RESUMEN
A 76-year-old man with a history of multiple laparotomies and severe coronary artery disease was referred to our hospital after the sudden development of pain and numbness in the lower extremities. Computed tomography showed a thrombosed abdominal aortic aneurysm and diffuse aortic atherosclerosis; compatible with a "shaggy aorta." A good response to thrombolytic therapy permitted elective scheduling of abdominal aortic surgery after coronary artery bypass grafting. We operated via an extended left retroperitoneal approach through a thoracoabdominal incision. Epiaortic ultrasonography revealed that only the supraceliac aorta was free of mobile thrombi and had minimal plaque; we therefore placed a proximal aortic cross-clamp there. Anatomic aortic reconstruction was then performed successfully using an aorto-biiliac graft to restore adequate distal blood flow. There were no vital-organ ischemic complications, and the postoperative course was satisfactory.
Asunto(s)
Aorta Abdominal/patología , Aneurisma de la Aorta Abdominal/cirugía , Aterosclerosis/cirugía , Trombosis/cirugía , Anciano , Aneurisma de la Aorta Abdominal/complicaciones , Aneurisma de la Aorta Abdominal/patología , Aterosclerosis/complicaciones , Aterosclerosis/patología , Humanos , Arteria Ilíaca/patología , Masculino , Trombosis/complicaciones , Procedimientos Quirúrgicos Vasculares/métodosRESUMEN
BACKGROUND: Platelet-derived endothelial cell growth factor (PD-ECGF), also known as thymidine phosphorylase (TP) reportedly inhibits vascular smooth muscle cells (VSMCs) migration and proliferation. We hypothesized that adventitial administration of the PD-ECGF/TP gene will suppress intimal hyperplasia and prevent vein graft failure. METHODS: The study used 68 female rabbits. Rabbit jugular vein was autogenously transplanted into carotid artery with a cuff anastomotic technique. To define vascular wall gene transfer efficiency, poloxamer hydrogel (20%) containing plasmid vector encoding the LacZ gene and different concentrations of trypsin (0%, 0.1%, 0.25%, and 0.5%, n = 5 for each group) was applied to the adventitia of the vein graft. Gene transfer efficiency was evaluated 7 days later by X-gal staining. An additional 48 rabbits received poloxamer hydrogel (20%) containing 0.25% trypsin and the human PD-ECGF/TP gene, LacZ gene, or saline. Intima thickness was evaluated at 2 and 8 weeks after grafting (n = 8 for each group at each time point). Transgene expression was examined by reverse transcriptase-polymerase chain reaction, immunoblotting assay, and immunohistochemical staining. Immunohistochemical staining was also used to determine VSMC proliferation, heme oxygenase-1 expression, and macrophage infiltration. RESULTS: Incorporation of trypsin into the poloxamer hydrogel significantly increased vessel wall gene transfer. Trypsin at 0.25% and 0.5% resulted in higher gene transfer at the same level without effecting intimal hyperplasia and inflammation; thus, trypsin at 0.25% concentration was used for subsequent experiments. Compared with the LacZ and saline groups, grafts receiving the PD-ECGF/TP gene significantly reduced intimal thickness at 2 and 8 weeks after treatment. The ratio of proliferative VSMC was lower in PD-ECGF/TP treated grafts. Histologic examination of the PD-ECGF/TP transgene grafts demonstrated high expression of heme oxygenase-1, which has been reported to inhibit VSMC proliferation, suggesting that heme oxygenase-1 may be important in the inhibition effect of PD-ECGF/TP on VSMC. No neoplastic or morphologic changes were found in the remote organs. CONCLUSIONS: A safe and highly efficient gene transfer method was developed by using poloxamer hydrogel and a low concentration of trypsin. Neointimal hyperplasia was significantly reduced by adventitial application of the PD-ECGF/TP gene to the vein graft. Our data suggest that adventitial delivery of the PD-ECGF/TP gene after grafting may be promising method for preventing vein graft failure.
Asunto(s)
Terapia Genética/métodos , Oclusión de Injerto Vascular/prevención & control , Venas Yugulares/trasplante , Músculo Liso Vascular/patología , Timidina Fosforilasa/genética , Animales , Tejido Conectivo , ADN/genética , Modelos Animales de Enfermedad , Femenino , Expresión Génica , Oclusión de Injerto Vascular/metabolismo , Oclusión de Injerto Vascular/patología , Hiperplasia/patología , Hiperplasia/prevención & control , Immunoblotting , Venas Yugulares/metabolismo , Venas Yugulares/patología , Músculo Liso Vascular/metabolismo , Conejos , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Timidina Fosforilasa/biosíntesis , Resultado del TratamientoRESUMEN
BACKGROUND: We previously reported the 2-week benefits of platelet-derived endothelial cell growth factor (PD-ECGF) gene therapy in chronically ischemic myocardium. However, the long-term effects and safety using this gene have not been reported. METHODS: Chronic myocardial ischemia was created in 24 dogs by stenosing the origin of the left anterior descending coronary artery (LAD) using an ameroid constrictor. Two weeks later, the PD-ECGF gene, the LacZ gene, or saline was infused directly into the myocardium in the LAD area. The myocardial blood volume and myocardial function were examined prior to ischemia, immediately before gene injection, and for 6 months following injection, and then the organs were harvested for histological and molecular examination. RESULTS: PD-ECGF gene treatment significantly attenuated endocardial infarction at 6 months. Myocardial blood volume and myocardial function decreased in all three groups after ameroid implantation, but recovered after 2 weeks in the PD-ECGF-treated group, and maintained a higher level of function during the examination period. Histological analysis demonstrated that angiogenesis and arteriogenesis occurred after PD-ECGF gene treatment. There was a decreased expression of the pro-apoptotic proteins, active caspase-3 and Bax, and the number of apoptotic myocardial cells was lower in the PD-ECGF-treated group. Histological examination demonstrated that no abnormal histological changes or neoplasms were found in any organs. CONCLUSIONS: We conclude that gene targeting of ischemic myocardium using PD-ECGF generated long-term improvement in cardiac function by causing angiogenesis, arteriogenesis and inhibiting apoptosis, but did not induce neoplasms in the remote organs, and may be a promising therapy.
Asunto(s)
Terapia Genética , Isquemia Miocárdica/terapia , Timidina Fosforilasa/genética , Animales , Apoptosis , Enfermedad Crónica , Circulación Coronaria , Perros , Vectores Genéticos , Corazón/fisiopatología , Humanos , Isquemia Miocárdica/patología , Isquemia Miocárdica/fisiopatología , Miocardio/patología , Neovascularización Fisiológica , Plásmidos , Transgenes , Resultado del TratamientoRESUMEN
OBJECTIVES: Platelet-derived endothelial cell growth factor (PD-ECGF) is identical to thymidine phosphorylase (TP), and it can induce angiogenesis, including arteriogenesis, in chronically ischemic canine myocardium. Because its effect on peripheral arterial disease has not been elucidated, we investigated whether overexpression of PD-ECGF/TP could ameliorate chronic limb ischemia in rabbits. METHODS: Left femoral arteries were resected from 24 male rabbits. After 10 days, a plasmid vector containing human PD-ECGF/TP complimentary DNA was injected into 10 sites in the adductor muscles. Control groups received either the LacZ plasmid vector or saline vehicle only (n = 8 per group). Blood pressure was measured in the calf before surgery, at the onset of ischemia, 10 days later, and 20 and 30 days after gene transfer. Collateral vessel development and limb perfusion were assessed by angiography, and resected tissues underwent molecular and histologic examination. RESULTS: In the PD-ECGF/TP group, human PD-ECGF/TP messenger RNA and protein were still detected at 30 days after treatment. Calf blood pressure decreased significantly after femoral artery resection in all three groups. It subsequently showed a greater increase in the PD-ECGF/TP group than in either control group, and the difference was significant at 20 days after treatment (PD-ECGF/TP, 97.4 +/- 7.4; LacZ, 58.6 +/- 6.9; saline, 41.3 +/- 3.6). Immunohistochemical staining demonstrated an increased ratio of capillaries and arterioles to muscle fibers in the PD-ECGF/TP group (2.14 +/- 0.13 and 1.51 +/- 0.06), but not in the LacZ group (1.39 +/- 0.04 and 0.71 +/- 0.05) or the saline group (1.34 +/- 0.05 and 0.71 +/- 0.04, P < .01). The angiographic score was higher in the PD-ECGF/TP group (0.96 +/- 0.08) than in the LacZ group (0.50 +/- 0.02) or saline group (0.51 +/- 0.03) at 30 days after gene transfer (P < .01). CONCLUSIONS: This study demonstrated that PD-ECGF/TP gene transfer induced angiogenesis and decreased ischemia in a rabbit hindlimb model by promoting arteriogenesis, suggesting that targeting this gene may be a promising therapeutic strategy for peripheral vascular disease.
Asunto(s)
Extremidades/irrigación sanguínea , Terapia Genética , Isquemia/metabolismo , Isquemia/terapia , Neovascularización Fisiológica , Timidina Fosforilasa/biosíntesis , Timidina Fosforilasa/genética , Animales , Presión Sanguínea , Modelos Animales de Enfermedad , Terapia Genética/métodos , Vectores Genéticos , Isquemia/patología , Isquemia/fisiopatología , Masculino , Músculo Esquelético/irrigación sanguínea , Músculo Esquelético/patología , Plásmidos/genética , ARN Mensajero/metabolismo , Conejos , Flujo Sanguíneo Regional , Factores de Tiempo , TransfecciónRESUMEN
OBJECTIVE: This study was performed to evaluate the clinical usefulness of the adventitial inversion technique in acute type A aortic dissection, with special attention to the impact of this procedure on the postoperative status of false lumen evaluated by computed tomographic scan. METHODS: From March 2001 to November 2004, 18 consecutive patients underwent emergent surgery for acute type A aortic dissection. Supracoronary graft replacement was performed in all the patients (ascending aorta/hemiarch replacement: 13/18=72%, total arch replacement: 5/18=28%). The adventitial inversion technique was used for both the proximal and the distal stump constructions of the dissected aortic wall without the aid of Teflon felt or biologic glue. Aortic regurgitation was treated with resuspension of the aortic commissures. RESULTS: There were two hospital deaths and the overall hospital mortality rate was 11.1%. The mean postoperative blood loss was 635+/-214 ml and no reexploration was required in any of the patients. Postoperative computed tomography showed closure of the false lumen in aortic root, aortic arch, and proximal descending thoracic aorta in all of the surviving patients. Postoperative echocardiography demonstrated no aortic regurgitation in any of the patients. Two patients died late postoperatively from unrelated causes to aortic dissection. The remaining 14 patients are doing well without a second-stage operation for aortic root or distal aortic lesions during the follow-up period of 7-51 months (mean: 28+/-14 months). CONCLUSIONS: The adventitial inversion technique provides an excellent immediate hemostasis and facilitates thrombotic closure of the proximal and the distal false lumen in the treatment for acute type A aortic dissection.
Asunto(s)
Aneurisma de la Aorta/cirugía , Disección Aórtica/cirugía , Tejido Conectivo/cirugía , Enfermedad Aguda , Anciano , Anciano de 80 o más Años , Anastomosis Quirúrgica/métodos , Disección Aórtica/diagnóstico por imagen , Aneurisma de la Aorta/diagnóstico por imagen , Aortografía , Implantación de Prótesis Vascular/métodos , Femenino , Mortalidad Hospitalaria , Humanos , Masculino , Persona de Mediana Edad , Politetrafluoroetileno , Cuidados Posoperatorios/métodos , Complicaciones Posoperatorias , Pronóstico , Estudios Retrospectivos , Adhesivos Tisulares , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
OBJECTIVE: Thymidine phosphorylase (TP) reportedly promotes endothelial cell migration and induces heme oxygenase (HO)-1 expression. However, its effect on vascular smooth muscle cells (VSMCs) is poorly understood. In this study, we examined the effect of TP on VSMCs in vitro and in vivo. METHODS AND RESULTS: Phagemid vector encoding human TP gene was transfected into rat VSMCs, and a clone overexpressing TP was selected (C2). C2 showed a slower migration and proliferation than VSMCs cloned with empty vector (pC) under basal, serum-stimulated, and hypoxic conditions. This decrease in proliferation correlated with TP-induced HO-1 expression and was reversed by inhibitors of either TP or HO activity. Furthermore, in C2, the cyclin-dependent kinase inhibitor (p27KIP1) was much more abundant than in pC, and the cell cycle was arrested at the G1 phase. TP or HO activity inhibitors decreased p27(KIP1) expression in C2 to the level seen in pC. Adventitial TP gene delivery significantly reduced neointimal VSMC migration and neointima formation in balloon-injured rat carotid arteries. CONCLUSIONS: TP overexpression upregulated HO-1 expression and consequently increased p27(KIP1) in cultured VSMCs, and inhibited VSMC migration and proliferation in vitro and in vivo. TP represents a promising target for treating vascular obstructive disease.
Asunto(s)
Angioplastia de Balón/efectos adversos , Traumatismos de las Arterias Carótidas/fisiopatología , Estenosis Carotídea/terapia , Inhibidor p27 de las Quinasas Dependientes de la Ciclina/metabolismo , Hemo-Oxigenasa 1/genética , Músculo Liso Vascular/fisiología , Timidina Fosforilasa/genética , Animales , Traumatismos de las Arterias Carótidas/patología , Proteínas de Ciclo Celular/genética , División Celular/fisiología , Línea Celular , Movimiento Celular/fisiología , Inducción Enzimática , Técnicas de Transferencia de Gen , Hemo-Oxigenasa 1/metabolismo , Humanos , Técnicas In Vitro , Masculino , Músculo Liso Vascular/citología , Músculo Liso Vascular/lesiones , Ratas , Ratas Sprague-Dawley , Túnica Íntima/patología , Túnica Íntima/fisiología , Regulación hacia Arriba/fisiologíaRESUMEN
PURPOSE: In cooperation with JMS Co., Ltd. (Hiroshima, Japan), we have developed a new intraluminal coronary shunt tube to allow easier, safer, and more accurate off-pump coronary artery bypass grafting (OPCABG). DESCRIPTION: Between September 2000 and July 2002, the new shunt tube was used in 100 consecutive patients undergoing OPCABG. Patient characteristics, experimental data, and clinical results for our new shunt tube are provided. EVALUATION: Our new coronary shunt tube was easily implanted in nearly all (97.2%) target vessels during reconstructions. All 100 cases were performed completely during off-pump operation. Early postoperative coronary angiography was performed in all 100 cases, demonstrating excellent patency in arterial grafts (99.5%) and venous grafts (96.2%). The shunt tube displayed good flow rates under experimental conditions according to diameter, and effectively prevented ischemia during coronary arterial reconstructions in all cases. No target vessels were injured on insertion or removal of shunt tubes. Neither perioperative complications nor hospital deaths were encountered. CONCLUSIONS: This new shunt tube improves the safety, accuracy, and ease of OPCABG surgery.
Asunto(s)
Puente de Arteria Coronaria Off-Pump/instrumentación , Anciano , Angiografía Coronaria , Diseño de Equipo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Isquemia Miocárdica/diagnóstico por imagen , Isquemia Miocárdica/cirugía , Resultado del Tratamiento , Grado de Desobstrucción VascularRESUMEN
BACKGROUND: In off-pump coronary artery bypass grafting (OPCABG) surgery, the most critical complication is hemodynamic deterioration, which can occur during displacement of the heart to expose the target vessels. Preoperative intraaortic balloon pump (IABP) therapy improves cardiac performance and facilitates access to the target coronary artery while maintaining hemodynamic stability, especially in high-risk patients. METHODS: One hundred thirty-three consecutive patients who underwent OPCABG through sternotomy between April 2000 and July 2003 were studied. We compared the clinical results of 32 patients who underwent preoperative IABP placement (group 1) with those of 101 patients who did not have IABP placement (group 2). Of the 32 patients satisfying the insertion criteria, 15 had critical left main artery disease, 20 had unstable angina, 5 had acute myocardial infarction, and 5 had left ventricular dysfunction. RESULTS: There were no significant differences in the average number of distal anastomoses performed between group 1 and group 2 (3.1 +/- 0.8 versus 3.3 +/- 0.9, p = not significant). The complete revascularization rate was 95% in both group. There was no conversion to on-pump surgery in either group. There was no operative death in group 1 and only 1 death in group 2. In group 1, the number of patients who required prolonged ventilatory support (longer than 48 hours) was higher (3 versus 1, p = 0.036), and there was a higher incidence of low cardiac output syndrome (1 versus 0, p = 0.074). There were no IABP-related complications in group 1. CONCLUSIONS: Preoperative IABP therapy for high-risk coronary patients is very effective in preventing hemodynamic instability and providing surgical results comparable with those in moderate- to lower-risk patients.
Asunto(s)
Puente de Arteria Coronaria , Contrapulsador Intraaórtico , Cuidados Preoperatorios , Adulto , Anciano , Anciano de 80 o más Años , Puente Cardiopulmonar , Puente de Arteria Coronaria/efectos adversos , Puente de Arteria Coronaria/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias , Factores de RiesgoRESUMEN
BACKGROUND: Complete revascularization has been difficult in off-pump coronary artery bypass grafting (OPCAB). Hemodynamic deterioration often prevents access to the circumflex territory. This study presents instrumentation for accessing the circumflex territory, and our clinical experience. METHODS: From August 1999 through December 2002, 140 patients underwent OPCAB via sternotomy in our institution. The 114 requiring reconstruction of the circumflex artery are the subjects of this study. There were no exclusion criteria. A series of techniques and instruments were developed to provide access to the circumflex area while hemodynamic stability was preserved, including the left pericardial traction technique, compression of the right pericardium, a right sternal retractor, and a type of shunt tube. RESULTS: Patients received an average of 3.2 grafts (range, 2 to 6). Complete revascularization was achieved in 95% of the cases. Complications included respiratory insufficiency (0.8%), renal dysfunction (7%), and sternal wound infection (0.8%). Blood transfusions were required in 10 patients (8%). No patient suffered perioperative myocardial infarction or stroke. No operation was converted to cardiopulmonary bypass. There was no operative death. Predischarge angiography demonstrated a 99% patency rate. CONCLUSIONS: With our techniques and instruments, off-pump coronary revascularizaion of the circumflex area may be performed safely to achieve complete revascularization. Early clinical results are excellent, but long-term longitudinal follow-up is required to assess the future effectiveness of OPCAB procedure with our techniques.