RESUMO
Symptomatic compression of the celiac trunk by crura of the diaphragm is a rare disorder. Even more infrequent external compression of renal arteries is found. Although the indication for surgical therapy is controversially discussed in the literature for celiac artery compression syndrome, it is unequivocally for renal artery entrapment. We present the case of a young woman who was assigned to our hospital with arterial hypertension and stenosis of the left renal artery. After percutaneous transluminal angioplasty was performed, immediate recoil occurred. Therefore, the suspicion of entrapment by diaphragmatic crura was expressed. Additionally performed diagnostic procedures including computed tomography (CT)-angiography verified our suspicion. Surgical decompression of both vessels was successfully performed.
Assuntos
Plexo Celíaco/patologia , Diafragma/anormalidades , Obstrução da Artéria Renal/etiologia , Obstrução da Artéria Renal/terapia , Angioplastia com Balão/métodos , Arteriopatias Oclusivas/diagnóstico , Arteriopatias Oclusivas/etiologia , Arteriopatias Oclusivas/terapia , Plexo Celíaco/diagnóstico por imagem , Constrição Patológica , Feminino , Seguimentos , Humanos , Hipertensão Renal/diagnóstico , Radiografia , Obstrução da Artéria Renal/diagnóstico , Medição de Risco , Índice de Gravidade de Doença , Resultado do Tratamento , Grau de Desobstrução Vascular , Adulto JovemRESUMO
BACKGROUND: Endothelin-1 (ET-1), a very potent mediator of vasoconstriction, leads to microcirculatory disturbances and release of proinflammatory cytokines under pathophysiologic conditions. Our aim was to evaluate the effect of a selective ET(A)-receptor antagonist (ET(A)-RA) on cold ischemia/reperfusion (I/R) injury in a pig model. METHODS: Twenty pigs revealed orthotopic liver transplantation. The animals were randomized into 2 groups: control pigs received isotonic saline; the treated group received the selective ET(A)-RA BSF 208075 at the beginning of reperfusion. On postoperative days 4 and 7, animals were re-laparotomized to obtain tissue specimens. Liver tissue samples were collected and quantitative mRNA expression for prepro-ET-1, ET(A) receptor, pro-IL-1beta, pro-IL-6, pro-TNF-alpha, and endothelial nitric oxide synthase was analyzed using the TaqMan system. Additionally, immunohistochemical analysis for ET-1 was performed. Hepatic microcirculation was evaluated by laser Doppler flow measurement and partial pressure of oxygen and carbon dioxide measurements with the Paratrend sensor. Postischemic liver damage was monitored by measurement of liver enzymes and by histologic analysis using a semiquantitative scoring classification. RESULTS: Treatment with the ET(A)-RA significantly reduced the severity of I/R injury evidenced by lower serum AST, ALT and GLDH. Analysis of partial pressure of oxygen and blood flow revealed a significant improvement of capillary perfusion and blood flow in the treated group and was associated with a relevant reduction of tissue injury. One hour after reperfusion, quantitative RT-PCR revealed significantly lower expression of prepro-ET-1, ET(A) receptor, endothelial nitric oxide synthase, pro-TNF-alpha, pro-IL-1beta and pro-IL-6 in the therapy group. Immunohistochemical analysis demonstrated significantly reduced ET-1 immunostaining after therapy. Histologic investigation suggested less tissue damage in treated animals. CONCLUSIONS: Treatment with the selective ET(A)-RA BSF 208075 has protective effects on microcirculation after liver transplantation. ET(A)-RA not only affects the expression of vasoactive genes, but also decreases gene expression of proinflammatory cytokines such as TNF-alpha, IL-1beta and IL-6.
Assuntos
Antagonistas do Receptor de Endotelina A , Mediadores da Inflamação/metabolismo , Circulação Hepática/efeitos dos fármacos , Transplante de Fígado , Fenilpropionatos/farmacologia , Animais , Fármacos Cardiovasculares/metabolismo , Endotelina-1/sangue , Endotelina-1/metabolismo , Feminino , Gases/sangue , Expressão Gênica/efeitos dos fármacos , Hemodinâmica/efeitos dos fármacos , Imuno-Histoquímica , Fluxometria por Laser-Doppler , Fígado/patologia , Transplante de Fígado/mortalidade , Microcirculação/efeitos dos fármacos , Período Pós-Operatório , Piridazinas , Análise de Sobrevida , SuínosRESUMO
Endothelin (ET) contributes to disturbances of hepatic microcirculation after ischemia/reperfusion (I/R) by causing vasoconstriction and enhancing leukocyte- and platelet-endothelium interactions. The aim of this study was to investigate a possible protective role of a selective endothelin(A) receptor antagonist (ET(A)-RA) in this setting. In a rat model, warm ischemia of the left lateral liver lobe was induced for 90 minutes under intraperitoneal anesthesia with xylazine and ketamine. Groups of rats consisted of sham-operated (SO, n=14), untreated ischemia (n=14), and treatment with BSF208075 (5 mg/kg body weight IV, n=14). The effect of the ET(A)-RA on I/R was assessed by in vivo microscopy 20 to 90 minutes after reperfusion; by measurement of local tissue Po(2), serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and glutathione S-transferase alpha levels, and by histologic investigation. In the untreated group, sinusoidal constriction to 69.4+/-6.7% of diameters of SO rats was observed, leading to a significant decrease in perfusion rate (74.3+/-2.1% of SO) and liver tissue Po(2) (43.5+/-3.2% of SO) (P < 0.05). In addition, we found an increased percentage of stagnant leukocytes (142.9+/-11.9%) and platelets (450.1+/-62.3%) in sinusoids and in postsinusoidal venules (P < 0.05). Hepatocellular damage (AST and ALT increase to 1330+/-157 U/L and 750+/-125 U/L respectively; previously, 27.1+/-3.5 U/L and 28.5+/-3.6 U/L) was detected 6 hours after reperfusion (P < 0.05). Administration of the ET(A)-RA before reperfusion significantly reduced I/R injury. Sinusoidal diameters were maintained (108.5+/-6.6%), and perfusion rate (93.1+/-1.8%) and tissue Po(2) (95.3+/-5.7%) were significantly increased (P < 0.05). According to reduced leukocyte-endothelium interactions after therapy, both platelet rolling and adhesion were significantly reduced (P < 0.05). The number of stagnant platelets in sinusoids was 199.5+/-12.3% of 50 (P < 0.05). After treatment, hepatocellular damage was decreased (AST and ALT levels after 6 hours of reperfusion: 513+/-106 U/L and 309+/-84 U/L, respectively; P < 0.05), and histologic changes were reduced in the long term. Our results provide evidence that the new therapeutic approach with an ET(A)-RA is effective in reducing hepatic I/R injury. In addition to reduced leukocyte-endothelium interactions, the number of stagnant and rolling platelets in sinusoids and venules was significantly reduced. The reduction in microcirculatory damages is responsible for better organ outcome.
Assuntos
Aspartato Aminotransferases/sangue , Antagonistas do Receptor de Endotelina A , Circulação Hepática , Fígado/irrigação sanguínea , Microcirculação/efeitos dos fármacos , Fenilpropionatos/farmacologia , Traumatismo por Reperfusão/fisiopatologia , Animais , Plaquetas/fisiologia , Células Endoteliais/fisiologia , Feminino , Fluxometria por Laser-Doppler , Fígado/enzimologia , Adesividade Plaquetária , Piridazinas , Ratos , Ratos WistarRESUMO
INTRODUCTION: The objective of this study was to determine whether the simultaneous measurement of tissue pH, pCO(2), and pO(2) with a multiple-parameter fiberoptic sensor (Paratrend 7) can be used for continuous monitoring of hepatic microperfusion in a pig model of hepatic ischemia given endothelin(A) receptor antagonist (ET(A)-RA) or isotonic saline. METHODS: Fourteen anesthetized swine were subjected to 2 h of hepatic vascular exclusion. The animals were randomized into two groups: control group (n = 7, saline solution iv) and therapy group (n = 7, ET(A)-RA). For evaluation of ischemia-reperfusion injury, the data of the multiple-parameter sensor (pO(2para), pCO(2para), and pH(para)) were compared with partial oxygen pressure in tissue (p(ti)O(2)), laser Doppler flow, and systemic hemodynamic, metabolic data, and time course of transaminases. RESULTS: In the control group 30 and 60 min after reperfusion, the following values were measured: p(ti)O(2): 34.0 +/- 8.6 / 36.3 +/- 7.0 mm Hg (P < 0.05 vs. preop.: 49.8 +/- 12.1 mm Hg), laser Doppler area: 133.3 +/- 23.2 / 156.4 +/- 15.4 (P < 0.05 vs. preop.: 215.9 +/- 14.8). Animals in the therapy group revealed significantly improved values (p(ti)O(2): 54.0 +/- 8.6 / 58.1 +/- 7.8 mm Hg, laser Doppler: 210.2 +/- 38.5 / 225.2 +/- 21.3; P < 0.05). Using the Paratrend, also an improvement in the therapy group was seen 30 and 60 min after reperfusion. The values showed a strong correlation with p(ti)O(2) (r = 0.895; P < 0.05) and laser Doppler flow (r = 0.807; P < 0.05). In the treatment group, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and glutamate dehydrogenase (GLDH) were reduced 6 and 18 h after reperfusion, respectively, indicating hepatoprotection by the therapy (P < 0.05 vs. control). CONCLUSIONS: The Paratrend sensor offers the opportunity to study postischemic organ hemodynamics through the simultaneous measurement of interstitial pH, pCO(2), and pO(2) in a small tissue region. This method offers a prognostic tool for the study of the effects of experimental vasoactive therapy on liver microcirculation and perspectives for continuous monitoring of human liver microperfusion after liver surgery and trauma.
Assuntos
Dióxido de Carbono/metabolismo , Fígado/patologia , Oxigênio/metabolismo , Receptor de Endotelina A/fisiologia , Traumatismo por Reperfusão , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Feminino , Glutamato Desidrogenase/sangue , Artéria Hepática/patologia , Concentração de Íons de Hidrogênio , Fluxometria por Laser-Doppler , Fígado/metabolismo , Microcirculação , Pressão Parcial , Veia Porta/patologia , Receptor de Endotelina A/metabolismo , Suínos , Fatores de TempoRESUMO
The objective of this study was to investigate the effect of a specific endothelin-A receptor antagonist on mRNA expression of genes encoding vasoactive mediators and proinflammatory cytokines following complete vascular exclusion of the porcine liver. Fourteen adult German Landrace pigs were subjected to 120 minutes of warm hepatic ischemia by total vascular exclusion. The animals were divided into two groups: the control group received saline solution and the therapy group was given the selective endothelin-A receptor antagonist BSF 208075. Liver tissue samples were collected 1 hour after reperfusion and mRNA expression for preproendothelin-1, prointerleukin-1beta, prointerleukin- 6, pro-tumor necrosis factor-alpha and endothelial nitric oxide synthase was analyzed quantitatively using the TaqMan system. Additionally, immunohistochemical analysis using a semiquantitative score for endothelin-1 and endothelin-A receptor was performed. One hour after reperfusion, quantitative reverse transcriptase-polymerase chain reaction revealed significantly lower expression of preproendothelin-1, pro-tumor necrosis factor-alpha, and prointerleukin-6 in the therapy group compared to controls. Immunohistochemical analysis demonstrated significantly reduced endothelin-1 immunostaining after therapy. Treatment with the selective endothelin-A receptor antagonist exerts a protective effect on the microcirculation after liver ischemia and reperfusion. We were able to show that the endothelin-A receptor antagonist not only has effects on the expression of vasoactive genes, it also decreases gene expression of proinflammatory cytokines such as tumor necrosis factor-alpha and interleukin-6.
Assuntos
Proteínas Angiogênicas/genética , Fármacos Cardiovasculares/farmacologia , Citocinas/genética , Antagonistas do Receptor de Endotelina A , Fígado/irrigação sanguínea , Fenilpropionatos/farmacologia , Piridazinas/farmacologia , Traumatismo por Reperfusão/tratamento farmacológico , Proteínas Angiogênicas/metabolismo , Animais , Citocinas/metabolismo , Modelos Animais de Doenças , Regulação para Baixo , Endotelina-1/genética , Feminino , Interleucina-1beta/genética , Interleucina-6/genética , Microcirculação/efeitos dos fármacos , Microcirculação/metabolismo , Óxido Nítrico Sintase Tipo III/genética , RNA Mensageiro/metabolismo , Receptor de Endotelina A/genética , Receptor de Endotelina A/metabolismo , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/metabolismo , Suínos , Fatores de Tempo , Fator de Necrose Tumoral alfa/genética , Isquemia QuenteRESUMO
It is well established that endothelin-1 (ET-1) is a very potent mediator of vasoconstriction that leads to microcirculatory disturbances. The aim of the study was to evaluate the effect of a selective endothelin A receptor antagonist on severe ischemia/reperfusion injury in a pig model. Fourteen pigs were subjected to 120 minutes of complete vascular exclusion of the liver with a passive bypass. The animals were randomized into two groups: a control group, which was given isotonic saline solution, and a therapy group, which received the selective endothelin A receptor antagonist BSF 208075 at the beginning of reperfusion. On postoperative days 4 and 7, animals were relaparotomized to obtain tissue specimens. Blood monitoring included aspartate aminotransferase (AST), alanine aminotransferase (ALT), glutamate dehydrogenase (GLDH), alkaline phosphatase, and ET-1. Partial oxygen tension (p(ti)O(2)) was measured by a Clarke-type electrode and blood flow by laser Doppler. A semiquantitative scoring index was used for assessment of histologic injury and for immunohistochemical analysis of ET-1. Treatment with the endothelin A receptor antagonist significantly reduced the severity of the ischemia/reperfusion injury, as evidenced by lower levels of AST, ALT, and GLDH. The dramatic increase in plasma ET-1 in the therapy group is clear evidence of effective receptor blockade. Analysis of p(ti)O(2) and blood flow revealed a significant improvement in capillary perfusion and blood flow in the treated group and was associated with relevant reduction of tissue injury. In summary, in the control group we observed serious microcirculatory disturbances and severe histologic damage in the liver after reperfusion. Treatment with a selective endothelin A receptor antagonist attenuated the ischemia/reperfusion injury in a porcine model of severe ischemia/reperfusion, as demonstrated by improved microcirculation, a reduction in histologic damage, and an decrease in liver enzymes.