Perioperative Evaluation of Arterial and Venous Whole Blood in the Lamb (Ovis aries) Fontan Model.

Whole blood analysis can evaluate numerous parameters, including pH, pCO2, pO2, HCO3 - , base excess, glucose, electrolytes, lactate, blood urea nitrogen, creatinine, bilirubin, and hemoglobin. This valuable tool enables clinicians to make more informed decisions about patient care. However, the current body of literature describing perioperative whole blood analysis in Dorset sheep (Ovis aries) is small, so clinicians lack adequate information to guide their decision-making when evaluating test results. We evaluated arterial and venous whole blood pH, bicarbonate, pCO2, lactate, creatinine, and blood urea nitrogen before and for the first 24 hours after surgery in 2 cohorts of male and female Ovis arie s undergoing one of 2 major cardiovascular procedures, a Single-Stage Fontan or an inferior vena cava to pulmonary artery extracardiac conduit implantation (IP-ECC). The cohort undergoing a Single-Stage Fontan, which is the more complex procedure, exhibited greater deviation from baseline measurements than did the cohort undergoing the IP-ECC for lactate, bicarbonate, and creatinine. The cohort undergoing the IP-ECC showed no significant deviation from baseline for any parameters, potentially indicating a better safety margin than expected when compared with the Single-Stage Fontan. Together, these results indicate the clinical value of arterial and venous whole blood measurements in perioperative management of sheep and can provide a reference for clinicians managing sheep after significant cardiovascular procedures.

The lysosomal trafficking regulator "LYST": an 80-year traffic jam.

Lysosomes and lysosome related organelles (LROs) are dynamic organelles at the intersection of various pathways involved in maintaining cellular hemostasis and regulating cellular functions. Vesicle trafficking of lysosomes and LROs are critical to maintain their functions. The lysosomal trafficking regulator (LYST) is an elusive protein important for the regulation of membrane dynamics and intracellular trafficking of lysosomes and LROs. Mutations to the LYST gene result in Chédiak-Higashi syndrome, an autosomal recessive immunodeficiency characterized by defective granule exocytosis, cytotoxicity, etc. Despite eight decades passing since its initial discovery, a comprehensive understanding of LYST's function in cellular biology remains unresolved. Accumulating evidence suggests that dysregulation of LYST function also manifests in other disease states. Here, we review the available literature to consolidate available scientific endeavors in relation to LYST and discuss its relevance for immunomodulatory therapies, regenerative medicine and cancer applications.

Tissue engineered vascular grafts are resistant to the formation of dystrophic calcification.

Advancements in congenital heart surgery have heightened the importance of durable biomaterials for adult survivors. Dystrophic calcification poses a significant risk to the long-term viability of prosthetic biomaterials in these procedures. Herein, we describe the natural history of calcification in the most frequently used vascular conduits, expanded polytetrafluoroethylene grafts. Through a retrospective clinical study and an ovine model, we compare the degree of calcification between tissue-engineered vascular grafts and polytetrafluoroethylene grafts. Results indicate superior durability in tissue-engineered vascular grafts, displaying reduced late-term calcification in both clinical studies (p < 0.001) and animal models (p < 0.0001). Further assessments of graft compliance reveal that tissue-engineered vascular grafts maintain greater compliance (p < 0.0001) and distensibility (p < 0.001) than polytetrafluoroethylene grafts. These properties improve graft hemodynamic performance, as validated through computational fluid dynamics simulations. We demonstrate the promise of tissue engineered vascular grafts, remaining compliant and distensible while resisting long-term calcification, to enhance the long-term success of congenital heart surgeries.

Effects of a recombinant humanized anti-cocaine monoclonal antibody on the metabolism and distribution of cocaine in vitro and in mice.

The anti-cocaine monoclonal antibody, h2E2, is a candidate for treating cocaine-use disorder. h2E2 binds to and sequesters cocaine in the plasma compartment, effectively decreasing cocaine concentrations in the brains of rats and mice. Despite the binding of cocaine to h2E2, plasma cocaine concentrations decline rapidly in rodents over time, but there was a drastic decrease in the urinary elimination of cocaine in the presence of h2E2. Since cocaine is not being renally excreted, the apparent disappearance of cocaine from the plasma must be explained by either metabolism or distribution. However, binding of cocaine to h2E2 may restrict the availability of cocaine for hydrolysis by endogenous esterases. Therefore, the antibody would be expected to extend the elimination half-life of cocaine. In contrast, previous studies reported h2E2 as having no effect on the rate of cocaine clearance. It is important to examine the ultimate clearance of the cocaine to ascertain its half-life and potential for re-intoxication. Therefore, we investigated the effects of h2E2 on cocaine hydrolysis in vitro and on cocaine metabolism and disposition in vivo over a 6-h time course. The spontaneous and enzyme-mediated in vitro hydrolysis of cocaine was drastically decreased in the presence of h2E2 in vitro. Additionally, in mice, h2E2 significantly increased the distribution and elimination half-lives of cocaine relative to vehicle controls over an extended time course. Therefore, we concluded that h2E2 slowing the distribution and elimination of cocaine is the most appropriate explanation for the initial disappearance of cocaine from the plasma in vivo.