RESUMEN
This study was designed to determine if a viable biodegradable three-dimensional fibroblast construct (3DFC) patch implanted on the left ventricle after myocardial infarction (MI) improves left ventricular (LV) function and blood flow. We ligated the left coronary artery of adult male Sprague-Dawley rats and implanted the 3DFC at the time of the infarct. Three weeks after MI, the 3DFC improved LV systolic function by increasing (p < 0.05) ejection fraction (37 +/- 3% to 62 +/- 5%), increasing regional systolic displacement of the infarcted wall (0.04 +/- 0.02 to 0.11 +/- 0.03 cm), and shifting the passive LV diastolic pressure volume relationship toward the pressure axis. The 3FDC improved LV remodeling by decreasing (p < 0.05) LV end-systolic and end-diastolic diameters with no change in LV systolic pressure. The 3DFC did not change LV end-diastolic pressure (LV EDP; 25 +/- 2 vs. 23 +/- 2 mmHg) but the addition of captopril (2mg/L drinking water) lowered (p < 0.05) LV EDP to 12.9 +/- 2.5 mmHg and shifted the pressure-volume relationship toward the pressure axis and decreased (p < 0.05) the LV operating end-diastolic volume from 0.49 +/- 0.02 to 0.34 +/- 0.03 ml. The 3DFC increased myocardial blood flow to the infarcted anterior wall after MI over threefold (p < 0.05). This biodegradable 3DFC patch improves LV function and myocardial blood flow 3 weeks after MI. This is a potentially new approach to cell-based therapy for heart failure after MI.
Asunto(s)
Circulación Coronaria/fisiología , Matriz Extracelular/trasplante , Fibroblastos/trasplante , Infarto del Miocardio/fisiopatología , Implantación de Prótesis , Función Ventricular Izquierda/fisiología , Enfermedad Aguda , Animales , Presión Sanguínea/efectos de los fármacos , Captopril/farmacología , Circulación Coronaria/efectos de los fármacos , Ecocardiografía , Matriz Extracelular/efectos de los fármacos , Factor VIII/metabolismo , Fibroblastos/efectos de los fármacos , Fibroblastos/ultraestructura , Hemodinámica/efectos de los fármacos , Ratas , Flujo Sanguíneo Regional/efectos de los fármacos , Sístole/efectos de los fármacos , Función Ventricular Izquierda/efectos de los fármacosRESUMEN
Despite the fact that the incidence of cardiac tumors is low, the prompt evaluation and adequate intervention of these is highly important. Although most tumors of the heart are considered histologically benign, there are significant risks associated with these "benign" tumors. These are associated with significant morbidity and mortality due to obstruction of blood flow, alterations of conduction, propagation of arrhythmias, and thromboembolism, depending on their size, location, and nature. With the advent of noninvasive imaging modalities--traditionally echocardiography; but more recently using cross-sectional imaging with cardiac computed tomography and magnetic resonance imaging--cardiac tumors can be optimally assessed providing a greater opportunity for curative treatments by cardiothoracic surgery.
Asunto(s)
Ecocardiografía/métodos , Neoplasias Cardíacas/diagnóstico por imagen , Neoplasias Cardíacas/diagnóstico , Imagen por Resonancia Magnética/métodos , Diagnóstico Diferencial , Neoplasias Cardíacas/epidemiología , Humanos , PrevalenciaRESUMEN
BACKGROUND: This study was designed to determine the effects of pretreatment with an angiotensin receptor blocker on left ventricular (LV) function and remodeling during acute myocardial infarction (MI). METHODS AND RESULTS: Sprague-Dawley rats were pretreated with candesartan (10 mg x kg(-1) x d(-1)) for 2 weeks and studied at 1, 3, and 6 minutes after MI. Compared with untreated rats, pretreatment with candesartan lowered (P<0.05) LV systolic pressure and the first derivative of LV pressure with respect to time but did not change LV end-diastolic pressure or improve LV regional function. With candesartan pretreatment, LV fractional shortening and ejection fraction increased (P<0.05) by 37% and 28%, and LV chamber dilation was attenuated (P<0.05). At 6 minutes after MI, LV endothelial nitric oxide synthase decreased in the infarcted and noninfarcted wall 47% (P=0.04) and 70% (P=0.002), and constitutive microtubulin increased 260% (P=0.0005) and 111% (P=0.003). Candesartan had no effect on LV tissue endothelial nitric oxide synthase levels but attenuated the increase in constitutive microtubulin by 77% (P=0.004) and 37% (P<0.05). CONCLUSIONS: Pretreatment with candesartan before an acute MI improves global LV function, prevents LV dilation, and blunts the increase in constitutive microtubulin, with minimal effects on LV hemodynamics, regional function, or tissue endothelial nitric oxide synthase. Thus, candesartan given before an MI attenuates LV remodeling and alters the cytoskeleton matrix of the left ventricle.