Post-operative Anticoagulation Strategy Following Comprehensive Stage 2 Procedure for Single Ventricle Physiology.

Thrombosis, especially thrombosis of the pulmonary artery, is a large contributor to morbidity and mortality following comprehensive stage 2 procedure for single ventricle cardiac physiology. A peri-operative management protocol was implemented at our institution in March 2010. It includes 6 weeks of therapeutic anticoagulation post-operatively to mitigate the thrombotic risks in this patient population. This is a retrospective study of hospitalized children who received post-operative anticoagulation following a comprehensive stage 2 procedure for single ventricle cardiac physiology at a free-standing children's hospital. The primary objectives are to describe our institution's anticoagulation strategy and report on the number of thromboses and major bleeding episodes in the 6 weeks post-operatively. Secondary objectives include the dose of enoxaparin required to obtain a therapeutic low-molecular weight anti-factor-Xa (AFXaLMWH) level, and the number of patients outside of the therapeutic range. A total of 71 infants were included in the final analysis. Four patients experienced a thrombosis episode and three patients experienced clinically significant bleeding. The mean dose of enoxaparin required to obtain a therapeutic AFXaLMWH level between 0.5-1 unit/mL was 1.23 mg/kg SQ every 12 h and 37% of patients achieved goal AFXaLMWH levels with the initial starting dose of enoxaparin 1 mg/kg SQ every 12 h. We describe a 9-year experience of anticoagulation after single ventricle palliation. Anticoagulation with therapeutic AFXaLMWH goals of 0.5-1 unit/mL may reduce the rates of clinically significant thrombosis post-operatively in this population and appears safe without increase in significant bleeding episodes when compared to a historical cohort. Further studies comparing this population to those who do not receive post-operative anticoagulation are warranted.

Substituted oxazolidinones as novel NPC1L1 ligands for the inhibition of cholesterol absorption.

Cholesterol absorption inhibition (CAI) represents an important treatment option for hypercholesterolemia. Herein, we report the design and evaluation of a series of substituted oxazolidinones as ligands for the Niemann Pick C1 Like 1 (NPC1L1) protein, a key mediator of cholesterol transport. Novel analogs were initially evaluated in a brush border membrane NPC1L1 binding assay; subsequently, promising compounds were evaluated in vivo for acute inhibition of cholesterol absorption. These studies identified analogs with low micromolar NPC1L1 binding affinity and acute in vivo efficacy of >50% absorption inhibition at 3mg/kg.