Prolonged Anhepatic State as a Bridge to Retransplantation: A Challenging Case of a 35-Year-Old Male Liver Transplant Patient with a Temporary Portacaval Shunt.

BACKGROUND Liver transplantation is a life-saving intervention for patients with a diagnosis of acute liver failure or end-stage liver disease. Despite advances in surgical techniques and immunosuppressive therapies, primary nonfunction remains a concern, often necessitating retransplantation. In these scenarios, the anhepatic state, achieved through total hepatectomy with a temporary portacaval shunt, serves as a bridge to retransplantation. However, the challenge lies in the uncertain survival period and several potential complications associated with this procedure. CASE REPORT We present a case of a 35-year-old male patient with autoimmune hepatitis who underwent liver transplantation from a deceased donor. Seven days later, he experienced acute liver failure, leading to an urgent listing for retransplantation. To prevent the intense systemic inflammatory response, the patient underwent a total hepatectomy with a temporary portacaval shunt while awaiting another graft and endured a 57-h anhepatic state. On day 17 following retransplantation, he had cerebral death due to a hemorrhagic stroke. CONCLUSIONS This case underscores one of the most prolonged periods of anhepatic state as a bridge to retransplantation, highlighting the complexities associated with this technique. The challenges include sepsis, hypotension, coagulopathy, metabolic acidosis, renal failure, electrolyte disturbances, hypoglycemia, and hypothermia. Vigilant monitoring and careful management are crucial to improve patient outcomes. Further research is needed to optimize the duration of the anhepatic state and minimize complications for liver transplantation recipients.

Small-for-Size Syndrome: Systemic Review in a Porcine Experimental Model.

BACKGROUND: The small-for-size syndrome (SFSS) is characterized by prolonged hyperbilirubinemia, coagulopathy, and/or encephalopathy caused by a small liver graft that cannot sustain the metabolic demands of the recipient after a partial liver transplant (PLT). Models of PLT in pigs are excellent for studying this syndrome. This review aimed to identify the different porcine models of SFSS in the literature and compare their technical aspects and therapeutics methods focused on portal inflow modulation (PIM). METHODS: We performed a systematic review of the porcine experimental model and SFSS. The MEDLINE-PubMed, EMBASE, Cochrane Library, LILACS, and SciELO databases were electronically searched and updated until June 20, 2021. The MeSH terms used were ''ORGAN SIZE'' AND ''LIVER TRANSPLANTATION". RESULTS: Thirteen SFSS porcine models were reported. Four were performed with portocaval shunt to PIM and 3 with mesocaval shunt to PIM. A few studies focused on clinical therapeutics to PIM; a study described somatostatin infusion to avoid SFSS. Initially, studies on PIM showed its potentially beneficial effects without mentioning the minimum portal flow that permits liver regeneration. However, an excessive portal diversion could be detrimental to this process. CONCLUSIONS: The use of porcine models on SFSS resulted in a better understanding of its pathophysiology and led to the establishment of various types of portal modulation, surgical techniques with different complexities, and pharmaceutical strategies such as somatostatin, making clear that without reducing the portal vein pressure the outcomes are poor. With the improvement of these techniques, SFSS can be avoided.

Recovery from Liver Failure and Fibrosis in a Rat Portacaval Anastomosis Model after Neurointermediate Pituitary Lobectomy.

Liver diseases, including cirrhosis, viral hepatitis, and hepatocellular carcinoma, account for approximately two million annual deaths worldwide. They place a huge burden on the global healthcare systems, compelling researchers to find effective treatment for liver fibrosis-cirrhosis. Portacaval anastomosis (PCA) is a model of liver damage and fibrosis. Arginine vasopressin (AVP) has been implicated as a proinflammatory-profibrotic hormone. In rats, neurointermediate pituitary lobectomy (NIL) induces a permanent drop (80%) in AVP serum levels. We hypothesized that AVP deficiency (NIL-induced) may decrease liver damage and fibrosis in a rat PCA model. Male Wistar rats were divided into intact control (IC), NIL, PCA, and PCA+NIL groups. Liver function tests, liver gene relative expressions (IL-1, IL-10, TGF-ß, COLL-I, MMP-9, and MMP-13), and histopathological assessments were performed. In comparison with those in the IC and PCA groups, bilirubin, protein serum, and liver glycogen levels were restored in the PCA+NIL group. NIL in the PCA animals also decreased the gene expression levels of IL-1 and COLL-I, while increasing those of IL-10, TGF-ß, and MMP-13. Histopathology of this group also showed significantly decreased signs of liver damage with lower extent of collagen deposition and fibrosis. Low AVP serum levels were not enough to fully activate the AVP receptors resulting in the decreased activation of cell signaling pathways associated with proinflammatory-profibrotic responses, while activating cell molecular signaling pathways associated with an anti-inflammatory-fibrotic state. Thus, partial reversion of liver damage and fibrosis was observed. The study supports the crucial role of AVP in the inflammatory-fibrotic processes and maintenance of immune competence. The success of the AVP deficiency strategy suggests that blocking AVP receptors may be therapeutically useful to treat inflammatory-fibrotic liver diseases.

Cerebellar spongiform degeneration is accompanied by metabolic, cellular, and motor disruption in male rats with portacaval anastomosis.

The episodes of cerebral dysfunction, known as encephalopathy, are usually coincident with liver failure. The primary metabolic marker of liver diseases is the increase in blood ammonium, which promotes neuronal damage. In the present project, we used an experimental model of hepatic encephalopathy in male rats by portacaval anastomosis (PCA) surgery. Sham rats had a false operation. After 13 weeks of surgery, the most distinctive finding was vacuolar/spongiform neurodegeneration exclusively in the molecular layer of the cerebellum. This cerebellar damage was further characterized by metabolic, histopathological, and behavioral approaches. The results were as follows: (a) Cellular alterations, namely loss of Purkinje cells, morphological changes, such as swelling of astrocytes and Bergmann glia, and activation of microglia; (b) Cytotoxic edema, shown by an increase in aquaporin-4 and N-acetylaspartate and a reduction in taurine and choline-derivate osmolytes; (c) Metabolic adjustments, noted by the elevation of circulating ammonium, enhanced presence of glutamine synthetase, and increase in glutamine and creatine/phosphocreatine; (d) Inflammasome activation, detected by the elevation of the marker NLRP3 and microglial activation; (e) Locomotor deficits in PCA rats as assessed by the Rotarod and open field tests. These results lead us to suggest that metabolic disturbances associated with PCA can generate the cerebellar damage that is similar to morphophysiological modifications observed in amyloidogenic disorders. In conclusion, we have characterized a distinctive cerebellar multi-disruption accompanied by high levels of ammonium and associated with spongiform neurodegeneration in a model of hepatic hypofunctioning.

Trombosis venosa portal extrahepática, manejo quirúrgico con derivación meso-Rex. Serie de 3 casos / Extrahepatic portal vein thrombosis, surgical management with meso-Rex shunt. Series of 3 cases

La vena porta es un conducto que drena el flujo esplácnico al hígado y se puede ocluir por diferentes patologías, variando su presentación clínica de acuerdo con la causa de la obstrucción. Es muy importante diferenciar la trombosis portal asociada o no a la cirrosis, ya que su tratamiento y pronóstico es diferente. La trombosis venosa portal extrahepática es una condición netamente de origen vascular, y es la principal causa de trombosis portal en niños y adultos. Presentamos tres casos tratados con derivación meso-Rex, con seguimiento a 6 meses

The portal vein is a conduit that drains splanchnic flow to the liver, it can be occluded by different pathologies and its clinical presentation varies according to the cause of the obstruction. It is very important to differentiate portal thrombosis associated or not with cirrhosis, since its treatment and prognosis is different. Extrahepatic portal vein thrombosis (PEVT) is a condition of purely vascular origin, being the main cause of portal thrombosis in children and adults. We present three cases with meso-Rex shunt, with a 6-month follow-up

Reduced Liver Lipid Peroxidation in Subcellular Fractions Is Associated with a Hypometabolic State in Rats with Portacaval Anastomosis.

A surgical connection between portal and inferior cava veins was performed to generate an experimental model of high circulating ammonium and hepatic hypofunctioning. After 13 weeks of portacaval anastomosis (PCA), hyperammonemia and shrinkage in the liver were observed. Low glycemic levels accompanied by elevated levels of serum alanine aminotransferase were recorded. However, the activity of serum aspartate aminotransferase was reduced, without change in circulating urea. Histological and ultrastructural observations revealed ongoing vascularization and alterations in the hepatocyte nucleus (reduced diameter with indentations), fewer mitochondria, and numerous ribosomes in the endoplasmic reticulum. High activity of hepatic caspase-3 suggested apoptosis. PCA promoted a marked reduction in lipid peroxidation determined by TBARs in liver homogenate but specially in the mitochondrial and microsomal fractions. The reduced lipoperoxidative activity was also detected in assays supplemented with Fe2+. Only discreet changes were observed in conjugated dienes. Fluorescent probes showed significant attenuation in mitochondrial membrane potential, reactive oxygen species (ROS), and calcium content. Rats with PCA also showed reduced food intake and decreased energy expenditure through indirect calorimetry by measuring oxygen consumption with an open-flow respirometric system. We conclude that experimental PCA promotes an angiogenic state in the liver to confront the altered blood flow by reducing the prooxidant reactions associated with lower metabolic rate, along with significant reduction of mitochondrial content, but without a clear hepatic dysfunction.

Escleroterapia endoscópica asistida mediante balón oclusivo como tratamiento de varices gástricas cardiofúndicas de alto riesgo: reporte de dos casos y revisión de la literatura / Fundal variceal bleeding treated with balloon occluded endoscopic inyection sclerotherapy: report of two cases

Management of gastrointestinal bleeding caused by fundal varices is particularly difficult to manage. The options are: transjugular intrahepatic portosystemic shunt (TIPS), endoscopic injection of cyanoacrylate or balloon-occluded retrograde transvenous obliteration (BRTO). We report a 63 year-old male with a cirrhosis caused by hepatitis C and a 66 year-old female with a cirrhosis caused by a non-alcoholic steatohepatitis. Both patients had a gastrointestinal bleeding caused by fundal varices and were treated with sclerotherapy with cyanoacrylate assisted with BRTO. Flow was interrupted in the gastro-renal shunt by a femoral access in both patients. The male patient had a new bleeding two months later and died. In the female patient an endosonography performed nine months after the procedure showed absence of remaining varices.

[Fundal variceal bleeding treated with balloon occluded endoscopic inyection sclerotherapy. Report of two cases]. / Escleroterapia endoscópica asistida mediante balón oclusivo como tratamiento de varices gástricas cardiofúndicas de alto riesgo: Reporte de dos casos y revisión de la literatura.

Management of gastrointestinal bleeding caused by fundal varices is particularly difficult to manage. The options are: transjugular intrahepatic portosystemic shunt (TIPS), endoscopic injection of cyanoacrylate or balloon-occluded retrograde transvenous obliteration (BRTO). We report a 63 year-old male with a cirrhosis caused by hepatitis C and a 66 year-old female with a cirrhosis caused by a non-alcoholic steatohepatitis. Both patients had a gastrointestinal bleeding caused by fundal varices and were treated with sclerotherapy with cyanoacrylate assisted with BRTO. Flow was interrupted in the gastro-renal shunt by a femoral access in both patients. The male patient had a new bleeding two months later and died. In the female patient an endosonography performed nine months after the procedure showed absence of remaining varices.

Direct intrahepatic portocaval shunt for treatment of portal thrombosis and Budd-Chiari syndrome.

Budd-Chiari syndrome (BCS) refers to hepatic venous outflow obstruction that in severe cases can lead to acute liver failure prompting consideration of revascularization or transplantation. Here, a 22 year old female with angiographically proven BCS secondary to JAK2/V617F positive Polycythemia vera on therapeutic warfarin presented with acute liver failure (ALF). Imaging revealed a new, near complete thrombotic occlusion of the main portal vein with extension into the superior mesenteric vein. An emergent direct intrahepatic portocaval shunt (DIPS) was created and liver function promptly normalized. She has been maintained on rivaroxaban since that time. Serial assessment over 1 year demonstrated continued shunt patency and improved flow in the mesenteric vasculature on ultrasound as well as normal liver function. DIPS is a viable alternative in the treatment of ALF from BCS when standard recanalization is not feasible. Improved blood flow may also improve portal/mesenteric clot burden. While further investigation is needed, new targeted anticoagulants may be viable as a long term anticoagulation strategy.

A modified microsurgical model for end-to-side selective portacaval shunt in the rat. Intraoperative microcirculatory investigations.

PURPOSE: To investigate the intraoperative microcirculatory changes of the affected organs (small bowel, liver and kidney) during the making of a modified selective portacaval (PC) shunt. METHODS: On ten anaesthetized Sprague-Dawley rats the selective end-to-side mesocaval anastomosis was performed, where only the rostral mesenteric vein is utilized and the portal vein with the splenic vein are left intact. Morphometric and microcirculatory investigations using a LDF device determining flux units (BFU) were carried out. RESULTS: After completing the shunts the microcirculatory flux values did not recover in the same manner on the surface of the small intestine, the liver or the kidney. BFU values showed deterioration in the small intestine and in the liver (p<0.001). During the reperfusion the BFU values improved, but not in the same manner. The small intestine values left behind the kidney and liver data. CONCLUSIONS: Technically, the advantages of the models include the selective characteristic, the mesocaval localization and the relatively easy access to those vessels. However, its major disadvantage is the time needed for positioning the vessels without coiling or definitive stretching. Intraoperative LDF may provide useful data on the microcirculatory affection of the organs suffering from hypoperfusion or ischemia during creating the shunts.

A modified microsurgical model for end-to-side selective portacaval shunt in the rat: intraoperative microcirculatory investigations

PURPOSE: To investigate the intraoperative microcirculatory changes of the affected organs (small bowel, liver and kidney) during the making of a modified selective portacaval (PC) shunt. METHODS: On ten anaesthetized Sprague-Dawley rats the selective end-to-side mesocaval anastomosis was performed, where only the rostral mesenteric vein is utilized and the portal vein with the splenic vein are left intact. Morphometric and microcirculatory investigations using a LDF device determining flux units (BFU) were carried out. RESULTS: After completing the shunts the microcirculatory flux values did not recover in the same manner on the surface of the small intestine, the liver or the kidney. BFU values showed deterioration in the small intestine and in the liver (p<0.001). During the reperfusion the BFU values improved, but not in the same manner. The small intestine values left behind the kidney and liver data. CONCLUSIONS: Technically, the advantages of the models include the selective characteristic, the mesocaval localization and the relatively easy access to those vessels. However, its major disadvantage is the time needed for positioning the vessels without coiling or definitive stretching. Intraoperative LDF may provide useful data on the microcirculatory affection of the organs suffering from hypoperfusion or ischemia during creating the shunts.

Derivaciones portosistemáticas congénitas: reporte de caso en un canino / Congenital portosystemics shunts: case report in a dog

Las derivaciones portocava extrahepáticas son anomalías vasculares donde la circulación portal se conecta con la circulación sistemática. En los caninos constituyen el 45% de las anomalías portovasculares, registrándose un predisposición racial. El objetivo de este trabajo es presentar los hallazgos ecográficos en un canino de raza Yorkshire. Se observó disminución del tamaño hepático, con la presencia de un vaso anómalo que comunicaba la vena porta con la vena cava, y donde el Doppler color registró turbulencia. Luego de la corrección quirúrgica, se observó un aumento del diámetro de la vena porta, con aumento del tamaño del órgano. En el diagnóstico de las derivaciones vasculares extra hepáticas, la ecografía tiene la ventaja de ser un método no invasivo que da información sobre el parénquima hepático y la vasculatura, sirviendo de guía para la selección de los procedimientos quirúrgicos.

Derivaciones portosistemáticas congénitas: reporte de caso en un canino / Congenital portosystemics shunts: case report in a dog

Las derivaciones portocava extrahepáticas son anomalías vasculares donde la circulación portal se conecta con la circulación sistemática. En los caninos constituyen el 45% de las anomalías portovasculares, registrándose un predisposición racial. El objetivo de este trabajo es presentar los hallazgos ecográficos en un canino de raza Yorkshire. Se observó disminución del tamaño hepático, con la presencia de un vaso anómalo que comunicaba la vena porta con la vena cava, y donde el Doppler color registró turbulencia. Luego de la corrección quirúrgica, se observó un aumento del diámetro de la vena porta, con aumento del tamaño del órgano. En el diagnóstico de las derivaciones vasculares extra hepáticas, la ecografía tiene la ventaja de ser un método no invasivo que da información sobre el parénquima hepático y la vasculatura, sirviendo de guía para la selección de los procedimientos quirúrgicos.(AU)

Survey of adult liver transplantation techniques (SALT): an international study of current practices in deceased donor liver transplantation.

BACKGROUND: There has been little focus lately on operative techniques for full graft liver transplantation, and the standard technique is unclear. METHODS: An internet survey addressing the key technical issues was e-mailed to programme directors. RESULTS: Responses were obtained from 93 out of 128 (73%) directors contacted. Programmes performed a median of 60 (8-240) transplants per year. Maximum mean cold time of 13 ± 3 h and maximum median steatosis of 40% (15-90%) were tolerated. The inferior vena cava was preserved by 48% of centres all the time and 43% selectively. European centres used temporary portacaval shunting (42%) four times more often than USA programmes. Venous bypass was always used when not preserving the inferior vena cava by less than 25%, and used selectively by approximately 40% of centres. Portal vein anastomosis with room for expansion (88%), graft hepatic artery to native gastroduodenal/common hepatic artery bifurcation (57%) and bile duct-to-duct (47%) were the favoured techniques. DISCUSSION: A standard international operative technique for deceased donor liver transplantation does not exist, although there is a trend towards inferior vena cava preservation. Donor selection criteria were more homogenous across programmes. As suggested by the high response rate, there likely exists interest to investigate technical variations on an international scale.

La derivación portocava en la era del TIPS, la endoscopia y los trasplantes de hígado, su utilidad en la hemorragia esofágica aguda: [revisión] / Portocaval shunts in the era of TIPS, endoscopy and liver transplantation: indications in acute esophageal hemorrhage: [review]

Las derivaciones portocava marcaron un hito en el devenir histórico de la cirugía para el manejo de la hipertensión portal. El sangrado por várices esofágicas representa una urgencia quirúrgica que demanda intervención inmediata. El tratamiento de las várices esofágicas por abordaje endoscópico o por TIPS y, por otra parte, el advenimiento del trasplante hepático como un procedimiento estándar, ha disminuido la frecuencia con que se realizan tales derivaciones. Sin embargo, estos procedimientos tienen indicaciones precisas, tanto como intervenciones de urgencia en algunos casos de hemorragia esofágica, como en forma electiva en determinados pacientes con hipertensión portal.Hemos hecho una revisión de la literatura y de los conocimientos actuales de las derivaciones portocava a raíz de un caso tratado en forma exitosa en el Hospital Occidente de Kennedy en Bogotá, Colombia.

Portocaval shunts constitute a milestone in the history of the surgical treatment of portal hypertension. Bleeding from esophageal varices is a surgical emergency that demands immediate intervention. The endoscopic management of esophageal varices and the advent of TIPS, plus the development of liver transplantation have diminished the frequency of the use of portocaval shunts. However, these procedures have precise indications, both as emergency operations in some cases of esophageal varicose hemorrhage as well as elective procedures in selected patients with portal hypertension. We hereby present a literature review of the “state of the art” of portocaval shunts motivated by a patient that was successfully treated at Hospital Occidente de Kennedy in Bogotá, Colombia.

Cavoportal hemitransposition for the simultaneous thrombosis of the caval and portal systems - a review of the literature.

Portal venous thrombosis was originally considered to be a contraindication for liver transplantation. Currently, several methods exist to re-establish blood flow to the hepatic portal system. Cavoportal hemitransposition is a surgical procedure that can be used in liver transplantation when the portal venous system is thrombosed and portal flow cannot be re-established from the mesenteric venous system. In cavoportal hemitransposition the blood flow from the inferior vena cava of the recipient is directed to the portal vein of the donor liver to compensate for the lost portal venous supply. This can either be done by end-to-end or end-to-side anastomosis. Seventy-one cases of cavoportal hemitransposition have been reported worldwide. All patients reported had been in a critical and life-threatening condition, presenting with either end-stage-liver disease or acute hepatic failure combined with severe vascular pathology. Of the cases reported, 32 patients died for reasons non-related to the surgical procedure. Seven of the 71 patients had Budd-Chiari syndrome complicated by thrombosis of the portal-venous system. This means thrombosis in two different venous systems at the same time, the mesenteric and main venous system. To date this <> venous thrombosis of both the caval and portal system has only been reviewed together with the possible medical, radiological and non-transplant treatment options. This article evaluates the available literature and reviews the evolution of the surgical procedure of cavoportal hemitransposition emphasising its role in combined thrombosis of the hepatic veins and portal venous systems.

Derivación portocava transitoria en el trasplante hepático con preservación de la cava / Temporary portocaval shunt in the liver transplant with vena cava preservation

El uso de la derivación portocava durante el trasplante hepático ortotópico mejora la hemodinámica, puede contribuir a reducir los requerimientos de glóbulos y protege la función renal, aunque incrementa moderadamente el tiempo quirúrgico...

The use of the portocaval shunt during the liver orthotopic transplantation improves the hemodynamics, contributes to reduce the requirements of red blood cells and and protects the renal function, although it moderately increases the surgical time...

Derivação meso-porta (shunt Rex): tratamento atual da obstrução extra-hepática da veia porta / Meso-portal bypass (Rex shunt): current treatment of extrahepatic portal vein obstruction

Objetivo: Apresentar a caso de uma criança brasileira, provavelmente a primeira, portadora de obstrução extra-hepática da veia porta (OEHVP), submetida ao shunt Rex (derivação cirúrgica meso-porta) para tratamento da hipertensão porta pré-hepatica. Descrição: Menino de um ano e nove meses, 11 kg, previamente hígido, apresentou hematemese e melena. Foi realizada endoscopia digestiva alta, que demonstrou varizes de esôfago sangrantes grau III. Foi iniciado tratamento com propranolol e escleroterapia. Apresentou mais três episódios de sangramento importante e sinais laboratoriais de hiperesplenismo e aumento da amônia sérica. Realizado diagnóstico de cavernoma da veia porta. Foi indicado tratamento cirúrgico, após avaliação da coagulação e biopsia hepática normais. Foi feita opção pela derivação meso-porta ou shunt Rex, que consiste na colocação de um enxerto de veia jugular entre a veia mesentérica superior e o ramo esquerdo intra-hepatico da veia porta, restaurando o fluxo sanguíneo portal para o fígado. O paciente foi submetido com dois anos e seis meses, em março de 2004, à cirurgia no Children's Hospital de Chicago, sem intercorrências, tendo recebido alta no quinto dia pós-operatório. Retornou após um mês da cirurgia ao Brasil, onde seguiu fazendo controles periódicos. Atualmente, quase três anos apos o shunt Rex, o menino tem vida normal, com provas de função hepática normais, sem esplenomegalia, sem varizes e nem sinais de hipertensão porta. O shunt encontra-se pérvio e com bom fluxo pela ultra-sonografia. Conclusões: A cirurgia de derivação mesoporta e uma opção terapêutica recente e, muito provavelmente, tornar-se-á o método de escolha no manejo da hipertensão porta pré-hepática, por OEHVP. É superior aos outros procedimentos cirúrgicos, já que elimina totalmente a hipertensão porta e suas seqüelas.

Role of ammonia and nitric oxide in the decrease in plasma prolactin levels in prehepatic portal hypertensive male rats.

OBJECTIVES: Since very little is known about neuroendocrine changes that occur in portal-systemic hepatic encephalopathy, we studied plasma prolactin (PRL) levels and the involvement of hyperammonemia, nitric oxide (NO) and dopaminergic and adrenergic systems in the control of this hormone secretion in a male rat model of prehepatic portal hypertension (PH). METHODS: We conducted in vivo studies to determine plasma ammonia and PRL levels. Dopamine (DA), dihydroxyphenylacetic acid (DOPAC), epinephrine and norepinephrine content in medial basal hypothalamus (MBH) and anterior pituitary (AP) were measured. In addition, NO synthase (NOS) activity and protein expression were evaluated in APs. In in vitro studies, the APs from intact rats were incubated with different doses of ammonia and PRL secretion was determined. In ex vivo studies, the APs from normal and PH rats were incubated in the presence of ammonia and/or a NOS inhibitor, NG-nitro-L-arginine-methyl ester (L-NAME) and PRL secretion was determined. RESULTS: PH rats had a significant increase in plasma ammonia levels (p < 0.001) and a decrease in plasma PRL levels (p < 0.05). Neither DA nor DOPAC content or DOPAC/DA ratios were modified in both MBH and APs; however, we observed a significant increase in norepinephrine content in both MBH and AP (p < 0.001 and p < 0.05, respectively) and a significant increase in epinephrine in APs (p < 0.001). Moreover, PH produced an increase in NOS activity (p < 0.01) and NOS protein expression (p < 0.0001) in APs. The ammonia (100 microM) significantly reduced PRL secretion from APs in vitro (p < 0.05). The presence of L-NAME, an inhibitor of NOS, abrogated the inhibitory effect of ammonia on PRL secretion from APs from control and PH rats. CONCLUSIONS: We found that plasma PRL levels were decreased in PH rats probably due to the high ammonia levels. The central noradrenergic system could also mediate this decrease. Also, the increase in NOS activity and/or content in AP induced NO production that directly inhibited PRL secretion from the AP, without the participation of the dopaminergic system.