Increased level of C-reactive protein (CRP) is a risk factor for cardiovascular diseases, including myocardial infarction and hypertension. Here, we analyzed the effects of CRP overexpression on cardiac susceptibility to ischemia/reperfusion (I/R) injury in adult spontaneously hypertensive rats (SHR) expressing human CRP transgene (SHR-CRP). Using an in vivo model of coronary artery occlusion, we found that transgenic expression of CRP predisposed SHR-CRP to repeated and prolonged ventricular tachyarrhythmias. Excessive ischemic arrhythmias in SHR-CRP led to a significant reduction in infarct size (IS) compared with SHR. The proarrhythmic phenotype in SHR-CRP was associated with altered heart and plasma eicosanoids, myocardial composition of fatty acids (FAs) in phospholipids, and autonomic nervous system imbalance before ischemia. To explain unexpected IS-limiting effect in SHR-CRP, we performed metabolomic analysis of plasma before and after ischemia. We also determined cardiac ischemic tolerance in hearts subjected to remote ischemic perconditioning (RIPer) and in hearts ex vivo. Acute ischemia in SHR-CRP markedly increased plasma levels of multiple potent cardioprotective molecules that could reduce IS at reperfusion. RIPer provided IS-limiting effect in SHR that was comparable with myocardial infarction observed in naïve SHR-CRP. In hearts ex vivo, IS did not differ between the strains, suggesting that extra-cardiac factors play a crucial role in protection. Our study shows that transgenic expression of human CRP predisposes SHR-CRP to excess ischemic ventricular tachyarrhythmias associated with a drop of pump function that triggers myocardial salvage against lethal I/R injury likely mediated by protective substances released to blood from hypoxic organs and tissue at reperfusion.

• MeSH
• akční potenciály MeSH
• C-reaktivní protein genetika   metabolismus   MeSH
• fibrilace komor etiologie   metabolismus   patofyziologie   MeSH
• hypertenze komplikace   metabolismus   patofyziologie   MeSH
• komorová tachykardie etiologie   metabolismus   patofyziologie   MeSH
• krevní tlak MeSH
• lidé MeSH
• modely nemocí na zvířatech MeSH
• myokard metabolismus   patologie   MeSH
• potkani inbrední SHR MeSH
• potkani transgenní MeSH
• reperfuzní poškození myokardu etiologie   metabolismus   patofyziologie   prevence a kontrola   MeSH
• srdeční frekvence MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Kazuistika opisuje polymorbídneho 53-ročného dlhoročnéh o diabetika, hospitalizovaného pre nehojaci sa defekt na pravej dolnej končatine, febrility a dýchavicu. Pri prijatí pacient udával bolesti a opuch pravej dolnej končatiny, následne mu rana začala hnisať. Pridružila sa dýchavica a zvýšenie telesnej teploty do 39 °C. V laboratórnom náleze sa zistili zvýšené hodnoty renálnych parametrov zlyhávania a zápalových ukazovateľov. Počas hospitalizácie sa re- alizovala diferenciálna diagnostika dyspnoe v spolupráci s pneumológom a pokračovalo sa v necielenej antibiotic- kej liečbe. V 9. deň hospitalizácie došlo k nečakanému kolapsu pacienta so stratou vedomia a vzniku komorovej fi b- rilácie, preto bola realizovaná bezodkladná kardiopulmonáln a resuscitácia, ktorá bola úspešná – obnovili sa vitálne funkcie a vedomie pacienta. Po prechodnom zlepšení zdravotného stavu pacienta sa ďalší priebeh hospitalizácie komplikoval rozvojom fl egmóny pravej dolnej končatiny s následným vývojom syndrómu systémovej zápalovej odpovede (systemic infl ammatory response syndrome – SIRS) a so syndrómom multiorgánového zlyhávania (mul- tiple organ dysfunction syndrome – MODS). Pacient bol akútne hemodialyzovaný a antibiotická liečba bola zme- nená na cielenú. Aj napriek opätovnému zlepšeniu klinického stavu a laboratórneho nálezu sa stav pacienta prog- resívne zhoršoval a na 40. deň hospitalizácie došlo ku kardiopulmonálnemu zlyhaniu. Druhá kardiopulmonálna re- suscitácia nebola úspešná a pacient exitoval.

Case report describes 53 years old longtime diabetic patient, hospitalized due to unhealed defect in the right lower extremity, fever and shortness of breath. When patient was admitted, complained about pain and swelling of the right lower extremity, defect with excretion of pus. Associated with shortness of breath and fever up to 39 °C. Laboratory fi ndings revealed increased kidney parameters and infl ammation indicators. Diff erential diagnosis of dyspnea was realized in cooperation with pulmonologist during hospitalilzation while empirical antibiotics treat- ment was continued. On the ninth day of hospitalization occurred unexpected collapse with loss of consciousness and development of ventricular fi brillation, therefore cardiopulmonary re suscitation was performed immediately, which was successful - vital functions and consciousness of the patient were restored. After temporal improvement of patient ́s condition further inpatient period was complicated with the development of right lower limb phleg- mona followed by systemic infl ammatory response syndrome (SIRS) and the multiple organ dysfunction syndrome (MODS). The patient underwent acute hemodialysis and antibiotic treatment was changed according to microbi- ological sensitivity. In spite of improv ed clinical status and laboratory results, the patient ́s condition deteriorated progressively and on the 40th day of hospitalization c ardiopulmonary failure occurred. The second cardiopulmo- nary resuscitation was not successful and the patient died.

• MeSH
• diabetes mellitus 2. typu * farmakoterapie   komplikace   krev   metabolismus   MeSH
• fibrilace komor * etiologie   komplikace   metabolismus   MeSH
• kardiovaskulární nemoci * diagnóza   etiologie   farmakoterapie   komplikace   krev   metabolismus   mortalita   terapie   MeSH
• komorbidita MeSH
• lidé středního věku MeSH
• lidé MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH

We hypothesized that hypertension-related myocardial remodeling characterized by hypertrophy and fibrosis might be accompanied by cell-to-cell gap junction alterations that may account for increased arrhythmogenesis. Intercellular junctions and expression of gap junction protein connexin-43 were analyzed in rat heart tissues from both spontaneous (SHR) and L-NAME model of hypertension. Isolated heart preparation was used to examine susceptibility of the heart to lethal ventricular fibrillation induced by low potassium perfusion. Ultrastructure observation revealed enhanced neoformation of side-to-side type while internalization of end-to-end type (intercalated disc-related) of gap junctions prevailed in the myocardium of rats suffering from either spontaneous or L-NAME-induced hypertension. In parallel, immunolabeling showed increased number of connexin-43 positive gap junctions in lateral cell membrane surfaces, particularly in SHR. Besides, focal loss of immunopositive signal was observed more frequently in hearts of rats treated with L-NAME. There was a significantly higher incidence of hypokalemia-induced ventricular fibrillation in hypertensive compared to normotensive rat hearts. We conclude that adaptation of the heart to hypertension-induced mechanical overload results in maladaptive gap junction remodeling that consequently promotes development of fatal arrhythmias.

• MeSH
• draslík MeSH
• fibrilace komor chemicky indukované   metabolismus   MeSH
• fyziologická adaptace MeSH
• hypertenze metabolismus   patologie   MeSH
• hypokalemie metabolismus   MeSH
• konexin 43 metabolismus   MeSH
• krysa rodu rattus MeSH
• mezerový spoj metabolismus   MeSH
• myokard metabolismus   ultrastruktura   MeSH
• potkani inbrední SHR MeSH
• potkani Wistar MeSH
• srdeční komory mikrobiologie   virologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH

Direct cell-to-cell communication in the heart is maintained via gap junction channels composed of proteins termed connexins. Connexin channels ensure molecular and electrical signals propagation and hence are crucial in myocardial synchronization and heart function. Disease-induced gap junctions remodeling and/or an impairment or even block of intercellular communication due to acute pathological conditions results in derangements of myocardial conduction and synchronization. This is critical in the development of both ventricular fibrillation, which is a major cause of sudden cardiac death and persistent atrial fibrillation, most common arrhythmia in clinical practice often resulting in stroke. Many studies suggest that alterations in topology (remodeling), expression, phosphorylation and particularly function of connexin channels due to age or disease are implicated in the development of these life-threatening arrhythmias. It seems therefore challenging to examine whether compounds that could prevent or attenuate gap junctions remodeling and connexin channels dysfunction can protect the heart against arrhythmias that cause sudden death in humans. This assumption is supported by very recent findings showing that an increase of gap junctional conductance by specific peptides can prevents atrial conduction slowing or re-entrant ventricular tachycardia in ischemic heart. Suppression of ischemia-induced dephosphorylation of connexin seems to be one of the mechanisms involved. Another approach for identifying novel treatments is based on the hypothesis that even non-antiarrhythmic drugs with antiarrhythmic ability can modulate gap junctional communication and hence attenuate arrhythmogenic substrates.

• MeSH
• antiarytmika terapeutické užití   MeSH
• fibrilace komor farmakoterapie   metabolismus   MeSH
• fibrilace síní farmakoterapie   metabolismus   MeSH
• fosforylace MeSH
• konexin 43 metabolismus   MeSH
• lidé MeSH
• mezerový spoj účinky léků   metabolismus   patologie   MeSH
• mezibuněčná komunikace účinky léků   MeSH
• myokard metabolismus   patologie   MeSH
• srdeční arytmie farmakoterapie   metabolismus   patologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

Hypertension-induced myocardial metabolic, structural and electrophysiological remodeling deteriorates with aging and contributes to both heart failure and occurrence of malignant arrhythmias. It has been shown in clinical trials that n-3 polyunsaturated fatty acids (n-3 PUFA) reduce the incidence of cardiovascular diseases and sudden cardiac death. We investigated the cardioprotective effects of n-3 PUFA in aged spontaneously hypertensive rats (SHR) and possible cellular mechanisms involved. Male and female 14-moth-old SHR were fed with n-3 PUFA (Vesteralens, Norway, 20 mg/day for two months) and compared with untreated SHR. Results showed that n-3 PUFA supplementation led to 1) significant decline of blood pressure; 2) suppression of inducible ventricular fibrillation (VF) by 57 % (male) and 67 % (female), although the arrhythmogenic substrates, like fibrosis, hypertrophy and abnormal gap junctions distribution were not eliminated; 3) preservation of the cardiomyocytes and the integrity of their junctions; 4) enhancement of energetic metabolism enzyme activity; 5) augmentation of capillary density associated with increased alkaline phosphatase and decreased dipeptidyl peptidase-4 (DPP4) activity and 6/ increase in gap junction channel connexin-43 expression. Thus, aged male as well as female SHR benefit from n-3 PUFA supplementation that results in decrease in VF susceptibility, partly due to an improvement of myocardial metabolic state, cardiomyocyte and cell-to-cell junctions integrity and Cx43 up-regulation.

• MeSH
• energetický metabolismus účinky léků   MeSH
• fibrilace komor etiologie   metabolismus   patofyziologie   prevence a kontrola   MeSH
• hypertenze komplikace   farmakoterapie   metabolismus   patofyziologie   MeSH
• kapiláry účinky léků   MeSH
• kardiomyocyty účinky léků   metabolismus   MeSH
• konexin 43 metabolismus   MeSH
• krevní tlak účinky léků   MeSH
• krysa rodu rattus MeSH
• kyseliny mastné omega-3 farmakologie   MeSH
• modely nemocí na zvířatech MeSH
• myokard enzymologie   metabolismus   patologie   MeSH
• potkani inbrední SHR MeSH
• potravní doplňky * MeSH
• těsný spoj účinky léků   metabolismus   MeSH
• věkové faktory MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

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 microg/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.

• MeSH
• časové faktory MeSH
• fibrilace komor metabolismus   patofyziologie   prevence a kontrola   MeSH
• kardiomyocyty metabolismus   patologie   MeSH
• krysa rodu rattus MeSH
• modely nemocí na zvířatech MeSH
• morčata MeSH
• potkani Wistar MeSH
• převodní systém srdeční patofyziologie   MeSH
• srdeční frekvence MeSH
• thyroxin aplikace a dávkování   metabolismus   MeSH
• trijodthyronin aplikace a dávkování   metabolismus   MeSH
• věkové faktory MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• morčata MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH