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1.
Artif Organs ; 42(12): E427-E434, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30252945

RESUMEN

Ovines are a common animal model for the study of cardiovascular devices, where consideration of blood biocompatibility is an essential design criterion. In the ovine model, tools to assess blood biocompatibility are limited and continued investigation to identify and apply additional assays is merited. Toward this end, the thrombelastograph, clinically utilized to assess hemostasis, was used to characterize normal ovine parameters. In addition, platelet labeling with biotin was evaluated for its potential applicability to quantify ovine platelet life span. Mean ovine thrombelastograph values were reaction-time: 4.9 min, K-time: 2 min, angle: 64.1°, maximum amplitude: 68.6mm, actual clot strength: 11.9 kd/s, and coagulation index: 1.5. Reaction time was significantly shorter and maximum amplitude, actual clot strength, and coagulation index were all significantly higher when compared to normal human thrombelastograph values suggesting some hypercoagulability of sheep blood. Biotinylation and reinfusion of ovine platelets allowed temporal tracking of the labeled platelet cohort with flow cytometry. These data indicated a mean ovine platelet life span of 188h with a half-life of 84h. The collection of these parameters for normal ovines demonstrates the applicability of these techniques for subsequent studies where cardiovascular devices may be evaluated and provides an indication of normal ovine values for comparison purposes.


Asunto(s)
Plaquetas/fisiología , Ovinos/sangre , Tromboelastografía , Animales , Biotinilación , Femenino , Citometría de Flujo , Masculino , Valores de Referencia
2.
Nicotine Tob Res ; 18(4): 437-46, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25995160

RESUMEN

INTRODUCTION: Menthol cigarette smoking may increase the risk for tobacco smoke exposure and inhibit nicotine metabolism in the liver. Nicotine metabolism is primarily mediated by the enzyme CYP2A6 and the nicotine metabolite ratio (NMR = trans 3' hydroxycotinine/cotinine) is a phenotypic proxy for CYP2A6 activity. No studies have examined differences in this biomarker among young adult daily menthol and nonmenthol smokers. This study compares biomarkers of tobacco smoke exposure among young adult daily menthol and nonmenthol smokers. METHODS: Saliva cotinine and carbon monoxide were measured in a multiethnic sample of daily smokers aged 18-35 (n = 186). Nicotine, cotinine, the cotinine/cigarette per day ratio, trans 3' hydroxycotinine, the NMR, and expired carbon monoxide were compared. RESULTS: The geometric means for nicotine, cotinine, and the cotinine/cigarette per day ratio did not significantly differ between menthol and nonmenthol smokers. The NMR was significantly lower among menthol compared with nonmenthol smokers after adjusting for race/ethnicity, gender, body mass index, and cigarette smoked per day (0.19 vs. 0.24, P = .03). White menthol smokers had significantly higher cotinine/cigarettes per day ratio than white nonmenthol smokers in the adjusted model. White menthol smokers had a lower NMR in the unadjusted model (0.24 vs. 0.31, P = .05) and the differences remained marginally significant in the adjusted model (0.28 vs. 0.34, P = .06). We did not observe these differences in Native Hawaiians and Filipinos. CONCLUSIONS: Young adult daily menthol smokers have slower rates of nicotine metabolism than nonmenthol smokers. Studies are needed to determine the utility of this biomarker for smoking cessation treatment assignments.


Asunto(s)
Mentol/metabolismo , Nicotina/metabolismo , Fumar/metabolismo , Productos de Tabaco , Adolescente , Adulto , Biomarcadores/análisis , Biomarcadores/metabolismo , Monóxido de Carbono/análisis , Cotinina/análogos & derivados , Cotinina/metabolismo , Femenino , Humanos , Masculino , Mentol/análisis , Nicotina/análisis , Saliva/química , Fumar/etnología , Productos de Tabaco/análisis , Adulto Joven
3.
Methods Mol Biol ; 2803: 239-258, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38676898

RESUMEN

Decompensated right ventricular failure (RVF) in pulmonary hypertension (PH) is fatal, with limited medical treatment options. Developing and testing novel therapeutics for PH requires a clinically relevant large animal model of increased pulmonary vascular resistance and RVF. This manuscript describes the method to induce an ovine PH-RVF model that utilizes left pulmonary artery (LPA) ligation, progressive main pulmonary artery (MPA) banding, and insertion of an RV pressure line for monitoring. The PA cuff and RV pressure tubing are connected to subcutaneous access ports. This model of PH-RVF is a versatile platform to control not only the disease severity, but also the RV's phenotypic response. Subjects undergo progressive PA band adjustments twice per week for approximately 9 weeks with sequential measures of RV pressure, PA cuff pressures, and mixed venous blood gas (SvO2). Subjects can further be exercised on a livestock treadmill while hemodynamic parameters are captured. At the initiation and endpoint of this model, ventricular function and dimensions are assessed using echocardiography. In this model, RV mean and systolic pressure increased to 28 ± 5 and 57 ± 7 mmHg at week 1, and further to 44 ± 7 and 93 ± 18 mmHg by week 9, respectively. Echocardiography demonstrates characteristic findings of PH-RVF, notably RV dilation, increased wall thickness, and septal bowing. The rate of PA banding has a significant impact on SvO2 and thus the model can be titrated to elicit varying RV phenotypes. When the PA cuff is tightened rapidly, it can lead to a precipitous decline in SvO2, leading to RV decompensation, whereas a slower, more paced strategy leads to an adaptive RV stress-load response that maintains physiologic SvO2. A faster rate of PA banding will also lead to more severe liver fibrosis. The addition of controlled exercise provides a useful platform for assessing the effects of physical exertion in a PH-RVF model. This chronic PH-RVF model provides a valuable tool for studying molecular mechanisms, developing diagnostic biomarkers, and evaluating mechanical circulatory support systems.


Asunto(s)
Modelos Animales de Enfermedad , Insuficiencia Cardíaca , Hipertensión Pulmonar , Disfunción Ventricular Derecha , Animales , Hipertensión Pulmonar/fisiopatología , Hipertensión Pulmonar/etiología , Ovinos , Disfunción Ventricular Derecha/etiología , Disfunción Ventricular Derecha/fisiopatología , Insuficiencia Cardíaca/fisiopatología , Insuficiencia Cardíaca/etiología , Arteria Pulmonar/fisiopatología , Ecocardiografía , Hemodinámica
4.
J Heart Lung Transplant ; 43(2): 293-302, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37907183

RESUMEN

BACKGROUND: Right heart failure is the major cause of death in pulmonary hypertension. Lung transplantation is the only long-term treatment option for patients who fail medical therapy. Due to the scarcity of donor lungs, there is a critical need to develop durable mechanical support for the failing right heart. A major design goal for durable support is to reduce the size and complexity of devices to facilitate ambulation. Toward this end, we sought to deploy wearable mechanical support technology in a sheep disease model of chronic right heart failure. METHODS: In 6 sheep with chronic right heart failure, a mechanical support system consisting of an extracorporeal blood pump coupled with a gas exchange unit was attached in a right atrium-to-left atrium configuration for up to 7 days. Circuit performance, hematologic parameters, and animal hemodynamics were analyzed. RESULTS: Six subjects underwent the chronic disease model for 56 to 71 days. Three of the subjects survived to the 7-day end-point for circulatory support. The circuit provided 2.8 (0.5) liter/min of flow compared to the native pulmonary blood flow of 3.5 (1.1) liter/min. The animals maintained physiologically balanced blood gas profile with a sweep flow of 1.2 (1.0) liter/min. Two animals freely ambulated while wearing the circuit. CONCLUSIONS: Our novel mechanical support system provided physiologic support for a large animal model of pulmonary hypertension with right heart failure. The small footprint of the circuit and the low sweep requirement demonstrate the feasibility of this technology to enable mobile ambulatory applications.


Asunto(s)
Oxigenación por Membrana Extracorpórea , Insuficiencia Cardíaca , Corazón Auxiliar , Hipertensión Pulmonar , Humanos , Animales , Ovinos , Hipertensión Pulmonar/terapia , Insuficiencia Cardíaca/cirugía , Hemodinámica/fisiología , Atrios Cardíacos
5.
J Memb Sci ; 404-404: 25-31, 2012 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-22962517

RESUMEN

Current artificial lungs and respiratory assist devices designed for carbon dioxide removal (CO(2)R) are limited in their efficiency due to the relatively small partial pressure difference across gas exchange membranes. To offset this underlying diffusional challenge, bioactive hollow fiber membranes (HFMs) increase the carbon dioxide diffusional gradient through the immobilized enzyme carbonic anhydrase (CA), which converts bicarbonate to CO(2) directly at the HFM surface. In this study, we tested the impact of CA-immobilization on HFM CO(2) removal efficiency and thromboresistance in blood. Fiber surface modification with radio frequency glow discharge (RFGD) introduced hydroxyl groups, which were activated by 1M CNBr while 1.5M TEA was added drop wise over the activation time course, then incubation with a CA solution covalently linked the enzyme to the surface. The bioactive HFMs were then potted in a model gas exchange device (0.0084 m(2)) and tested in a recirculation loop with a CO(2) inlet of 50mmHg under steady blood flow. Using an esterase activity assay, CNBr chemistry with TEA resulted in 0.99U of enzyme activity, a 3.3 fold increase in immobilized CA activity compared to our previous method. These bioactive HFMs demonstrated 108 ml/min/m(2) CO(2) removal rate, marking a 36% increase compared to unmodified HFMs (p < 0.001). Thromboresistance of CA-modified HFMs was assessed in terms of adherent platelets on surfaces by using lactate dehydrogenase (LDH) assay as well as scanning electron microscopy (SEM) analysis. Results indicated HFMs with CA modification had 95% less platelet deposition compared to unmodified HFM (p < 0.01). Overall these findings revealed increased CO(2) removal can be realized through bioactive HFMs, enabling a next generation of more efficient CO(2) removal intravascular and paracorporeal respiratory assist devices.

6.
Artif Organs ; 35(6): 602-13, 2011 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-21463346

RESUMEN

The PediaFlow pediatric ventricular assist device (VAD) is a magnetically levitated turbodynamic pump under development for circulatory support of small children with a targeted flow rate range of 0.3-1.5 L/min. As the design of this device is refined, ensuring high levels of blood biocompatibility is essential. In this study, we characterized platelet activation during the implantation and operation of a second generation prototype of the PediaFlow VAD (PF2) and also performed a series of surgical sham studies to examine purely surgical effects on platelet activation. In addition, a newly available monoclonal antibody was characterized and shown to be capable of quantifying ovine platelet activation. The PF2 was implanted in three chronic ovine experiments of 17, 30, and 70 days, while surgical sham procedures were performed in five ovines with 30-day monitoring. Blood biocompatibility in terms of circulating activated platelets was measured by flow cytometric assays with and without exogenous agonist stimulation. Platelet activation following sham surgery returned to baseline in approximately 2 weeks. Platelets in PF2-implanted ovines returned to baseline activation levels in all three animals and showed an ability to respond to agonist stimulation. Late-term platelet activation was observed in one animal corresponding with unexpected pump stoppages related to a manufacturing defect in the percutaneous cable. The results demonstrated encouraging platelet biocompatibility for the PF2 in that basal platelet activation was achieved early in the pump implant period. Furthermore, this first characterization of the effect of a major cardiothoracic procedure on temporal ovine platelet activation provides comparative data for future cardiovascular device evaluation in the ovine model.


Asunto(s)
Materiales Biocompatibles/metabolismo , Corazón Auxiliar , Activación Plaquetaria , Animales , Niño , Diseño de Equipo , Humanos , Ensayo de Materiales , Implantación de Prótesis , Ovinos
7.
Artif Organs ; 35(1): 9-21, 2011 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-20626737

RESUMEN

The PediaFlow pediatric ventricular assist device is a miniature magnetically levitated mixed flow pump under development for circulatory support of newborns and infants (3-15 kg) with a targeted flow range of 0.3-1.5 L/min. The first generation design of the PediaFlow (PF1) was manufactured with a weight of approximately 100 g, priming volume less than 2 mL, length of 51 mm, outer diameter of 28 mm, and with 5-mm blood ports. PF1 was evaluated in an in vitro flow loop for 6 h and implanted in ovines for three chronic experiments of 6, 17, and 10 days. In the in vitro test, normalized index of hemolysis was 0.0087 ± 0.0024 g/100L. Hemodynamic performance and blood biocompatibility of PF1 were characterized in vivo by measurements of plasma free hemoglobin, plasma fibrinogen, total plasma protein, and with novel flow cytometric assays to quantify circulating activated ovine platelets. The mean plasma free hemoglobin values for the three chronic studies were 4.6 ± 2.7, 13.3 ± 7.9, and 8.8 ± 3.3 mg/dL, respectively. Platelet activation was low for portions of several studies but consistently rose along with observed animal and pump complications. The PF1 prototype generated promising results in terms of low hemolysis and platelet activation in the absence of complications. Hemodynamic results validated the magnetic bearing design and provided the platform for design iterations to meet the objective of providing circulatory support for young children with exceptional biocompatibility.


Asunto(s)
Corazón Auxiliar , Ensayo de Materiales , Animales , Diseño de Equipo , Hematócrito , Hemodinámica , Hemólisis , Humanos , Implantes Experimentales , Lactante , Recién Nacido , Magnetismo , Miniaturización , Activación Plaquetaria , Ovinos
8.
Artif Organs ; 34(5): 439-42, 2010 May.
Artículo en Inglés | MEDLINE | ID: mdl-20633159

RESUMEN

Hollow fiber membrane (HFM)-based artificial lungs can require a large blood-contacting membrane surface area to provide adequate gas exchange. However, such a large surface area presents significant challenges to hemocompatibility. One method to improve carbon dioxide (CO(2)) transfer efficiency might be to immobilize carbonic anhydrase (CA) onto the surface of conventional HFMs. By catalyzing the dehydration of bicarbonate in blood, CA has been shown to facilitate diffusion of CO(2) toward the fiber membranes. This study evaluated the impact of surface modifying a commercially available microporous HFM-based artificial lung on fiber blood biocompatibility. A commercial poly(propylene) Celgard HFM surface was coated with a siloxane, grafted with amine groups, and then attached with CA which has been shown to facilitate diffusion of CO(2) toward the fiber membranes. Results following acute ovine blood contact indicated no significant reduction in platelet deposition or activation with the siloxane coating or the siloxane coating with grafted amines relative to base HFMs. However, HFMs with attached CA showed a significant reduction in both platelet deposition and activation compared with all other fiber types. These findings, along with the improved CO(2) transfer observed in CA modified fibers, suggest that its incorporation into HFM design may potentiate the design of a smaller, more biocompatible HFM-based artificial lung.


Asunto(s)
Anhidrasas Carbónicas/metabolismo , Enzimas Inmovilizadas/metabolismo , Máquina Corazón-Pulmón , Ensayo de Materiales , Membranas Artificiales , Animales , Dióxido de Carbono/metabolismo , Ovinos , Propiedades de Superficie
9.
J Arthroplasty ; 24(1): 158.e9-158.e13, 2009 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-18534412

RESUMEN

Acute hematogenous septic arthritis caused by the genus Klebsiella is extremely rare. This case report describes a prosthetic joint infected with Klebsiella pneumoniae via acute hematogenous spread. This is the first reported case of K pneumoniae pyogenic arthritis with a coexisting occult colonic adenocarcinoma. The patient was treated successfully with open irrigation, debridement, polyethylene spacer exchange, and chronic suppressive antibiotics. The underlying colon cancer was recognized early, and the patient responded well to surgery and adjuvant chemotherapy. This case illustrates the importance of having a high index of suspicion for underlying pathologic processes when an unusual organism presents as the cause of septic arthritis.


Asunto(s)
Adenocarcinoma/diagnóstico , Neoplasias del Colon/diagnóstico , Infecciones por Klebsiella/diagnóstico , Klebsiella pneumoniae , Prótesis de la Rodilla/microbiología , Neoplasias Primarias Desconocidas/diagnóstico , Infecciones Relacionadas con Prótesis/diagnóstico , Adenocarcinoma/secundario , Adenocarcinoma/terapia , Antibacterianos/uso terapéutico , Artritis Infecciosa/complicaciones , Artritis Infecciosa/diagnóstico , Artritis Infecciosa/tratamiento farmacológico , Artroplastia de Reemplazo de Rodilla , Neoplasias del Colon/secundario , Neoplasias del Colon/terapia , Terapia Combinada , Desbridamiento , Humanos , Infecciones por Klebsiella/complicaciones , Infecciones por Klebsiella/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Neoplasias Primarias Desconocidas/complicaciones , Neoplasias Primarias Desconocidas/terapia , Infecciones Relacionadas con Prótesis/complicaciones , Infecciones Relacionadas con Prótesis/tratamiento farmacológico
10.
Innovations (Phila) ; 14(2): 159-167, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-31039682

RESUMEN

OBJECTIVE: Aortic root enlargement may be necessary to implant adequately sized valves to avoid patient-prosthetic mismatch. Our objective was to assess the feasibility of annular enlargement during aortic valve replacement via a right anterior minithoracotomy. METHODS: Twelve consecutive patients undergoing elective minimally invasive aortic valve replacement requiring annular enlargement over a 2-year period were retrospectively reviewed. A right anterior minithoracotomy was performed in all patients. Cardiopulmonary bypass and aortic crossclamp times, hospital length of stay, postoperative complications, rate of reoperation, echocardiographic data, and mortality were analyzed. RESULTS: Mean age was 66 years ± 14. Mean body mass index was 34 ± 7.8 kg/m2. All patients had normal preoperative ejection fractions. Indications for aortic valve replacement were severe (3/12, 25%) or critical (9/12, 75%) aortic stenosis due to degenerative aortic valve disease (10/12, 83%) and congenitally bicuspid aortic valve (2/12, 17%). Cardiopulmonary bypass and aortic crossclamp times were 144.7 ± 14.7 minutes and 111.7 ± 10.6 minutes, respectively. The median postoperative length of stay was 4 days. Peak and mean aortic valve gradients on postreplacement intraoperative transesophageal echocardiography were 14.5 ± 9.4 mmHg and 7.2 ± 4.2 mmHg, respectively, with no perivalvular leak on intraoperative or follow-up transthoracic echocardiogram. Postoperative transthoracic echocardiography had peak and mean aortic valve gradients of 12.1 ± 6.9 mmHg and 6.3 ± 3.7 mmHg, respectively. There were no postoperative mortalities. Freedom from reoperation was 100%. CONCLUSIONS: Annular enlargement performed during minimally invasive aortic valve replacement is feasible. Basic minimally invasive skills are recommended prior to instituting these more advanced techniques.


Asunto(s)
Estenosis de la Válvula Aórtica/cirugía , Válvula Aórtica/cirugía , Anuloplastia de la Válvula Cardíaca/métodos , Implantación de Prótesis de Válvulas Cardíacas/métodos , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Anciano , Anciano de 80 o más Años , Válvula Aórtica/anomalías , Válvula Aórtica/diagnóstico por imagen , Válvula Aórtica/patología , Estenosis de la Válvula Aórtica/etnología , Anuloplastia de la Válvula Cardíaca/mortalidad , Puente Cardiopulmonar/normas , Ecocardiografía/métodos , Estudios de Factibilidad , Femenino , Implantación de Prótesis de Válvulas Cardíacas/mortalidad , Humanos , Tiempo de Internación , Persona de Mediana Edad , Complicaciones Posoperatorias , Estudios Retrospectivos , Toracotomía/métodos , Toracotomía/tendencias
11.
Ann Thorac Surg ; 107(1): 128-134, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30170012

RESUMEN

BACKGROUND: Optimal pain control continues to be a concern in cardiac surgery. Current strategies for postoperative pain management often yield suboptimal results. The superiority of Exparel (Pacira Pharmaceuticals, Inc, Parsippany, NJ) in providing postoperative pain control and opioid sparing is equivocal. This prospective, randomized, double-blind study examines the efficacy of Exparel as a novel single-dose application parasternal nerve block in postoperative pain control and opioid sparing. METHODS: This single-surgeon study included 79 patients undergoing median sternotomy for coronary revascularization. Study participants were randomized to either the drug or a control arm. Each participant received Exparel or normal saline placebo administered as a parasternal nerve block. Postoperative pain was rated according to the nonverbal pain scale or numeric rating scale. Total amount of narcotic pain medication used and patients' pain scores within the first 72 hours postoperatively were compared. Secondary outcomes compared the intensive care unit length of stay, hospital length of stay, time to extubation, time to return of bowel function, and time to return to work or daily activities. RESULTS: The primary endpoint of pain levels between the two groups demonstrated no significant difference when analyzing the individual time points postoperatively. However, overall pain levels were significantly lower in the study drug group (p = 0.04). There was no significant difference in the amount of analgesics required postoperatively or in secondary endpoints between the groups. CONCLUSIONS: Exparel does not provide an opioid-sparing benefit or any secondary outcome benefit compared with placebo. Exparel may be associated with a marginal decrease in postoperative pain levels. (Parasternal Nerve Bock in Cardiac Patients; NCT01826851.).


Asunto(s)
Bupivacaína/administración & dosificación , Bloqueo Nervioso/métodos , Dolor Postoperatorio/tratamiento farmacológico , Esternotomía/métodos , Anciano , Anestésicos Locales/administración & dosificación , Procedimientos Quirúrgicos Cardíacos/métodos , Método Doble Ciego , Femenino , Estudios de Seguimiento , Humanos , Nervios Intercostales , Masculino , Persona de Mediana Edad , Dimensión del Dolor , Dolor Postoperatorio/diagnóstico , Estudios Prospectivos , Resultado del Tratamiento
12.
J Clin Invest ; 129(11): 5005-5019, 2019 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-31437130

RESUMEN

The interleukin-3 receptor α subunit, CD123, is expressed in many hematologic malignancies including acute myeloid leukemia (AML) and blastic plasmacytoid dendritic cell neoplasm (BPDCN). Tagraxofusp (SL-401) is a CD123-targeted therapy consisting of interleukin-3 fused to a truncated diphtheria toxin payload. Factors influencing response to tagraxofusp other than CD123 expression are largely unknown. We interrogated tagraxofusp resistance in patients and experimental models and found that it was not associated with CD123 loss. Rather, resistant AML and BPDCN cells frequently acquired deficiencies in the diphthamide synthesis pathway, impairing tagraxofusp's ability to ADP-ribosylate cellular targets. Expression of DPH1, encoding a diphthamide pathway enzyme, was reduced by DNA CpG methylation in resistant cells. Treatment with the DNA methyltransferase inhibitor azacitidine restored DPH1 expression and tagraxofusp sensitivity. We also developed a drug-dependent ADP-ribosylation assay in primary cells that correlated with tagraxofusp activity and may represent an additional novel biomarker. As predicted by these results and our observation that resistance also increased mitochondrial apoptotic priming, we found that the combination of tagraxofusp and azacitidine was effective in patient-derived xenografts treated in vivo. These data have important implications for clinical use of tagraxofusp and led to a phase 1 study combining tagraxofusp and azacitidine in myeloid malignancies.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Células Dendríticas/metabolismo , Sistemas de Liberación de Medicamentos , Neoplasias Hematológicas , Subunidad alfa del Receptor de Interleucina-3/metabolismo , Leucemia Mieloide Aguda , Proteínas de Neoplasias/metabolismo , Animales , Azacitidina/farmacología , Línea Celular Tumoral , Metilación de ADN , Células Dendríticas/patología , Femenino , Neoplasias Hematológicas/tratamiento farmacológico , Neoplasias Hematológicas/metabolismo , Neoplasias Hematológicas/patología , Humanos , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patología , Masculino , Ratones , Ratones Desnudos , Antígenos de Histocompatibilidad Menor/metabolismo , Proteínas Recombinantes de Fusión/farmacología , Proteínas Supresoras de Tumor/metabolismo , Ensayos Antitumor por Modelo de Xenoinjerto
13.
Artif Organs ; 32(2): 136-45, 2008 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-18005275

RESUMEN

Ovines are a common animal model for preclinical evaluation of cardiovascular devices including heart valves, endovascular grafts, and ventricular assist devices. Biocompatibility is essential to the success of these devices; however, tools to assess biocompatibility in ovines are limited. To address this need, antibodies that bind to activated human and bovine platelets and annexin V protein were evaluated for potential cross-reactivity to activated ovine platelets. These candidate markers were incubated with stimulated and quiescent ovine whole blood, and binding to platelets was quantified by flow cytometry. Several antihuman CD62P antibodies including one polyclonal antibody, three monoclonal antibodies, and annexin V selectively bound to activated ovine platelets. An assay to quantify platelet microaggregates was also developed. The availability of assays to quantify ovine platelet activation can increase the quality of biocompatibility data obtainable during preclinical development of artificial organs in the ovine model, potentially aiding in the evaluation of design refinements to enhance device biocompatibility.


Asunto(s)
Citometría de Flujo/métodos , Activación Plaquetaria , Recuento de Plaquetas/métodos , Animales , Anticuerpos Monoclonales , Especificidad de Anticuerpos , Órganos Artificiales , Materiales Biocompatibles , Bovinos , Técnica del Anticuerpo Fluorescente/métodos , Humanos , Modelos Animales , Recuento de Plaquetas/instrumentación , Oveja Doméstica
14.
Artículo en Inglés | MEDLINE | ID: mdl-29781589

RESUMEN

Bentall procedures are traditionally performed through a median sternotomy. However, minimally invasive approaches are increasingly being utilized. A right mini-thoracotomy approach may improve postoperative recovery.  A 5-cm mini-thoracotomy is performed in the right 2nd intercostal space. A camera port is placed lateral to this incision. Peripheral cannulation is performed. The ascending aorta is cross-clamped. Cardioplegia is administered and the patient is placed in deep hypothermic circulatory arrest to construct the distal aortic anastomosis. Aortic leaflets are excised and the annulus is sized. Annular and prosthetic sutures are placed using shafted instruments or automated suturing devices. The coronary buttons are reimplanted and a graft-to-graft anastomosis is constructed.  The Bentall procedure can be done safely through a right mini-thoracotomy in select patients and we demonstrate our technique in this video tutorial. Automated suturing devices and video guidance may facilitate this procedure.


Asunto(s)
Aorta/cirugía , Aneurisma de la Aorta Torácica/cirugía , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Técnicas de Sutura/instrumentación , Toracotomía/métodos , Procedimientos Quirúrgicos Vasculares/métodos , Anciano , Diseño de Equipo , Humanos , Persona de Mediana Edad
15.
Ann Transl Med ; 6(15): 314, 2018 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-30211202

RESUMEN

Focused research targeting an identified clinical problem may result in more rapid development of medical devices, technologies, and surgical techniques that directly impact patient care. These medical advances to improve patient care may be expedited by adopting an interactive translational research model in which inventors, designers, and engineers work in collaboration with surgeons. In addition, cadaveric simulation is a high-fidelity model that is bridging the translational and logistical gap to bring new surgical devices, technologies, and techniques to patients. We describe the partnership between the University of Rochester and LSI SOLUTIONS® in which an interactive translational research model utilizing cadaveric simulation has been successfully applied to accelerate bringing minimally invasive cardiac surgical techniques and innovative devices to patients.

16.
Innovations (Phila) ; 13(5): 361-364, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30394954

RESUMEN

OBJECTIVE: The objective of this study was to investigate the feasibility of using titanium fasteners for securement of the inflow sewing ring during HeartMate 3 implantation. The secondary objective was to compare cardiopulmonary bypass and total operative times between the titanium fastener and hand-tied knot groups. METHODS: Clearance between the sewing ring and the HeartMate 3 device was assessed in vitro. Thirty-one patients undergoing HeartMate 3 implantation via median sternotomy at a single center from April 2017 to February 2018 were reviewed. The sewing ring was secured with hand-tied knots (n = 18) or titanium fasteners (n = 13). Cannulation strategy and implantation technique were otherwise identical between groups. Central arterial and venous cannulation was performed for cardiopulmonary bypass. The left ventricular apex was cored, and the sewing ring was attached with hand-tied knots or titanium fasteners. RESULTS: There was adequate clearance for the titanium fastener to secure the inflow sewing ring and then connect to the HeartMate 3 in vitro. The inflow sewing ring was successfully secured during HeartMate 3 implantation in the titanium fastener group. Cardiopulmonary bypass time was 75 and 92 minutes for the titanium fastener and hand-tied groups, respectively (P < 0.03). Total operative time was 177 and 193 minutes for the titanium fastener and hand-tied groups, respectively (P = 0.513). CONCLUSIONS: The inflow sewing ring of the HeartMate 3 was efficiently secured using titanium fasteners. Titanium fasteners resulted in shorter cardiopulmonary bypass times compared with the hand-tied group. There was no difference in total operative time.


Asunto(s)
Procedimientos Quirúrgicos Cardíacos , Corazón Auxiliar , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Implantación de Prótesis/métodos , Titanio/uso terapéutico , Procedimientos Quirúrgicos Cardíacos/instrumentación , Procedimientos Quirúrgicos Cardíacos/métodos , Femenino , Insuficiencia Cardíaca/cirugía , Humanos , Masculino , Persona de Mediana Edad , Tempo Operativo , Diseño de Prótesis , Estudios Retrospectivos
17.
Innovations (Phila) ; 13(6): 428-432, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30547896

RESUMEN

OBJECTIVE: Subaortic membrane is an anatomical intracardiac anomaly that may cause discrete subaortic stenosis and aortic insufficiency. Patients requiring subaortic membrane resection may benefit from a minimally invasive approach; however, subaortic membranes are typically resected through a median sternotomy. We present our initial clinical experience of adult patients who have undergone a mini-thoracotomy subaortic membrane resection. METHODS: Eight patients who underwent an elective subaortic membrane resection performed through a mini-thoracotomy were retrospectively reviewed. A 5-cm mini-thoracotomy incision was made in the 2nd intercostal space; a videoscope was inserted through a separate incision within the same interspace. Cardiopulmonary bypass (CPB) was instituted via central arterial and peripheral venous cannulation and an aortotomy was made. The subaortic membrane was resected with shafted instruments. The left ventricular outflow tract was inspected and CPB was weaned. Thirty-day mortality, intensive care and hospital length of stay, ventilation time, operative times, postoperative morbidity, and need for additional procedures were evaluated. RESULTS: The median CPB and cross-clamp times were 60 and 42 minutes, respectively. The median time to extubation was 3.6 hours. The median intensive care unit and hospital stay were 22 hours and 3 days, respectively. The postoperative left ventricular outflow tract mean gradients decreased significantly (26.5 vs. 9.4 mm Hg, P = 0.001). There were no conversions to sternotomy, perioperative strokes, or 30-day mortality. CONCLUSIONS: Subaortic membranes can be resected through a mini-thoracotomy approach with excellent clinical results.


Asunto(s)
Aorta/cirugía , Cirugía Torácica Asistida por Video/métodos , Toracotomía/métodos , Adulto , Anciano , Puente Cardiopulmonar , Femenino , Humanos , Tiempo de Internación/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/epidemiología , Reoperación/estadística & datos numéricos , Estudios Retrospectivos , Cirugía Torácica Asistida por Video/efectos adversos , Cirugía Torácica Asistida por Video/estadística & datos numéricos , Toracotomía/efectos adversos , Toracotomía/estadística & datos numéricos
18.
J Vis Surg ; 4: 38, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29552520

RESUMEN

Aortic root replacement is typically performed through a median sternotomy. The right anterior mini-thoracotomy approach has been shown to decrease hospital length of stay in aortic valve surgery when compared to sternotomy. This approach is rare in ascending aortic surgery due to technical challenges which include exposure and annular suture placement. Automated suturing technology is now available to facilitate the placement of annular sutures. The use of a camera greatly enhances visualization of the aortic root. A right anterior mini-thoracotomy is performed via a 5 cm incision in the right second intercostal space with a camera port placed lateral to the incision. Peripheral arterial and venous cannulation are performed. The aortic cross clamp is placed through a 5 mm incision in the third interspace anterior to mid axillary line. Histidine tryptophan ketoglutarate (HTK) cardioplegia is administered and deep hypothermic circulatory arrest is achieved followed by completion of the distal anastomosis with a 4-0 polypropylene running suture. After aortic leaflet removal, annular and prosthetic sutures are placed with shafted instruments or with automated suturing technology. Coronary button suturing and graft-to-graft anastomoses are performed with shafted instruments. Aortic root procedures can be performed safely through a right anterior mini-thoracotomy. The use of a camera and automated suturing technology may further facilitate this procedure, enabling more surgeons to offer this less invasive approach to patients.

19.
J Vis Surg ; 4: 39, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29552521

RESUMEN

Aortic valve replacement through minimally invasive access is increasing. These procedures have several advantages over conventional sternotomy including decreased intensive care unit and hospital length of stay and decreased ventilation time. The right anterior mini-thoracotomy (RAM) approach is potentially attractive in that it completely spares the sternum leading to improved cosmesis, reduced blood loss, and improved patient satisfaction. However, this approach is underutilized due to anticipated technical challenges including difficulty with visualization and annular suture placement. We employ a camera and automated suturing technology for supra-annular valve implant. A RAM is performed via a 5 cm incision in the right second intercostal space with a camera port placed lateral to the incision. Peripheral venous cannulation is performed along with central arterial cannulation. Aortic cross clamp is placed through a 5 mm incision in the third interspace anterior to mid axillary line. Histidine tryptophan ketoglutarate (HTK) cardioplegia is administered. After aortic leaflet removal, annular and prosthetic sutures are placed with shafted instruments or with automated suturing technology. Aortic valve replacement can be performed safely through a RAM. The use of a camera and automated suturing technology facilitates this procedure, potentially enabling more surgeons to offer this less invasive approach to patients.

20.
Innovations (Phila) ; 13(5): 328-331, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30407927

RESUMEN

OBJECTIVE: Bentall procedures are traditionally performed through a median sternotomy. The right mini-thoracotomy approach is increasingly used in aortic valve replacement. This approach has been shown to have decreased blood loss and hospital length of stay compared with sternotomy. A right mini-thoracotomy approach may also be beneficial in selected patients requiring aortic root surgery. We present our initial clinical experience of patients who have undergone a right mini-thoracotomy Bentall. METHODS: This is a single-center retrospective review of seven patients who underwent a primary elective right anterior mini-thoracotomy Bentall. A thoracoscope was used in each case. Automated suturing technology was used for annular suturing in three of the seven patients. Clinical outcomes evaluated include 30-day mortality, intensive care and hospital length of stay, time to extubation, operative times, as well as postoperative sequelae including stroke, infection, and bleeding. RESULTS: Median cardiopulmonary bypass, cross-clamp, and circulatory arrest time were 217, 153, and 28 minutes, respectively. Median time to extubation was 10 hours and median intensive care unit and hospital stay was 1 and 4 days, respectively. One patient had a wound infection and one returned to the operating room for bleeding. There were no in-hospital or 30-day mortalities. CONCLUSIONS: The Bentall procedure can be performed through a right anterior mini-thoracotomy in selected patients with excellent clinical results.


Asunto(s)
Aorta/cirugía , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Toracotomía/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Procedimientos Quirúrgicos Mínimamente Invasivos/mortalidad , Procedimientos Quirúrgicos Mínimamente Invasivos/estadística & datos numéricos , Morbilidad , Tempo Operativo , Estudios Retrospectivos , Toracotomía/mortalidad , Toracotomía/estadística & datos numéricos
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