RESUMO
INTRODUCTION: One of the most helpful aspects of intracardiac echocardiography (ICE) implementation in electrophysiological studies (EPS) is the real-time visualisation of catheters and cardiac structures. In this prospective study, we investigated ICE-guided zero-fluoroscopy catheter navigation during radiofrequency (RF) ablation of the cavotricuspid isthmus (CTI) in patients with typical atrial flutter (AFL). METHODS AND RESULTS: Thirty consecutive patients (mean age 72.9 ± 11.4 years, 23 male) with ongoing (n = 23) or recent CTI-dependent AFL underwent an EPS, solely utilizing ICE for catheter navigation. Zero-fluoroscopy EPS could be successfully accomplished in all patients. Mean EPS duration was 41.4 ± 19.9 min, and mean ablation procedure duration was 20.8 ± 17.1 min. RF ablation was applied for 6.0 ± 3.1 min (50W, irrigated RF ablation). Echocardiographic parameters, such as CTI length, prominence of the Eustachian ridge (ER), and depth of the CTI pouch on the ablation plane, were assessed to analyse their correlation with EPS- or ablation procedure duration. The CTI pouch was shallower in patients with an ablation procedure duration above the median (4.8 ± 1.1 mm vs. 6.4 ± 0.9 mm, p = 0.04), suggesting a more lateral ablation plane in these patients, where the CTI musculature is stronger. CTI length or ER prominence above the respective median did not correlate with longer EPS duration. CONCLUSIONS: Zero-fluoroscopy CTI ablation guided solely by intracardiac echocardiography in patients with CTI-dependent AFL is feasible and safe. ICE visualisation may help to localise the optimal ablation plane, detect and correct poor tissue contact of the catheter tip, and recognise early potential complications during the ablation procedure.
Assuntos
Flutter Atrial , Ablação por Cateter , Humanos , Masculino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Flutter Atrial/diagnóstico , Flutter Atrial/cirurgia , Resultado do Tratamento , Estudos Prospectivos , Catéteres , Ecocardiografia , Valva Tricúspide/diagnóstico por imagem , Valva Tricúspide/cirurgia , FluoroscopiaRESUMO
BACKGROUND: Smart devices that are able to measure blood pressure (BP) are valuable for hypertension or heart failure management using digital technology. Data regarding their diagnostic accuracy in comparison to standard noninvasive measurement in accordance to Riva-Rocci are sparse. This study compared a wearable watch-type oscillometric BP monitor (Omron HeartGuide), a wearable watch-type infrared BP monitor (Smart Wear), a conventional ambulatory BP monitor, and auscultatory sphygmomanometry. METHODS: Therefore, 159 consecutive patients (84 male, 75 female, mean age 64.33 ± 16.14 years) performed observed single measurements with the smart device compared to auscultatory sphygmomanometry (n = 109) or multiple measurements during 24 h compared to a conventional ambulatory BP monitor on the upper arm (n = 50). The two BP monitoring devices were simultaneously worn on the same arm throughout the monitoring period. In a subgroup of 50 patients, single measurements were also performed with an additional infrared smart device. RESULTS: The intraclass correlation coefficient (ICC) between the difference and the mean of the oscillometric Omron HeartGuide and the conventional method for the single measurement was calculated for both systole (0.765) and diastole (0.732). This is exactly how the ICC was calculated for the individual mean values calculated over the 24 h long-term measurement of the individual patients for both systole (0.880) and diastole (0.829). The ICC between the infrared device and the conventional method was "bad" for SBP (0.329) and DBP (0.025). Therefore, no further long-term measurements were performed with the infrared device. CONCLUSION: The Omron HeartGuide device provided comparable BP values to the standard devices for single and long-term measurements. The infrared smart device failed to acquire valid measurement data.
Assuntos
Determinação da Pressão Arterial , Hipertensão , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Monitorização Ambulatorial da Pressão Arterial , Monitores de Pressão Arterial , Pressão Sanguínea/fisiologia , Hipertensão/diagnósticoRESUMO
Aims: Feasibility study of accurate three lead ECG recording (Einthoven I, II and III) using an Apple Watch Series 4. Methods: In 50 healthy subjects (18 male; age: 40 ± 12 years) without known cardiac disorders, a 12-lead ECG and three bipolar ECGs, corresponding to Einthoven leads I, II and III were recorded using an Apple Watch Series 4. Einthoven I was recorded with the watch on the left wrist and the right index finger on the crown, Einthoven II with the watch on the left lower abdomen and the right index finger on the crown, Einthoven III with the watch on the left lower abdomen and the left index finger on the crown. Four experienced cardiologists were independently asked to assign the watch ECGs to Einthoven leads from 12-lead ECG for each subject. Results: All watch ECGs showed an adequate signal quality with 134 ECGs of good (89%) and 16 of moderate signal quality (11%). Ninety-one percent of all watch ECGs were assigned correctly to corresponding leads from 12-lead ECG. Thirty-nine subjects (78%) were assigned correctly by all cardiologists. All assignment errors occurred in patients with similar morphologies and amplitudes in at least two of the three recorded leads. Erroneous assignment of all watch ECGs to leads from standard ECG occurred in no patient. Conclusion: Recording of Einthoven leads I-III by a smartwatch is accurate and highly comparable to standard ECG. This might contribute to an earlier detection of cardiac disorders, which are associated with repolarization abnormalities or arrhythmias.
Assuntos
Arritmias Cardíacas/diagnóstico , Transtorno Bipolar/diagnóstico , Eletrocardiografia/métodos , Adulto , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Smartwatches that are able to record a bipolar ECG and Einthoven leads were recently described. Nevertheless, for detection of ischemia or other cardiac diseases more leads are required, especially Wilson's chest leads. OBJECTIVES: Feasibility study of six single-lead smartwatch (Apple Watch Series 4) ECG recordings including Einthoven (I, II, III) and Wilson-like pseudo-unipolar chest leads (Wr, Wm, Wl). METHODS: In 50 healthy subjects (16 males; age: 36 ± 11 years, mean ± SD) without known cardiac disorders, a standard 12-lead ECG and a six single-lead ECG using an Apple Watch Series 4 were performed under resting conditions. Recording of Einthoven I was performed with the watch on the left wrist and the right index finger on the crown, Einthoven II was recorded with the watch on the left lower abdomen and the right index finger on the crown, Einthoven III was recorded with the watch on the left lower abdomen and the left index finger on the crown. Wilson-like chest leads were recorded corresponding to the locations of V1 (Wr), V4 (Wm) and V6 (Wl) in the standard 12-lead ECG. Wr was recorded in the fourth intercostal space right parasternal, Wm was recorded in the fifth intercostal space on the midclavicular line, and Wl was recorded in the fifth intercostal space in left midaxillary line. For all Wilson-like chest lead recordings, the smartwatch was placed on the described three locations on the chest, the right index finger was placed on the crown and the left hand encompassed the right wrist. Both hands and forearms also had contact to the chest. Three experienced cardiologists were independently asked to allocate three bipolar limb smartwatch ECGs to Einthoven I-III leads, and three smartwatch Wilson-like chest ECGs (Wr, Wm, Wl) to V1, V4 and V6 in the standard 12-lead ECG for each subject. RESULTS: All 300 smartwatch ECGs showed a signal quality useable for diagnostics with 281 ECGs of good signal quality (143 limb lead ECGs (95%), 138 chest lead ECGs (92%). Nineteen ECGs had a moderate signal quality (7 limb lead ECGs (5%), 12 chest lead ECGs (8%)). One-hundred percent of all Einthoven and 92% of all Wilson-like smartwatch ECGs were allocated correctly to corresponding leads from 12-lead ECG. Forty-six subjects (92%) were assigned correctly by all cardiologists. Allocation errors were due to similar morphologies and amplitudes in at least two of the three recorded Wilson-like leads. Despite recording with a bipolar smartwatch device, morphology of all six leads was identical to standard 12-lead ECG. In two patients with acute anterior myocardial infarction, all three cardiologists recognized the ST-elevations in Wilson-like leads and assumed an occluded left anterior descending coronary artery correctly. CONCLUSION: Consecutive recording of six single-lead ECGs including Einthoven and Wilson-like leads by a smartwatch is feasible with good ECG signal quality. Thus, this simulated six-lead smartwatch ECG may be useable for the detection of cardiac diseases necessitating more than one ECG lead like myocardial ischemia or more complex cardia arrhythmias.
Assuntos
Eletrocardiografia/instrumentação , Cardiopatias/diagnóstico , Adulto , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/fisiopatologia , Diagnóstico Diferencial , Diagnóstico Precoce , Feminino , Cardiopatias/fisiopatologia , Humanos , Masculino , Isquemia Miocárdica/diagnóstico , Isquemia Miocárdica/fisiopatologia , Registros , Tórax/fisiopatologia , Dispositivos Eletrônicos VestíveisRESUMO
The If channel inhibitor ivabradine is recommended for treatment of chronic heart failure. However, ivabradine also inhibits human ether-a-go-go (hERG) mediated potassium currents. The aim of the present study was to assess the electrophysiologic effects of ivabradine in an experimental model of short-QT-syndrome. Twelve rabbit hearts were isolated and Langendorff-perfused. After obtaining baseline data, pinacidil, an IK-ATP channel opener, was infused (1 µmol/L). Eight endo- and epicardial monophasic action potentials and a 12-lead ECG showed a significant abbreviation of QT interval (-32 ms, P<.05) and shortening of action potential duration at 90% of repolarization (APD90; -22 ms, P<.05). The shortening of ventricular repolarization was accompanied by a reduction of effective refractory period (ERP; -20 ms, P<.05). Thereafter, hearts were additionally treated with ivabradine (5 µmol/L) leading to an increase of QT interval (+31 ms, P<.05), APD90 (+15 ms, P<.05) as well as of ERP (+38 ms, P<.05) and post-repolarization refractoriness (PRR, +33 ms, P<.05) as compared with sole pinacidil infusion. Under baseline conditions, ventricular fibrillation (VF) was inducible by a standardized pacing protocol including programmed stimulation and burst stimulation in 3 of 12 hearts (6 episodes). After application of 1 µmol/L pinacidil, 6 of 12 hearts were inducible (22 episodes). Additional infusion of 5 µmol/L ivabradine led to a significant suppression of VF. Only two episodes could be induced in 1 of 12 hearts. In the present study ivabradine reversed the electrophysiologic effects of pharmacologically simulated short-QT syndrome. Ivabradine demonstrated antiarrhythmic properties based on an increase of both ERP and PRR.
Assuntos
Antiarrítmicos/farmacologia , Arritmias Cardíacas/tratamento farmacológico , Benzazepinas/farmacologia , Animais , Antiarrítmicos/uso terapêutico , Arritmias Cardíacas/fisiopatologia , Benzazepinas/uso terapêutico , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Ivabradina , Período Refratário Eletrofisiológico/efeitos dos fármacos , Disfunção Ventricular/tratamento farmacológicoRESUMO
AIM: The most recent European Society of Cardiology (ESC) update on atrial fibrillation has introduced vernakalant (VER) for pharmacological cardioversion of atrial fibrillation. The aim of the present study was to investigate the safety profile of VER in a sensitive model of proarrhythmia. METHODS AND RESULTS: In 36 Langendorff-perfused rabbit hearts, VER (10, 30 µM, n = 12); ranolazine (RAN, 10, 30 µM, n = 12), or sotalol (SOT, 50; 100 µM, n = 12) were infused after obtaining baseline data. Monophasic action potentials and a 12-lead electrocardiogram showed a significant QT prolongation after application of VER as compared with baseline (10 µM: +25 ms, 30 µM: +50 ms, P < 0.05) accompanied by an increase of action potential duration (APD). The increase in APD90 was accompanied by a more marked increase in effective refractory period (ERP) leading to a significant increase in post-repolarization refractoriness (PRR, 10 µM: +30 ms, 30 µM: +36 ms, P < 0.05). Vernakalant did not affect the dispersion of repolarization. Lowered potassium concentration in bradycardic hearts did not provoke early afterdepolarizations (EADs) or polymorphic ventricular tachycardia (pVT). Comparable results were obtained with RAN. Hundred micromolars of SOT led to an increase in QT interval (+49 ms) and APD90 combined with an increased ERP and PRR (+23 ms). In contrast to VER, 100 µM SOT led to a significant increase in dispersion of repolarization and to the occurrence of EAD in 10 of 12 and pVT in 8 of 12 hearts. CONCLUSION: In the present study, application of VER and SOT led to a comparable prolongation of myocardial repolarization. Both drugs increased the PRR. However, VER neither affect the dispersion of repolarization nor induce EAD and therefore did not cause proarrhythmia.
Assuntos
Anisóis/toxicidade , Antiarrítmicos/toxicidade , Arritmias Cardíacas/induzido quimicamente , Técnicas Eletrofisiológicas Cardíacas , Sistema de Condução Cardíaco/efeitos dos fármacos , Pirrolidinas/toxicidade , Acetanilidas/toxicidade , Potenciais de Ação , Animais , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/fisiopatologia , Sistema de Condução Cardíaco/fisiopatologia , Técnicas In Vitro , Modelos Animais , Perfusão , Piperazinas/toxicidade , Bloqueadores dos Canais de Potássio/toxicidade , Coelhos , Ranolazina , Medição de Risco , Fatores de Risco , Bloqueadores dos Canais de Sódio/toxicidade , Sotalol/toxicidade , Fatores de TempoRESUMO
BACKGROUND: Mechanical circulatory support devices are able to generate additional cardiac output or maintain sufficient circulation during high-risk PCI. We prospectively compared the hemodynamic and clinical performance of the new iVAC2L® device with the Impella 2.5® device during high-risk PCI. MATERIALS AND METHODS: In 40 patients [10 female, age 75 ± 8 years, left ventricular ejection fraction (LVEF) 44 ± 11%] high-risk PCIs were performed under iVAC (n = 20) or Impella (n = 20) support. Hemodynamic parameters were collected before and after device placement as well as immediately after PCI. Blood parameters of hemolysis were analyzed before and after support. RESULTS: Correct device placement was achieved in 17 patients (85%) under iVAC use and in 19 patients (95%) under Impella use. PCI success was 98%. Under iVAC2L® support, systolic, diastolic and mean aortic blood pressure increased significantly with increasing support time. In contrast, aortic pressure increased directly under Impella support, but the increase was comparable between both devices. Impella support generated a significantly higher additional blood flow, as compared to iVAC support (2.07 ± 0.09 l/min vs. 1.25 ± 0.05 l/min, p < 0.001). Five patients (iVAC n = 3) suffered from critical events during high-risk PCI, but both devices were able to maintain stable hemodynamic conditions. After PCI, one severe bleeding occurred in each group. After Impella support, haptoglobin was significantly decreased, indicating potential hemolysis. CONCLUSIONS: High-risk PCIs under support by both devices are feasible and safe and ensure stable hemodynamic conditions also if complications occur. Aortic pressure increases significantly with both devices, but later under iVAC use. Potential hemolysis occurs more frequent under Impella support.
Assuntos
Coração Auxiliar , Intervenção Coronária Percutânea , Idoso , Idoso de 80 Anos ou mais , Feminino , Hemólise , Humanos , Estudos Retrospectivos , Volume Sistólico , Resultado do Tratamento , Função Ventricular EsquerdaRESUMO
INTRODUCTION: Fulminant pulmonary embolism (PE) may lead to cardiogenic shock or cardiac arrest with high mortality rates (65%) despite treatment with thrombolysis. Patients not responding to this therapy might benefit from extracorporeal life support (ECLS). Only occasional case reports of ECLS in PE patients are available. We studied the use of ECLS after thrombolysis in patients suffering from refractory cardiogenic shock due to PE. MATERIAL AND METHODS: Patients who were admitted to our university intensive care unit (ICU) with PE, not responding to throm-bolysis, and who received subsequent ECLS treatment were studied. RESULTS: 12 patients with severe PE were included. 6 patients were admitted by emergency medical services, 5 patients were transferred to the ICU from other hospitals and one patient presented at the emergency department by herself. 11 of 12 patients suffered from cardiac arrest and needed cardiopulmonary resuscitation (CPR) before ECLS implantation. Three ECLS were im-planted during CPR and nine ECLS were implanted during emergency conditions in patients with cardiogenic shock. All patients received thrombolysis before implementation of ECLS. Mean duration of ICU treatment was 22.4 ± 23.0 days. Mean duration of ECLS therapy was 5.6 ± 6.5 days. Bleeding complications occurred in four patients. Complications directly related to the ECLS system occurred in two patients (overall complication rate 42%). Overall, 6 of 12 patients (50%) survived. CONCLUSIONS: ECLS may be considered as abailout therapy in PE patients not responding to prior definitive treatment such as thrombolysis. ECLS therapy seems to be feasible with an acceptable complication rate even after thrombolysis.
Assuntos
Reanimação Cardiopulmonar/métodos , Oxigenação por Membrana Extracorpórea/métodos , Cuidados para Prolongar a Vida/métodos , Embolia Pulmonar/terapia , Choque Cardiogênico/terapia , Terapia Trombolítica/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Embolia Pulmonar/complicações , Choque Cardiogênico/etiologia , Análise de Sobrevida , Resultado do TratamentoRESUMO
Cardiac arrhythmias and cardiovascular diseases are a major public health problem in developed countries. A major goal in preventive medicine is the reduction of cardiovascular death by early detection of atrial fibrillation (AF), which may cause stroke, or early detection of life-threatening myocardial ischemia in acute coronary syndrome. Detection of arrhythmia is often challenging if symptoms occur when patients have no chance for immediate electrocardiogram (ECG) diagnostic testing, or if the observation time period is short or an immediate visit to their doctor is not possible. Smartwatches and other wearable devices are able to record a single lead ECG recording, but a single lead ECG is often not sufficient for diagnosis of cardiovascular disorders. Even diagnosis of AF can be difficult with only information from a single lead bipolar ECG. Some smart devices use photoplethysmography for detection of cardiac rhythm, but this technique can only give indirect hints of the underlying cardiac rhythm, is prone to interferences, and cannot be used for detection of myocardial ischemia. A three-lead bipolar ECG like the Einthoven leads used in regular ECGs can add useful information concerning arrhythmia detection or even diagnosis of other cardiovascular diseases like ischemia. Therefore, we describe a protocol for the patient-directed recording of an Einthoven three-lead ECG using a smartwatch.
Assuntos
Eletrocardiografia/métodos , Dispositivos Eletrônicos Vestíveis , Adulto , Fibrilação Atrial/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/diagnósticoRESUMO
BACKGROUND: The cardiac sodium/calcium (Na+/Ca2+) exchanger (NCX) contributes to diastolic depolarization in cardiac pacemaker cells. Increased NCX activity has been found in heart failure and atrial fibrillation. The influence of increased NCX activity on resting heart rate, beta-adrenergic-mediated increase in heart rate, and cardiac conduction properties is unknown. OBJECTIVE: The purpose of this study was to investigate the influence of NCX overexpression in a homozygous transgenic whole-heart mouse model (NCX-OE) on sinus and AV nodal function. METHODS: Langendorff-perfused, beating whole hearts of NCX-OE and the corresponding wild-type (WT) were studied ± isoproterenol (ISO; 0.2 µM). Epicardial ECG, AV nodal Wenckebach cycle length (AVN-WCL), and retrograde AVN-WCL were obtained. RESULTS: At baseline, basal heart rate was unaltered between NCX-OE and WT (WT: cycle length [CL] 177.6 ± 40.0 ms, no. of hearts [n] = 20; NCX-OE: CL 185.9 ± 30.5 ms, n = 18; P = .21). In the presence of ISO, NCX-OE exhibited a significantly higher heart rate compared to WT (WT: CL 133.4 ± 13.4 ms, n = 20; NCX-OE: CL 117.7 ± 14.2 ms, n = 18; P <.001). ISO led to a significant shortening of the anterograde and retrograde AVN-WCL without differences between NCX-OE and WT. CONCLUSION: This study is the first to demonstrate that increased NCX activity enhances beta-adrenergic increase of heart rate. Mechanistically, increased NCX inward mode activity may promote acceleration of diastolic depolarization in sinus nodal pacemaker cells, thus enhancing chronotropy in NCX-OE. These findings suggest a novel potential therapeutic target for heart rate control in the presence of increased NCX activity, such as heart failure.
Assuntos
Insuficiência Cardíaca/tratamento farmacológico , Frequência Cardíaca/fisiologia , Isoproterenol/farmacologia , Contração Miocárdica/fisiologia , Miócitos Cardíacos/patologia , Nó Sinoatrial/fisiopatologia , Trocador de Sódio e Cálcio/biossíntese , Agonistas Adrenérgicos beta/farmacologia , Animais , Cálcio/metabolismo , Modelos Animais de Doenças , Insuficiência Cardíaca/metabolismo , Camundongos , Camundongos Transgênicos , Miócitos Cardíacos/metabolismo , Nó Sinoatrial/metabolismo , Trocador de Sódio e Cálcio/efeitos dos fármacosRESUMO
INTRODUCTION: Coxsackievirus B3 (CVB3) is known to induce acute and chronic myocarditis. Most infections are clinically unapparent but some patients suffer from ventricular arrhythmias (VA) and sudden cardiac death (SCD). Studies showed that acute CVB3 infection may cause impaired function of cardiac ion channels, creating a proarrhythmic substrate. However, it is unknown whether low level CVB3+ expression in myocytes may cause altered cardiac electrophysiology leading to VA. METHODS: Cellular electrophysiology was used to analyze cellular action potentials (APs) and occurrence of afterdepolarizations from isolated cardiomyocytes of wildtype (WT) and transgenic CVB3ΔVP0 (CVB3+) mice. Further, we studied surface ECGs, monophasic APs, ventricular effective refractory period (VERP) and inducibility of VAs in Langendorff-perfused whole hearts. All used cardiomyocytes and whole hearts originated from male mice. RESULTS: Cellular action potential duration (APD) in WT and CVB3+ myocytes was unchanged. No difference in mean occurrence or amplitude of afterdepolarizations in WT and CVB3+ myocytes was found. Interestingly, resting membrane potential in CVB3+ myocytes was significantly hyperpolarized (WT: -90.0±2.2 mV, n = 7; CVB3+: -114.1±3.0 mV, n = 14; p<0.005). Consistently, in Langendorff-perfused hearts, APDs were also not different between WT and CVB3+ whole hearts. Within both groups, we found a heart rate dependent shortening of ADP90 with increasing heart rate in Langendorff-perfused hearts. VERP was significantly prolonged in CVB3+ hearts compared to WT (WT: 36.0±2.7 ms, n = 5; CVB3+: 47.0±2.0 ms, n = 7; p = 0.018). Resting heart rate (HR) in Langendorff-perfused hearts was not significantly different between both genotypes. Electrical pacing protocols induced no VA in WT and CVB3+ hearts. CONCLUSION: In CVB3+ mice, prolonged ventricular refractoriness and hyperpolarized resting membrane potentials in presence of unchanged APD were observed, suggesting that low level CVB3 expression does not promote VA by altered cardiac electrophysiology in this type of chronic myocarditis. These findings may suggest that other mechanisms such as chronic myocardial inflammation or fibrosis may account for arrhythmias observed in patients with chronic enteroviral myocarditis.
Assuntos
Infecções por Coxsackievirus/fisiopatologia , Miocardite/fisiopatologia , Miocardite/virologia , Miócitos Cardíacos/fisiologia , Miócitos Cardíacos/virologia , Animais , Arritmias Cardíacas/fisiopatologia , Arritmias Cardíacas/virologia , Células Cultivadas , Doença Crônica , Modelos Animais de Doenças , Fenômenos Eletrofisiológicos , Frequência Cardíaca/fisiologia , Masculino , Potenciais da Membrana , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Técnicas de Patch-Clamp , Técnicas de Cultura de Tecidos , Proteínas Virais/genética , Proteínas Virais/metabolismoRESUMO
INTRODUCTION: The antihistaminic antazoline (ANT) was reported to be highly effective and safe for rapid conversion of atrial fibrillation (AF). We therefore analyzed underlying mechanisms in an experimental whole-heart model. METHODS AND RESULTS: Isolated and retrogradely perfused rabbit hearts underwent a standardized protocol employing atrial burst pacing-induced AF in five of 20 hearts under baseline conditions (seven episodes). Thereafter, a combination of acetylcholine and isoproterenol was employed to enhance AF occurrence. Two monophasic action potential recordings on the left- and two on the right atrial epicardium showed a decrease in atrial action potential duration (aAPD, -25 msec, P<.05) and atrial effective refractory period (aERP; -52 msec, P<.01) after infusion of acetylcholine (1 µmol/L) and isoproterenol (1 µmol/L). This led to induction of AF in 14 of 20 hearts (145 episodes). Simultaneous infusion of ANT (20 µmol/L) led to a complete suppression of AF in all inducible hearts. Treatment with ANT also led to a significant increase in aAPD (+41 msec, P<.01) and aERP (+74 msec, P<.05), leading to a marked increase in atrial postrepolarization refractoriness (aPRR, +33 msec, P<.01). Results were compared to 13 rabbits treated with flecainide. Flecainide induced a significant increase in aPRR and resulted in induction of AF in seven of 13 hearts (51 episodes) while 11 of 13 hearts were inducible with acetylcholine and isoproterenol (93 episodes). CONCLUSION: Administration of ANT was highly effective in suppressing AF. The antiarrhythmic effect could be explained by a significant increase in postrepolarization refractoriness as a result of a more marked increase in aERP as compared with aAPD.
Assuntos
Antazolina/farmacologia , Antiarrítmicos/farmacologia , Fibrilação Atrial/prevenção & controle , Frequência Cardíaca/efeitos dos fármacos , Antagonistas dos Receptores Histamínicos H1/farmacologia , Acetilcolina , Potenciais de Ação , Animais , Fibrilação Atrial/induzido quimicamente , Fibrilação Atrial/fisiopatologia , Estimulação Cardíaca Artificial , Relação Dose-Resposta a Droga , Descoberta de Drogas , Eletrocardiografia , Técnicas Eletrofisiológicas Cardíacas , Flecainida/farmacologia , Preparação de Coração Isolado , Isoproterenol , Coelhos , Período Refratário Eletrofisiológico , Fatores de TempoRESUMO
Background/Objective: The cardiac Na+/Ca2+ exchanger (NCX) has been identified as a promising target to counter arrhythmia in previous studies investigating the benefit of NCX inhibition. However, the consequences of NCX inhibition have not been investigated in the setting of altered NCX expression and function, which is essential, since major cardiac diseases (heart failure/atrial fibrillation) exhibit NCX upregulation. Thus, we here investigated the effects of the NCX inhibitor SEA0400 on the Ca2+ transient amplitude and on proarrhythmia in homozygous NCX overexpressor (OE) and heterozygous NCX knockout (hetKO) mice compared to corresponding wild-types (WTOE/WThetKO). Methods/Results: Ca2+ transients of field-stimulated isolated ventricular cardiomyocytes were recorded with fluo-4-AM or indo-1-AM. SEA0400 (1 µM) significantly reduced NCX forward mode function in all mouse lines. SEA0400 (1 µM) significantly increased the amplitude of field-stimulated Ca2+ transients in WTOE, WThetKO, and hetKO, but not in OE (% of basal; OE = 98.7 ± 5.0; WTOE = 137.8 ± 5.2*; WThetKO = 126.3 ± 6.0*; hetKO = 140.6 ± 12.8*; *p < 0.05 vs. basal). SEA0400 (1 µM) significantly reduced the number of proarrhythmic spontaneous Ca2+ transients (sCR) in OE, but increased it in WTOE, WThetKO and hetKO (sCR per cell; basal/+SEA0400; OE = 12.5/3.7; WTOE = 0.2/2.4; WThetKO = 1.3/8.8; hetKO = 0.2/5.5) and induced Ca2+ overload with subsequent cell death in hetKO. Conclusion: The effects of SEA0400 on Ca2+ transient amplitude and the occurrence of spontaneous Ca2+ transients as a proxy measure for inotropy and cellular proarrhythmia depend on the NCX expression level. The antiarrhythmic effect of SEA0400 in conditions of increased NCX expression promotes the therapeutic concept of NCX inhibition in heart failure/atrial fibrillation. Conversely, in conditions of reduced NCX expression, SEA0400 suppressed the NCX function below a critical level leading to adverse Ca2+ accumulation as reflected by an increase in Ca2+ transient amplitude, proarrhythmia and cell death. Thus, the remaining NCX function under inhibition may be a critical factor determining the inotropic and antiarrhythmic efficacy of SEA0400.
RESUMO
BACKGROUND: The prevalence of obesity in developed countries is rising. Currently, Europe has a prevalence of 9-30% with significant impact on public health systems. Obese patients in ICUs require special management and treatment. Altered anatomy in obese patients complicates procedures such as mechanical ventilation. Obesity affects cardiopulmonary physiology and requires elevated ventilation pressures. In our retrospective study, we determined the effect of early percutaneous dilatational tracheotomy (PDT) and cessation of sedation on respiratory parameters in severely obese subjects. METHODS: From June 2010 to July 2014, we included all subjects with a body weight of >130 kg (body mass index >35 kg/m(2)) and respiratory failure who were admitted to the medical ICU of the University Hospital of Münster. All subjects were treated with early PDT and immediate cessation of sedative drugs. We compared ventilator parameters and blood gas analysis before and after PDT. Parameters were recorded on days 0, 1, 3, and 5. Day 0 represents values during ventilation via an endotracheal tube, and days 1, 3, 5 represent values during ventilation via a tracheotomy tube. PDT was performed on day 0 after recording values during ventilation via an endotracheal tube. RESULTS: We included 23 subjects with a mean body mass index of 53.1 kg/m(2) and respiratory failure. After PDT and cessation of sedation, the required ventilation pressures and FIO2 could be rapidly reduced (P < .001), whereas blood gas parameters significantly improved. We observed no severe PDT-associated complications in our cohort. CONCLUSIONS: In severe obesity, respiratory failure might be increased by problems in mechanical ventilation due to required high pressures and obesity-induced pulmonary restriction. Rapid tracheotomy with reduction of dead-space ventilation and airway resistance as well as cessation of sedation to enable spontaneous breathing might be a key factor in the therapy of respiratory failure.
Assuntos
Obesidade/complicações , Respiração Artificial/efeitos adversos , Insuficiência Respiratória/terapia , Traqueotomia/métodos , Adulto , Idoso , Gasometria , Estado Terminal/terapia , Sedação Profunda , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Obesidade/fisiopatologia , Obesidade/cirurgia , Respiração Artificial/métodos , Insuficiência Respiratória/complicações , Estudos Retrospectivos , Traqueotomia/efeitos adversosRESUMO
In the general population, prevalence of obesity is increasing continuously. Concomitantly, a growing number of obese patients with severe illnesses presents at intensive care units (ICU). Particularly respiratory management of this patient group poses a challenge to intensive care physicians because of differences in respiratory anatomy and physiology in obese compared to non-obese individuals. Aim of this review is to present treatment options for critically ill obese patients requiring mechanical ventilation based on current studies concerning patient positioning, ventilatory regimen as well as extended therapy with veno-venous extracorporeal membrane oxygenation (ECMO). The ideal concept for respiratory management depends on multiple aspects and has to be determined individually. Knowledge of altered respiratory anatomy and physiology in obese patients and possible treatment options may facilitate respiratory management in this patient group.
Assuntos
Cuidados Críticos/estatística & dados numéricos , Atenção à Saúde/normas , Oxigenação por Membrana Extracorpórea/métodos , Obesidade/complicações , Insuficiência Respiratória/fisiopatologia , Estado Terminal/epidemiologia , Estado Terminal/terapia , Humanos , Obesidade/epidemiologia , Posicionamento do Paciente/métodos , Prevalência , Respiração Artificial/métodos , Testes de Função Respiratória/métodos , Insuficiência Respiratória/epidemiologia , Insuficiência Respiratória/terapia , Resultado do TratamentoRESUMO
In several case reports proarrhythmic effects of citalopram and escitalopram have been reported. Systematic analyses on prorarrhythmic effects of these drugs are not yet available. The aim of the present study was to investigate if application of citalopram, escitalopram or haloperidol provokes polymorphic ventricular tachycardia in a sensitive model of proarrhythmia. In isolated rabbit hearts monophasic action potentials and ECG showed a significant QT-prolongation after application of citalopram (2µM: +47ms, 4µM: +56ms, P<0.05) accompanied by an increase of action potential duration (APD) but not dispersion of repolarization. Reduced potassium concentration in bradycardic AV-blocked hearts provoked early afterdepolarizations (EAD) in 2 of 12 hearts but no polymorphic ventricular tachycardia (pVT). Application of escitalopram also increased QT-interval (2µM: +3ms, 4µM: +30ms, P<0.05) and APD without effects on dispersion. 3 of 10 hearts showed EAD and pVT in 2 of 10 hearts (32 episodes). The results were compared to 12 rabbits treated with haloperidol which led to an increase in QT-interval (1µM:+62ms; 2µM:+96ms; P<0.01), APD and dispersion (1µM:+15ms, 2µM:+40ms; P<0.01) and induced EAD in all 12 and pVT in 10 of 12 hearts (152 episodes). Citalopram and escitalopram demonstrated a rather safe electrophysiologic profile despite significant QT prolongation. In contrast, haloperidol led to significant increase of dispersion of repolarization while this parameter remained stable under the influence of citalopram or escitalopram. These results imply that application of citalopram or escitalopram is not as proarrhythmic as some case reports might suggest while haloperidol is torsadogenic.
Assuntos
Citalopram/efeitos adversos , Haloperidol/efeitos adversos , Coração/efeitos dos fármacos , Taquicardia Ventricular/induzido quimicamente , Potenciais de Ação/efeitos dos fármacos , Animais , Coração/fisiopatologia , Coelhos , Taquicardia Ventricular/fisiopatologiaRESUMO
Cardiac conduction is mediated by gap junction channels that are formed by connexin (Cx) protein subunits. The connexin family of proteins consists of more than 20 members varying in their biophysical properties and ability to combine with other connexins into heteromeric gap junction channels. The mammalian heart shows regional differences both in connexin expression profile and in degree of electrical coupling. The latter reflects functional requirements for conduction velocity which needs to be low in the sinoatrial and atrioventricular nodes and high in the ventricular conduction system. Over the past 20 years knowledge of the biology of gap junction channels and their role in the genesis of cardiac arrhythmias has increased enormously. This review focuses on the insights gained from transgenic mouse models. The mouse heart expresses Cx30, 30.2, 37, 40, 43, 45, and 46. For these connexins a variety of knock-outs, heart-specific knock-outs, conditional knock-outs, double knock-outs, knock-ins and overexpressors has been studied. We discuss the cardiac phenotype in these models and compare Cx expression between mice and men. Mouse models have enhanced our understanding of (patho)-physiological implications of Cx diversity in the heart. In principle connexin-specific modulation of electrical coupling in the heart represents an interesting treatment strategy for cardiac arrhythmias and conduction disorders.
RESUMO
The most frequently used animal species in experimental cardiac electrophysiology are mice, rabbits, and dogs. Murine and human electrocardiograms (ECGs) show salient differences, including the occurrence of a pronounced J-wave and a less distinctive T-wave in the murine ECG. Mouse models can resemble human cardiac arrhythmias, although mice differ from human in cardiac electrophysiology. Thus, arrhythmia mechanisms in mice may differ from those in humans and should be transferred to the human situation with caution. Further relevant cardiovascular animal models are rabbits, dogs, and minipigs, as they show similarities of cardiac ion channel distribution with the human heart and are suitable to study ventricular repolarization or pro- and antiarrhythmic drug effects. ECG recordings in large animals like goats and horses are feasible. Both goats and horses are a suitable animal model to study atrial fibrillation (AF) mechanisms. Horses frequently show spontaneous AF due to their high vagal tone and large atria. The zebrafish has become an important animal model. Models in "exotic" animals such as kangaroos may be suitable for particular studies.
Assuntos
Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/fisiopatologia , Modelos Animais de Doenças , Eletrocardiografia/métodos , Sistema de Condução Cardíaco/fisiopatologia , Frequência Cardíaca , Animais , Cães , Cabras , Cavalos , Humanos , Camundongos , Coelhos , Especificidade da Espécie , Suínos , Porco MiniaturaRESUMO
BACKGROUND: Ranolazine is evaluated for antiarrhythmic therapy of atrial fibrillation (AF). The electrophysiologic mechanisms of ranolazine in combination with class III drugs were studied in an isolated whole-heart model of stretch-related AF. METHODS AND RESULTS: Thirty rabbits were fed with amiodarone (50 mg/kg/day, n = 10), dronedarone (50 mg/kg/day, n = 10), or placebo (n = 10) for 6 weeks. Subsequently, in isolated hearts, AF was induced by high-rate atrial pacing and acute atrial dilatation. In placebo-treated hearts, d,l-sotalol (50 µM) was acutely administered. Ranolazine (10 µM) was additionally infused in all groups. Chronic amiodarone (+26 ± 7 ms, P < 0.05) or dronedarone (+22 ± 4 ms, P < 0.05) as well as acute application of d,l-sotalol (+20 ± 3 ms, P < 0.05) increased atrial action potential duration (aAPD90 ). Additional treatment with ranolazine did not significantly change aAPD90 (P = ns). Class III drugs did not affect interatrial conduction time, while ranolazine significantly increased it (amiodarone group: +15 ± 3 ms, dronedarone group: +11 ± 3 ms, sotalol group: +15 ± 6 ms; P < 0.05 each). Ranolazine led to an additional increase in atrial effective refractory period (aERP), thus leading to an enhanced atrial postrepolarization refractoriness (aPRR, +17 ± 6 ms, +21 ± 4 ms and +16 ± 8 ms, P < 0.05, respectively). Acute atrial dilatation increased AF incidence compared with baseline. Amiodarone-pretreated hearts showed a lower incidence of AF. Additional infusion of ranolazine further diminished AF. Dronedarone or acute infusion of sotalol did not significantly suppress AF, while additional treatment with ranolazine in these groups also reduced AF incidence. CONCLUSION: In this study, ranolazine on top of class III antiarrhythmic therapy had a beneficial effect. The increase in interatrial conduction time and marked atrial aPRR suppressed AF. These results shed further light on a potential therapeutic benefit of ranolazine on top of conventional antiarrhythmic therapy for rhythm control in AF.
Assuntos
Acetanilidas/farmacologia , Antiarrítmicos/administração & dosagem , Fibrilação Atrial/tratamento farmacológico , Piperazinas/farmacologia , Potenciais de Ação/efeitos dos fármacos , Amiodarona/administração & dosagem , Amiodarona/análogos & derivados , Animais , Modelos Animais de Doenças , Dronedarona , Quimioterapia Combinada , Feminino , Coelhos , Ranolazina , Período Refratário Eletrofisiológico/efeitos dos fármacos , Sotalol/administração & dosagemRESUMO
BACKGROUND AND METHODS: Atrial fibrillation (AF) is the most common cardiac arrhythmia in clinical practice. The substrate of AF is composed of a complex interplay between structural and functional changes of the atrial myocardium often preceding the occurrence of persistent AF. However, there are only few animal models reproducing the slow progression of the AF substrate to the spontaneous occurrence of the arrhythmia. Transgenic mice (TG) with cardiomyocyte-directed expression of CREM-IbΔC-X, an isoform of transcription factor CREM, develop atrial dilatation and spontaneous-onset AF. Here we tested the hypothesis that TG mice develop an arrhythmogenic substrate preceding AF using physiological and biochemical techniques. RESULTS: Overexpression of CREM-IbΔC-X in young TG mice (<8weeks) led to atrial dilatation combined with distension of myocardium, elongated myocytes, little fibrosis, down-regulation of connexin 40, loss of excitability with a number of depolarized myocytes, atrial ectopies and inducibility of AF. These abnormalities continuously progressed with age resulting in interatrial conduction block, increased atrial conduction heterogeneity, leaky sarcoplasmic reticulum calcium stores and the spontaneous occurrence of paroxysmal and later persistent AF. This distinct atrial remodelling was associated with a pattern of non-regulated and up-regulated marker genes of myocardial hypertrophy and fibrosis. CONCLUSIONS: Expression of CREM-IbΔC-X in TG hearts evokes abnormal growth and development of the atria preceding conduction abnormalities and altered calcium homeostasis and the development of spontaneous and persistent AF. We conclude that transcription factor CREM is an important regulator of atrial growth implicated in the development of an arrhythmogenic substrate in TG mice.