Improvement in hemodynamic performance, exercise capacity, inflammatory profile, and left ventricular reverse remodeling after intracoronary delivery of mesenchymal stem cells in an experimental model of pressure overload hypertrophy

ObjectivesIn a rat model of pressure overload hypertrophy, we studied the effects of intracoronary delivery of mesenchymal stem cells on hemodynamic performance, exercise capacity, systemic inflammation, and left ventricular reverse remodeling.MethodsSprague–Dawley rats underwent aortic banding and were followed up by echocardiographic scanning. After a decrease in fractional shortening of 25% from baseline, animals were randomized to intracoronary injection of mesenchymal stem cells (MSC group; n = 28) or phosphate-buffered saline solution (control group; n = 20). Hemodynamic and echocardiographic assessment, swim testing to exhaustion, and measurement of inflammatory markers were performed before the rats were humanely killed on postoperative day 7, 14, 21, or 28.ResultsInjection of mesenchymal stem cells improved systolic function in the MSC group compared with the control group (mean ± standard deviation: maximum dP/dt 3048 ± 230 mm Hg/s vs 2169 ± 97 mm Hg/s at 21 days and 3573 ± 741 mm Hg/s vs 1363 ± 322 mm Hg/s at 28 days: P < .001). Time to exhaustion was similarly increased in the MSC group compared with controls (487 ± 35 seconds vs 306 ± 27 seconds at 28 days; P < .01). Serum levels of interleukins 1 and 6, tumor necrosis factor–alpha, and brain natriuretic peptide-32 were significantly decreased in animals treated with mesenchymal stem cells. Stem cell transplantation improved left ventricular fractional shortening at 21 and 28 days. Left ventricular end-systolic and end-diastolic diameters were also improved at 28 days.ConclusionsIn this model of pressure overload hypertrophy, intracoronary delivery of mesenchymal stem cells during heart failure was associated with an improvement in hemodynamic performance, maximal exercise tolerance, systemic inflammation, and left ventricular reverse remodeling. This study suggests a potential role of this treatment strategy for the management of hypertrophic heart failure resulting from pressure overload

The incidence of bilateral well-differentiated thyroid cancer found at completion thyroidectomy

The purpose of this study was to evaluate the surgical outcome of completion thyroidectomy in patients with presumed unilateral well-differentiated thyroid cancer (WDTC). The medical records of all patients having had unilateral thyroid lobectomy for WDTC, who subsequently underwent completion thyroidectomy, were reviewed. From 1980 to 1991, 60 patients with WDTC underwent completion thyroidectomy. Forty-seven patients had presumed unilateral WDTC, with no evidence of residual disease prior to their completion thyroidectomy. Twenty-five (53%) of these patients were found to have residual neoplastic disease in the neck. In 20 (43%) of 47 patients, a focus of cancer was found in the remaining thyroid lobe and in 5 additional patients no cancer was found in the contralateral lobe, however, unsuspected nodal disease was found. The remaining 13 of the 60 patients presented with either regional recurrence (n=12) or distant metastases (n=1) at the time of their completion thyroidectomy. All (92%) but 1 of these 13 patients had cancer in the remaining thyroid lobe. Multifocal disease in the primary lobe was associated with bilateral thyroid cancer ( p <0.01). Complications were infrequent; transient hypocalcemia occurred in 5 (8%) patients, permanent hypoparathyroidism occurred in 1 (1.7%) patient, and transient recurrent laryngeal nerve palsy occurred in 3 (5%) patients. Residual WDTC was found in 37 (62%) of 60 patients undergoing completion thyroidectomy. Multifocal disease in the primary resected lobe was associated with a high incidence of contralateral thyroid cancer. Completion thyroidectomy is a safe procedure and may prevent the development of regional recurrence by eliminating an unsuspected focus of cancer. Le but de cette étude était d'évaluer l'évolution chirurgicale après thyroïdectomie totale des patients ayant un cancer thyroïdien présumé bien différencié et unilatéral (CTBD). Les données médicales de tous les patients ayant eu une lobectomie unilatérale de la thyroïde pour CTBD et qui ont eu secondairement une totalisation de la thyroïdectomie ont été revues. Entre 1980 et 1991, 60 patients ayant un CTBD ont eu une totalisation de la thyroïdectomie, quarante sept avaient un CTBD présumé unilatéral, sans argument pour une pathologie résiduelle avant la totalisation de la thyroïdectomie (groupe 1). Vingt cinq d'entre eux (53%) se sont avérés avoir un reliquat néoplasique persistant au niveau de la région cervicale. Chez 20/47 (43%) patients, on a retrouvé un foyer de cancer dans le lobe restant de la thyroïde. Chez 5 patients supplémentaires il n'a pas été retrouvé de cancer dans le lobe controlatéral mais une dystrophie nodulaire non suspecte. Les 13/60 patients restants présentaient soit une récidive régionale (12) soit des métastases à distance (1) au moment de la totalisation de la thyroïdectomie (groupe 2). Tous les patients du groupe 2 sauf un (92%) avaient un cancer dans le lobe restant. Une atteinte plurifocale dans le premier lobe était associée avec l'existence d'un cancer bilatéral ( p <0.01). Les complications ont été rares: une hypocalcémie transitoire est survenue chez 5 (8%) patients, une hypoparathyroïdie définitive est apparue chez 1 (1.7%) patient. Une paralysie récurentielle transitoire a été retrouvée chez 3 (5%) patients. Conclusions: Un reliquat de TCBD a été retrouvé chez 37/60 (62%) patients opérés d'une totalisation de thyroïdectomie. L'atteinte multifocale dans le premier lobe réséqué était associée avec une incidence élevée de cancer thyroïdien controlatéral. La totalisation de la thyroïdectomie est une procédure sans risque qui peut prévenir le développement d'une récidive régionale en éliminant un foyer de cancer non suspecté. El propósito del presente estudio fue valorar el resultado quirúrgico de completar a una tiroidectomía total la resección tiroidea realizada en pacientes con cáncer presumiblemente unilateral y bien diferenciado de la glándula tiroides (CTBD). Se revisaron las historias clínicas de todos los pacientes sometidos a lobectomía tiroidea unilateral por CTBD, en quienes subsiguientemente se completó la tiroidectomía, procedimiento que fue realizado en 60 pacientes con CTBD en el período 1980–1991. Cuarenta y siete pacientes tenían CTBD presumiblemente unilateral, sin evidencia de enfermedad residual antes de completarse la tiroidectomía (grupo 1); en veinticinco (53%) de estos pacientes se halló neoplasia residual en el cuello. En 20/47 (43%) pacientes se encontró un foco de cáncer en el lóbulo tiroideo remanente y en 5 casos adicionales aunque no se encontró cáncer en el lóbulo contralateral, se halló extensión ganglionar no sospechada. Los 13/60 pacientes restantes presentaron recurrencia (12) o metástasis distantes (1) en el momento de completarse la tiroidectomía (grupo 2). Todos los pacientes del grupo 2, excepto 1 (92%), presentaban cáncer en el lóbulo remanente. La presencia de enfermedad multifocal en el lóbulo primario apareció asociada con cáncer tiroideo bilateral ( p <0.01). Las complicaciones fueron raras; se presentó hipocalcemia transitoria en 5 (8%) pacientes, hipotiroidismo permanente en 1 (1.7%) y parálisis parcial y transitoria del nervio laríngeo recurrente en 3 (5%). Conclusiones: Se encontró CTBD en 37/60 (62%) pacientes en quienes se completó la tiroidectomía. La presencia de enfermedad multifocal en el lóbulo primario resecado apareció asociada con una alta incidencia de cáncer contralateral. El procedimiento de completar la tiroidectomía aparece como una operación segura que puede prevenir el desarrollo recurrencia regional al eliminar focos insospechados de cáncer.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41292/1/268_2005_Article_BF02067365.pd

Reverse remodeling is associated with changes in extracellular matrix proteases and tissue inhibitors after mesenchymal stem cell (MSC) treatment of pressure overload hypertrophy

Changes in ventricular extracellular matrix (ECM) composition of pressure overload hypertrophy determine clinical outcomes. The effects of mesenchymal stem cell (MSC) transplantation upon determinants of ECM composition in pressure overload hypertrophy have not been studied. Sprague–Dawley rats underwent aortic banding and were followed by echocardiography. After an absolute decrease in fractional shortening of 25% from baseline, 1 × 10 6 MSC ( n = 28) or PBS ( n = 20) was randomly injected intracoronarily. LV protein analysis, including matrix metalloproteinases (MMP-2, MMP-3, MMP-6, MMP-9) and tissue inhibitors of metalloproteinases (TIMP-1, TIMP-2, TIMP-3), was performed after sacrifice on postoperative day 7, 14, 21 or 28. Left ventricular levels of MMP-3, MMP-6, MMP-9, TIMP-1 and TIMP-3 were demonstrated to be decreased in the MSC group compared with controls after 28 days. Expression of MMP-2 and TIMP-2 remained relatively stable in both groups. Successful MSCs delivery was confirmed by histological analysis and visualization of labelled MSCs. In this model of pressure overload hypertrophy, intracoronary delivery of MSCs during heart failure was associated with specific changes in determinants of ECM composition. LV reverse remodeling was associated with decreased ventricular levels of MMP-3, MMP-6, MMP-9, TIMP-1 and TIMP-3, which were upregulated in the control group as heart failure progressed. These effects were most significant at 28 days following injection. Copyright © 2008 John Wiley & Sons, Ltd.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/61900/1/137_ftp.pd

ECMO Support for Adult Patients With Acute Respiratory Failure

The authors analyzed factors that may influence the outcome of adult patients with respiratory failure who were treated with ECMO. Between December 1990 and July 1995, the authors used ECMO to support 33 patients (age range, 17–56 years) with respiratory failure from adult respiratory distress syndrome (ARDS; n = 9), primary graft failure after lung transplantation (n = 16), late graft failure after lung transplantation (n = 5), and miscellaneous reasons (n = 3). Twenty (61%) patients were successfully weaned from ECMO, and 13 (39%) survived to hospital discharge. Venoarterial ECMO was used in 46% of survivors, compared with 60% of nonsurvivors (p = 0.43). The time on mechanical support before ECMO and the duration on ECMO for survivors and nonsurvivors was 2.9 ± 1.8 days vs 5.0 ± 1.3 days (p = 0.35), and 6.5 ± 1.8 days vs 5.7 ± 1.1 days (p = 0.68), respectively. Compared with the nonsurvivors, survivors had higher PF ratios (PaO2/FIO2; 104 ± 33 vs 81 ± 8, p = 0.43) before ECMO was initiated, although the differences were not significant. Among the patients who received ECMO for primary graft failure, 75% were weaned from ECMO, and 56% survived to discharge. ECMO is beneficial for adult patients with respiratory failure, especially those with primary graft failure after lung transplantation