In 60 randomized dogs the effects of epoprostenol infusion (100 ng/kg/min) on ischemia-induced premature ventricular contractions (PVCs), ventricular tachycardia (VT), ventricular flutters and ventricular fibrillation were studied. The circumflex coronary artery occlusion canine model of sudden death was used. The results demonstrate different effects of epoprostenol on ischemia-induced ventricular arrhythmias: 1) both postischemic (7 of 30 vs 15 of 30, p = 0.0298) and postreperfusion (5 of 23 vs 8 of 15, p = 0.0492) ventricular fibrillations were prevented in epoprostenol dogs with an improvement of the global survival rate (18 of 30 vs 7 of 30, p = 0.0019) as compared to controls; 2) in epoprostenol treated dogs a significantly increased incidence of non lethal arrhythmias-including ventricular flutters that occurred in 12 of 30 dogs vs 4 of 30 in controls (p = 0.0195)--was observed; 3) a positive correlation between the percent diastolic pressure fall 10 min after the start of epoprostenol infusion and the number of non lethal arrhythmias was noted. However, hemodynamic effects of the compound, suggesting an oxygen sparing action, did not preclude the antifibrillatory effectiveness. Thus, the antifibrillatory and antiarrhythmic effects of epoprostenol after circumflex coronary artery occlusion and reperfusion in dogs seem independent from one another.
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NPJ Syst Biol Appl
January 2025
United Therapeutics Corporation, Silver Spring, MD, USA.
Challenges in drug development for rare diseases such as pulmonary arterial hypertension can be addressed through the use of mathematical modeling. In this study, a quantitative systems pharmacology model of pulmonary arterial hypertension pathophysiology and pharmacology was used to predict changes in pulmonary vascular resistance and six-minute walk distance in the context of oral treprostinil clinical studies. We generated a virtual population that spanned the range of clinical observations and then calibrated virtual patient-specific weights to match clinical trials.
View Article and Find Full Text PDFActa Anaesthesiol Scand
January 2025
CAG Center for Endotheliomics, Department of Clinical Immunology, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark.
Background: Acute respiratory failure (ARF) is common in critically ill patients, and 50% of patients in intensive care units require mechanical ventilation [3, 4]. The COVID-19 pandemic revealed that COVID-19 infection induced ARF caused by damage to the microvascular pulmonary endothelium. In a randomized clinical trial, mechanically ventilated COVID-19 patients with severe endotheliopathy, as defined by soluble thrombomodulin (sTM) ≥ 4 ng/mL, were randomized to evaluate the effect of a 72-h infusion of low-dose prostacyclin 1 ng/kg/min or placebo.
View Article and Find Full Text PDFExpert Opin Drug Saf
December 2024
Department of Rheumatology, Chongqing Emergency Medical Center, Chongqing University Central Hospital, Chongqing, China.
Background: Adverse drug events (ADEs) for endothelin receptor antagonists (ERAs) and prostacyclin-related drugs (PRDs) have been reported in clinical trials, but large-scale, real-world evaluations for respiratory, thoracic, and mediastinal disorders (RTMD) remain scarce.
Methods: A pharmacovigilance analysis of the FAERS database (Q1 2004~Q2 2024) used the reporting odds ratio (ROR) method for disproportionality analysis to assess the adverse drug events (ADEs) of ERAs and PRDs in pulmonary arterial hypertension, focusing on risks related to RTMD.
Results: Reports of ADEs for ERAs (bosentan, ambrisentan, and macitentan) were 15,286, 36795, and 17,497, respectively, and for PRDs (epoprostenol, treprostinil, iloprost, and selexipag) were 5,477, 57265, 3,247, and 5,504.
Adv Neonatal Care
December 2024
Author's Affiliation: University of Pennsylvania School of Nursing, Philadelphia, Pennsylvania.
Background: Treprostinil is a prostacyclin analogue that is frequently used in the pediatric and adult population to treat pulmonary hypertension; however, it is not often a drug of choice for patients in the neonatal intensive care unit (NICU).
Purpose: To evaluate the efficacy of treprostinil as a treatment for pulmonary hypertension of the neonate.
Data Sources: Electronic databases such as PubMed, CINAHL, and Embase were used for this literature review.
Georgian Med News
October 2024
Department of Hepatobiliary Surgery, Jiaozhou Central Hospital of Qingdao, 266300 Shandong, China.
Objective: Explore the effectiveness of ultrasound-guided percutaneous catheter drainage (PCD) combined with somatostatin in the treatment of severe pancreatitis (SAP) patients.
Methods: A retrospective study method was adopted to select 95 patients with SAP who were treated in our hospital from January 2018 to June 2022 for clinical research. Among them, 48 patients received routine treatment+somatostatin (control group), and other 47 patients received ultrasound guided PCD treatment on the basis of the control group (research group).
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