Phosphodiesterase 5 inhibitors lower both portal and pulmonary pressure in portopulmonary hypertension: a case report

<p>Abstract</p> <p>Background</p> <p>Portopulmonary hypertension (PPHTN) is a severe complication in liver cirrhosis. PDE5 inhibitors lower pulmonary arterial pressure (PAP) in PPHTN. However, their effect on portal hypertension has not yet been investigated.</p> <p>Case presentation</p> <p>A 55 year old male patient presented with PPHTN and alcoholic liver cirrhosis. 10 mg of Tadalafil, a PDE5 inhibitor with a long half-life, was administered orally under continuous monitoring of pulmonary and portal hemodynamics. For maintenance therapy the patient received Sildenafil 20 mg bid.</p> <p>Tadalafil lowered mean PAP from 45 to 39 mmHg within 60 minutes. Cardiac output (CO) increased from 6.8 to 7.9 l/min. Central venous pressure (CVP) remained stable at 3 mmHg. Systolic and diastolic blood pressure was lowered from 167/89 to 159/86 mmHg. Pulse rate increased from 75 to 87 per min. Wedged hepatic vein pressure (WHVP) decreased from 21 to 18 mm Hg, hepatovenous pressure gradient (HVPG) decreased from 10 to 7 mmHg. Hemodynamic monitoring after 6 months of Sildenafil therapy revealed a sustained lowering of mean PAP. HVPG remained constant at 10 mmHg. Cardiac and pulmonary performance had further improved.</p> <p>Conclusion</p> <p>This case report shows for the first time, that phosphodiesterase 5 inhibitors lower both portal and pulmonary pressure in portopulmonary hypertension.</p

Phosphodiesterase-5 inhibitors have distinct effects on the hemodynamics of the liver

<p>Abstract</p> <p>Background</p> <p>The NO - cGMP system plays a key role in the regulation of sinusoidal tonus and liver blood flow with phosphodiesterase-5 (PDE-5) terminating the dilatory action of cGMP. We, therefore, investigated the effects of PDE-5 inhibitors on hepatic and systemic hemodynamics in rats.</p> <p>Methods</p> <p>Hemodynamic parameters were monitored for 60 min. after intravenous injection of sildenafil and vardenafil [1, 10 and 100 μg/kg (sil1, sil10, sil100, var1, var10, var100)] in anesthetized rats.</p> <p>Results</p> <p>Cardiac output and heart rate remained constant. After a short dip, mean arterial blood pressure again increased. Systemic vascular resistance transiently decreased slightly. Changes in hepatic hemodynamic parameters started after few minutes and continued for at least 60 min. Portal (var10 -31%, sil10 -34%) and hepatic arterial resistance (var10 -30%, sil10 -32%) decreased significantly (p < 0.05). At the same time portal venous (var10 +29%, sil10 +24%), hepatic arterial (var10 +34%, sil10 +48%), and hepatic parenchymal blood flow (var10 +15%, sil10 +15%) increased significantly (p < 0.05). The fractional liver blood flow (total liver flow/cardiac output) increased significantly (var10 26%, sil10 23%). Portal pressure remained constant or tended to decrease. 10 μg/kg was the most effective dose for both PDE-5 inhibitors.</p> <p>Conclusion</p> <p>Low doses of phosphodiesterase-5 inhibitors have distinct effects on hepatic hemodynamic parameters. Their therapeutic use in portal hypertension should therefore be evaluated.</p

Effect of helicobacter pylori eradication and antisecretory maintenance therapy on peptic ulcer recurrence in cirrhotic patients: A prospective, cohort 2-year follow-up study

BACKGROUND: The role of Helicobacter pylori eradication to cure peptic ulcer disease in patients with cirrhosis is not clear. AIM: To investigate the course of peptic ulcer disease in cirrhotics, first after healing with either H. pylori eradication or omeprazole therapy and second while on omeprazole maintenance therapy after recurrence. METHODS: Prospective cohort study in a tertiary-care hospital in Greece. Out of 365 consecutive cirrhotic patients who underwent endoscopy, 67 had peptic ulcer and 30 were enrolled. H. pylori positive patients received eradication therapy and H. pylori negative patients received omeprazole treatment. Follow-up endoscopies were performed at 12 and 24 months or when symptoms recurred. Patients with ulcer recurrence were treated with omeprazole maintenance therapy. The main outcome measurement of the study was peptic ulcer relapse rate during follow-up. RESULTS: Twenty-eight patients with healed ulcers were followed for up to 2 years. During follow-up, ulcer relapsed in 17 patients (8/18 H. pylori positive and 9/10 H. pylori negative at study entry, P=0.041), including 2 patients who died from ulcer bleeding. No further ulcer relapse was observed in the remaining 15 patients who received omeprazole maintenance therapy for the rest of follow-up. H. pylori negative status (P=0.002) and severity of cirrhosis (P=0.015) at study entry were independently related to shorter peptic ulcer relapse-free time. CONCLUSIONS: H. pylori eradication does not protect all cirrhotics from ulcer recurrence and the majority of ulcers recur in H. pylori negative patients. Therefore, omeprazole maintenance treatment is mandatory, irrespectively of H. pylori status. © 2008 by Lippincott Williams &amp; Wilkins

The Impact of Peri-operative Anti-TNF Treatment on Anastomosis-Related Complications in Crohn&apos;s Disease Patients. A Critical Review

Introduction: Tumor necrosis factor (TNF)α is a cytokine exerting pleiotropic effects on critical cell functions and, most importantly, is the main regulator of pro-inflammatory cytokine production and a key player in the pathophysiology of numerous autoimmune diseases, including Crohn&apos;s disease. Methods: TNFα became a therapeutic target and TNFα blocking agents are currently used in the treatment of inflammatory diseases. Beyond the therapeutic benefits deriving from TNFα neutralization, amendments in the cellular functions of the immune system may as well induce potent immunosuppressive effects. An attenuated immune response may compromise the intestinal healing ability, thus leading to weaker anastomosis and increased risk of anastomotic leak and septic complications. Results: This hypothesis raises great concerns about the safety of perioperative administration of anti-TNF and has been the endpoint of numerous studies. Conclusion: The aim of this review is to critically evaluate the evidence regarding the role of TNFα in anastomosis related complications after abdominal surgery in Crohn&apos;s disease patients. © 2014 The Society for Surgery of the Alimentary Tract

The role of variations within microRNA in inflammatory bowel disease

MicroRNAs (miRNAs) are small noncoding RNAs that are implicated in gene expression regulation at both a transcriptional and at a translational level. Single-nucleotide polymorphisms may occur in miRNA biogenesis pathway genes, primary miRNA, pre-miRNA, or a mature miRNA sequence. Such polymorphisms may be functional with respect to biogenesis and actions of mature miRNA. These single-nucleotide polymorphisms may have a potential to affect the efficiency of miRNA binding to the target sites or can create or disrupt binding sites. The resulting gene dysregulation may involve changes in phenotype and may eventually prove critical for the susceptibility to inflammatory bowel disease and its onset. In this review, we summarize their importance as candidate inflammatory bowel disease biomarkers. Copyright © 2013 Wolters Kluwer Health | Lippincott Williams and Wilkins