Asunto(s)
Oclusión Coronaria/terapia , Vasos Coronarios/diagnóstico por imagen , Lesiones Cardíacas/diagnóstico por imagen , Hematoma/diagnóstico por imagen , Intervención Coronaria Percutánea/efectos adversos , Ultrasonografía Intervencional , Enfermedad Crónica , Angiografía Coronaria , Oclusión Coronaria/diagnóstico por imagen , Vasos Coronarios/lesiones , Lesiones Cardíacas/etiología , Hematoma/etiología , Humanos , Masculino , Persona de Mediana Edad , Intervención Coronaria Percutánea/instrumentación , Valor Predictivo de las Pruebas , StentsRESUMEN
BACKGROUND: Ablation of right ventricular outflow tract (RVOT) ventricular arrhythmia (VA) within the left pulmonary sinus of Valsalva (LPSV) may increase the risk of left main coronary artery (LMCA) injury. PURPOSE: To delineate the anatomical characteristics between LMCA and LPSV and their association with atrial potential (AP) mapping in LPSV. METHODS: A total of 104 consecutive patients with RVOT-VA undergoing cardiac-gated computed tomography coronary angiography (CTCA) after ablation were retrospectively analyzed. RESULTS: The LMCA-LPSV anatomic relationship was classified into three types based on the CTCA measurements. Types 1 and 2 had a shorter LMCA-LPSV distance than that of type 3 (P < .001). The left atrial appendage (LAA)-LMCA distance and LAA-LPSV distance were associated with the incidence of AP in LPSV (odds ratio [OR] = 3.43, 95% confidence interval [CI]: 1.86-6.34, P < .001; OR = 1.196, 95% CI: 1.09-1.31, P < .001, respectively). Furthermore, the LMCA-LPSV distance showed a linear correlation with the LAA-LPSV distance (r2 = 0.93, P < .001). According to receiver operating characteristic (ROC) analysis, a LMCA-LPSV distance <5.4 mm could predict the possibility of AP during LPSV mapping (sensitivity 83%, specificity 81%, and area under the ROC curve 0.86). CONCLUSIONS: The presence of AP in the LPSV may be useful to predict a short distance from the LPSV to the LMCA and to identify patients at higher risk of LMCA injury. This information may contribute to efficient and safe ablation in this area but should be confirmed in future studies.
Asunto(s)
Potenciales de Acción , Angiografía por Tomografía Computarizada , Angiografía Coronaria , Vasos Coronarios/diagnóstico por imagen , Técnicas Electrofisiológicas Cardíacas , Frecuencia Cardíaca , Seno Aórtico/fisiopatología , Taquicardia Ventricular/diagnóstico , Complejos Prematuros Ventriculares/diagnóstico , Anciano , Anciano de 80 o más Años , Apéndice Atrial/diagnóstico por imagen , Técnicas de Imagen Sincronizada Cardíacas , Ablación por Catéter/efectos adversos , Vasos Coronarios/lesiones , Femenino , Lesiones Cardíacas/etiología , Lesiones Cardíacas/prevención & control , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Estudios Retrospectivos , Factores de Riesgo , Seno Aórtico/diagnóstico por imagen , Seno Aórtico/cirugía , Taquicardia Ventricular/fisiopatología , Taquicardia Ventricular/cirugía , Resultado del Tratamiento , Complejos Prematuros Ventriculares/fisiopatología , Complejos Prematuros Ventriculares/cirugíaAsunto(s)
Angioplastia Coronaria con Balón/métodos , Disección Aórtica , Traumatismos en Atletas/complicaciones , Dolor en el Pecho , Angiografía Coronaria/métodos , Ecocardiografía/métodos , Electrocardiografía/métodos , Artes Marciales , Infarto del Miocardio con Elevación del ST , Abciximab/administración & dosificación , Adulto , Disección Aórtica/diagnóstico , Disección Aórtica/etiología , Disección Aórtica/fisiopatología , Anticoagulantes/administración & dosificación , Dolor en el Pecho/diagnóstico , Dolor en el Pecho/etiología , Vasos Coronarios/diagnóstico por imagen , Vasos Coronarios/lesiones , Diagnóstico Diferencial , Humanos , Masculino , Fragmentos de Péptidos/análisis , Infarto del Miocardio con Elevación del ST/diagnóstico , Infarto del Miocardio con Elevación del ST/etiología , Infarto del Miocardio con Elevación del ST/fisiopatología , Infarto del Miocardio con Elevación del ST/terapia , Resultado del Tratamiento , Troponina I/análisisRESUMEN
A previously healthy 38-year-old man was admitted to hospital with chest pain. The day before the patient had been to a karate session and had received multiple punches and kicks to the chest region. An ECG showed Q-waves in V1 and V2 and flattening of the T-waves in V1-V6. Levels of cardiac enzyme markers were elevated. The patient subsequently underwent coronary angiography with supplemental optical coherence tomography that revealed a bifurcate dissection involving the proximal parts of left ramus interventricularis anterior and circumflex coronary artery. Two drug-eluting stents were implanted with good angiographic result.
Asunto(s)
Disección Aórtica/etiología , Vasos Coronarios/lesiones , Traumatismos Torácicos/complicaciones , Heridas no Penetrantes/complicaciones , Adulto , Disección Aórtica/diagnóstico por imagen , Disección Aórtica/cirugía , Angiografía Coronaria , Vasos Coronarios/cirugía , Stents Liberadores de Fármacos , Humanos , Masculino , Artes Marciales/lesiones , Traumatismos Torácicos/diagnóstico por imagen , Traumatismos Torácicos/cirugía , Tomografía de Coherencia Óptica , Heridas no Penetrantes/diagnóstico por imagen , Heridas no Penetrantes/cirugíaRESUMEN
Coronary artery injury such as acute coronary dissection is an uncommon and potentially life-threatening complication after blunt chest trauma. The authors report an unusual autopsy case of a 43-year-old healthy man who suddenly collapsed after receiving a punch to the chest during the practice of kung fu. The occurrence of the punch was supported by the presence of one recent contusion on the left lateral chest area at the external examination and by areas of hemorrhage next to the left lateral intercostal spaces at the internal examination. The histological examination revealed the presence of an acute dissection of the proximal segment of the left anterior descending coronary artery. Only few cases of coronary artery dissection have been reported due to trauma during sports activities such as rugby and soccer games, but never during the practice of martial arts, sports usually considered as safe and responsible for only minor trauma.
Asunto(s)
Vasos Coronarios/lesiones , Artes Marciales , Traumatismos Torácicos/complicaciones , Heridas no Penetrantes/complicaciones , Accidentes , Adulto , Contusiones/etiología , Contusiones/patología , Vasos Coronarios/patología , Resultado Fatal , Patologia Forense , Hemorragia/etiología , Hemorragia/patología , Humanos , Masculino , Traumatismos Torácicos/etiología , Heridas no Penetrantes/etiologíaRESUMEN
BACKGROUND: Catheter ablation for ventricular arrhythmia (VA) near the distal great cardiac vein (GCV) is often challenging, and data are limited. METHODS AND RESULTS: Analysis was performed in 30 patients (19 men; age, 52.8±15.5 years) who underwent catheter ablation for focal VA (11 ventricular tachycardia and 19 premature contractions) with early activation in the GCV (36.7±8.0 ms pre-QRS). Angiography in 27 patients showed earliest GCV site within 5 mm of a coronary artery in 20 (74%). Ablation was performed in the GCV in 15 patients and abolished VA in 8. Ablation was attempted at adjacent non-GCV sites in 19 patients and abolished VA in 5 patients (4 from the left ventricular endocardium and 1 from the left coronary cusp); all success had VA with an initial r wave in lead I and activation ≤7 ms after the GCV (GCV-non-GCV interval). In 13 patients, percutaneous epicardial mapping was performed, but because of adjacent coronaries only 2 received radiofrequency application with VA elimination in 1. Surgical cryoablation was performed in 3 patients and abolished VA in 2. Overall acute success was achieved in 16 (53%) patients. After a median of 2.8 months, 13 patients remained free of VA. Major complications occurred in 4 patients, including coronary injury requiring stenting. CONCLUSIONS: Ablation for this arrhythmia is challenging and often limited by the adjacent coronary vessels. Success of anatomically guided endocardial ablation may be identified by a short GCV-non-GCV interval and r wave in lead I.
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Vasos Coronarios , Ventrículos Cardíacos/cirugía , Taquicardia Ventricular/cirugía , Complejos Prematuros Ventriculares/cirugía , Adulto , Anciano , Ablación por Catéter/efectos adversos , Angiografía Coronaria , Vasos Coronarios/diagnóstico por imagen , Vasos Coronarios/lesiones , Electrocardiografía , Técnicas Electrofisiológicas Cardíacas , Femenino , Lesiones Cardíacas/etiología , Ventrículos Cardíacos/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Selección de Paciente , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Factores de Riesgo , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/fisiopatología , Resultado del Tratamiento , Lesiones del Sistema Vascular/etiología , Complejos Prematuros Ventriculares/diagnóstico , Complejos Prematuros Ventriculares/fisiopatologíaRESUMEN
We report a case of 62-year-old man with cardiac tamponade due to coronary artery injury after acupuncture into the substernum. After resuscitation of cardiac arrest, we performed emergent pericardiocentesis. Nevertheless, the cardiac arrest recurred, and the emergent operation on cardiopulmonary bypass was performed. We identified hemopericardium due to shredded acute marginal branch of right coronary artery, and it was ligated leading to termination of bleeding. The patient was discharged without any other complications.
Asunto(s)
Terapia por Acupuntura/efectos adversos , Taponamiento Cardíaco/diagnóstico , Vasos Coronarios/lesiones , Derrame Pericárdico/diagnóstico , Taponamiento Cardíaco/etiología , Humanos , Masculino , Persona de Mediana Edad , Derrame Pericárdico/etiologíaRESUMEN
We report a case of 62-year-old man with cardiac tamponade due to coronary artery injury after acupuncture into the substernum. After resuscitation of cardiac arrest, we performed emergent pericardiocentesis. Nevertheless, the cardiac arrest recurred, and the emergent operation on cardiopulmonary bypass was performed. We identified hemopericardium due to shredded acute marginal branch of right coronary artery, and it was ligated leading to termination of bleeding. The patient was discharged without any other complications.
Asunto(s)
Humanos , Masculino , Persona de Mediana Edad , Terapia por Acupuntura/efectos adversos , Taponamiento Cardíaco/diagnóstico , Vasos Coronarios/lesiones , Derrame Pericárdico/diagnósticoRESUMEN
OBJECTIVE: The objective of this study was to evaluate the use of continuous catheter impedance monitoring prior to ablation to facilitate differentiation of the coronary sinus ostium (CSO) and the middle cardiac vein (MCV) from the right atrial posteroseptal region (RPS). BACKGROUND: Empiric observations have suggested that continuous catheter impedance monitoring could differentiate the CSO and MCV from the RPS region. Radiofrequency ablation in the MCV or coronary sinus has been associated with coronary artery injury. Differentiation of these areas may be difficult with either fluoroscopy or electrogram characteristics. METHODS AND RESULTS: Continuous impedance measurements using a 4-mm Navistar (Biosense Webster) ablation catheter were conducted in 17 consecutive patients undergoing ablation for supraventricular tachycardia. The average impedance value was recorded at the right atrial septum (RS) posterior to the bundle of His, the RPS region, within 1 cm inside the CSO and in the MCV. These areas were confirmed and demarcated with 3-D mapping and biplane fluoroscopy. A significant increase in impedance was observed between the CSO (X = 146.6 ± 24.8) and RPS [Formula: see text] regions (p < 0.001). Furthermore, a significant rise in impedance was seen between the MCV [Formula: see text] and RPS and CSO, respectively (p < 0.001). No significant change in impedance was found between the RS [Formula: see text] and RPS regions. CONCLUSIONS: Continuous impedance measurements during mapping can facilitate differentiation of catheter locations inside the CSO and MCV from extracoronary sinus regions. This may reduce the risk of inadvertent coronary artery damage during the ablation procedure.
Asunto(s)
Ablación por Catéter/efectos adversos , Ablación por Catéter/instrumentación , Seno Coronario/lesiones , Vasos Coronarios/lesiones , Migración de Cuerpo Extraño/diagnóstico , Taquicardia por Reentrada en el Nodo Atrioventricular/cirugía , Adulto , Anciano , Cateterismo Cardíaco , Impedancia Eléctrica , Electrocardiografía , Técnicas Electrofisiológicas Cardíacas , Femenino , Humanos , Masculino , Persona de Mediana Edad , Taquicardia por Reentrada en el Nodo Atrioventricular/fisiopatología , Resultado del TratamientoRESUMEN
Early growth response 1 (Egr-1) over-expression has been demonstrated in myocardial ischemia-reperfusion injury, which is closely associated with endothelial dysfunction. In the present study we investigated the expression of Egr-1 on cultured cardiac microvascular endothelial cells (CMECs) to help define the mechanism of myocardial ischemia-reperfusion injury. A model of cultured CMECs exposed to hypoxia-reoxygenation was developed in which synthesized Egr-1 sense and antisense oligodeoxyribonucleotide were transfected into the cells. The expression of Egr-1 was examined by Western blot analysis. Lactate dehydrogenase, malondialdehyde, superoxide dismutase, tumor necrosis factor alpha, and intercellular adhesion molecule 1 were measured after hypoxia-reoxygenation to assess cell function and injury. Cell morphology, cell viability, and neutrophil adhesion to the CMECs were measured to assess the degree of injury and inflammation. Only cells transfected with Egr-1 antisense oligodeoxyribonucleotide showed a significant reduction in Egr-1 protein expression following hypoxia-reoxygenation. Consistent with the down-regulation of Egr-1 expression, other forms of cell injury were significantly reduced in this group of cells, as evidenced by less alteration in cell morphology, a decrease in expression of tumor necrosis factor alpha and intercellular adhesion molecule 1, improved cell survival, and reduced neutrophil adhesion.
Asunto(s)
Vasos Coronarios/lesiones , Proteína 1 de la Respuesta de Crecimiento Precoz/antagonistas & inhibidores , Daño por Reperfusión Miocárdica/prevención & control , Oligodesoxirribonucleótidos Antisentido/farmacología , Animales , Animales Recién Nacidos , Cardiotónicos/farmacología , Células Cultivadas , Vasos Coronarios/efectos de los fármacos , Vasos Coronarios/metabolismo , Vasos Coronarios/patología , Citoprotección/efectos de los fármacos , Citoprotección/genética , Evaluación Preclínica de Medicamentos , Proteína 1 de la Respuesta de Crecimiento Precoz/genética , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/patología , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Regulación de la Expresión Génica/genética , Masculino , Microvasos/efectos de los fármacos , Microvasos/lesiones , Microvasos/metabolismo , Microvasos/patología , Daño por Reperfusión Miocárdica/genética , Daño por Reperfusión Miocárdica/patología , Oligodesoxirribonucleótidos Antisentido/uso terapéutico , Ratas , Ratas Sprague-DawleyRESUMEN
Originalmente las arterias coronarias podían ser visualizadas directamente al abrir el tórax, luego mediante la cinecoronariografía e indirectamente con las pruebas no invasivas, que se desarrollaron para inferir el grado de obstrucción coronaria de acuerdo a la isquemia miocárdica inducida por el aumento de los requerimientos miocárdicos de oxígeno. La tomografía de las arterias coronarias permite su observación directa de una manera no invasiva, con las limitaciones propias de la irradiación y del contraste iodado. Sus indicaciones se están estableciendo en forma acelerada y su valor predictivo negativo es cercano al 100 por ciento, lo cual hace a esta nueva técnica una excelente herramienta para el diagnóstico de la enfermedad coronaria, a la vez de poder observar la función ventricular izquierda y órganos adyacentes al corazón.
Originally the coronary arteries could only be visualized when a thoracotomy was performed and thereafter with coronary arteriography. With the purpose of inferring the degree of coronary artery narrowing the so called non invasive test were developed to induce myocardial ischemia by an increase of myocardial oxygen demands. Multislice compared tomography offers the possibility of "seeing" the coronary arteries for the first time non-invasively, with the proper limitations of radiation and iodine contrast administration. Its indications are rapidly changing with a negative predictive value close to 100%, which makes this diagnostic tool unique for a better assessment not only of the coronary arteries but also of the left ventricular function and anatomy of its surrounding structures.
Asunto(s)
Humanos , Masculino , Femenino , Angiografía Coronaria/métodos , Enfermedad Coronaria/diagnóstico , Enfermedad Coronaria/patología , Isquemia Miocárdica/etiología , Vasos Coronarios/anatomía & histología , Vasos Coronarios/lesiones , Arritmias Cardíacas/fisiopatología , Técnicas Electrofisiológicas Cardíacas/métodos , Ultrasonografía , VenezuelaRESUMEN
Coronary sinus (CS) dissection during biventricular pacing electrode implantation is a complication that rarely develops. A 71-year-old female with recurrent ventricular tachycardia, heart decompensation, and poor left ventricular function because of dilated cardiomyopathy was admitted for the implantation of a cardioverter-defibrillator for biventricular pacing. During the operation, we experienced a CS dissection with hematoma in the left ventricle wall while introducing the guidance catheter into the CS. However, the pacing lead was successfully implanted into the posterolateral vein using the "over-the-wire" technique. The postoperative electrocardiogram showed a decreased QRS; meanwhile, the echocardiography revealed dimensional reduction and functional improvement of the left ventricle.
Asunto(s)
Estimulación Cardíaca Artificial/efectos adversos , Vasos Coronarios/lesiones , Anciano , Cateterismo Cardíaco/efectos adversos , Cardiomiopatía Dilatada/complicaciones , Electrodos Implantados/efectos adversos , Técnicas Electrofisiológicas Cardíacas , Femenino , Humanos , Taquicardia Ventricular/etiología , Taquicardia Ventricular/terapiaRESUMEN
Coronary artery disease remains a major problem for Western societies. The advent of percutaneous interventions, including stents has brought clinical care to a new level of efficacy, yet problems remain. Restenosis following stenting in human coronary arteries appears at last to be yielding to therapeutic strategies, especially drug eluting stents. Because therapeutic percutaneous coronary intervention is widely dominated by the intracoronary stent, restenosis therapies must include the stented coronary artery. Animal models and in particular the porcine coronary model seem to represent the human coronary artery reaction to stenting. It mimics several clinical conditions including thrombosis and neointimal formation. A key question in the era of intravascular technologies is how well this and other models can predict clinical events. This paper discusses the models and their application.
Asunto(s)
Enfermedad de la Arteria Coronaria/patología , Reestenosis Coronaria/patología , Modelos Animales de Enfermedad , Stents/efectos adversos , Animales , Enfermedad de la Arteria Coronaria/etiología , Enfermedad de la Arteria Coronaria/terapia , Reestenosis Coronaria/complicaciones , Reestenosis Coronaria/prevención & control , Trombosis Coronaria/etiología , Trombosis Coronaria/patología , Vasos Coronarios/lesiones , Vasos Coronarios/patología , Perros , Evaluación Preclínica de Medicamentos , Conejos , Ratas , Porcinos , Túnica Íntima/patologíaRESUMEN
HMG-CoA reductase inhibitors and calcium channel blockers have antiatherogenic effects; however, their mechanisms remain to be elucidated. This study examined the effect of cerivastatin and/or nifedipine on the endothelial dysfunction in porcine balloon-injured coronary arteries. Normal male pigs were randomly divided into the following four groups: control, cerivastatin (1 mg/kg/d PO), nifedipine (4 mg/kg/d PO), and their combination (n = 10 each). We started the treatments 3 days before balloon injury in the proximal left coronary arteries and continued for 4 weeks after the procedure. Then, we examined endothelial vasodilator functions ex vivo in organ chambers and in vitro by Western blotting for eNOS expression. Endothelium-dependent relaxations to serotonin, but not those to bradykinin or the calcium ionophore A23187 or endothelium-independent relaxations to sodium nitroprusside, were significantly impaired by balloon injury. The monotherapy with cerivastatin or nifedipine partially improved, and their combination supernormalized the relaxations to serotonin without affecting those to bradykinin or A23187 or endothelium-independent relaxations to sodium nitroprusside. The expression of eNOS was significantly reduced by balloon injury and normalized by the combination therapy. These results indicate that the combination therapy improves endothelial dysfunction after balloon injury, in which the up-regulation of eNOS may be involved.
Asunto(s)
Vasos Coronarios/efectos de los fármacos , Endotelio Vascular/efectos de los fármacos , Nifedipino/farmacología , Piridinas/farmacología , Administración Oral , Animales , Análisis Químico de la Sangre , Western Blotting , Bradiquinina/farmacología , Calcimicina/farmacología , Cateterismo/efectos adversos , Cateterismo/métodos , Angiografía Coronaria/métodos , Vasos Coronarios/lesiones , Vasos Coronarios/fisiopatología , Relación Dosis-Respuesta a Droga , Quimioterapia Combinada , Endotelio Vascular/lesiones , Endotelio Vascular/fisiopatología , Inhibidores de Hidroximetilglutaril-CoA Reductasas/administración & dosificación , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Técnicas In Vitro , Masculino , Nifedipino/administración & dosificación , Nifedipino/uso terapéutico , Donantes de Óxido Nítrico/farmacología , Óxido Nítrico Sintasa de Tipo III/metabolismo , Nitroprusiato/farmacología , Piridinas/administración & dosificación , Piridinas/uso terapéutico , Serotonina/farmacología , Porcinos , Vasodilatación/efectos de los fármacos , Vasodilatadores/administración & dosificación , Vasodilatadores/farmacología , Vasodilatadores/uso terapéuticoRESUMEN
OBJECTIVE: Allograft inflammatory factor-1 (AIF-1) is associated with vascular smooth muscle cell (VSMC) activation and vascular injury. The purpose of this study was to characterize the molecular mechanism of AIF-1 growth-enhancing effects in human VSMC. METHODS AND RESULTS: Primary human VSMCs were stably transduced with AIF-1 retrovirus (RV). Impact on cell growth was evaluated by the increase in cell number, and the effects on gene expression were determined by cDNA microarray analysis. AIF-RV overexpressing cells grew significantly more rapidly than empty-RV control cells in growth medium and serum-reduced medium (P<0.01 and 0.02, respectively). cDNA microarray analysis and Western blotting on serum-starved AIF-1-transduced VSMCs identified increased mRNA expression of several cell cycle proteins and, surprisingly, the cytokine G-CSF. Addition of G-CSF caused a 75% increase in proliferation of VSMCs in the absence of serum growth factors. The proliferative effects of AIF-1 were abrogated by neutralizing antibodies to G-CSF (P<0.05), and AIF-1-transduced VSMCs are chemotactic for human monocytes. Increased expression of G-CSF and colocalization with AIF-1 positive cells were seen in diseased, not normal human coronary arteries. CONCLUSIONS: This study indicates that AIF-1 enhances VSMC growth by autocrine production of G-CSF, and AIF-1 expression may influence VSMC-inflammatory cell communication.
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Comunicación Autocrina/fisiología , Proteínas de Unión al ADN/fisiología , Miocitos del Músculo Liso/metabolismo , Proteínas de Unión al Calcio , Proteínas de Ciclo Celular/biosíntesis , Proteínas de Ciclo Celular/genética , División Celular/efectos de los fármacos , Células Cultivadas/efectos de los fármacos , Células Cultivadas/metabolismo , Quimiotaxis/efectos de los fármacos , Vasos Coronarios/citología , Vasos Coronarios/lesiones , Vasos Coronarios/patología , ADN Complementario/genética , Proteínas de Unión al ADN/genética , Relación Dosis-Respuesta a Droga , Perfilación de la Expresión Génica , Factor Estimulante de Colonias de Granulocitos/biosíntesis , Factor Estimulante de Colonias de Granulocitos/genética , Factor Estimulante de Colonias de Granulocitos/farmacología , Humanos , Proteínas de Microfilamentos , Monocitos/efectos de los fármacos , Monocitos/metabolismo , Miocitos del Músculo Liso/citología , Análisis de Secuencia por Matrices de Oligonucleótidos , Proteínas Recombinantes de Fusión/fisiología , Transducción Genética , Túnica Íntima/patologíaRESUMEN
We investigated effects of sasanquasaponin (SQS), a traditional Chinese herb's effective component, on ischemia and reperfusion injury in mouse hearts and the possible role of intracellular Cl- homeostasis on SQS's protective effects during ischemia and reperfusion. An in vivo experimental ischemia model was made in mice (weight 27-45 g) using ligation of left anterior descending coronary artery, and in vitro models were made in perfused hearts by stopping flow or in isolated ventricular myocytes by hypoxia. The in vivo results showed that SQS inhibited cardiac arrhythmias during ischemia and reperfusion. Incidence of arrhythmias during ischemia and reperfusion, including ventricular premature beats and ventricular fibrillation, was significantly decreased in the SQS-pretreated group (P<0.05). Results in perfused hearts showed that SQS suppressed the arrhythmias, prevented against ischemia-induced decrease in contract force and promoted the force recovery from reperfusion. Furthermore, intracellular Cl- concentrations ([Cl-]i) were measured using a MQAE fluorescence method in isolated ventricular myocytes in vitro. SQS slightly decreased [Cl-]i in non-hypoxic myocytes and delayed the hypoxia/reoxygenation-induced increase in [Cl-]i during ischemia and reperfusion (P<0.05). Our results showed that SQS protected against ischemia/reperfusion-induced cardiac injury in mouse hearts and that modulation of intracellular Cl- homeostasis by SQS would play a role in its anti-arrhythmia effects during ischemia and reperfusion.
Asunto(s)
Medicamentos Herbarios Chinos/uso terapéutico , Isquemia/tratamiento farmacológico , Daño por Reperfusión Miocárdica/tratamiento farmacológico , Saponinas/uso terapéutico , Potenciales de Acción/efectos de los fármacos , Animales , Arritmias Cardíacas/complicaciones , Arritmias Cardíacas/tratamiento farmacológico , Arritmias Cardíacas/prevención & control , Presión Sanguínea/efectos de los fármacos , Cloruros/metabolismo , Vasos Coronarios/lesiones , Vasos Coronarios/patología , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos/métodos , Frecuencia Cardíaca/efectos de los fármacos , Inyecciones Intravenosas , Espacio Intracelular/efectos de los fármacos , Espacio Intracelular/metabolismo , Isquemia/complicaciones , Isquemia/fisiopatología , Masculino , Medicina Tradicional China , Ratones , Ratones Endogámicos ICR , Contracción Miocárdica/efectos de los fármacos , Contracción Miocárdica/fisiología , Daño por Reperfusión Miocárdica/complicaciones , Daño por Reperfusión Miocárdica/fisiopatología , Miocitos Cardíacos/metabolismo , Músculos Papilares/citología , Músculos Papilares/efectos de los fármacos , Músculos Papilares/fisiología , Perfusión/métodos , Plantas Medicinales/química , Saponinas/química , Saponinas/aislamiento & purificación , Saponinas/farmacología , Factores de TiempoRESUMEN
1. Peroxisome proliferator activated receptor gamma (PPARgamma) has been implicated in several cellular pathways assumed to beneficially affect heart failure progression. In contrast, population-based studies demonstrate an increased incidence of heart failure in patients treated with PPARgamma agonists. Therefore, we examined the effect of pioglitazone, a PPARgamma agonist, on chronic left ventricular remodeling after experimental myocardial infarction (MI) in mice. 2. Mice were treated with placebo or pioglitazone (20 mg x kg(-1) by gavage) from week 1 to week 6 after ligation of the left anterior descending artery. Serial transthoracic echocardiography was performed at weeks 1, 3, and 6. 3. Over 6 weeks, there was no difference in mortality (placebo 12%, pioglitazone 10%). Echocardiography showed significant left ventricular dilatation in animals with MI (week 6, end-systolic area, placebo sham 9.6+/-1.3 vs placebo MI 14.4+/-2.5 mm(2)). However, there was no difference between the placebo and pioglitazone groups (week 6, end-systolic area, pioglitazone MI 14.8+/-2.9 mm(2), P=NS vs placebo). 4. Moreover, there were no changes in metabolic parameters, inflammation, and collagen deposition. Endothelial function in the aorta was not changed by PPARgamma activation. 5. In conclusion, PPARgamma activation did not adversely affect left ventricular remodeling and survival in mice with chronic MI. However, we were also not able to identify a protective effect of pioglitazone.
Asunto(s)
Modelos Animales de Enfermedad , Infarto del Miocardio/fisiopatología , Remodelación Ventricular/fisiología , Animales , Aorta/citología , Aorta/efectos de los fármacos , Glucemia , Peso Corporal/efectos de los fármacos , Enfermedad Crónica , Colágeno/química , Vasos Coronarios/lesiones , Citocinas/sangre , Evaluación Preclínica de Medicamentos , Ecocardiografía/métodos , Endotelina-1/sangre , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/fisiología , Mediadores de Inflamación/sangre , Intubación Gastrointestinal , Masculino , Ratones , Ratones Endogámicos C57BL , Infarto del Miocardio/etiología , Infarto del Miocardio/mortalidad , Miocardio/química , Miocardio/ultraestructura , Tamaño de los Órganos/efectos de los fármacos , Fenilefrina/farmacología , Pioglitazona , Tiazolidinedionas/administración & dosificación , Tiazolidinedionas/farmacocinética , Tiazolidinedionas/uso terapéutico , Triglicéridos/sangre , Vasoconstricción/efectos de los fármacos , Disfunción Ventricular Izquierda/diagnóstico , Remodelación Ventricular/efectos de los fármacosRESUMEN
BACKGROUND: We used a novel lipopolymeric gene delivery system, TeplexDNA, to transfect myocardium with plasmid vascular endothelial growth factor-165 (pVEGF) and evaluated the ability of pVEGF to preserve left ventricular function and structure after coronary ligation in a rabbit model. METHODS: New Zealand white rabbits underwent circumflex coronary ligation after direct intramyocardial injection of either Terplex alone or Terplex + 50 microg pVEGF-165. Serial echocardiography and histologic studies were performed (n = 12/group). Mortality did not differ between groups. The data is reported as the mean +/- standard deviation. RESULTS: Over the 21 days following coronary ligation, pVEGF-165-treated animals demonstrated significant improvement in fractional shortening (20-25%, p = 0.02), long axis two-dimensional ejection fraction (42-51%, p=0.02) and short axis m-mode ejection fraction (46-54%, p = 0.02). No significant improvements were noted in the control group. VEGF-treated animals had a 50% increase in peri-infarct vessel density and a trend towards a smaller infarct size (20% vs. 29%, p = 0.10). In animals receiving pVEGF-165, the diastolic ventricular area increased from 1.87 +/- 0.24 cm2 prior to ligation to 2.19 +/- 0.23 cm2 at 21 days following ligation, compared to an increase from 1.84 +/- 0.38 to 2.54 +/- 0.55 cm2 over the same period in control animals (p = 0.03). Similarly, the systolic ventricular area in VEGF-165 animals increased from 1.06 +/- 0.26 cm2 prior to ligation to 1.50 +/- 0.29 cm2 at 21 days following ligation, compared to an increase from 1.16 +/- 0.30 to 1.86 +/- 0.43 cm2 over the same period in the control animals (p = 0.04). CONCLUSION: TerplexDNA mediated delivery of plasmid VEGF administered at the time of coronary occlusion improves left ventricular function and reduces left ventricular dilation following myocardial infarction.