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We are reporting a patient with discrete intra-His conduction block and describe a refined technique of permanent His bundle pacing assuring reliable ventricular capture. Meticulous mapping of the site of block with lead placement distal to the site of block and non-selective His bundle pacing with local myocardial capture as an additional safety back up appears to be the technique of choice.
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Fascículo Atrioventricular/fisiopatología , Bloqueo de Rama/fisiopatología , Bloqueo de Rama/terapia , Estimulación Cardíaca Artificial/métodos , Electrocardiografía/métodos , Humanos , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVE: Although preconditioning remains one of the most powerful maneuvers to reduce myocardial infarct size, it is not feasible in the clinical setting to pretreat patients prior to acute myocardial infarction (MI). The purpose of this study was to investigate the effect of more clinically relevant therapies of remote perconditioning, postconditioning, and the combined effect of remote perconditioning and postconditioning on myocardial infarct size in an anesthetized rat model. METHODS: Anesthetized rats were subjected to 45 minutes of proximal left coronary artery occlusion followed by 2 hours of reperfusion. Remote perconditioning was performed 5 minutes after left coronary occlusion with 4 cycles of 5 minutes of occlusion and reperfusion of both the femoral arteries. Postconditioning was applied immediately prior to 2 hours of full reperfusion with 6 cycles of 10 seconds occlusion-reperfusion of the coronary artery. The combined effect was produced by preceding the postconditioning regimen with remote perconditioning, after 5 minutes of left coronary occlusion. RESULTS: Remote perconditioning and postconditioning alone failed to reduce infarct size expressed as percentage of the risk zone (42.2% ± 3.9% and 45.0% ± 4.3%). The combination of remote perconditioning and postconditioning also failed to reduce infarct size (45.3% ± 4.1%) as compared to the untreated ischemia-reperfusion group (48.7% ± 3.4%). Hemodynamics including left ventricular end-systole and end-diastolic pressures, +dP/dt, -dP/dt, and heart rate did not show any improvement in the conditioning groups. CONCLUSION: This study shows that remote perconditioning and postconditioning alone or combined neither improve hemodynamics nor reduce infarct size in the rat model of MI.
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Oclusión Coronaria/terapia , Poscondicionamiento Isquémico/métodos , Precondicionamiento Isquémico/métodos , Músculo Esquelético/irrigación sanguínea , Contracción Miocárdica , Infarto del Miocardio/prevención & control , Daño por Reperfusión Miocárdica/prevención & control , Miocardio/patología , Disfunción Ventricular Izquierda/prevención & control , Función Ventricular Izquierda , Animales , Oclusión Coronaria/complicaciones , Oclusión Coronaria/patología , Oclusión Coronaria/fisiopatología , Modelos Animales de Enfermedad , Femenino , Frecuencia Cardíaca , Miembro Posterior , Infarto del Miocardio/etiología , Infarto del Miocardio/patología , Infarto del Miocardio/fisiopatología , Daño por Reperfusión Miocárdica/etiología , Daño por Reperfusión Miocárdica/patología , Daño por Reperfusión Miocárdica/fisiopatología , Ratas , Ratas Sprague-Dawley , Factores de Tiempo , Disfunción Ventricular Izquierda/etiología , Disfunción Ventricular Izquierda/patología , Disfunción Ventricular Izquierda/fisiopatología , Presión VentricularRESUMEN
AIMS: We determined whether implantation of heart tissue-derived decellularized matrix, which contains native biochemical and structural matrix composition, could thicken the infarcted left ventricular (LV) wall and improve LV function in a rat myocardial infarction model. METHODS AND RESULTS: Myocardial infarction was induced by left coronary ligation in Fischer rats. One week later, saline (75 µL, n = 17) or matrix (75 µL, n = 19) was directly injected into the infarcted area. At 6 weeks after injection, cardiac function was assessed by left ventriculogram, echocardiography, and Millar catheter. The hearts were pressure fixed to measure postmortem LV volume and processed for histology. Left ventriculogram demonstrated that LV ejection fraction (EF) was significantly greater in the matrix-treated (56.7% ± 1.4%) than in the saline-treated group (52.4% ± 1.5%; P = .043), and paradoxical LV systolic bulging was significantly reduced in the matrix-treated group (6.2% ± 1.6% of the LV circumference) compared to the saline-treated group (10.3% ± 1.3%; P = .048). Matrix implantation significantly increased the thickness of infarcted LV wall (0.602 ± 0.029 mm) compared to the saline-treated group (0.484 ± 0.03 mm; P = .0084). Infarct expansion index was significantly lower in the matrix-treated group (1.053 ± 0.051) than in the saline-treated group (1.382 ± 0.096, P = .0058). Blood vessel density and c-kit positive staining cells within the infarct area were comparable between the 2 groups. CONCLUSIONS: Implantation of heart tissue-derived decellularized matrix thickens the LV infarcted wall, prevents paradoxical LV systolic bulging, and improves LV EF after myocardial infarction in rats. This benefit was not dependent on the enhanced angiogenesis or the recruitment of endogenous stem cells to the injury site.
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Cardiotónicos/uso terapéutico , Matriz Extracelular/química , Ventrículos Cardíacos/efectos de los fármacos , Infarto del Miocardio/tratamiento farmacológico , Miocardio/química , Extractos de Tejidos/uso terapéutico , Inductores de la Angiogénesis/administración & dosificación , Inductores de la Angiogénesis/química , Inductores de la Angiogénesis/uso terapéutico , Animales , Biomarcadores/metabolismo , Cardiotónicos/administración & dosificación , Cardiotónicos/química , Vasos Coronarios/efectos de los fármacos , Vasos Coronarios/metabolismo , Vasos Coronarios/patología , Femenino , Ventrículos Cardíacos/metabolismo , Ventrículos Cardíacos/patología , Ventrículos Cardíacos/fisiopatología , Inyecciones Intralesiones , Infarto del Miocardio/fisiopatología , Neovascularización Fisiológica/efectos de los fármacos , Tamaño de la Partícula , Proteínas Proto-Oncogénicas c-kit/metabolismo , Ratas , Ratas Endogámicas F344 , Células Madre/efectos de los fármacos , Células Madre/metabolismo , Células Madre/patología , Volumen Sistólico/efectos de los fármacos , Extractos de Tejidos/administración & dosificación , Extractos de Tejidos/química , Función Ventricular Izquierda/efectos de los fármacos , Remodelación Ventricular/efectos de los fármacosRESUMEN
The closed chest convergent procedure is a multidisciplinary approach to atrial fibrillation (AF) treatment. Epicardial posterior left atrial (PLA) ablation is performed by a cardiac surgeon using a transdiaphragmatic endoscope, immediately followed by percutaneous pulmonary vein (PV) isolation performed by a cardiac electrophysiologist. Interim outcomes for the treatment of non-paroxysmal AF (NPAF) were evaluated based on peri-procedural safety and complications, freedom from recurrent AF, and need for cardioversion or repeat catheter ablation at three, six and 12 months post-procedure. A total of 43 patients (86 % NPAF) underwent the convergent procedure. Patients were 84 % male, with mean age 58.6 ± 8.7 years. Mean AF duration was 45.4 ± 40.3 months. Pre-procedure left atrium (LA) volumetric data using cardiac magnetic resonance imaging (MRI) or computed tomography (CT) was available for 30 patients (70 %). Average LA volume was 155.5 ± 48.4 millilitres (ml); two-thirds of patients had a LA volume >130 ml. There was no operative or peri-operative mortality. Sinus rhythm (SR) was recorded at three months in 31 of 39 (79 %) patients, at six months in 24 of 27 (89 %) patients and at 12 months in nine patients. The convergent procedure is a safe and effective option for both PV isolation and PLA substrate ablation in NPAF patients. Long-term follow-up is required and randomised clinical trials warranted.
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AIMS: Human embryonic stem cell-derived cardiomyocytes (hESC-CMs) or mesenchymal stem cells (MSCs) facilitate post-infarct recovery, but the potential benefit of combination therapy using MSCs and hESC-CMs has not been examined. Our objective was to define the gene expression changes in donor and host-derived cells that are induced in vivo after co-transplantation of cardiomyocytes with and without mesenchymal stem cells expressing the prosurvival gene heme oxygenase 1. METHODS AND RESULTS: Human MSCs were engineered to over-express heme oxygenase-1 (HO-1) following lentiviral vector-mediated transduction. Athymic nude rats were subjected to myocardial infarction and received hESC-CMs alone, hESC-CMs plus human MSCs, hESC-CMs plus MSCs overexpressing HO-1, or saline. Real time PCR identified gene expression changes. Cardiac function was assessed by angiography. Co-transplantation of unmodified MSCs plus hESC-CMs elevated CXCR4, HGF, and IGF expression over levels induced by injection of hESC-derived cardiomyocytes alone. In animals co-transplanted with MSC over-expressing HO-1, the expression of these genes was further elevated. Gene expression levels of VEGF, TGF-ß, CCL2, SMAD7, STAT3 and cardiomyocyte transcription factors were highest in the HO-1 MSC plus hESC-CM group at 30 days. Human CD31+, CD34+, isl-1+, NXK2.5 and c-kit+ transcripts were elevated. Rodent genes encoding NKX2.5, troponin T and CD31 were elevated and cell cycle genes were induced. Ejection fraction improved by six to seven percent. CONCLUSIONS: Co-administration of HO-1 MSCs plus hESC-CMs increased expression of pro-survival and angiogenesis-promoting genes in human cells and transcripts of cardiac and endothelial cell markers in rodent cells, consistent with activation of tissue repair in both transplanted hESC-CMs and the host heart.
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PURPOSES: We determined whether a small molecule inhibitor of apoptosis signal-regulating kinase 1 (ASK1-i) could reduce myocardial infarct size in a rat ischemia/reperfusion model. METHODS AND RESULTS: Sprague-Dawley rats were randomized to 3 groups: ASK1-i infusion (n = 16), vehicle infusion (n = 16), or ischemic preconditioning (IPC; n = 15). Infusion of ASK1-i (10 mg/kg, iv) or vehicle commenced 45 minutes before myocardial ischemia. IPC consisted of 3 cycles of 3 minutes of coronary occlusion followed by 5 minutes of reperfusion immediately before index myocardial ischemia, which consisted of 30-minute left coronary occlusion followed by 180 minutes of reperfusion. Pathologic analysis revealed no significant difference in the ischemic risk size among the 3 groups. ASK1-I and IPC significantly reduced myocardial infarct size (27.7% ± 3.3%, 16.5% ± 3.4%, and 41.5% ± 4.8% in the ASK1-i group, the IPC group, and the vehicle group, respectively; P = 0.0002) and apoptosis (the percentage of apoptotic nuclei averaged 11.6% ± 1.0%, 10.2% ± 1.7%, and 17.7% ± 2.0% in the ASK1-i group, IPC group, and vehicle group, respectively, P = 0.0055). CONCLUSIONS: A small molecule inhibitor of ASK1 was shown for the first time to reduce apoptosis and myocardial infarct size in a rat model of ischemia/reperfusion.
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Apoptosis/efectos de los fármacos , Modelos Animales de Enfermedad , MAP Quinasa Quinasa Quinasa 5/antagonistas & inhibidores , Infarto del Miocardio/tratamiento farmacológico , Daño por Reperfusión Miocárdica/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/uso terapéutico , Animales , Apoptosis/fisiología , MAP Quinasa Quinasa Quinasa 5/metabolismo , Masculino , Infarto del Miocardio/enzimología , Infarto del Miocardio/patología , Daño por Reperfusión Miocárdica/enzimología , Daño por Reperfusión Miocárdica/patología , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/enzimología , Miocitos Cardíacos/patología , Inhibidores de Proteínas Quinasas/farmacología , Ratas , Ratas Sprague-DawleyRESUMEN
Acute myocardial infarction (AMI) with subsequent left ventricular dysfunction and heart failure continues to be a major cause of morbidity and mortality in the Western world. Rapid advances in the treatment of AMI, mainly through timely reperfusion, have substantially improved outcomes in patients presenting with acute coronary syndrome and particularly ST-segment elevation myocardial infarction. A vast amount of research, both translational and clinical, has been published on various pharmacological and interventional techniques to prevent myocardial cell death during the time of ischemia and subsequent reperfusion. Several methods of cardioprotection have shown the ability to limit myocardial infarction size in clinical trials. Examples of interventional techniques that have proven beneficial are ischemic post-conditioning and remote ischemic per-conditioning, both of which can reduce infarction size. Lowering core body temperature with cold saline infusion and cooling catheters have also been shown to be effective in certain circumstances. The most promising pharmaceutical cardioprotective agents at this time appear to be adenosine, atrial natriuretic peptide, and cyclosporine, with other potentially effective medications in the pipeline. Additional pre-clinical and clinical research is needed to further investigate newer cardioprotective strategies to continue the current trend of improving outcomes following AMI.
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Cardiotónicos/uso terapéutico , Infarto del Miocardio/terapia , Daño por Reperfusión/prevención & control , Adenosina/uso terapéutico , Antagonistas Adrenérgicos beta/uso terapéutico , Factor Natriurético Atrial/uso terapéutico , Quimioterapia Adyuvante , Ensayos Clínicos como Asunto , Vasos Coronarios , Humanos , Poscondicionamiento IsquémicoRESUMEN
The attempt to find treatments that will reduce myocardial cell death during periods of ischemia and subsequent reperfusion has spanned nearly 40 years. Although many therapies have shown promise in animal models, relatively few have been successful in clinical trials. Some of the most effective clinical therapies involve techniques designed to elicit the heart's own innate capacity to protect itself. The ability of the heart to render itself more resistant to ischemia/reperfusion injury was not appreciated until the description of ischemic preconditioning in 1986. Following the discovery that brief, nonlethal episodes of ischemia conditioned the heart to better tolerate a subsequent prolonged episode of ischemia, alternative ways of evoking this endogenous cardioprotection were described. Ischemic postconditioning and remote conditioning are potentially useful tools for protecting ischemic myocardium, and have been shown to be beneficial in small clinical trials. Several pharmacologic agents have the ability to mimic the effects of ischemic conditioning and can also reduce the amount of cell death during ischemia/reperfusion. This article provides the clinician with an overview of the different techniques of ischemic conditioning and how they can protect the myocardium from ischemia/reperfusion injury. Additionally, several pharmacologic agents that can protect the heart in a similar manner are discussed.
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Cardiotónicos/uso terapéutico , Precondicionamiento Isquémico Miocárdico/métodos , Animales , Procedimientos Quirúrgicos Cardíacos/métodos , Corazón/fisiopatología , Humanos , Infarto del Miocardio/complicaciones , Infarto del Miocardio/fisiopatologíaRESUMEN
A 72-year-old man was hospitalized for transurethral resection of bladder cancer. Two days after the procedure, the patient continued to have gross hematuria and a computed tomography (CT) scan of the abdomen and pelvis with intravenous contrast was performed to check the integrity of the resection site. Later that day, the patient underwent technetium-99m methylene diphosphonate (MDP) bone scintigraphy to investigate the possibility of bone metastasis. The bone scan showed no signs of metastasis but did reveal increased uptake of the left hand and forearm on the opposite side of the injection site.