ABSTRACT
Portopulmonary hypertension, a type of pulmonary arterial hypertension in the setting of cirrhotic or noncirrhotic portal hypertension, is associated with elevated morbidity and mortality during and after transplantation. Uncontrolled portopulmonary hypertension may prevent or delay listing for transplant candidates, and the prognosis without treatment and ultimately transplant is extremely poor. We present a 29-year-old White woman, who had a post-liver transplant at infancy due to biliary atresia. Later on, she developed extensive portal vein thrombosis and portopulmonary hypertension and underwent a multivisceral transplant (liver, stomach, pancreaticoduodenal complex, and small and large intestine). Preoperative mean pulmonary artery pressure was <30 mm Hg with a pulmonary vascular resistance of <300 dynes.s/cm5 on oral sildenafil and intravenous epoprostenol. Intraoperatively, management required comprehensive transfusion protocols, a careful balance between correcting blood loss and preventing thrombosis. Intravenous epoprostenol, sildenafil, milrinone, and inhaled nitric oxide were used to reduce elevated mean pulmonary artery pressure and right ventricular strain associated with vascular clamping, reperfusion, and massive fluid shifts. Nitric oxide and epoprostenol use unleashed antiplatelet effects on a patient already susceptible to coagulopathy. A multimodal and multidisciplinary approach continued throughout the surgery and in the postoperative period, which led to a successful outcome.
Subject(s)
Hypertension, Portal , Hypertension, Pulmonary , Pulmonary Arterial Hypertension , Adult , Antihypertensive Agents/therapeutic use , Epoprostenol/therapeutic use , Female , Humans , Hypertension, Portal/complications , Hypertension, Pulmonary/complications , Milrinone , Nitric Oxide , Sildenafil Citrate/therapeutic useABSTRACT
2,6-Dimethyl-3,5-dimethoxycarbonyl-4-(o-difluoromethoxyphenyl)-1, 4-dihydropyridine (ryodipine, PP-1466) at oral administration in the form of a suspension with Tween (polysorbate) 80 addition is comparatively rapidly absorbed in the gastro-intestinal tract and circulates in blood for a long period of time. PP-1466 practically does not bind to plasma proteins. The drug is mainly excreted via the kidneys and with faeces by 49 and 46% of the dose administered after 96 h, respectively. PP-1466 metabolites are present in rat urine-2,6-dimethyl-4-arylpyridine-3,5-dicarbonic acid derivatives: oxidation product of PP-1466 dihydropyridine cycle into pyridine one, products of partial or complete hydrolysis of ester groups of PP-1466 oxidized form, lactones. There have been performed the synthesis of labelled 14C-PP-1466 as well as counter-synthesis of PP-1466 metabolites. Unchanged PP-1466 is not detected in urine.
Subject(s)
Antihypertensive Agents/metabolism , Nifedipine/analogs & derivatives , Animals , Bile/metabolism , Biotransformation , Chemical Phenomena , Chemistry , Chromatography, High Pressure Liquid , Chromatography, Thin Layer , Intestinal Absorption , Kinetics , Male , Mass Spectrometry , Nifedipine/metabolism , Rats , Tissue DistributionABSTRACT
A novel effective antihypertensive agent, 2,6-dimethyl-3,5-dimethoxycarbonyl-4-(o-difluoromethoxyphenyl++ +)-1,4-dihydropyridine (ryodipine, PP-1466) has been obtained. A method for ryosidine synthesis has been developed, side products of PP-1466 synthesis have been isolated and identified. Special characteristics (IRS, UVS, NMR, MS) and chromatography data (TLC, HPLC) are cited.
