RESUMEN
Low case volume has been associated with poor outcomes in a wide spectrum of procedures. Our objective was to study the association of low case volume and worse outcomes in pediatric heart transplant centers, taking the novel approach of including waitlist outcomes in the analysis. We studied a cohort of 6482 candidates listed in the Organ Procurement and Transplantation Network for pediatric heart transplantation between 2002 and 2014; 4665 (72%) of the candidates underwent transplantation. Candidates were divided into groups according to the average annual transplantation volume of the listing center during the study period: more than 10, six to 10, three to five, or fewer than three transplantations. We used multivariate Cox regression analysis to identify independent risk factors for waitlist and posttransplantation mortality. Of the 6482 candidates, 24% were listed in low-volume centers (fewer than three annual transplantations). Of these listed candidates in low-volume centers, only 36% received a transplant versus 89% in high-volume centers (more than 10 annual transplantations) (p < 0.001). Listing at a low-volume center was the most significant risk factor for waitlist death (hazard ratio [HR] 4.5, 95% confidence interval [CI] 3.5-5.7 in multivariate Cox regression and HR 5.6, CI 4.4-7.3 in multivariate competing risk regression) and was significant for posttransplantation death (HR 1.27, 95% CI 1.0-1.6 in multivariate Cox regression). During the study period, one-fourth of pediatric transplant candidates were listed in low-volume transplant centers. These children had a limited transplantation rate and a much greater risk of dying while on the waitlist.
Asunto(s)
Rechazo de Injerto/mortalidad , Trasplante de Corazón/mortalidad , Hospitales de Bajo Volumen/estadística & datos numéricos , Complicaciones Posoperatorias , Obtención de Tejidos y Órganos , Listas de Espera , Adolescente , Niño , Preescolar , Femenino , Estudios de Seguimiento , Supervivencia de Injerto , Humanos , Lactante , Recién Nacido , Masculino , Pronóstico , Estudios Retrospectivos , Factores de RiesgoRESUMEN
The rapid development of angiogenic growth factor therapy for patients with advanced ischemic heart disease over the last 5 years offers hope of a new treatment strategy based on generation of new blood supply in the diseased heart. However, as the field of therapeutic coronary angiogenesis is maturing from basic and preclinical investigations to clinical trials, many new and presently unresolved issues are coming into focus. These include in-depth understanding of the biology of angiogenesis, selection of appropriate patient populations for clinical trials, choice of therapeutic end points and means of their assessment, choice of therapeutic strategy (gene versus protein delivery), route of administration, and the side effect profile. The present article presents a summary statement of a panel of experts actively working in the field, convened by the Angiogenesis Foundation and the Angiogenesis Research Center during the 72nd meeting of the American Heart Association to define and achieve a consensus on the challenges facing development of therapeutic angiogenesis for coronary disease.
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Ensayos Clínicos como Asunto , Vasos Coronarios , Cardiopatías/terapia , Neovascularización Fisiológica , Inductores de la Angiogénesis/efectos adversos , Inductores de la Angiogénesis/genética , Inductores de la Angiogénesis/uso terapéutico , Animales , Angiografía Coronaria , Factores de Crecimiento Endotelial/efectos adversos , Factores de Crecimiento Endotelial/genética , Factores de Crecimiento Endotelial/uso terapéutico , Factor 2 de Crecimiento de Fibroblastos/efectos adversos , Factor 2 de Crecimiento de Fibroblastos/genética , Factor 2 de Crecimiento de Fibroblastos/uso terapéutico , Terapia Genética/efectos adversos , Cardiopatías/diagnóstico por imagen , Humanos , Linfocinas/efectos adversos , Linfocinas/genética , Linfocinas/uso terapéutico , Imagen por Resonancia Magnética , Selección de Paciente , Tomografía Computarizada de Emisión , Tomografía Computarizada de Emisión de Fotón Único , Factor A de Crecimiento Endotelial Vascular , Factores de Crecimiento Endotelial VascularRESUMEN
BACKGROUND: Therapeutic angiogenesis, a new experimental strategy for the treatment of vascular insufficiency, uses the administration of mediators known to induce vascular development in embryogenesis to induce neovascularization of ischemic adult tissues. This report summarizes a phase I clinical experience with a gene-therapy strategy that used an E1(-)E3(-) adenovirus (Ad) gene-transfer vector expressing human vascular endothelial growth factor (VEGF) 121 cDNA (Ad(GV)VEGF121.10) to induce therapeutic angiogenesis in the myocardium of individuals with clinically significant coronary artery disease. METHODS AND RESULTS: Ad(GV)VEGF121.10 was administered to 21 individuals by direct myocardial injection into an area of reversible ischemia either as an adjunct to conventional coronary artery bypass grafting (group A, n=15) or as sole therapy via a minithoracotomy (group B, n=6). There was no evidence of systemic or cardiac-related adverse events related to vector administration. In both groups, coronary angiography and stress sestamibi scan assessment of wall motion 30 days after therapy suggested improvement in the area of vector administration. All patients reported improvement in angina class after therapy. In group B, in which gene transfer was the only therapy, treadmill exercise assessment suggested improvement in most individuals. CONCLUSIONS: The data are consistent with the concept that direct myocardial administration of Ad(GV)VEGF121.10 to individuals with clinically significant coronary artery disease appears to be well tolerated, and initiation of phase II evaluation of this therapy is warranted.
Asunto(s)
Adenoviridae , Circulación Coronaria , Enfermedad Coronaria/terapia , Factores de Crecimiento Endotelial/genética , Terapia Genética/métodos , Vectores Genéticos , Linfocinas/genética , Neovascularización Fisiológica/genética , Adulto , Anciano , Anciano de 80 o más Años , Terapia Combinada , Puente de Arteria Coronaria , Enfermedad Coronaria/fisiopatología , Enfermedad Coronaria/cirugía , ADN Complementario/biosíntesis , Prueba de Esfuerzo , Femenino , Humanos , Inyecciones , Masculino , Persona de Mediana Edad , Miocardio , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Factor A de Crecimiento Endotelial Vascular , Factores de Crecimiento Endotelial VascularRESUMEN
The feasibility of a single administration of a replication-deficient adenovirus (Ad) vector encoding the cDNA for human vascular endothelial growth factor (VEGF) (AdCMV.VEGF) to induce neovascularization in vivo in normal tissue was evaluated in retroperitoneal adipose tissue. Following administration of AdCMV.VEGF (10(9) pfu/50 microliters), maximal VEGF cDNA expression was observed at 2-5 days in the injected adipose tissue. No VEGF protein was detected at > or = 10 days in injected adipose tissue, and there was no increase in serum VEGF levels at any time. In vivo quantification of the number of blood vessels using 30x visualization of the adipose tissue demonstrated an increase in vessel number by 10 days, plateauing by 30 days with a 123% increase in vessel number compared to the control vector AdCMV.Null, despite the fact that no VEGF protein was detected after 5 days. Consistent with the in vivo data, histologic quantification of capillary number demonstrated an increase by day 5, reaching a 38% increase over AdCMV.Null by day 30. These observations demonstrate that an Ad vector carrying the VEGF cDNA is capable of inducing the growth of new blood vessels in a regional fashion in a relatively avascular, normal organ. This suggests in vivo Ad-mediated gene transfer may be useful for therapeutic angiogenesis in the treatment of ischemic cardiovascular disease.
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Adenoviridae/genética , Tejido Adiposo/irrigación sanguínea , Factores de Crecimiento Endotelial/genética , Factores de Crecimiento Endotelial/farmacología , Vectores Genéticos/genética , Linfocinas/genética , Linfocinas/farmacología , Neovascularización Fisiológica/efectos de los fármacos , Abdomen/irrigación sanguínea , Tejido Adiposo/efectos de los fármacos , Animales , Factores de Crecimiento Endotelial/administración & dosificación , Técnicas de Transferencia de Gen , Vectores Genéticos/administración & dosificación , Vectores Genéticos/farmacología , Humanos , Linfocinas/administración & dosificación , Masculino , Ratas , Ratas Sprague-Dawley , Factores de Tiempo , Factor A de Crecimiento Endotelial Vascular , Factores de Crecimiento Endotelial VascularRESUMEN
A gene therapy strategy involving direct myocardial administration of an adenovirus (Ad) vector encoding the vascular endothelial growth factor 121 cDNA (Ad(GV)VEGF121.10) has been shown to be capable of "biological revascularization" of ischemic myocardium in an established porcine model [Mack, C.A. (1998). J. Thorac. Cardiovasc. Surg. 115, 168-177]. The present study evaluates the local and systemic safety of this therapy in this porcine ischemia model and in normal mice. Myocardial ischemia was induced in Yorkshire swine with an ameroid constrictor 21 days prior to vector administration. Ad(GV)VEGF121.10 (10(9) or 10(10) PFU), Ad5 wild type (10(9) PFU), AdNull (control vector with no transgene; 10(9) PFU), saline, or no injection (naive) was administered in 10 sites in the ischemic, circumflex distribution of the myocardium. Toxicity was assessed by survival, serial echocardiography, blood analyses, and myocardial and liver histology at 3 and 28 days after vector administration. All pigs survived to sacrifice, except for one animal in the Ad(GV)VEGF121.10 (10(10) PFU) group, which died as a result of oversedation. Echocardiograms of Ad(GV)VEGF121.10-treated pigs demonstrated no differences in pericardial effusion, mitral valve regurgitation, or regional wall motion compared with control pigs. Intramyocardial administration of Ad(GV)VEGF121.10 included only minimal myocardial inflammation and necrosis, and no hepatic inflammation or necrosis. Only a mild elevation of the white blood cell count was encountered on day 3, which was transient and self-limited in the Ad(GV)VEGF121.10 group as compared with the saline-treated animals. As a measure of inadvertent intravascular administration of vector, normal C57/BL6 mice received intravenous Ad(GV)VEGF121.10 (10(4), 10(6), 5 x 10(7), or 10(9) PFU), AdNull (5 x 10(7) or 10(9) PFU), or saline. Toxicity was assessed by survival, blood analyses, and organ histology at 3 and 7 days after vector administration. A separate group of C57/BL6 mice received intravenous AdmVEGF164 (Ad vector encoding the murine VEGF164 cDNA), Ad(GV)VEGF121.10, AdNull (10(8) PFU each group), or saline to assess duration of expression and safety of a homologous transgene. All mice survived to sacrifice except for 40% of the mice in the highest (10(9) PFU; a dose more than 10(3)-fold higher by body weight than the efficacious dose in pigs) Ad(GV)VEGF121.10 dose group, which died on days 5-6 after vector administration. The only differences seen in the blood analyses between treated and control mice were in the very high Ad(GV)VEGF121.10 dose group (10(9) PFU), which demonstrated an anemia as well as an increase in alkaline phosphatase when compared with all other treatment groups. Hepatic VEGF levels by ELISA in AdmVEGF164-treated mice did not persist beyond 14 days after vector administration, suggesting that persistent expression of a homologous VEGF gene transferred with an Ad vector is not a significant safety risk. Although this is not a chronic toxicity study, these data demonstrate the safety of direct myocardial administration of Ad(GV)VEGF121.10, and support the potential use of this strategy to treat human myocardial ischemia.
Asunto(s)
Adenovirus Humanos , Factores de Crecimiento Endotelial/genética , Técnicas de Transferencia de Gen , Vectores Genéticos , Linfocinas/genética , Isquemia Miocárdica/terapia , Animales , Seguridad de Productos para el Consumidor , Modelos Animales de Enfermedad , Ecocardiografía , Pruebas Hematológicas , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Isquemia Miocárdica/diagnóstico por imagen , Isquemia Miocárdica/patología , Isquemia Miocárdica/fisiopatología , Miocardio/patología , Porcinos , Transgenes , Factor A de Crecimiento Endotelial Vascular , Factores de Crecimiento Endotelial VascularRESUMEN
OBJECTIVE: Because of the relative inaccessibility of the heart for repeated gene therapy, it would be useful to regulate the expression of transgenes delivered in a single dose of a gene therapy vector. Incorporation into the vector of a regulatable promoter that is responsive to pharmacologic agents that are widely used and well tolerated in clinical practice represents such a control strategy. METHODS: A replication-deficient adenovirus or an adeno-associated virus containing a chimeric promoter composed of 5 glucocorticoid response elements and the murine thrombopoietin complementary DNA (AdGRE.mTPO or AAVGRE.mTPO) was administered to the hearts of Sprague-Dawley rats. Platelet levels were evaluated as a reporter of transgene activity with or without dexamethasone. For comparison, rats received a control adenovirus vector, AdCMV.mTPO or AdCMV.Null, and the control adeno-associated virus vector AAVCMV.luc, which encodes for the firefly luciferase (luc) gene. RESULTS: Platelet elevation in the AdGRE.mTPO group peaked 4 days after dexamethasone administration, with a return to baseline 1 week after the initial corticosteroid dose. Subsequent dexamethasone administration at 2 and 4 weeks resulted in similar but progressively decreased responses. The AAVGRE.mTPO group had 5 peak platelet levels to a minimum of 2.2-fold with respect to baseline without diminution with subsequent dexamethasone administrations out to 169 days. In contrast, the AdCMV.Null and AAVCMV.luc groups demonstrated no increase in platelet counts and the AdCMV.mTPO group demonstrated a slow rise to a single peak platelet count independent of dexamethasone administration. CONCLUSION: It may be possible to control on demand the expression of a gene transferred to the heart. This strategy should be useful in cardiac gene therapy.
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Antiinflamatorios/administración & dosificación , Dexametasona/administración & dosificación , Sistemas de Liberación de Medicamentos/métodos , Técnicas de Transferencia de Gen , Terapia Genética/métodos , Cardiopatías/terapia , Regiones Promotoras Genéticas/genética , Trombopoyetina/genética , Transgenes/genética , Animales , Antiinflamatorios/farmacocinética , Plaquetas/efectos de los fármacos , Dependovirus/genética , Dexametasona/farmacocinética , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos , Regulación de la Expresión Génica/genética , Vectores Genéticos/genética , Cardiopatías/genética , Masculino , Datos de Secuencia Molecular , Ratas , Ratas Sprague-Dawley , Proteínas Recombinantes de Fusión/genética , Factores de TiempoRESUMEN
OBJECTIVES: The obligatory hemodilution resulting from crystalloid priming of the cardiopulmonary bypass circuit represents a major risk factor for blood transfusion in cardiac operations. We therefore examined whether retrograde autologous priming of the bypass circuit would result in decreased hemodilution and red cell transfusion. METHODS: Sixty patients having first-time coronary bypass were prospectively randomized to cardiopulmonary bypass with or without retrograde autologous priming. Retrograde autologous priming was performed at the start of bypass by draining crystalloid prime from the arterial and venous lines into a recirculation bag (mean volume withdrawal: 880 +/- 150 ml). Perfusion and anesthetic techniques were otherwise identical for the two groups. The hematocrit value was maintained at a minimum of 16% and 23% during and after cardiopulmonary bypass, respectively, in all patients. Patients were well matched for all preoperative variables, including established transfusion risk factors. Subsequent hemodynamic parameters, pressor requirements, and fluid requirements were equivalent in the two groups. RESULTS: The lowest hematocrit value during cardiopulmonary bypass was 22% +/- 3% versus 20% +/- 3% in patients subjected to retrograde autologous priming and in control patients, respectively (p = 0.002). One (3%) of 30 patients subjected to retrograde autologous priming had intraoperative transfusion, and seven (23%) of 30 control patients required transfusion during the operation (p = 0.03). The number of patients receiving any homologous red cell transfusions in the two groups during the entire hospitalization was eight of 30 (27%; retrograde autologous priming) versus 16 of 30 (53%; control) (p = 0.03). CONCLUSIONS: These data suggest that retrograde autologous priming is a safe and effective means of significantly decreasing hemodilution and the number of patients requiring red cell transfusion during cardiac operations.
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Transfusión de Componentes Sanguíneos , Transfusión de Sangre Autóloga , Puente Cardiopulmonar/instrumentación , Puente Cardiopulmonar/métodos , Hemodilución , Anciano , Transfusión de Sangre Autóloga/instrumentación , Transfusión de Sangre Autóloga/métodos , Estudios de Casos y Controles , Femenino , Hematócrito , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores de Riesgo , Factores de Tiempo , Resultado del TratamientoRESUMEN
OBJECTIVES: Vascular endothelial growth factor (VEGF), a potent angiogenic mediator, can be delivered to targeted tissues by means of a replication-deficient adenovirus (Ad) vector. We hypothesized that direct administration of Ad vector expressing the VEGF121 complementary deoxyribonucleic acid (AdGVVEGF121.10) into regions of ischemic myocardium would enhance collateral vessel formation and improve regional perfusion and function. METHODS: Yorkshire swine underwent thoracotomy and placement of an Ameroid constrictor (Research Instruments & MFG, Corvallis, Ore.) on the circumflex coronary artery. Three weeks later, myocardial perfusion and function were assessed by single photon emission computed tomography imaging (SPECT) with 99mTc-labeled sestamibi and by echocardiography during rest and stress. AdGVVEGF121.10 (n = 7) or the control vector, AdNull (n = 8), was administered directly into the myocardium at 10 sites in the circumflex distribution (10(8) pfu/site). Four weeks later, these studies were repeated and ex vivo angiography was performed. RESULTS: SPECT imaging 4 weeks after vector administration demonstrated significant reduction in the ischemic area at stress in AdGVVEFG121.10-treated animals compared with AdNull control animals (p = 0.005). Stress echocardiography at the same time demonstrated improved segmental wall thickening in AdGVVEGF121.10 animals compared with AdNull control animals (p = 0.03), with AdGVVEGF121.10 animals showing nearly normalized function in the circumflex distribution. Collateral vessel development assessed by angiography was also significantly greater in AdGVVEGF121.10 animals than in AdNull control animals (p = 0.04), with almost complete reconstitution of circumflex filling in AdGVVEGF121.10 animals. CONCLUSIONS: An Ad vector expressing the VEGF121 cDNA induces collateral vessel development in ischemic myocardium and results in significant improvement in both myocardial perfusion and function. Such a strategy may be useful in patients with ischemic heart disease in whom complete revascularization is not possible.
Asunto(s)
ADN Complementario/uso terapéutico , Factores de Crecimiento Endotelial/uso terapéutico , Técnicas de Transferencia de Gen , Vectores Genéticos , Linfocinas/uso terapéutico , Isquemia Miocárdica/terapia , Neovascularización Fisiológica/efectos de los fármacos , Adenoviridae/genética , Animales , Ecocardiografía , Prueba de Esfuerzo , Humanos , Contracción Miocárdica/fisiología , Isquemia Miocárdica/diagnóstico , Isquemia Miocárdica/fisiopatología , Radiofármacos , Porcinos , Tecnecio Tc 99m Sestamibi , Tomografía Computarizada de Emisión de Fotón Único , Factor A de Crecimiento Endotelial Vascular , Factores de Crecimiento Endotelial VascularRESUMEN
Reoperative coronary artery bypass grafting is being performed with increasing frequency, in part as a function of the increasing pool of patients who have undergone initial coronary artery bypass grafting and in part because of the natural progression of atherosclerosis. The great majority of patients require reoperation because of graft atherosclerosis or because of a combination of graft and native-vessel disease. Significant risk factors for reoperation include the lack of an internal mammary artery graft or incomplete revascularization at the time of the primary operation, age, and New York State Heart Association classification. Despite an increasing experience with reoperations, operative mortality remains high, approximately three to five times that of initial bypass operation. Similarly, reoperations are associated with increased morbidity, including increased rates of bleeding and low output states. Specific problems encountered at reoperation include graft atherosclerosis, progression of native-vessel disease, and a significant increase in perioperative bleeding. Bypass ischemic times tend to be longer. The use of retrograde cardioplegia and blood conservation programs may prove to be effective solutions for these problems. If perioperative results can be improved, it would appear that the long-term outlook for these patients is reasonably good.
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Puente de Arteria Coronaria , Anciano , Puente de Arteria Coronaria/mortalidad , Enfermedad de la Arteria Coronaria/cirugía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud , Reoperación/mortalidad , Factores de Riesgo , Factores de Tiempo , Grado de Desobstrucción VascularRESUMEN
Fifty-four patients underwent repair of atrial septal defects through a right thoracotomy between January 1985 and December 1991. The average patient was 5.7 years old. Defects repaired included 51 secundum, 2 sinus venosus, and 1 ostium primum defect. The average bypass time was 24 minutes. There was no operative or late mortality, and no morbidity directly related to the thoracotomy approach. The right thoracotomy incision is a safe and effective alternative to a median sternotomy for repair of atrial septal defects. The cosmetic result is superior to that of median sternotomy or bilateral submammary incision.
Asunto(s)
Defectos del Tabique Interatrial/cirugía , Toracotomía/métodos , Adolescente , Mama , Puente Cardiopulmonar , Niño , Preescolar , Procedimientos Quirúrgicos Dermatologicos , Femenino , Atrios Cardíacos/cirugía , Humanos , Hipotermia Inducida , Lactante , Tiempo de Internación , Masculino , Pericardio/cirugía , Costillas , Técnicas de Sutura , Factores de TiempoRESUMEN
Pulmonary sarcomas may extend into the left atrium through the pulmonary veins, requiring the use of cardiopulmonary bypass for resection. The operative strategy for these complicated resections must account for the laterality of the tumor, the extent of atrial involvement, the severity of local invasion within the hemithorax, and intrinsic surgical heart disease, if present. We discuss these issues using an illustrative case of a patient with a right pulmonary sarcoma extending from the lateral chest wall into the left atrium.
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Neoplasias Cardíacas/cirugía , Leiomiosarcoma/cirugía , Neoplasias Pulmonares/cirugía , Adulto , Femenino , Atrios Cardíacos , Neoplasias Cardíacas/patología , Humanos , Leiomiosarcoma/patología , Neoplasias Pulmonares/patología , Métodos , Invasividad NeoplásicaRESUMEN
Heparin-induced thrombocytopenia and thrombosis syndrome was diagnosed in a 63-year-old woman 11 days after coronary artery bypass grafting. Her only presenting complaints were incisional leg pain and vague chest discomfort. The syndrome was suspected when her platelet count was found to be 37,000/microL. A subsequent ventilation-perfusion lung scan showed findings highly probable for pulmonary embolism. An inferior venacavogram obtained before a pulmonary angiogram revealed a large retrohepatic thrombus at the right atrial junction. The patient was successfully treated with the defibrinogenating agent ancrod (Arvin). A diagnosis of heparin-induced thrombocytopenia and thrombosis syndrome should be considered and heparin therapy should be avoided in patients with low platelet counts who have been previously treated with heparin.
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Puente de Arteria Coronaria , Heparina/efectos adversos , Complicaciones Posoperatorias/inducido químicamente , Trombocitopenia/inducido químicamente , Trombosis/inducido químicamente , Ancrod/uso terapéutico , Enfermedad Coronaria/cirugía , Femenino , Vena Femoral , Humanos , Persona de Mediana Edad , Embolia Pulmonar/inducido químicamente , Embolia Pulmonar/tratamiento farmacológico , Trombosis/tratamiento farmacológico , Vena Cava InferiorRESUMEN
From 1955 to 1990, 111 patients have been treated for multiple primary lung carcinomas. Criteria for diagnosis were: (1) different histology (n = 44); or (2) same histology, but disease-free interval at least 2 years (n = 39), origin from carcinoma in situ (n = 19), or metachronous disease in different lobe (n = 9) with no cancer in common lymphatics or extrapulmonary metastasis at the time of diagnosis. The second cancer was synchronous in 33 patients (30%) and metachronous in 78 (70%). Metachronous disease developed at a median interval of 48 months. Five-year survival for patients with metachronous and synchronous disease from the time of initial diagnosis of cancer was 70% and 44%, and 10-year survival was 42% and 23%, respectively. Survival after the development of a metachronous lesion was 23% at 5 years. Survival from the time of initial diagnosis was significantly better for metachronous versus synchronous, late (24 month disease-free interval) versus early metachronous disease, and adenocarcinoma versus epidermoid carcinoma. The first cancer was completely resected in 103 patients (93%), but complete resection of a metachronous tumor was possible in only 54 patients (69%). Complete resection of second primary cancers resulted in significantly (p less than 0.0001) prolonged 5-year survival compared with incomplete resection (38% versus 9%). Excluding patients requiring pneumonectomy, initial resection limited subsequent resection in only 7 patients (9%) with metachronous disease. We conclude that patients surviving treatment of primary lung cancers require lifelong screening for multiple primary lung carcinoma, and complete resection is recommended whenever possible.
Asunto(s)
Neoplasias Pulmonares/patología , Neoplasias Primarias Múltiples/patología , Neoplasias Primarias Secundarias , Femenino , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/terapia , Masculino , Persona de Mediana Edad , Neoplasias Primarias Múltiples/diagnóstico , Neoplasias Primarias Múltiples/terapia , PronósticoRESUMEN
Myocardial revascularization had its beginnings in the early 1900s with extracardiac operations, such as sympathetic denervation and thyroid ablation. From there it evolved through neovascularization via pericardial poudrage and cardiopexy in the 1930s to 1950s, to mammary artery myocardial implantation in the 1940s and endarterectomy in the 1950s, to saphenous vein- and mammary artery-coronary artery bypass grafting in the 1960s. The history of the surgical treatment of myocardial ischemia is presented here in chronologic sequence to highlight the prescient thinking and the persistence of efforts, as well as the false starts and the rediscovery of old ideas, that have marked the development of this treatment.
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Isquemia Miocárdica/historia , Isquemia Miocárdica/cirugía , Revascularización Miocárdica/historia , Animales , Historia del Siglo XX , HumanosRESUMEN
A rare case of aorta to right ventricle tunnel with associated pulmonary stenosis was corrected on cardiopulmonary bypass in a 3-month-old infant. Both the aortic and ventricular openings were closed with a patch. Although the repair was successful and the child was discharged from the hospital, septicemia developed and she died later. Early repair of this defect is recommended.
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Defectos de la Almohadilla Endocárdica/cirugía , Defectos de la Almohadilla Endocárdica/diagnóstico por imagen , Humanos , Lactante , Métodos , Complicaciones Posoperatorias , RadiografíaRESUMEN
Despite recent advances in blood conservation techniques, major risks persist for excessive bleeding and blood transfusion after open heart operations. We reviewed the records of 100 consecutive patients undergoing first-time coronary artery bypass grafting at our institution to define these risks and develop a multimodality blood conservation program based on the results. This program was subsequently applied on a prospective basis to a select group of patients who refuse blood transfusion on religious grounds (Jehovah's Witnesses [JW]) (n = 15). Encouraging initial results with coronary artery bypass grafting in this group (n = 8) led to the application of the program to more complex operations (n = 7), including repeat bypass grafting with use of the internal mammary artery, repeat mitral valve replacement, aortic and mitral valve replacement with coronary artery bypass grafting, mitral valve replacement with bypass grafting, chronic type 1 dissection repair, aortic valve replacement, and atrial septal defect repair in 1 patient each. The blood conservation program employed in these patients included the use of (1) aprotinin (full Hammersmith regimen), (2) high-dose erythropoietin, (3) "maximal"-volume intraoperative autologous blood donation, (4) low-prime cardiopulmonary bypass, (5) exclusive use of intraoperative cell salvage, and (6) continuous reinfusion of shed mediastinal blood. There were no deaths in the JW group. Thromboembolic complications consisted of a transient posterior circulation stroke in only 1 patient (dissection repair). No blood or blood products were transfused compared with the transfusion of 5.1 +/- 7.8 units (mean +/- standard deviation) in the 100 primary coronary bypass patients in whom the blood conservation program was not employed.(ABSTRACT TRUNCATED AT 250 WORDS)
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Aprotinina/administración & dosificación , Pérdida de Sangre Quirúrgica/prevención & control , Procedimientos Quirúrgicos Cardíacos , Cristianismo , Eritropoyetina/administración & dosificación , Transfusión de Sangre Autóloga , Hematócrito , Humanos , Estudios Prospectivos , Estudios RetrospectivosRESUMEN
The occurrence of unanticipated and seemingly unexplicable major complications of hepatic, pulmonary, and cardiac dysfunction after palliative operation for obstructive hypertrophic cardiomyopathy prompted a review of 71 sequential patients. Fifty-five patients had been treated preoperatively with beta-blockers, calcium-channel inhibitors, or both, and 16 had received amiodarone for six to 566 days (mean time, 210 days) at total doses ranging from 8 to 175 g (mean dose, 82 g) and had drug-free intervals prior to operation of zero to 457 days (mean time, 91 days). Comparisons were made between the two treatment groups and between those with and without major complications within the amiodarone-treated group. Preoperative cardiac studies, sex, age, functional class, and type of operation were not related to outcome for the entire patient cohort. In amiodarone-treated patients, the major findings were as follows: a 50% incidence of hepatic dysfunction with a tenfold increase in concentrations of serum glutamic-oxaloacetic transaminase and serum glutamic-pyruvic transaminase; a 25% incidence of pulmonary dysfunction necessitating a fourfold increase in the number of days of ventilator support; and a 19% incidence of low cardiac output syndrome with two deaths. Only 44% of the amiodarone-treated group had no serious complications. The incidence of major complications of the liver, lungs, and heart was 2%, 0%, and 2%, respectively, in patients not treated with amiodarone. Abnormal preoperative pulmonary function studies were predictive of prolonged postoperative ventilatory support. Discontinuation of amiodarone for several months prior to operation appeared to reduce the incidence of major complications. The necessary drug-free interval required preoperatively could not be determined from this retrospective experience.(ABSTRACT TRUNCATED AT 250 WORDS)
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Amiodarona/efectos adversos , Cardiomiopatía Hipertrófica/cirugía , Adulto , Amiodarona/uso terapéutico , Arritmias Cardíacas/tratamiento farmacológico , Arritmias Cardíacas/etiología , Gasto Cardíaco Bajo/inducido químicamente , Cardiomiopatía Hipertrófica/complicaciones , Enfermedad Hepática Inducida por Sustancias y Drogas , Femenino , Humanos , Enfermedades Pulmonares/inducido químicamente , Masculino , Complicaciones Posoperatorias , Estudios RetrospectivosRESUMEN
The aorta is a commonly unrecognized source of systemic embolization. Transesophageal echocardiography is a reliable method for visualization of the intima of the thoracic aorta and identification of aortic thrombi. Balloon embolectomy of the aorta can be used to remove thrombi and prevent further embolic events.
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Enfermedades de la Aorta/complicaciones , Embolia/etiología , Trombosis/complicaciones , Anciano , Aorta Torácica , Enfermedades de la Aorta/diagnóstico por imagen , Enfermedades de la Aorta/cirugía , Cateterismo , Ecocardiografía Transesofágica , Embolectomía/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia , Trombosis/diagnóstico por imagen , Trombosis/cirugíaRESUMEN
BACKGROUND: Transmyocardial laser revascularization (TMR) appears to provide symptomatic relief to patients with ischemic heart disease, but evidence that TMR enhances perfusion to ischemic myocardium remains limited. Furthermore, it is uncertain whether there exists a TMR dose-response relationship that is a function of channel number. We therefore compared restoration of blood flow as analyzed by rest and stress 99mTc-sestamibi scans and histologic grading of neovascularization after 50-channel, 25-channel, or 10-channel TMR using the excimer laser in an established model of porcine myocardial ischemia. METHODS: Yorkshire swine underwent a thoracotomy and placement of an ameroid constrictor around the proximal circumflex coronary artery. Three weeks later, the animals underwent resting and adenosine stress 99mTc-sestamibi scans for evaluation of ischemia immediately before repeat thoracotomy and TMR with either 50 channels (n = 4), 25 channels (n = 4), or 10 channels (n = 4) in the circumflex territory. The animals underwent repeat perfusion analyses 4 weeks later, after which the animals were sacrificed and the hearts were perfusion fixed for histologic evaluation of neovascularization. RESULTS: All animals survived to sacrifice. Semiquantitative analyses of the sestamibi perfusion scans 4 weeks after lasing demonstrated significant improvement (p < 0.04) in stress-induced ischemia in the 50-channel TMR animals, but not in the 25- or 10-channel TMR groups, as compared with scans obtained immediately before lasing. A computerized image analysis of perfusion scans similarly demonstrated an improvement in the area of ischemia of 42% +/- 22% in the scans obtained 4 weeks after lasing compared with scans obtained immediately before lasing in the 50-channel group (p < 0.004), but only a 12% +/- 9% improvement in the 25-channel group and an 8% +/- 4% improvement in the 10-channel group (p > 0.05). Histologic assessment of neovascularization demonstrated significantly greater number of microvessels per low-power field in the 50- versus the 25- and 10-channel groups (p < 0.001). CONCLUSIONS: In an animal model of myocardial ischemia, TMR appears to enhance myocardial perfusion. A dose-response relationship related to channel number may be of significance when evaluating the efficacy of various treatment strategies.
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Circulación Coronaria , Terapia por Láser , Isquemia Miocárdica/cirugía , Revascularización Miocárdica/métodos , Adenosina , Animales , Masculino , Isquemia Miocárdica/diagnóstico por imagen , Isquemia Miocárdica/patología , Isquemia Miocárdica/fisiopatología , Miocardio/patología , Neovascularización Fisiológica , Radiofármacos , Porcinos , Tecnecio Tc 99m Sestamibi , Tomografía Computarizada de Emisión de Fotón ÚnicoRESUMEN
BACKGROUND: Direct myocardial gene transfer is a mordality that involves the introduction of genetic information into myocardial tissue to achieve a therapeutic effect. This study was designed to characterize the temporal and spatial limits of gene expression and to determine the safety of direct myocardial gene transfer in a large animal model using replication-deficient adenovirus vectors. METHODS: Mongrel dogs underwent left thoracotomy and direct myocardial injections (100 microL/injection) of adenovirus vectors (10(9) pfu) carrying the DNA for the reporter enzyme chloramphenicol acetyl transferase or the angiogenic protein vascular endothelial growth factor. Two to 14 days after vector administration, regional protein expression was evaluated in myocardium and distant organs. Left ventricular function, assessed by echocardiography, and routine hematologic and biochemical indices were evaluated before and after vector administration. RESULTS: Peak levels of chloramphenicol acetyl transferase activity were detected 2 days after vector administration, and levels above baseline persisted for at least 14 days. Local chloramphenicol acetyl transferase activity was detected at distances at least as far as 1.5 cm from the site of injection. Chloramphenicol acetyl transferase activity in distant organs was less than 0.1% of that in injected myocardium 7 days after vector administration. Localized expression of vascular endothelial growth factor was achieved for up to 7 days after a single vector administration. Cardiac function and laboratory values were unchanged during the study. CONCLUSIONS: Adenovirus-mediated direct myocardial gene transfer can be accomplished safely in a large animal model, providing high levels of protein expression in a greater spatial distribution than previously reported, with minimal transfection of distant organs. Sustained and localized expression of a potent angiogenic mediator has been accomplished, which may provide an innovative strategy to stimulate angiogenesis in ischemic myocardium.