RESUMO
Early postoperative wound complications in revascularization procedures in the groin very often include complications associated with injury to the lymphatic system such as lymphocele and lymphorrhea with subsequent local infectious complications and the risk of infection of prosthetic grafts. We present a case report of successful treatment of postoperative lymphocele with subsequent lymphatic fistula and dehiscence of the surgical wound by intranodal embolization of the injured lymph node with Histoacryl tissue glue.
Assuntos
Embolização Terapêutica , Virilha , Linfocele , Humanos , Linfocele/etiologia , Linfocele/terapia , Embolização Terapêutica/métodos , Masculino , Embucrilato/uso terapêutico , Linfonodos/transplante , Pessoa de Meia-Idade , Complicações Pós-Operatórias/terapia , Adesivos Teciduais/uso terapêutico , IdosoRESUMO
Retroperitoneal hematoma is a life-threatening condition where early diagnosis and correct treatment are of utmost importance. Bleeding in the retroperitoneal space has a high mortality rate. The aim of this study was to present current published scientific evidence regarding the incidence, mechanism of injury, diagnostic methods and treatment based on a review of international literature covering the last 40 years. The systematic review of the literature was performed using the SCOPUS and PUBMED databases. Publications in English were included. We have not included publications dealing with this issue in children. Systematic reviews showed an increasing trend toward nonsurgical management of retroperitoneal injuries.
Assuntos
Traumatismos Abdominais , Doenças Peritoneais , Criança , Hemorragia Gastrointestinal , Hematoma/diagnóstico por imagem , Hematoma/terapia , Humanos , Espaço Retroperitoneal/diagnóstico por imagemRESUMO
Veno-arterial extracorporeal membrane oxygenation (VA ECMO) is a technique used in patients with severe heart failure. The aim of this study was to evaluate its effects on left ventricular afterload and fluid accumulation in lungs with electrical impedance tomography (EIT). In eight swine, incremental increases of extracorporeal blood flow (EBF) were applied before and after the induction of ischemic heart failure. Hemodynamic parameters were continuously recorded and computational analysis of EIT was used to determine lung fluid accumulation. With an increase in EBF from 1 to 4 l/min in acute heart failure the associated increase of arterial pressure (raised by 44%) was accompanied with significant decrease of electrical impedance of lung regions. Increasing EBF in healthy circulation did not cause lung impedance changes. Our findings indicate that in severe heart failure EIT may reflect fluid accumulation in lungs due to increasing EBF.
Assuntos
Oxigenação por Membrana Extracorpórea/métodos , Insuficiência Cardíaca/terapia , Pulmão/fisiopatologia , Insuficiência Respiratória/patologia , Animais , Circulação Coronária/fisiologia , Modelos Animais de Doenças , Impedância Elétrica , Oxigenação por Membrana Extracorpórea/efeitos adversos , Feminino , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/patologia , Hemodinâmica , Insuficiência Respiratória/etiologia , SuínosRESUMO
The growth in the experimental research of facilities to support extracorporeal circulation requires the further development of models of acute heart failure that can be well controlled and reproduced. Two types of acute heart failure were examined in domestic pigs (Sus scrofa domestica): a hypoxic model (n=5) with continuous perfusion of the left coronary artery by hypoxic deoxygenated blood and ischemic model (n=9) with proximal closure of the left coronary artery and controlled hypoperfusion behind the closure. The aim was a severe, stable heart pump failure defined by hemodynamic parameters changes: a) decrease in cardiac output by at least 50 %; b) decrease in mixed venous blood saturation to under 60 %; c) left ventricular ejection fraction below 25 %; and d) decrease in flow via the carotid arteries at least 50 %. Acute heart failure developed in the first group in one animal with no acute mortality and in the second group in 8 animals with no acute mortality. In the case of ischemic model the cardiac output fell from 6.70+/-0.89 l/min to 2.89+/-0.75 l/min. The saturation of the mixed venous blood decreased from 83+/-2 % to 58+/-8 %. The left ventricular ejection fraction decreased from 50+/-8 % to 19+/-2 %. The flow via the carotid arteries decreased from 337+/-78 ml/min to 136+/-59 ml/min (P=0.001 for all comparisons). The proposed ischemic model is not burdened with acute mortality in the development of heart failure and is suitable for further use in experimental research into extracorporeal circulatory support.
Assuntos
Modelos Animais de Doenças , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Índice de Gravidade de Doença , Doença Aguda , Animais , Feminino , Hemodinâmica/fisiologia , Sus scrofa , SuínosRESUMO
Subclavian steal-carotid recovery phenomenon appears to be related to the occlusion of the truncus brachiocephalicus and can be a rare cause of neurological deficit. In this syndrome, the right common carotid artery and right subclavian artery are filled with retrograde flow from the ipsilateral vertebral artery. We present a patient with this type of steal syndrome managed by a classical surgical procedure for stent reocclusion in the truncus brachiocephalicus.Key words: steal phenomenon endarterectomy truncus brachiocephalicus.
Assuntos
Síndrome do Roubo Subclávio , Humanos , Stents , Artéria Subclávia , Artéria VertebralRESUMO
Stone disease has afflicted mankind since centuries; records from ancient civilisations of India and Egypt have shown stones in human bodies. The scientific mind of humans has always made smart endeavours to remove the kidney stones. From large instruments made like the beaks of different animals and birds in 600 BC (Indian civilisation) to extremely sophisticated and miniaturised endoscopic intruments of today the human race has travelled a long way. The theme has always been to remove the stones with minimal morbidity and mortality and with minimum pain to the patient. The article takes you through the journey of instruments used in 600 BC until today. The story of instrumentation is a symbiosis of the medical minds along with engineering advances. The story of miniaturisation could not have moved further without the development of lasers, fiberoptics and sophisticated cameras. As the field stands today, we remove more complex stones by larger endoscopic intervention and smaller stones by miniaturised instruments. The article discusses all the merits and shortcomings of various techniques: from open surgery to standard PCNL to Mini PCNL to Ultra- Mini PCNL to Micro-PCNL.
Assuntos
Cálculos Renais/cirurgia , Nefrostomia Percutânea/instrumentação , Nefrostomia Percutânea/métodos , Desenho de Equipamento , História do Século XX , História do Século XXI , História Antiga , Humanos , Miniaturização , Nefrostomia Percutânea/históriaRESUMO
Ultra mini PCNL (UMP) has been described as a less invasive technique of PCNL for the treatment of small to medium sized stones in attempt to reduce the surgical morbidity. OBJECTIVE: Evaluate prospectively the outcomes of UMP. METHODS: Single surgeon prospective concurrent cohort study of UMP in India. Effectiveness was assessed by stone-free rates, operative time, complications including transfusion, sepsis rates, length of stay and analgesic requirements. RESULTS: In 2013, data on 98 consecutive patients who underwent UMP was collected prospectively. Mean stone size (±SD)was 15.85 ± 4.53mm. The mean Hounsfield unit (HU) was 1105 ± 165HU. Access to the kidney was from the upper pole (8), interpolar (36) and lower pole(55) with no instances of failed access. Mean operating time was 54 minutes (range 28-120 minutes). The mean change in haemoglobin was -0.81g/dl and mean change in creatinine was 0.05mg/dl. No patients were transfused or suffered acute kidney injury. There were fiveClavien-Dindo complications (Grade I x4, IIIb x 1) with the most serious being a perinephric collection requiring intervention. Post-operative oral analgesia was sufficient in 89 patients (91%) with 9 patients (9%) requiring IM or IV analgesia. Median length of stay was 30 hours (IQR 10 hours). 13 patientshad nephrostomy drainage. 8 patients required a stent for one week. Intraoperatively, 98% of patients were stone free on fluoroscopy, which was 76% on day 1 post op ultrasound and 83% on CT at 1 month. Stone free was the absence of detectable calculi. CONCLUSIONS: UMP for 10-20mm stones appears to be effective and safe with few complications and a short length of stay. Further multicentre studies are required but if confirmed, UMP may be a valuable addition to the armamentarium of the endourologist.
Assuntos
Cálculos Renais/cirurgia , Nefrostomia Percutânea/métodos , Cálculos Ureterais/cirurgia , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Miniaturização , Estudos Prospectivos , Resultado do TratamentoRESUMO
Stone disease has afflicted mankind since centuries; records from ancient civilisations of India and Egypt have shown stones in human bodies. The scientific mind of humans has always made smart endeavours to remove the kidney stones. From large instruments made like the beaks of different animals and birds in 600 BC (Indian civilisation) to extremely sophisticated and miniaturised endoscopic intruments of today the human race has travelled a long way. The theme has always been to remove the stones with minimal morbidity and mortality and with minimum pain to the patient. The article takes you through the journey of instruments used in 600 BC until today. The story of instrumentation is a symbiosis of the medical minds along with engineering advances. The story of miniaturisation could not have moved further without the development of lasers, fiberoptics and sophisticated cameras.As the field stands today, we remove more complex stones by larger endoscopic intervention and smaller stones by miniaturised instruments. The article discusses all the merits and shortcomings of various techniques: from open surgery to standard PCNL to Mini PCNL to Ultra- Mini PCNL to Micro-PCNL
La enfermedad litiásica ha afligido a la humanidad desde hace siglos. Registros de antiguas civilizaciones de India y Egipto han mostrado piedras en cuerpos humanos. La mente humana científica siempre ha realizado esfuerzos inteligentes para eliminar las piedras renales. Desde los instrumentos grandes hechos como los picos de diferentes animales y pájaros en 600 AC (Civilización India) a los instrumentos endoscópicos extremadamente sofisticados y miniaturizados de hoy en día la raza humana ha recorrido un largo camino. El tema ha sido siempre eliminar las piedras con una mínima morbilidad y mortalidad y con el mínimo dolor para el paciente. El artículo le lleva a través del viaje de los instrumentos utilizados en 600 AC hasta hoy en día. La historia de la instrumentación es una simbiosis de las mentes médicas a lo largo de los avances de la ingeniería. La historia de la miniaturización no podría haber avanzado sin el desarrollo de los láseres, fibras ópticas y cámaras sofisticadas. Actualmente, eliminamos las piedras más complejas con intervenciones endoscópicas mayores y las piedras más pequeñas con instrumentos miniaturizados. El artículo discute todos los méritos y deficiencias de diferentes técnicas: desde cirugía abierta hasta NLPC estándar, mini NLPC
Assuntos
Humanos , Urolitíase/cirurgia , Cálculos Urinários/cirurgia , Nefrolitíase/cirurgia , Nefrostomia Percutânea/métodos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Complicações Pós-Operatórias/prevenção & controleRESUMO
Ultra mini PCNL (UMP) has been described as a less invasive technique of PCNL for the treatment of small to medium sized stones in attempt to reduce the surgical morbidity. Objective: Evaluate prospectively the outcomes of UMP. Methods: Single surgeon prospective concurrent cohort study of UMP in India. Effectiveness was assessed by stone-free rates, operative time, complications including transfusion, sepsis rates, length of stay and analgesic requirements. Results: In 2013, data on 98 consecutive patients who underwent UMP was collected prospectively. Mean stone size (±SD) was 15.85 ± 4.53mm. The mean Hounsfield unit (HU) was 1105 ± 165HU. Access to the kidney was from the upper pole (8), interpolar (36) and lower pole (55) with no instances of failed access. Mean operating time was 54 minutes (range 28-120 minutes). The mean change in haemoglobin was -0.81g/dl and mean change in creatinine was 0.05mg/dl. No patients were transfused or suffered acute kidney injury. There were fiveClavien-Dindo complications (Grade I x4, IIIb x 1) with the most serious being a perinephric collection requiring intervention. Post-operative oral analgesia was sufficient in 89 patients (91%) with 9 patients (9%) requiring IM or IV analgesia. Median length of stay was 30 hours (IQR 10 hours). 13 patientshad nephrostomy drainage. 8 patients required a stent for one week. Intraoperatively, 98% of patients were stone free on fluoroscopy, which was 76% on day 1 post op ultrasound and 83% on CT at 1 month. Stone free was the absence of detectable calculi.Conclusions: UMP for 10-20mm stones appears to be effective and safe with few complications and a short length of stay. Further multicentre studies are required but if confirmed, UMP may be a valuable addition to the armamentarium of the endourologist
La ultra mini NLPC (UMP) ha sido descrita como una técnica de NLPC menos invasiva para el tratamiento de las piedras pequeñas y medianas en un intento de reducir la morbilidad quirúrgica. Objetivo: Evaluar prospectivamente los resultados de la UMP. Metodos: Estudio prospectivo de una cohorte concurrente de UMP con un único cirujano en India. La eficacia fue evaluada mediante el porcentaje de pacientes libres de litiasis, el tiempo operatorio, las complicaciones, incluyendo transfusión, tasas de sepsis, tiempo de estancia y necesidades analgésicas. Resultados: En 2013, se recogieron prospectivamente los datos de 98 pacientes consecutivos que habían sido sometidos a UMP. El tamaño medio (± DE) de la piedra fue de 15,85 ± 4,53mm. La media de unidades Hounsfield (UH) fue de 1105 ± 165. El acceso al riñón se realizó por el polo superior (8), interpolar (36) y por el polo inferior (55), con ningún caso de acceso fallido. El tiempo operatorio medio fue de 54 minutos (Rango 28-120 minutos). La media del descenso de la hemoglobina fue de -0,81g/dl y el cambio medio de la creatinina de 0,05mg/dL. Ningún paciente fue transfundido o sufrió daño renal agudo. Hubo cinco complicaciones (4 de Grado I Clavien- Dindo, 1 Grado IIIb) siendo la más grave una colección perinéfrica que requería intervención. La analgesia oral postoperatoria fue suficiente en 89 pacientes (91%) y 9 pacientes (9%) requirieron analgesia IM o IV. La mediana de estancia hospitalaria fue de 30 horas (Rango interquartílico 10 horas). 13 pacientes tuvieron tubo de nefrostomía. 8 Pacientes necesitaron un catéter durante 8 días. Intraoperatoriamente, 98% de los pacientes quedaron libres de litiasis en fluoroscopia, siendo el 76% en ecografía el primer día postoperatorio y 83% en TAC al mes. Se definió libre de litiasis como la ausencia de cálculos detectables. Conclusiones: La UMP parece ser eficaz para piedras entre 10-20 mm, con pocas complicaciones y una estancia corta. Se requieren más estudios multicéntricos, pero, si se confirma, la UMP puede ser una adición valiosa para el armamentario del endourólogo
Assuntos
Humanos , Nefrostomia Percutânea/métodos , Nefrolitíase/cirurgia , Estudos Prospectivos , Litotripsia/métodos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Resultado do Tratamento , Estudos de CoortesRESUMO
Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is a method used for the treatment most severe cases of decompensated heart failure. The purpose of this study was to evaluate the risk of the formation of microembolisms during VA-ECMO-based therapy. Heart failure was induced with simultaneous detection of microembolisms and the measurement of blood flow rate in the common carotid artery (CCA) without VA-ECMO (0 l/min) and at the VA-ECMO blood flow rate of 1, 2, 3 and 4 l/min. If embolisms for VA-ECMO 0 l/min and the individual regimes for VA-ECMO 1, 2, 3, 4 l/min are compared, a higher VA-ECMO flow rate is accompanied by a higher number of microembolisms. The final microembolism value at 16 min was for the VA-ECMO flow rate of 0 l/min 0.0 (0, 1), VA-ECMO l/min 7.5 (4, 19), VA-ECMO 2 l/min 12.5 (4, 26), VA-ECMO 3 l/min, 21.0 (18, 57) and VA-ECMO 4 l/min, 27.5 (21, 64). Such a comparison is statistically significant if VA-ECMO 0 vs. 4 l/min p<0.0001, 0 vs. 3 l/min p<0.01 and 1 vs. 4 l/min p<0.01 are compared. The results confirm that high VA-ECMO flow rates pose a risk with regards to the formation of a significantly higher number of microemboli in the blood circulation and that an increase in blood flow rates in the CCA corresponds to changes in the VA-ECMO flow rates.
Assuntos
Artéria Carótida Primitiva/diagnóstico por imagem , Modelos Animais de Doenças , Embolia/diagnóstico por imagem , Oxigenação por Membrana Extracorpórea/efeitos adversos , Insuficiência Cardíaca/diagnóstico por imagem , Ultrassonografia Doppler/métodos , Doença Aguda , Animais , Velocidade do Fluxo Sanguíneo/fisiologia , Artéria Carótida Primitiva/fisiopatologia , Embolia/fisiopatologia , Oxigenação por Membrana Extracorpórea/tendências , Feminino , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/terapia , Microcirculação/fisiologia , Suínos , Ultrassonografia Doppler/tendênciasRESUMO
Venoarterial extracorporeal membrane oxygenation (VA ECMO) is widely used in treatment of decompensated heart failure. Our aim was to investigate its effects on regional perfusion and tissue oxygenation with respect to extracorporeal blood flow (EBF). In five swine, decompensated low-output chronic heart failure was induced by long-term rapid ventricular pacing. Subsequently, VA ECMO was introduced and left ventricular (LV) volume, aortic blood pressure, regional arterial flow and tissue oxygenation were continuously recorded at different levels of EBF. With increasing EBF from minimal to 5 l/min, mean arterial pressure increased from 47+/-22 to 84+/-12 mm Hg (P<0.001) and arterial blood flow increased in carotid artery from 211+/-72 to 479+/-58 ml/min (P<0.01) and in subclavian artery from 103+/-49 to 296+/-54 ml/min (P<0.001). Corresponding brain and brachial tissue oxygenation increased promptly from 57+/-6 to 74+/-3 % and from 37+/-6 to 77+/-6 %, respectively (both P<0.01). Presented results confirm that VA ECMO is a capable form of heart support. Regional arterial flow and tissue oxygenation suggest that partial circulatory support may be sufficient to supply brain and peripheral tissue by oxygen.
Assuntos
Velocidade do Fluxo Sanguíneo/fisiologia , Vasos Coronários/metabolismo , Oxigenação por Membrana Extracorpórea/métodos , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/terapia , Oximetria/métodos , Animais , Artérias Carótidas/metabolismo , Doença Crônica , Feminino , Artéria Femoral/metabolismo , Veia Femoral/metabolismo , Artéria Subclávia/metabolismo , Suínos , Resultado do TratamentoRESUMO
We report a successful surgical and endovascular procedure in a patient with increasing chronic varicose veins resulting from a chronic post-traumatic closure of the left pelvic vein. The endovascular intervention involves an effective and fast part of the procedure dealing with the primary cause of the patients pathology with subsequent surgical treatment, which radically eliminates the secondary developing pathology of massive prepubic and convoluted varicose veins in limbs.
Assuntos
Procedimentos Endovasculares , Varizes/cirurgia , Doença Crônica , Extremidades/irrigação sanguínea , Humanos , Masculino , Pelve/irrigação sanguínea , Varizes/prevenção & controle , VeiasRESUMO
Infection of prosthetic hemodialysis (HD) shunts is one of the most common complications of vascular access in hemodialysis patients. The incidence of anaerobic infection is very rare. In such a case, management of treatment represents a great challenge for the surgeon. We report a complicated case of autologous hemodialysis shunt infected by Clostridium perfringens on the right forearm in a polymorbid female patient with chronic renal failure and myelodysplastic syndrome. The patient has undergone repeated establishment of HD shunt with subsequent polybacterial local infectious complications. Destructive clostridial infection developed at the site of the infectious complications. This very rare complication involving infection by an atypical bacterial agent requires rapid diagnosis and comprehensive multimodal treatment including surgical, antibiotic and supportive therapy. Clinical implications and optimal therapy is not precisely defined in these cases.
Assuntos
Infecções Relacionadas a Cateter/microbiologia , Cateteres de Demora , Infecções por Clostridium/diagnóstico , Diálise Renal , Idoso , Clostridium perfringens , Feminino , HumanosRESUMO
Early recognition of collapsing hemodynamics in pulmonary embolism is necessary to avoid cardiac arrest using aggressive medical therapy or mechanical cardiac support. The aim of the study was to identify the maximal acute hemodynamic compensatory steady state. Overall, 40 dynamic obstructions of pulmonary artery were performed and hemodynamic data were collected. Occlusion of only left or right pulmonary artery did not lead to the hemodynamic collapse. When gradually obstructing the bifurcation, the right ventricle end-diastolic area expanded proportionally to pulmonary artery mean pressure from 11.6 (10.1, 14.1) to 17.8 (16.1, 18.8) cm(2) (p<0.0001) and pulmonary artery mean pressure increased from 22 (20, 24) to 44 (41, 47) mmHg (p<0.0001) at the point of maximal hemodynamic compensatory steady state. Similarly, mean arterial pressure decreased from 96 (87, 101) to 60 (53, 78) mmHg (p<0.0001), central venous pressure increased from 4 (4, 5) to 7 (6, 8) mmHg (p<0.0001), heart rate increased from 92 (88, 97) to 147 (122, 165) /min (p<0.0001), continuous cardiac output dropped from 5.2 (4.7, 5.8) to 4.3 (3.7, 5.0) l/min (p=0.0023), modified shock index increased from 0.99 (0.81, 1.10) to 2.31 (1.99, 2.72), p<0.0001. In conclusion, instead of continuous cardiac output all of the analyzed parameters can sensitively determine the individual maximal compensatory response to obstructive shock. We assume their monitoring can be used to predict the critical phase of the hemodynamic status in routine practice.
Assuntos
Modelos Animais de Doenças , Artéria Pulmonar/fisiopatologia , Circulação Pulmonar , Embolia Pulmonar/complicações , Embolia Pulmonar/fisiopatologia , Choque/etiologia , Choque/fisiopatologia , Animais , Velocidade do Fluxo Sanguíneo , Pressão Sanguínea , Débito Cardíaco , Feminino , Frequência Cardíaca , Humanos , SuínosRESUMO
Patients with implanted mechanical cardiac support are exposed to the risk of various complications in the early postoperative period. Although thromboembolic and bleeding events occur most frequently in these patients, we cannot disregard other complications that can have a significant impact on the further development of the implanted patients condition. These include abdominal complications. Literature data show clearly that mortality in implanted patients who developed an abdominal complication is significantly higher than that in patients without postoperative abdominal complications.
Assuntos
Doenças do Sistema Digestório/etiologia , Coração Auxiliar/efeitos adversos , Enteropatias/etiologia , Insuficiência Cardíaca/terapia , Humanos , Infecção da Ferida Cirúrgica/etiologiaRESUMO
INTRODUCTION: Jehovah's Witnesses who require cardiac operation represent a specific challenge to the physicians. Members of this faith will not accept blood or blood products under any circumstances on the basis of religious grounds. Nevertheless cardiac operations belong to surgical interventions with potential severe bleeding and necessity of blood transfusions. THE AIM OF THE STUDY: The aim of this retrospective study was to analyze clinical data, operative and postoperative courses of patients operated at IKEM who refused blood transfusions. METHODS AND RESULTS: From January 1995 to August 2010, 73 Jehovah's Witnesses ranging in age from 19 to 82 years underwent cardiac surgery at our institute. Aortocoronary bypass were performed in 34 patients, valve surgery in 25 patients, 6 patients underwent concomitant aortocoronary bypass and valve surgery, 2 patients underwent aortocoronary bypass and resection of the left ventricle aneurysm and 2 patients underwent atrial septal defect repair and tricuspid valve anuloplasty. Ventricular septal sefect repair, atrial septal defect repair, Cor Cap device implantation and left ventricular epicardial electrodes implantation were performed in the other patients. Early 30-days mortality was 2.8 % (2 patients). CONCLUSION: We can conclude that cardiac surgery in Jehovah's Witnesses can be performed safety without blood transfusion and belongs to standard operating procedures at our institution.
Assuntos
Transfusão de Sangue , Procedimentos Cirúrgicos Cardíacos , Testemunhas de Jeová , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Recusa do Paciente ao Tratamento , Adulto JovemRESUMO
Tracer studies are analyzed almost universally by multicompartmental models where the state variables are tracer amounts or activities in the different pools. The model parameters are rate constants, defined naturally by expressing fluxes as fractions of the source pools. We consider an alternative state space with tracer enrichments or specific activities as the state variables, with the rate constants redefined by expressing fluxes as fractions of the destination pools. Although the redefinition may seem unphysiological, the commonly computed fractional synthetic rate actually expresses synthetic flux as a fraction of the product mass (destination pool). We show that, for a variety of structures, provided the structure is linear and stationary, the model in the enrichment state space has fewer parameters than that in the activities state space, and is hence better both to study identifiability and to estimate parameters. The superiority of enrichment modeling is shown for structures where activity model unidentifiability is caused by multiple exit pathways; on the other hand, with a single exit pathway but with multiple untraced entry pathways, activity modeling is shown to be superior. With the present-day emphasis on mass isotopes, the tracer in human studies is often of a precursor, labeling most or all entry pathways. It is shown that for these tracer studies, models in the activities state space are always unidentifiable when there are multiple exit pathways, even if the enrichment in every pool is observed; on the other hand, the corresponding models in the enrichment state space have fewer parameters and are more often identifiable. Our results suggest that studies with labeled precursors are modeled best with enrichments.
Assuntos
Isótopos/metabolismo , Modelos Biológicos , Humanos , Cinética , Proteínas/metabolismoRESUMO
Tracer enrichment data are fitted by multicompartmental models to estimate rate constants and fluxes or transport rates. In apolipoprotein turnover studies, mass measurements are also available, for example, apolipoprotein B levels in very low-density lipoprotein, intermediate-density lipoprotein, and low-density lipoprotein, and are often essential to calculate some of the rate constants. The usual method to use mass measurements is to estimate pool masses along with rate constants. A systematic alternative approach is developed to use flux balances around pools to express some rate constants in terms of the other rate constants and the measured masses. The resulting reduction in the number of parameters to be estimated makes the modeling more efficient. In models that would be unidentifiable without mass measurements, the usual approach and the proposed approach yield identical results. In a simple two-pool model, the number of unknown parameters is reduced from 4 to 2. In a published five-pool model for apolipoprotein B kinetics with three mass measurements, the number of parameters is reduced from 12 to 9. With m mass measurements, the number of responses to be fitted and the number of parameters to be estimated are each reduced by m, a simplification by 1/4 to 1/3 in a typical pool model. Besides a proportionate reduction in computational effort, there is a further benefit because the dimensionality of the problem is also decreased significantly, which means ease of convergence and a smaller likelihood of suboptimal solutions. Although our approach is conceptually straightforward, the dependencies get considerably more complex with increasing model size. To generate dependency definitions automatically, a Web-accessible program is available at http://biomath.info/poolfit/constraints.