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Pared Abdominal/cirugía , Toma de Decisiones Clínicas , Técnicas de Sutura , Vísceras/cirugía , Colostomía/métodos , Conversión a Cirugía Abierta/métodos , Fascia , Humanos , Hernia Incisional/prevención & control , Hernia Incisional/cirugía , Laparoscopía/métodos , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/cirugía , Reoperación , Factores de Riesgo , Mallas Quirúrgicas , Herida QuirúrgicaRESUMEN
OBJECTIVE: Acute cholecystitis is a common disease, and laparoscopic surgery is the standard of care. BACKGROUND: Optimal timing of surgery for acute cholecystitis remains controversial: either early surgery shortly after hospital admission or delayed elective surgery after a conservative treatment with antibiotics. METHODS: The ACDC ("Acute Cholecystitis-early laparoscopic surgery versus antibiotic therapy and Delayed elective Cholecystectomy") study is a randomized, prospective, open-label, parallel group trial. Patients were randomly assigned to receive immediate surgery within 24 hours of hospital admission (group ILC) or initial antibiotic treatment, followed by delayed laparoscopic cholecystectomy at days 7 to 45 (group DLC). For infection, all patients were treated with moxifloxacin for at least 48 hours. Primary endpoint was occurrence of predefined relevant morbidity within 75 days. Secondary endpoints were as follows: (1) 75-day morbidity using a scoring system; (2) conversion rate; (3) change of antibiotic therapy; (4) mortality; (5) costs; and (6) length of hospital stay. RESULTS: Morbidity rate was significantly lower in group ILC (304 patients) than in group DLC (314 patients): 11.8% versus 34.4%. Conversion rate to open surgery and mortality did not differ significantly between groups. Mean length of hospital stay (5.4 days vs 10.0 days; P < 0.001) and total hospital costs (2919 vs 4262; P < 0.001) were significantly lower in group ILC. CONCLUSIONS: In this large, randomized trial, laparoscopic cholecystectomy within 24 hours of hospital admission was shown to be superior to the conservative approach concerning morbidity and costs. Therefore, we believe that immediate laparoscopic cholecystectomy should become therapy of choice for acute cholecystitis in operable patients. (NCT00447304).
Asunto(s)
Colecistectomía Laparoscópica/métodos , Colecistitis Aguda/cirugía , Adulto , Anciano , Antibacterianos/economía , Antibacterianos/uso terapéutico , Compuestos Aza/economía , Compuestos Aza/uso terapéutico , Colecistectomía Laparoscópica/economía , Colecistitis Aguda/tratamiento farmacológico , Colecistitis Aguda/economía , Colecistitis Aguda/mortalidad , Terapia Combinada , Conversión a Cirugía Abierta/estadística & datos numéricos , Análisis Costo-Beneficio , Esquema de Medicación , Femenino , Fluoroquinolonas , Alemania , Costos de Hospital/estadística & datos numéricos , Humanos , Análisis de Intención de Tratar , Tiempo de Internación/economía , Tiempo de Internación/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Moxifloxacino , Complicaciones Posoperatorias/epidemiología , Estudios Prospectivos , Quinolinas/economía , Quinolinas/uso terapéutico , Eslovenia , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: Ischemic preconditioning (IP) and intermittent clamping (IC) increase the ischemic tolerance of the liver. The underlying mechanisms are not completely understood. Heat shock proteins protect cellular integrity in stress and have been discussed as mediators in preconditioning. IP and IC in rat livers were compared with respect to HSP induction and postischemic microcirculation. METHODS: All animals were exposed to 70min of partial warm liver ischemia. Different clamping protocols were used: in control animals (C) 70min continuous ischemia was applied. IP was performed by 5min ischemia and 10min reperfusion before the 70min ischemia time. In IC-groups, ischemia time of 70min was divided into four intervals. Each group included 21 animals with 3 different reperfusion intervals; either 30min, 12 or 36h. Intravital microscopy was performed after 30min of reperfusion. AST-levels and HSP induction were analysed 90min, 12 and 36h after reperfusion. RESULTS: IP and IC significantly improved sinusoidal perfusion (IP: 83.4±2.8%; IC: 84.4±4.6% vs. C: 60.4±3.9%; p<0.001) and leucocyte adherence in sinusoids (IP: 51.9±12.0, IC: 40.9±4.7 vs. C: 90.1±17.7/mm(2) liver surface; p<0.001) and postsinusoidal venules. AST-levels were minimized in IP and IC compared to controls (12h after reperfusion: IP: 969±934U/l, IC: 675±562U/l vs. C: 2373±792U/l; p=0.004). In the course of reperfusion HSP70 protein expression doubled between 90min and 12h in IC (0.529±0.227 vs. 0.992±0.246; p<0.05) and control-groups (0.572±0.314 vs. 1.106±0.309; p<0.05) whereas it remained unchanged in the IP-group (0.437±0.383 vs. 0.412±0.439; n.s.). CONCLUSION: Microcirculation is similarly preserved by IP and IC. The early protection derived by IP prevents further induction of HSP70 in opposite to IC. Therefore, IP may offer a more comprehensive protection against I/R on a cellular and transcriptional level.
Asunto(s)
Proteínas HSP70 de Choque Térmico/metabolismo , Precondicionamiento Isquémico , Hígado/irrigación sanguínea , Microvasos/metabolismo , Daño por Reperfusión/prevención & control , Animales , Aspartato Aminotransferasas/sangre , Adhesión Celular , Constricción , Modelos Animales de Enfermedad , Proteínas HSP70 de Choque Térmico/genética , Leucocitos/inmunología , Circulación Hepática , Masculino , Microcirculación , Microscopía Fluorescente , Microvasos/inmunología , Microvasos/fisiopatología , ARN Mensajero/metabolismo , Ratas , Ratas Wistar , Daño por Reperfusión/etiología , Daño por Reperfusión/metabolismo , Daño por Reperfusión/fisiopatología , Factores de Tiempo , Regulación hacia Arriba , Isquemia Tibia/efectos adversosRESUMEN
Several authors suggest that local ablative therapies, specifically transarterial chemoembolization (TACE), may control tumor progression of hepatocellular carcinoma (HCC) in patients who are on the waiting list for liver transplantation (orthotopic liver transplantation, OLT). There is still no evidence if TACE followed by OLT is able to prevent recurrence of tumor, to prolong survival rate of the patients on the waiting list, or to improve the survival after OLT. We report 27 patients with HCC who underwent OLT. From these patients, 15 were pre-treated with TACE alone or in combination with percutaneous ethanol injection (PEI) or laser-induced thermo therapy (LITT). Mean time on the waiting list was 214 d for treated patients and 133 d for untreated patients. Comparing pre-operative imaging and histopathological staging post-transplant, we found 13 patients with tumor progression out of which five were treated with TACE. In two of the TACE patients a decrease of lesions could be achieved. In a single patient, there was no evidence of any residual tumor. Only one patient displayed tumor progression prior to OLT despite undergoing TACE. Comparison of outcome in patients undergoing TACE or having no TACE was not statistically significant (p = 0.5). In addition, our analysis showed that progression either in the total study population or in the TACE group alone is associated with a significant poorer outcome concerning overall survival (p = 0.02 and p = 0.02).
Asunto(s)
Carcinoma Hepatocelular/terapia , Quimioembolización Terapéutica , Neoplasias Hepáticas/terapia , Trasplante de Hígado , Adulto , Anciano , Carcinoma Hepatocelular/cirugía , Femenino , Humanos , Neoplasias Hepáticas/cirugía , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Análisis de Supervivencia , Listas de Espera , Adulto JovenRESUMEN
The inhibitory effect of Cyclosporine A (CsA) and Tacrolimus (Tacr) on interleukin 2 (IL-2) are well known, and the importance of Th1-type (IL-2, interferon gamma), and Th2-type (IL-4, IL-6, and IL-10) cytokine secretion in preventing allograft rejection is a controversial issue. The immunological mechanisms involved in long-term liver transplant recipients under CsA and Tacr were not studied precisely. This study was designed to evaluate the effects of CsA and Tacr on the immune response of 62 long-term survivors following liver transplantation. T-cell and B-cell subpopulations, the T helper (Th) cell activity, T-cell cytokine production, Staphylococcus aureus Cowan strain I (SAC-I)-stimulated B-cell responses and PWM-stimulated B-cell responses were examined. CsA and Tacr decreased whole T-cell populations as well as CD4+T-cell IL-2 responses (p < 0.005, Tacr and p = 0.02, CsA), impaired CD4+ cell Th activity (p < 0.01, Tacr and p = 0.02, CsA) and reduced SAC-I-stimulated B-cell responses (immunoglobulin-secreting cells [ISC]: p = 0.001, Tacr and p < 0.05, CsA). A significantly impaired T-cell IL-10 secretion (p = 0.0001) and decreased Th function of whole T cells was found in Tacr-treated patients only, whereas unstimulated Th1 responses and SAC-I-stimulated B-cell IL-6 responses were reduced in CsA-treated patients. Our data show that Tacr suppresses T-, CD4+-, and B-cell responses more effectively than CsA which may be relevant in the maintenance of long-term stable liver graft function.
Asunto(s)
Ciclosporina/farmacología , Citocinas/efectos de los fármacos , Inmunosupresores/farmacología , Trasplante de Hígado , Tacrolimus/farmacología , Adulto , Linfocitos B/efectos de los fármacos , Linfocitos T CD4-Positivos/efectos de los fármacos , Estudios de Casos y Controles , Células Cultivadas , Técnicas de Cocultivo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Subgrupos de Linfocitos T/efectos de los fármacosRESUMEN
BACKGROUND: Ischemia/reperfusion injury is an unavoidable complication in liver surgery and transplantation. Hemodilution with colloids can reduce postischemic injury but limits oxygen transport. Hemoglobin-based oxygen carriers have been evaluated as blood substitute and provide a plasma-derived oxygen transport. It was the aim of our study to evaluate the combined benefits of hemodilution with a better oxygen supply to reperfused liver tissue by the use of HBOC-201 (Hemopure). MATERIAL AND METHODS: A model of partial warm liver ischemia in the rat was used. One group served as untreated control, the other groups were hemodiluted either with Ringer's lactate, Dextran-70, HBOC-201 or a mixture of Dextran and HBOC-201. After reperfusion, intravital microscopy studies were done and tissue pO(2) levels and transaminases measured. Statistical analysis was done by one- and two-way ANOVA, followed by pairwise comparison. RESULTS: Hemodilution with Ringer's lactate did not show any improvement compared to the control group. Dextran and HBOC group were superior to the Ringer and control animals in all parameters studied. Leucocyte adherence in postsinusoidal venules improved from 569.03+/-171.87 and 364.52+/-167.32 in control and Ringer group to 131.68+/-58.34 and 68.44+/-20.31/mm(2) endothelium in Dextran and HBOC group (p<0.001). Concerning tissue pO(2) levels, HBOC (23.4+/-5.0 mmHg) proved to be superior to Dextran (7.9+/-4.4 mmHg; p=0.007). CONCLUSION: HBOC was equivalent to Dextran in reducing I/R injury in the liver, but improved oxygenation of postreperfusion liver tissue.
Asunto(s)
Sustitutos Sanguíneos/farmacología , Hemodilución/métodos , Hemoglobinas/farmacología , Hígado/irrigación sanguínea , Daño por Reperfusión/tratamiento farmacológico , Isquemia Tibia/efectos adversos , Alanina Transaminasa/metabolismo , Animales , Aspartato Aminotransferasas/metabolismo , Adhesión Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Células Endoteliales/efectos de los fármacos , Leucocitos/citología , Leucocitos/efectos de los fármacos , Hígado/metabolismo , Oxígeno/metabolismo , Ratas , Daño por Reperfusión/metabolismoRESUMEN
PURPOSE: The crush syndrome caused by drug-induced compartment syndrome (DCS) is a challenge for surgeons because it is regularly associated with potentially fatal complications. Drug-induced compartment syndrome can often be distinguished from other forms of compartment syndrome by the presence of severe rhabdomyolysis with kidney crush and severe postoperative complications such as local and generalized infection, persistent nerve damage, coagulopathy, and multiorgan failure. METHODS: In the past 15 years, eight prospectively documented, operatively managed, DCS with subsequent crush syndrome cases were recorded. RESULTS: All of the patients required renal replacement therapy. The creatine kinase (CK) values in the context of rhabdomyolysis reached an average of 86 (range 47-144) kU/l. The renal function recovered in all surviving patients. The analysis showed that the diagnosis of a DCS is usually made after an average of 13 h. It then took an average of an additional 7 h before a fasciotomy was performed. Six operational revisions were necessary. In three out of eight patients the extremities had to be amputated. CONCLUSIONS: In DCS the decision to open the compartment should be made immediately upon the clinical diagnosis. A protracted intensive phase is expected. The benefit to patients is closely associated with surgical wound debridement along with rigorous intensive therapy.
Asunto(s)
Síndromes Compartimentales/inducido químicamente , Lesión Renal Aguda/etiología , Lesión Renal Aguda/terapia , Adulto , Anciano , Síndromes Compartimentales/cirugía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Rabdomiólisis/etiología , Adulto JovenRESUMEN
Changes in liver microcirculation are considered essential in assessing ischemia-reperfusion injury, which in turn has an impact on liver graft function and outcome following liver transplantation (LTx). The aim of this study was to introduce dynamic magnetic resonance imaging (dMRI) as a new technique for overall quantification of hepatic microcirculation and compare it to perfusion measured by laser Doppler flowmetry (LDF; hepatic artery/portal vein) and thermal diffusion (TD). The study included 3 groups, measuring hepatic blood flow and microcirculation with the help of TD, LDF, and dMRI. In group I (9 landrace pigs; 26 +/- 5 kg), the native liver before and after partial portal occlusion was studied; in group II (6 landrace pigs; 25.5 +/- 4.4 kg), the liver 24 hours after LTx was studied; and in group III (14 patients), the liver on days 4 to 7 following LTx was studied. A close correlation was found between dMRI measurements and TD (r = 0.7-0.9, P < 0.01) in 4 defined regions of interest. Portal blood flow and partial occlusion of the portal vein were accurately detected by LDF flowmetry and correlated well with dMRI (r = 0.95, P < 0.01). In the clinical setting, representative TD measurements in segment 4b of the transplanted liver correlated well with dMRI analysis in other segments. Quantification of the portal blood flow and imaging of the whole liver could be performed simultaneously by dMRI. In conclusion, dMRI has been proved to be a sensitive modality for the quantification of liver microcirculation and hepatic blood flow in experimental and clinical LTx. It allows for a synchronous, noninvasive assessment of macrocirculation and microcirculation of the liver and could become a valuable diagnostic tool in advanced liver surgery and transplantation.
Asunto(s)
Trasplante de Hígado/métodos , Hígado/patología , Imagen por Resonancia Magnética/métodos , Adulto , Animales , Femenino , Humanos , Flujometría por Láser-Doppler , Hígado/irrigación sanguínea , Masculino , Microcirculación , Persona de Mediana Edad , Perfusión , Proyectos Piloto , Porcinos , Resultado del TratamientoRESUMEN
Although the use of non-heart-beating donors (NHBD) is the oldest type of organ transplantation, the results were and still are disappointing. To consider using a liver from NHBD, it is of importance to assess the graft viability. Our aim was to assess the role of reduced liver glutathione (rGSHL) as a potential predictive marker of liver function before transplantation. Autotransplanted livers were subjected to 0, 60, and 90 minutes of ischemia in 20 pigs. We analyzed systemic cardiocirculatory parameters, bowel ischemia by endotoxin, endotoxin-neutralizing capacity, oxidative stress, hepatic perfusion parameters, liver enzymes, local bowel ischemia, and liver oxidative stress (rGSHL and oxidized glutathione in the liver). Autotransplantation was comparable to donor explantation/recipient transplantation with respect to systemic and hepatic parameters. Liver ischemia for 0, 60, and 90 minutes resulted in survival in 100% (NHBD-0), 71% (NHBD-60), and 57% (NHBD-90) of animals. Of all parameters, only hepatic microperfusion, pHi of the sigmoid colon, and bowel ischemia by endotoxin in the NHBD-90 group showed significant changes compared to NHBD-60 and control animals. Although systemic endotoxin-neutralizing capacity and total glutathione in erythrocytes levels were mainly influenced by cold perfusion, hepatic oxidative stress increased with ischemia time. The cut-off value of 11.5 ng/mmol of rGSHL could distinguish survivors from nonsurvivors, independent of the ischemia time. In conclusion, rGSHL has the potential of becoming an important viability marker, as it could predict survival in autotransplantation NHBD model regardless of the ischemia time. Further investigation to declare reasons for differing rGSHL levels within the liver is required.
Asunto(s)
Glutatión/metabolismo , Trasplante de Hígado/métodos , Hígado/metabolismo , Animales , Biomarcadores/metabolismo , Cadáver , Endotoxinas/metabolismo , Eritrocitos/metabolismo , Supervivencia de Injerto , Humanos , Isquemia , Hígado/patología , Hepatopatías/patología , Hepatopatías/terapia , Estrés Oxidativo , Porcinos , Factores de TiempoRESUMEN
Ischemia/reperfusion (I/R) injury is a variable yet unavoidable complication in liver surgery and transplantation. Selenium-dependent glutathione-peroxidases (GPx) and selenoproteins function as antioxidant defense systems. One target in preventing I/R injury is enhancing the capacity of endogenous redox defense. It was the aim of this study to analyze the effects of selenium substitution on liver microcirculation, hepatocellular injury and glutathione status in a model of partial warm liver ischemia in the rat. Sodium selenite was administered in three different dosages i.v.: 0.125 microg/g, 0.25 microg/g and 0.375 microg/g body weight and compared to an untreated control group (each n=10). Intravital microscopy was performed after 70 min of partial warm liver ischemia and 90 min of reperfusion. Liver tissue and plasma samples were taken at the end of the experiment for laboratory analysis. Microcirculation improved significantly in all therapy groups in contrast to control animals. ALT levels decreased significantly whereas malondialdehyde levels remained unchanged. In liver tissue, selenium supplementation caused an increase in the amount of total and reduced glutathione without changes in oxidized glutathione. This effect is likely mediated by selenite itself and selenoprotein P rather than by modulating GPx activity. We were able to show that selenite substitution has an immediate protective effect on I/R injury after warm hepatic ischemia by acting as a radical scavenger and preserving the antioxidative capacity of the liver.
Asunto(s)
Glutatión/metabolismo , Circulación Hepática/efectos de los fármacos , Hígado/efectos de los fármacos , Daño por Reperfusión/fisiopatología , Selenito de Sodio/farmacología , Alanina Transaminasa/sangre , Animales , Aspartato Aminotransferasas/sangre , Adhesión Celular/efectos de los fármacos , Leucocitos/efectos de los fármacos , Leucocitos/patología , Hígado/metabolismo , Hígado/fisiopatología , Masculino , Malondialdehído/sangre , Microcirculación/efectos de los fármacos , Microcirculación/fisiopatología , Ratas , Ratas Wistar , Daño por Reperfusión/sangre , Selenio/sangreRESUMEN
The mainstay of treatment for blunt or sharp liver trauma is conservative in 50%-80% of cases. When surgery is indicated, it is demanding and associated with substantial morbidity and mortality. Felt has been used extensively in cardiothoracic and vascular surgery to seal stitches and exposed surfaces. We describe how we used soft polyglycolic acid (PGA) felt to stop bleeding of a lacerated liver in two patients. To our knowledge, this is the first report of PGA felt being used to repair a lacerated liver. The main advantage of this felt lies in its combined effect of compressing the wound edges and applying a sealant that cannot be washed away. We compare soft PGA felt repair with the standard surgical approaches, including compression with packing or wrapping and local hemostasis with hemostatic felt or fibrin glue.
Asunto(s)
Traumatismos Abdominales/cirugía , Hemorragia/terapia , Hemostáticos/administración & dosificación , Hígado/lesiones , Ácido Poliglicólico/administración & dosificación , Traumatismos Abdominales/complicaciones , Administración Tópica , Anciano , Femenino , Hemorragia/etiología , Hemostasis Quirúrgica/métodos , Humanos , Laceraciones , Hígado/cirugía , MasculinoRESUMEN
Liver resection offers the only chance of cure for patients with advanced colorectal cancer (CRC). Typically, the 5-year survival rates following liver resection range from 25% to 40%. Unfortunately, approximately 85% of patients with stage IV CRC have liver disease which is considered unresectable at presentation. However, the rapid expansion in the use of improved combination therapy regimens has increased the percentage of patients eligible for potentially curative surgery. Despite this, the selection criteria for patients potentially suitable for resection are not well documented and patient management by multidisciplinary teams, although essential, is still evolving. The goal of the European Colorectal Metastases Treatment Group is to establish pan-European guidelines for the treatment of patients with CRC liver metastases that can be adopted more widely by established treatment centres and to develop more accurate staging systems and evaluation criteria.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales , Hepatectomía/métodos , Neoplasias Hepáticas/tratamiento farmacológico , Quimioterapia Adyuvante , Humanos , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/cirugía , Cuidados Preoperatorios/métodosRESUMEN
The liver function and perfusion following brain death is mainly influenced by the sympathetic nerves and hormones. We examined the specific influence of surgical liver denervation on systemic and hepatic perfusion parameters, bowel ischemia and oxidative stress in hemodynamically stable BD and control (living donor [LD]) pigs. Brain death was induced in 8 pigs via saline infusion into the balloon of an epidural Tieman-catheter (1 mL/15 minutes) and compared to the control group (n = 6) over 4 hours. At 2 hours postoperatively, complete liver denervation was initiated. We analyzed systemic cardiocirculatory parameters (mean arterial pressure, aortic flow, bowel ischemia (endotoxin, and endotoxin-neutralizing capacity) and oxidative stress (total glutathione in erythrocytes [tGSH(E)]) and compared them to local/hepatic perfusion parameters (hepatic artery and portal venous flow, liver blood flow index, and microperfusion), local bowel ischemia (intramucosal pH [pHi] of stomach [pHi(S)]/colon[pHi(C)]), and liver oxidative stress (glutathione [rGSH(L), GSSG(L)]). Following brain death, the parameters including mean arterial pressure, aortic flow, pHi, endotoxin, and tGSH(E) showed no significant changes at 2 hours. Portal venous flow and microperfusion were decreased significantly and hepatic arterial buffer response was ineffective. Hepatic oxidative stress was increased in BD animals (decrease rGSH(L), increase GSSG(L)). Surgical denervation/manipulation increased portal venous flow significantly, hepatic arterial buffer response became effective, and stomach pHi decreased (BD and LD groups). Hepatic oxidative stress was reduced in the BD group (increase rGSH(L)/GSSG(L); P < 0.001) while it was increased in the LD group (decrease rGSH(L)/GSSG(L); P < 0.001). In conclusion, denervation reduces hepatic oxidative stress in BD only in contrast to the LD. The reciprocal effect of denervation depends on the state of neural activation and postulates a potential benefit of surgical denervation before organ harvesting in brain death.
Asunto(s)
Muerte Encefálica , Desnervación/métodos , Tracto Gastrointestinal/irrigación sanguínea , Hígado/inervación , Donadores Vivos , Estrés Oxidativo , Animales , Velocidad del Flujo Sanguíneo , Presión Sanguínea , Arteria Hepática/fisiología , Isquemia/fisiopatología , Hígado/irrigación sanguínea , Hígado/fisiología , Modelos Animales , Perfusión , Vena Porta/fisiología , PorcinosRESUMEN
Catecholamines are often administered during and after liver transplantation (LTx) to support systemic perfusion and to increase organ oxygen supply. Some vasoactive agents can compromise visceral organ perfusion. We followed the hypothesis that the vasculature of transplanted livers presents with a higher sensitivity, which leads to an increased vulnerability for flow derangement after application of epinephrine (Epi) or norepinephrine (NorEpi). Hepatic macroperfusion and microperfusion during systemic Epi or NorEpi infusion were measured by Doppler flow and thermodiffusion probes in porcine native, denervated, and transplanted livers (n = 16 in each group). Epi or NorEpi were infused (n = 8 in each subgroup) in predefined dosages (low dose = 5 microg/kg/minute and high dose = 10 microg/kg/minute) over 240 minutes. Systemic cardiocirculatory parameters were monitored continuously. Hepatic perfusion data were compared between all groups at comparable time points and dosages. In all native, denervated, and transplanted liver groups, Epi and NorEpi induced an inconsistent rise of mean arterial pressure and heart rate shortly after onset of infusion in both dosages compared with baseline. No significant differences of cardiovascular parameters at comparable time points were observed. In native livers, Epi and NorEpi induced only temporary alterations of hepatic macrocirculation and microcirculation, which returned to baseline 2 hours after onset of infusion. No significant alterations of hepatic blood flow were detected after isolated surgical denervation of the liver. By contrast, transplanted livers showed a progressive decline of hepatic macrocirculation (33-75% reduction) and microcirculation (39-58% reduction) during catecholamine infusions in a dose-dependent fashion. Characteristics of liver blood flow impairment were comparable for both vasoactive agents. In conclusion, pronounced disturbances of hepatic macrocirculation and microcirculation were observed during systemic Epi and NorEpi infusion after LTx compared with native and denervated livers. Microcirculation disturbances after LTx might be explained by impairment of hepatic blood flow regulation caused by an increased sensitivity of hepatic vasculature after ischemia-reperfusion and by lengthening of vasopressor effects caused by reduced hepatocyte metabolism. Clinicians should be aware of this potentially hazardous effect. Therefore, application of catecholamines after clinical LTx should be indicated carefully.
Asunto(s)
Catecolaminas/administración & dosificación , Circulación Hepática/efectos de los fármacos , Trasplante de Hígado , Animales , Femenino , Hemodinámica , Hígado/irrigación sanguínea , Hígado/inervación , Microcirculación , Periodo Posoperatorio , Distribución Aleatoria , Flujo Sanguíneo Regional , PorcinosRESUMEN
BACKGROUND: Despite the growing use of kidneys from living donors, organs harvested from brain dead donors are the dominant graft types used in renal transplantation. It is accepted that brain death (BD) has a damaging effect on the renal allograft, with a lower graft survival. Amongst various causes, changes in renal microperfusion could be responsible. Renocortical microperfusion was assessed during BD using thermal diffusion in a porcine model. METHODS: Two types of BD were induced in two groups of pigs [hypotension (Hypo-BD): n = 11; normotension (Normo-BD): n = 10] and compared to controls (n = 5) over a period of 210 min. We analysed systemic parameters [heart rate (HR), mean arterial blood pressure (MAP)], aortic blood flow (ABF) and renal perfusion [renal artery blood flow (RABF) and renocortical blood flow (RCBF)]. RESULTS: Following the two distinct forms of BD induction, a stable normo- or hypotension was observed. Haemodynamic parameters were only slightly changed (control group: MAP, 62+/-2 mmHg; HR, 95+/-3/min; Normo-BD: MAP, 56+/-4 mmHg; HR, 104+/-8/min; Hypo-BD: MAP, 43+/-3 mmHg; HR, 112+/-7/min). Solely dependent on systemic haemodynamics, RABF and RCBF decreased in the Hypo-BD (RABF: 142+/-19 to 94+/-9 ml/100 g/min; RCBF: 80+/-4 to 52+/-2 ml/100 g/min), while in Normo-BD group RABF mildly changed (158+/-13 ml/100 g/min) and RCBF decreased slightly from 76+/-3 to 70+/-6 ml/100 g/min. As opposed to the Normo-BD group, animals with Hypo-BD showed a significant decrease in RABF (reduction of 34%) and RCBF (reduction of 35%) with a sharp drop of MAP (reduction of 25%), however ABF remained relatively constant. CONCLUSIONS: In this model, a reduction of renocortical microperfusion in brain dead pigs was only found during haemodynamic instability (hypotension) and could not be attributed to BD as such. Our findings would support intensive cardiocirculatory stabilization for potential BD donors in order to minimize kidney preservation damage.
Asunto(s)
Muerte Encefálica/fisiopatología , Hipotensión/fisiopatología , Corteza Renal/irrigación sanguínea , Circulación Renal , Animales , Presión Sanguínea , Frecuencia Cardíaca , Microcirculación , PorcinosRESUMEN
Kupffer cell depletion by gadolinium chloride (GdCl(3)) in rat livers has previously been proven to minimize hepatic ischemia/reperfusion injury after experimental liver transplantation (LTX). In the current study, we evaluated the effects of donor pretreatment with GdCl(3) on hepatic ischemia/reperfusion injury, macro- and microcirculation, and endotoxin clearance of the liver in a porcine model of experimental LTX. Two groups of 12 pigs were treated either with intravenous NaCl (0.9%; control) or GdCl(3) (20 mg/kg). Twenty-four hours after pretreatment, hepatic macrocirculation was quantified by Doppler flowmetry and liver parenchymous microcirculation by implanted thermodiffusion electrodes. The liver grafts were transplanted after 4-6 h of cold ischemia in University of Wisconsin (UW) solution. At 1 and 24 h after LTX, the perfusion values were re-evaluated and histology, biochemical (aspartate aminotransferase, AST) and functional parameters (partial thromboplastin time, prothrombin time, and bilirubin) were analyzed. Furthermore, endotoxin clearance of the liver was evaluated at all time points. In GdCl(3)-treated animals 80% of the Kupffer cells were destroyed, and 24 h after LTX ischemia/reperfusion injury in treated grafts was significantly lower in comparison to controls, as shown by histology, AST levels (741+/-490 U/l in controls vs 379+/-159 U/l in treated grafts, P<0.05), survival (67% vs 92%), and enhanced macro- (total transhepatic blood flow [THBF]=112+/-22 ml/min per 100 g in controls vs 157+/-45 ml/min per 100 g in treated grafts, PAsunto(s)
Gadolinio/farmacología
, Supervivencia de Injerto/efectos de los fármacos
, Trasplante de Hígado
, Hígado/fisiopatología
, Cuidados Preoperatorios
, Donantes de Tejidos
, Animales
, Recuento de Células
, Endotoxinas/sangre
, Macrófagos del Hígado/efectos de los fármacos
, Macrófagos del Hígado/patología
, Hígado/efectos de los fármacos
, Circulación Hepática/efectos de los fármacos
, Microcirculación/efectos de los fármacos
, Sistema Porta/efectos de los fármacos
, Sistema Porta/fisiopatología
, Tasa de Supervivencia
, Porcinos
RESUMEN
BACKGROUND: Brain death (BD) is an important multifactorial variable contributing to donor-specific liver damage. Our study aimed at assessing the specific effects of hemodynamic instability on systemic and hepatic parameters of perfusion, bowel ischemia, and oxidative stress in a porcine model of BD. METHODS: BD was induced in 16 pigs (German Landrace, 18-28 kg) in two groups (hypotension-BD [HYPO-BD], n=8; normotension-BD [NORM-BD], n=8), which were compared with control animals/living donors (n=6) for a period of 2 hr. We analyzed systemic hemodynamic parameters, bowel ischemia (intramucosal pH in the stomach and colon, plasma endotoxin levels, and endotoxin-neutralizing capacity [ENC]), and oxidative stress (total glutathione levels in erythrocytes) and compared the findings with hepatic parameters of perfusion (hepatic arterial flow, portal venous flow, and microperfusion) and liver oxidative stress (reduced glutathione and oxidized glutathione levels in the liver). RESULTS: Independent of the hemodynamic stability, liver macrocirculation and microcirculation decreased (HYPO-BD, 79+/-6 to 69+/-10 mL/100 g/min; NORM-BD, 81+/-10 to 73+/-7 mL/100 g/min; P<0.05). Hepatocellular damage (aspartate aminotransferase: NORM-BD, 49+/-20 units/L; HYPO-BD, 170+/-140 units/L; P<0.01) and hepatic oxidative stress (reduced glutathione in the liver/oxidized glutathione in the liver: NORM-BD, 29.4+/-2.3 to 13.0+/-1.3; HYPO-BD, 29.4+/-2.3 to 9.05+/-0.81; P<0.001) increased in both BD groups. With dependence on systemic hemodynamic parameters, bowel ischemia increased (intramucosal pH in the colon, 7.22+/-0.01, P<0.01; ENC, 75+/-14 endotoxin-neutralizing units/mL, P<0.01; endotoxin levels, 7+/-2 to 43+/-10 pg/mL, P<0.01) in the HYPO-BD group but not in the NORM-BD group or the living donor group. Furthermore, systemic oxidative stress was increased in the HYPO-BD group only (total glutathione levels in erythrocytes, 2.65+/-0.25 to 0.15+/-0.25 mM; P<0.01). CONCLUSIONS: During BD, liver-specific parameters (portal venous flow, microperfusion, aspartate aminotransferase activity, ENC, and hepatic oxidative stress) were compromised, independent of the hemodynamic status. Therefore, the systemic hemodynamic status does not reflect the functional status of the liver during BD.