RESUMEN
OBJECTIVE: Therapeutic angiogenesis is an alternative method of revascularization for end-stage coronary artery disease. We determined the effects of intramyocardial and intracoronary basic fibroblast growth factor 2 on myocardial blood flow and function in a porcine model of hibernating myocardium. METHODS: Twenty-four mini-swine with 90% left circumflex artery stenosis and documented hibernating myocardium by positron emission tomography and dobutamine stress echocardiography were randomized to intramyocardial basic fibroblast growth factor 2 at 0.6 microg/kg (mid-dose, n = 6, 30 injections/animal), 6 microg/kg (high-dose, n = 6, 30 injections/animal), or intramyocardial vehicle control (n = 6). The intracoronary group received 6 microg/kg basic fibroblast growth factor 2 (n = 6) into the right and left circumflex artery coronary arteries. Positron emission tomography and dobutamine stress echocardiography were repeated at 1 and 3 months. RESULTS: In the vehicle group, normalized left circumflex artery myocardial blood flow was 0.74 +/- 0.04 at 1 month and 0.75 +/- 0.07 at 3 months compared with 0.68 +/- 0.03 at baseline. In the intracoronary group, myocardial blood flow was 0.71 +/- 0.03 at 1 month and 0.72 +/- 0.04 at 3 months compared with 0.67 +/- 0.04 at baseline. In the mid group, myocardial blood flow was 0.73 +/- 0.06 at 1 month and 0.85 +/- 0.05 at 3 months (P <.001) compared with 0.67 +/- 0.04 at baseline. In the high group, myocardial blood flow was 0.81 +/- 0.06 at 1 month and 0.83 +/-.04 at 3 months (P =.03) compared with 0.71 +/- 0.02 at baseline. No significant improvements in ischemia were demonstrated in any of the groups by dobutamine stress echocardiography at 1 or 3 months. CONCLUSIONS: In porcine hibernating myocardium, intramyocardial basic fibroblast growth factor 2 significantly improved regional myocardial blood flow 3 months after treatment. There was no significant change in function in any of the 4 groups. These data suggest that intramyocardial dosing of basic fibroblast growth factor 2 (0.6 microg/kg) may be an optimal dose for improving perfusion in the treatment of end-stage coronary artery disease.
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Factor 2 de Crecimiento de Fibroblastos/farmacología , Isquemia Miocárdica/tratamiento farmacológico , Reperfusión Miocárdica/métodos , Análisis de Varianza , Animales , Circulación Coronaria/efectos de los fármacos , Circulación Coronaria/fisiología , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Ecocardiografía Doppler , Femenino , Inyecciones Intralesiones , Masculino , Isquemia Miocárdica/patología , Aturdimiento Miocárdico , Probabilidad , Distribución Aleatoria , Valores de Referencia , Medición de Riesgo , Sensibilidad y Especificidad , Porcinos Enanos , Tomografía Computarizada de EmisiónRESUMEN
OBJECTIVE: Poststernotomy mediastinitis, although infrequent, is a potentially life-threatening complication of cardiac surgery that continues to have a significant morbidity and mortality despite aggressive therapy. Vacuum-assisted closure uses controlled suction to provide evacuation of wound fluid, decrease bacterial colonization, stimulate granulation tissue, and reduce the need for dressing changes. METHODS: One hundred two patients from Duke University Hospital, The Durham Veterans Administration Hospital, and referring institutions underwent vacuum-assisted closure treatment. There were 63 men and 39 women, with a mean age of 67. The infection was noticed between postoperative days 8 and 34, at which time the wounds were opened and debrided. RESULTS: Ninety-six of the 102 patients received vacuum-assisted therapy while the remaining 6 underwent daily multiple dressing changes without vacuum-assisted therapy. Fifty-three of the 96 patients required only sternal debridement, followed by wound vacuum therapy and closure by secondary intention, while the remaining 43 had an additional procedure. Of these, 33 patients underwent omental transposition and 10 patients had a pectoralis flap. The length of stay for all patients was 27 +/- 12 days. This was related in part to intravenous antibiotics. Hospital mortality for all patients was 3.7% (4 patients). Two of these patients underwent vascular flap and succumbed to multisystemic organ failure, while the other 2 received only wound vacuum therapy following debridement and succumbed to overwhelming sepsis. CONCLUSION: Vacuum-assisted drainage is an effective therapy for mediastinitis following debridement or before placement of a vascularized tissue flap.
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Procedimientos Quirúrgicos Cardíacos , Mediastinitis/etiología , Mediastinitis/terapia , Complicaciones Posoperatorias/etiología , Esternón/cirugía , Infección de la Herida Quirúrgica/etiología , Infección de la Herida Quirúrgica/terapia , Vacio , Anciano , Vendajes , Terapia Combinada , Desbridamiento , Femenino , Mortalidad Hospitalaria , Humanos , Tiempo de Internación , Masculino , North Carolina , Reoperación , Colgajos Quirúrgicos , Resultado del TratamientoRESUMEN
BACKGROUND: Ischemia is known to be a potent stimulus for the upregulation of angiogenic growth factors, such as basic fibroblast growth factor (bFGF). While previous investigations have shown that many angiogenic growth factors are upregulated in animal models of myocardial ischemia, the models used are limited in their ability to produce stable ischemia beyond a few weeks. Our laboratory uses a stable model of hibernating myocardium where later time points may be examined. Therefore, the goal of this study was to examine bFGF protein levels in the myocardium at baseline and 3 or 6 months following the onset of myocardial ischemia. METHODS: A total of 18 miniswine were studied. Basal endogenous levels of bFGF were measured in control animals (n = 6) immediately following sacrifice, while 12 other pigs underwent a 90% left circumflex artery occlusion with documented hibernating myocardium by positron emission tomography ((13)N-ammonia) and dobutamine stress echocardiography. These animals were studied at 3 (n = 7) and 6 months (n = 5) postoperatively. At sacrifice, six 3 x 3 mm samples were harvested from the left circumflex (hibernating) myocardium. Basic FGF levels (picograms per microgram of protein) were determined using ELISA kits. RESULTS: Basic FGF protein levels 3 months after the creation of hibernating myocardium were three times greater than in nonischemic control animals (P < 0.05), while levels at 6 months were increased sixfold compared to control animals (P < 0.05 versus both control and 3-month groups). CONCLUSIONS: Endogenous bFGF production is upregulated at 3 and 6 months in hibernating porcine myocardium. The angiogenic effects of exogenous bFGF delivered into ischemic myocardium with varying levels of endogenous growth factors must be determined.
Asunto(s)
Factor 2 de Crecimiento de Fibroblastos/metabolismo , Aturdimiento Miocárdico/metabolismo , Miocardio/metabolismo , Animales , Masculino , Valores de Referencia , Porcinos , Porcinos Enanos , Factores de Tiempo , Regulación hacia ArribaRESUMEN
BACKGROUND: Although robotically assisted coronary arterial anastomoses are being performed clinically, the short-term and long-term quality and integrity of the left internal thoracic artery (LITA) to left anterior descending artery (LAD) anastomosis remains unknown. The goal of this study was to perform a histologic and angiographic assessment of porcine beating heart LITA to LAD anastomoses using either robotic assistance or a conventional freehand technique. METHODS: Twelve pigs underwent beating heart LITA to LAD anastomoses using either the robotically assisted (n = 6) or conventional freehand techniques (n = 6). Quantitative histologic analysis was performed in all animals in order to determine the degree of vascular wall damage. Selective coronary arteriography was performed in all animals immediately after the procedure in order to evaluate anastomotic patency. The unpaired Student's t test was used for all comparisons between groups. RESULTS: There were no differences in vascular wall damage between the robotically assisted and freehand techniques. Postoperative angiography revealed no stenoses in either group. CONCLUSIONS: Use of the robotically assisted technique for creation of a LITA to LAD anastomosis was not associated with increased histologic damage when compared with the freehand technique in a beating heart porcine model. Furthermore, there was no difference between the two techniques in postoperative patency rate. These results support further clinical investigation of robotically assisted coronary bypass surgery.