may be associated with the absent upregulation of RISK proteins and the pro-ferroptotic effect manifested by reduced glutathione peroxidase 4 (GPX4) levels. However, combination with IPC suppressed the negative effects of iron resulting in cardioprotection.

• MeSH
• ischemické přivykání * MeSH
• krysa rodu rattus MeSH
• myokard metabolismus   MeSH
• potkani Wistar MeSH
• přivykání k ischémii * metody   MeSH
• reperfuzní poškození myokardu * metabolismus   MeSH
• srdce MeSH
• železo metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Melatonin has been reported to cause myocardial electrophysiological changes and prevent ventricular tachycardia or fibrillation (VT/VF) in ischemia and reperfusion. We sought to identify electrophysiological targets responsible for the melatonin antiarrhythmic action and to explore whether melatonin receptor-dependent pathways or its antioxidative properties are essential for these effects. Ischemia was induced in anesthetized rats given a placebo, melatonin, and/or luzindole (MT1/MT2 melatonin receptor blocker), and epicardial mapping with reperfusion VT/VFs assessment was performed. The oxidative stress assessment and Western blotting analysis were performed in the explanted hearts. Transmembrane potentials and ionic currents were recorded in cardiomyocytes with melatonin and/or luzindole application. Melatonin reduced reperfusion VT/VF incidence associated with local activation time in logistic regression analysis. Melatonin prevented ischemia-related conduction slowing and did not change the total connexin43 (Cx43) level or oxidative stress markers, but it increased the content of a phosphorylated Cx43 variant (P-Cx43368). Luzindole abolished the melatonin antiarrhythmic effect, slowed conduction, decreased total Cx43, protein kinase Cε and P-Cx43368 levels, and the IK1 current, and caused resting membrane potential (RMP) depolarization. Neither melatonin nor luzindole modified INa current. Thus, the antiarrhythmic effect of melatonin was mediated by the receptor-dependent enhancement of impulse conduction, which was associated with Cx43 phosphorylation and maintaining the RMP level.

• MeSH
• antiarytmika farmakologie   terapeutické užití   MeSH
• kardiomyocyty metabolismus   MeSH
• konexin 43 * metabolismus   MeSH
• krysa rodu rattus MeSH
• melatonin * farmakologie   terapeutické užití   MeSH
• melatoninové receptory metabolismus   MeSH
• srdeční arytmie farmakoterapie   prevence a kontrola   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Atherosclerosis is the most common cause of coronary steno-occlusive disease and acute myocardial infarction is the leading cause of death in industrialized countries. In patients with acute ST elevation myocardial infarction (STEMI), there is unquestionable evidence that primary percutaneous coronary intervention providing recanalization of the infarct related artery (IRA) is the preferred reperfusion strategy. Nevertheless, up to 50% of patients with STEMI have multivessel coronary artery disease defined as at least 50% stenosis exclusive of IRA. There is conflicting data regarding the optimal treatment strategy and timing in such patients. Currently, it is assumed that stable patients might benefit from complete revascularization particularly in reducing the need for future unplanned procedures but only culprit lesion should be treated during index procedure in unstable patients. In this article, we provide a comprehensive overview of this important and currently highly debated topic.

• MeSH
• akutní koronární syndrom * etiologie   chirurgie   MeSH
• infarkt myokardu s elevacemi ST úseků * etiologie   chirurgie   MeSH
• infarkt myokardu * MeSH
• koronární angioplastika * škodlivé účinky   MeSH
• lidé MeSH
• nemoci koronárních tepen * komplikace   chirurgie   MeSH
• srdeční arytmie MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Cardiovascular and heart diseases are leading causes of morbidity and mortality. Coronary artery endothelial and vascular dysfunction, inflammation, and mitochondrial dysfunction contribute to progression of heart diseases such as arrhythmias, congestive heart failure, and heart attacks. Classes of fatty acid epoxylipids and their enzymatic regulation by soluble epoxide hydrolase (sEH) have been implicated in coronary artery dysfunction, inflammation, and mitochondrial dysfunction in heart diseases. Likewise, genetic and pharmacological manipulations of epoxylipids have been demonstrated to have therapeutic benefits for heart diseases. Increasing epoxylipids reduce cardiac hypertrophy and fibrosis and improve cardiac function. Beneficial actions for epoxylipids have been demonstrated in cardiac ischemia reperfusion injury, electrical conductance abnormalities and arrhythmias, and ventricular tachycardia. This review discusses past and recent findings on the contribution of epoxylipids in heart diseases and the potential for their manipulation to treat heart attacks, arrhythmias, ventricular tachycardia, and heart failure.

• MeSH
• epoxid hydrolasy antagonisté a inhibitory   metabolismus   MeSH
• epoxidové sloučeniny chemie   metabolismus   MeSH
• infarkt myokardu farmakoterapie   enzymologie   metabolismus   MeSH
• inhibitory enzymů terapeutické užití   MeSH
• komorová tachykardie farmakoterapie   enzymologie   metabolismus   MeSH
• lidé MeSH
• mastné kyseliny metabolismus   MeSH
• nemoci srdce farmakoterapie   enzymologie   metabolismus   MeSH
• rozpustnost MeSH
• srdeční arytmie farmakoterapie   enzymologie   metabolismus   MeSH
• srdeční selhání farmakoterapie   enzymologie   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Research Support, N.I.H., Extramural MeSH

Contractile dysfunction and fatal arrhythmias are the hallmarks of myocardial ischemia/reperfusion (I/R) injury. Pterostilbene has notable cardioprotective effects, but its main mechanisms are not fully understood. Here, we investigated the effect of PTE on myocardial hemodynamics, arrhythmias, inflammatory/oxidative responses, and the causal role of the JAK2/STAT3 pathway in rats with acute myocardial I/R injury. Sixty male 7-8 months Sprague-Dawley rats (n=10/each group) experienced in vivo model of myocardial I/R injury through 40-min LAD coronary artery occlusion and subsequent 24-h reperfusion. PTE at concentrations of 5 and 25 mg/kg was intraperitoneally administered to rats five min before reperfusion. Cardiac hemodynamics, reperfusion-induced ventricular arrhythmias, infarct size, inflammatory cytokines, oxidative stress markers, the activity of the JAK2/STAT3 pathway were measured as the endpoints. Administration of PTE to I/R-injured rats recovered myocardial contractile function and reduced infarct size and ventricular arrhythmias counts and incidence in a dose-dependent manner. PTE at 25 mg/kg significantly and more potently reduced the levels of inflammatory mediators NF-?B, TNF-?, and IL-1?, suppressed intracellular ROS production, augmented the activity of glutathione, and manganese-superoxide dismutase, and upregulated the JAK2 and STAT3 phosphorylation. Importantly, pretreatment of rats with Ag490 as a JAK2 inhibitor significantly abolished the cardioprotective and signaling effects of PTE in I/R rats. PTE exerts significant protective effects on reducing arrhythmias and myocardial infarction and enhancing cardiac function by stimulating JAK2/STAT3-related suppression of inflammatory and oxidative reactions in the I/R injury setting.

• MeSH
• apoptóza MeSH
• cytokiny MeSH
• glutathion MeSH
• infarkt myokardu * metabolismus   MeSH
• interleukin-1 farmakologie   MeSH
• Janus kinasa 2 MeSH
• krysa rodu rattus MeSH
• mangan MeSH
• mediátory zánětu MeSH
• potkani Sprague-Dawley MeSH
• reaktivní formy kyslíku MeSH
• reperfuzní poškození myokardu * metabolismus   MeSH
• reperfuzní poškození * metabolismus   MeSH
• stilbeny MeSH
• superoxiddismutasa metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH