Aminophylline, a bronchodilator mainly used to treat severe asthma attacks, may induce arrhythmias. Unfortunately, the underlying mechanism is not well understood. We have recently described a significant, on average inhibitory effect of aminophylline on inward rectifier potassium current IK1, known to substantially contribute to arrhythmogenesis, in rat ventricular myocytes at room temperature. This study was aimed to examine whether a similar effect may be observed under clinically relevant conditions. Experiments were performed using the whole cell patch clamp technique at 37°C on enzymatically isolated healthy porcine and failing human ventricular myocytes. The effect of clinically relevant concentrations of aminophylline (10-100 μM) on IK1 did not significantly differ in healthy porcine and failing human ventricular myocytes. IK1 was reversibly inhibited by ∼20 and 30 % in the presence of 30 and 100 μM aminophylline, respectively, at -110 mV; an analogical effect was observed at -50 mV. To separate the impact of IK1 changes on AP configuration, potentially interfering ionic currents were blocked (L-type calcium and delayed rectifier potassium currents). A significant prolongation of AP duration was observed in the presence of 100 μM aminophylline in porcine cardiomyocytes which well agreed with the effect of a specific IK1 inhibitor Ba2+ (10 μM) and with the result of simulations using a porcine ventricular cell model. We conclude that the observed effect of aminophylline on healthy porcine and failing human IK1 might be involved in its proarrhythmic action. To fully understand the underlying mechanism, potential aminophylline impact on other ionic currents should be explored.
- MeSH
- akční potenciály účinky léků MeSH
- aminofylin * farmakologie MeSH
- draslíkové kanály dovnitř usměrňující * metabolismus MeSH
- kardiomyocyty * účinky léků metabolismus MeSH
- lidé MeSH
- metoda terčíkového zámku MeSH
- prasata MeSH
- srdeční komory účinky léků metabolismus MeSH
- srdeční selhání metabolismus farmakoterapie MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- kardiologie * dějiny MeSH
- lidé MeSH
- významné osobnosti MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- biografie MeSH
- O autorovi
- Němec, Petr, 1954- Autorita
OBJECTIVES: Both aortic root remodelling and aortic valve (AV) reimplantation have been used for valve-sparing root replacement in patients with aortic root aneurysm with or without aortic regurgitation. There is no clear evidence to support one technique over the another. This study aimed to compare remodelling with basal ring annuloplasty versus reimplantation on a multicentre level with the use of propensity-score matching. METHODS: This was a retrospective international multicentre study of patients undergoing remodelling or reimplantation between 2010 and 2021. Twenty-three preoperative covariates (including root dimensions and valve characteristics) were used for propensity-score matching. Perioperative outcomes were analysed along with longer-term freedom from AV reoperation/reintervention and other major valve-related events. RESULTS: Throughout the study period, 297 patients underwent remodelling and 281 had reimplantation. Using propensity-score matching, 112 pairs were selected and further compared. We did not find a statistically significant difference in perioperative outcomes between the matched groups. Patients after remodelling had significantly higher reintervention risk than after reimplantation over the median follow-up of 6 years (P = 0.016). The remodelling technique (P = 0.02), need for decalcification (P = 0.03) and degree of immediate postoperative AV regurgitation (P < 0.001) were defined as independent risk factors for later AV reintervention. After exclusion of patients with worse than mild AV regurgitation immediately after repair, both techniques functioned comparably (P = 0.089). CONCLUSIONS: AV reimplantation was associated with better valve function in longer-term postoperatively than remodelling. If optimal immediate repair outcome was achieved, both techniques provided comparable AV function.
- MeSH
- anuloplastika srdeční chlopně metody MeSH
- aortální chlopeň * chirurgie MeSH
- aortální insuficience * chirurgie MeSH
- chirurgická náhrada chlopně metody MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- reoperace statistika a číselné údaje MeSH
- replantace * metody MeSH
- retrospektivní studie MeSH
- senioři MeSH
- tendenční skóre * MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- srovnávací studie MeSH
- MeSH
- akutní koronární syndrom * diagnóza komplikace prevence a kontrola terapie MeSH
- antihypertenziva aplikace a dávkování terapeutické užití MeSH
- antikoagulancia aplikace a dávkování terapeutické užití MeSH
- biologické markery krev MeSH
- elektrokardiografie MeSH
- fibrinolýza MeSH
- infarkt myokardu diagnóza komplikace terapie MeSH
- inhibitory agregace trombocytů aplikace a dávkování terapeutické užití MeSH
- koronární angioplastika metody MeSH
- lidé MeSH
- revaskularizace myokardu metody MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- směrnice pro lékařskou praxi MeSH
BACKGROUND: The optimal treatment of patients with severe symptomatic aortic regurgitation (AR) is state-of-the-art surgery. Asymptomatic patients with advanced left ventricular (LV) dilatation and/or impaired ejection fraction should undergo surgical treatment, but there is no guidelines consensus on cut-off values for this recommendation. Multimodality imaging has brought new tools for the accurate selection of asymptomatic patients at risk of early clinical deterioration, however, prospective and randomized data are pending. Cardiac magnetic resonance (CMR)-derived AR quantification along with LV remodeling assessment appears to be the most accurate tool for a selection of such patients at risk. TRIAL DESIGN: The objective of our prospective and multicenter study is to determine whether patients at risk of early clinical deterioration as per CMR assessment will benefit from early surgical treatment. The study is designed as a superiority trial to demonstrate that early surgical treatment is safe and more effective than the standard treatment. A total of 217 asymptomatic patients with severe AR, but without current guidelines-based surgical indication, will be enrolled across all centers. We expect 24 % of patients identified as high clinical risk and therefore eligible for 1:1 randomization to early surgical treatment within 3 months or a watchful waiting strategy. Follow-up will be annual. We expect a complete restoration of LV size and function along with improved quality of life and physical performance in a short-term follow-up of 12 months. The primary endpoint will be a composite safety and efficacy with all criteria mandatory: 15 % or larger reduction of baseline CMR-derived LV end-diastolic volume index, LV ejection fraction >50 %, and no major adverse cardiovascular events. The annual follow-up will continue for a minimum of 4 years until the required number of endpoints is achieved to show a statistically significant difference in cardiovascular morbidity and mortality in early surgically treated patients. CONCLUSION: The ELEANOR trial is the first multicenter randomized controlled study to compare early surgical treatment with a watchful waiting strategy in asymptomatic patients with chronic severe AR at high risk of early clinical deterioration as per CMR assessment but without guidelines-based indications for surgical treatment.
- Publikační typ
- časopisecké články MeSH
FTO and ALKBH5 proteins are essential erasers of N6-adenosine methylation in RNA. We studied how levels of FTO and ALKBH5 proteins changed during mouse embryonic development, aging, cardiomyogenesis, and neuroectodermal differentiation. We observed that aging in male and female mice was associated with FTO up-regulation in mouse hearts, brains, lungs, and kidneys, while the ALKBH5 level remained stable. FTO and ALKBH5 proteins were up-regulated during experimentally induced cardiomyogenesis, but the level of ALKBH5 protein was not changed when neuroectodermal differentiation was induced. HDAC1 depletion in mouse ES cells caused FTO down-regulation. In these cells, mRNA, carrying information from genes that regulate histone signature, RNA processing, and cell differentiation, was characterized by a reduced level of N6-adenosine methylation in specific gene loci, primarily regulating cell differentiation into neuroectoderm. Together, when we compared both RNA demethylating proteins, the FTO protein level undergoes the most significant changes during cell differentiation and aging. Thus, we conclude that during aging and neuronal differentiation, m6A RNA demethylation is likely regulated by the FTO protein but not via the function of ALKBH5.
- MeSH
- adenosin metabolismus MeSH
- alfa-ketoglutarát-dependentní dioxygenasa, AlkB homolog 5 * genetika metabolismus MeSH
- buněčná diferenciace MeSH
- embryonální vývoj MeSH
- gen pro FTO * genetika metabolismus MeSH
- myši MeSH
- RNA metabolismus MeSH
- stárnutí genetika MeSH
- upregulace MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: The prevalence and outcomes of the unicuspid aortic valve (UAV) in patients undergoing the Ross procedure have been strongly underreported in the current literature. We sought to evaluate this in comparison with bicuspid (BAV) and tricuspid valve (TAV) in our Ross cohort. METHODS: This was a retrospective observational study of patients undergoing the Ross procedure at 2 dedicated centers between 2009 and 2020. Primary end points were the risks of midterm autograft reoperation and the onset of at least moderate aortic regurgitation during follow-up. The secondary end point was to compare the perioperative outcomes between the groups. RESULTS: Included in the analysis were 286 patients, of those 39% with UAV, 52% with BAV, and 9% with TAV. UAV patients were operated on at the youngest age (P < .001) and more often for a combined hemodynamic aortic valve pathology (P = .02). They had the largest aortic root dimensions: annulus (P = .01), Valsalva sinuses (P = .11), sinotubular junction (P = .001), and ascending aorta (P < .0001). The risks of reoperation (P = .86) and the onset of aortic regurgitation (P = .75) were comparable among the groups over the follow-up of 4.1 years. There was no difference in perioperative outcomes. CONCLUSIONS: UAV is a separate unit characterized by a distinct hemodynamic pathology and generated aortopathy. It is not associated with a higher risk of reoperation or new onset of aortic regurgitation after the Ross procedure in the midterm postoperatively. At the current state, UAV remains acceptable for the Ross procedure.
Úvod: Intramyokardiální disekující hematom (IDH) je dutina ve stěně srdce vyplněná krví, která vzniká oslabením stěny nekrózou po infarktu myokardu. IDH se může vytvořit ve stěně levé komory, pravé komory nebo interventrikulárního septa. Popis případu: Kazuistika popisuje pacienta s IDH jako vzácnou komplikaci po infarktu myokardu. Pacient byl hospitalizován pro trvající obtěžující kašel tři měsíce po prodělání infarktu myokardu řešeném implantací stentu. Dle echokardiografie bylo podezření na krytou rupturu volné laterální stěny s obrazem pseudoaneu- rysmatu, pro kterou bylo rozhodnuto o operačním řešení. Při operaci byl nález plošné dutiny ve stěně levé komory komunikující otvorem s levou komorou. Vnitřní i vnější stěna dutiny obsahovala srdeční svalovinu, a tak byla dutina diagnostikována jako IDH. Otvor i dutina byly uzavřeny stehy přes meshové podložky a suturou přes meshový proužek. Pooperační průběh se obešel bez komplikací a pacient byl propuštěn osmý den po operaci. Diskuse: Diagnostika IDH se zakládá na anamnéze infarktu myokardu a na nálezech na echokardiografii. Mezi známky echokardiografického obrazu IDH patří vytvoření nové dutiny uvnitř srdeční stěny s echolucentním středem. Diferenciální diagnostika IDH zahrnuje aneurysma, pseudoaneurysma, trombus uvnitř dutiny LK nebo trabekuly komor. Závěr: IDH je komplikace infarktu myokardu, na kterou je třeba pomýšlet při diferenciální diagnostice nově vzniklé dutiny ve stěně levé komory na ultrazvukovém vyšetření. Konzervativní řešení je možné u IDH malých rozměrů, u kterých nedochází k progresi. U hemodynamické nestability pacienta nebo u velkých nebo progredujících IDH je namístě chirurgické řešení.
Background: Intramyocardial dissecting hematoma (IDH) is blood-filled cavitation in the cardiac wall that can occur as a complication of myocardial infarction, chest trauma, or percutaneous intervention. It can develop in the left ventricular free wall, the right ventricle, or the interventricular septum. Case report: The case report describes a patient with IDH as a rare complication of myocardial infarction. The patient was hospitalized for ongoing irritating cough three months after ST elevated myocardial infarction treated with percutaneous coronary intervention. The echocardiography showed the image of a pseudoaneu- rysm of the left ventricle. The patient underwent surgery where a cavitation inside the left ventricle myocardial wall communicating with the left ventricle was found. The inner and outer border of the cavitation included myocardium, therefore diagnosis of IDH was established. The communication and the cavitation were closed with pledgeted sutures and a direct suture with a mesh stripe. Postoperative hospitalization was without complications and the patient was dismissed the eighth day after the surgery. Discussion: Diagnosis of IDH consists of anamnestic information of myocardial infarction and assessment on echocardiography. On echocardiography the IDH shows as a neocavitation within the heart wall with an echo-lucent center. The differential diagnosis of IDH includes aneurysm, pseudoaneurysm of the heart, thrombus of the ventricle and trabeculae. Conclusion: The IDH is a post-infarction complication important to include in the differential diagnosis of newly formed cavitation inside the ventricle wall seen on echocardiography. Conservative management is suggested when the IDH is small and not growing. Surgery is indicated if the patient is unstable or the IDH is large or growing.
- MeSH
- arteriální okluzní nemoci diagnóza MeSH
- diferenciální diagnóza MeSH
- echokardiografie MeSH
- hematom * chirurgie diagnóza MeSH
- infarkt myokardu s elevacemi ST úseků * komplikace terapie MeSH
- kašel etiologie MeSH
- lidé MeSH
- nepravé aneurysma chirurgie diagnóza MeSH
- ruptura srdce chirurgie prevence a kontrola MeSH
- senioři MeSH
- srdeční komory chirurgie patologie MeSH
- ultrasonografie dopplerovská MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- Publikační typ
- kazuistiky MeSH
- Publikační typ
- abstrakt z konference MeSH
Dilatace kořene a/nebo ascendentní aorty je spjata s vyšším rizikem akutní disekce. U nemocných bez chlopenní vady, kteří nesplňují kritéria pro její náhradu, byla v posledních letech zavedena do praxe metoda PEARS (personalized external aortic root support). Spočívá v implantaci na míru vyrobené dakronové síťky, která zabrání progresi dilatace aorty. V práci jsou prezentovány výsledky prvních 100 implantací této síťky u pacientů v České republice. Soubor nemocných a metodika: Soubor tvořilo 77 mužů a 23 žen, průměrného věku 40,4 ± 15,3 roku. U 87 pacientů byla prokázána geneticky podmíněná aortopatie (porucha pojivové tkáně a/nebo bikuspidální aortální chlopeň). U 14 pacientů byla aortální regurgitace větší než 1. st, ale u žádného větší než 2. st. Maximální rozměry aortálního kořene a ascendentní aorty byly 60, resp. 59 mm. Výsledky: U všech pacientů byla síťka úspěšně implantována, u 35 za srdeční akce bez mimotělního oběhu. V časném pooperačním průběhu byly u 35 pacientů přítomny klinické nebo laboratorní známky zánětu, u 23 pacientů přechodné supraventrikulární poruchy srdečního rytmu. Průměrná doba hospitalizace činila 8,4 ± 2,4 dne a žádný pacient v časném pooperačním průběhu nezemřel. Pacienti byli sledováni v průměru 18,1 ± 17,2 měsíce a na kontrolním vyšetření došlo ve srovnání s předoperačními hodnotami k signifikantnímu zmenšení rozměrů kořene, sinotubulární junkce i ascendentní aorty. Závěr: Střednědobé sledování pacientů s dilatací aorty po implantaci PEARS ukázalo, že tato metoda brání dilataci aorty a je dobrým preventivním opatřením před možnou aortální disekcí.
Dilatation of the aortic root and/or ascending aorta is associated with an increased risk of acute dissection. Personalized external aortic root support (PEARS) is a new method that was introduced in last years for these patients without any significant valve disease who do not fulfil the criteria for aortic root or ascending aorta replacement. It is a custom-made macroporous mesh that stabilises the aortic wall. We present the results of the first 100 consecutive patients in whom PEARS was implanted.
- MeSH
- chirurgické síťky MeSH
- disekce aorty * chirurgie MeSH
- lidé MeSH
- retrospektivní studie MeSH
- Check Tag
- lidé MeSH