endothelin-1 and Dilatation--Pathologic

Hepatopulmonary syndrome is a pulmonary vascular complication of cirrhosis in which intrapulmonary vasodilatation (IPV) results in hypoxemia. Endothelin-1 (ET-1), produced by proliferating cholangiocytes, has been identified as a mediator of IPV in an animal model of HPS, but the pathophysiology of IPV in humans has not been defined.. The purpose of this study was to assess whether cirrhosis with IPV, which often leads to HPS, is associated with increased hepatic venous ET-1 blood levels.. We performed a prospective cohort pilot study of 40 patients with liver disease undergoing transjugular liver biopsy from November 1, 2008 to September 1, 2009. Patients were categorized according to absence (-) or presence (+) of IPV as determined by bubble-contrasted echocardiography. Hepatic venous blood was assayed for ET-1 by ELISA. The percent volume of cholangiocytes in the liver biopsy specimen was determined by morphometric analysis, as a measure of bile duct proliferation.. Nine subjects were excluded, due to absence of cirrhosis (6) and patent foramen ovale (3). Of the remaining 31 subjects, IPV was present in 18 (58%). Median hepatic venous ET-1 was higher with IPV+ than IPV- at levels of 9.1 pg/mL (range 7.5-11.7) versus 2.1 pg/mL (1.3-5.6), respectively (P = 0.004). ET-1 levels correlated positively with cholangiocyte percent volume (r = 0.72, P < 0.001) but not with measures of liver dysfunction (bilirubin, INR, MELD score, or hepatic venous pressure gradient).. In human cirrhosis, increased hepatic venous ET-1 is associated with IPV and increased hepatic cholangiocyte volume.

Topics: Bile Ducts; Cell Proliferation; Cross-Sectional Studies; Dilatation, Pathologic; Endothelin-1; Female; Hepatic Veins; Hepatopulmonary Syndrome; Humans; Immunohistochemistry; Liver Cirrhosis; Male; Middle Aged; Pilot Projects; Prospective Studies; Pulmonary Veins; Vasodilation

To examine the role of voided urine endothelin-1 (ET-1) in the diagnosis and follow-up of children with ureteropelvic junction obstruction.. The study included 35 children with unilateral ureteropelvic junction obstruction who underwent pyeloplasty and 30 control children, including 10 healthy children, 10 with vesicoureteral reflux, and 10 with renal stones. Voided urine samples were obtained from the children in the study group before surgery and from the renal pelvis by needle aspiration during pyeloplasty. Bladder urine samples were also collected from the study group 1, 2, 3, 6, 9, and 12 months postoperatively. Bladder urine samples were also collected from all 30 control children. ET-1 was measured in the urine samples collected from the study and control groups.. The preoperative ET-1 level in the voided urine of the study group was significantly greater than its level in each of the three control groups. For the whole study group, a cutoff value of 3 fmol/mg creatinine gave a sensitivity of 74.3%, a specificity of 90%, and an overall accuracy of 81.5%. In 8 children (1 year old or younger), a cutoff value of 4 fmol/mg creatinine gave a sensitivity and specificity of 100%. Compared with the preoperative value, ET-1 had decreased significantly at 12 months after pyeloplasty.. The ET-1 level in voided urine is a useful marker that could be used as a noninvasive tool for the diagnosis and long-term follow-up of children with ureteropelvic junction obstruction.

Topics: Age Factors; Biomarkers; Child; Child, Preschool; Creatinine; Dilatation, Pathologic; Endothelin-1; Female; Humans; Infant; Kidney; Kidney Pelvis; Male; Prospective Studies; ROC Curve; Sensitivity and Specificity; Ureteral Obstruction

The authors review 20 cases of segmental arterial mediolysis (SAM) including 3 newly reported cases. SAM developed in areas of vascular distention in 2 of the latter cases: 1 in utero in the heart of a recipient of a twin transfusion syndrome and the other in the jejunum secondary to partial venous obstruction. In the third case, it occurred in a patient with Raynaud disease. Characterizing SAM are injurious and reparative lesions that occur in the media and/or at the adventitial medial junction. Four distinctive alterations are recognized: (1) mediolysis, (2) a tearing separation of the outer media from adventitia, (3) arterial gaps, and (4) a florid reparative response that replaces zones of mediolysis and fills areas of medial adventitial separation. The repair can transform SAM into lesions indistinguishable from common types of fibromuscular dysplasia (FMD.) A venous angiopathy involving large and medium-sized veins accompanies SAM. It features medial muscle vacuolar change with lysis leading to apparent separation of residual muscle bundles. Immunostaining shows endothelin-1 (ET-1) decorating adventitial capillaries in SAM and neighboring arteries, in capillaries of adjoining tissues, and outlining smooth muscle cell membranes in adjacent veins including those of the venous angiopathy. The significance of these changes is uncertain. Vasospasm is believed to cause SAM, but ET-1 is not the direct pressor agent responsible for this condition. The reason(s) for synthesis and release of ET-1 in SAM are still hypothetical, but local perturbations in vascular tone may be an important factor. ET-1 may be indirectly play a role in SAM by cross-talking and potentiating the activities of other vasoconstrictors such as norepinephrine and by orchestrating its reparative phase.

Topics: Adult; Arteries; Arteritis; Biomarkers; Coronary Vessels; Dilatation, Pathologic; Endothelin-1; Female; Fetal Diseases; Fetofetal Transfusion; Humans; Jejunum; Male; Middle Aged; Muscle, Smooth, Vascular; Peripheral Vascular Diseases; Pregnancy; Raynaud Disease; Tunica Media; Veins

Topics: Animals; Bradykinin; Cold Temperature; Constriction, Pathologic; Dilatation, Pathologic; Dinoprost; Endothelin-1; Endothelin-3; Male; Middle Cerebral Artery; Nitroprusside; Parietal Lobe; Rats