Bicarbonate-based Purge Solution As A Bleeding Reduction Strategy in Patients on Impella Support

Study: The Impella Catheters require a heparin-containing purge solution to maintain proper pump function by reducing the risk of biomaterial deposition in the purge gaps. A bicarbonate-based purge solution (BBPS) has been proposed as an alternative to a heparin-based purge solution. We review performance in patients supported to date with a BBPS (heparin-induced thrombocytopenia patients were excluded from this analysis). Methods: This review includes patients (n=26) supported using sodium bicarbonate (25 mEq/1L of D5W) in the purge from September 2020 to February 2021. These patients were supported with BBPS post-operatively where heparin in the purge was not desired or were transitioned to BBPS because of bleeding issues. Case data were collected from an internal database to develop the clinical narrative and cross-referenced against Impella Controller data logs to assess purge trends and pump function. Results: All pumps were switched to BBPS in the purge if not started with BBPS (Figure 1A). The average time to initiating BBPS was 1.6 days (excluding n=3 outliers where time to switching was \u3e15 days). The average duration of support with BBPS was 5 days and a maximum duration of 22 days (Figure 1B). Figure 1C shows clinical indications for use. Purge pressure and purge flow remained stable while on BBPS (Figure 1D). In conclusion, this preliminary experience suggests the feasibility of using BBPS to maintain purge patency, ensure pump motor reliability, reduce bleeding risk, and simplify anticoagulation management. Use of a BBPS may be a safe and effective alternative to heparin in the purge for patients in which heparin is contraindicated or not feasible. More patient experience and analysis are needed to evaluate how bicarbonate compares to heparin in the purge for all patients

Bicarbonate Purge Solution to Support Impella Devices for Patients with Clinically Suspected or Confirmed Heparin-induced Thrombocytopenia

Study: The Impella catheter is a transvalvular, micro-axial left ventricular assist device that provides temporary mechanical circulatory support and requires a heparin-containing purge solution to reduce the risk of biomaterial deposition in the purge gaps and also maintain proper pump function. For patients with suspected or confirmed heparin-induced thrombocytopenia (HIT), direct thrombin inhibitors (DTI) have been proposed as an alternative to heparin in the purge, but have been associated with pump failure requiring temporary tPA in the purge solution to normalize pump function. In this report, we review HIT patients supported with a sodium bicarbonate-based purge solution (BBPS). Methods: Patients with suspected or confirmed HIT on Impella support using sodium bicarbonate (25 mEq in 1L D5W solution) in the purge from September 2020 to January 2021 were reviewed. Case data were obtained from Impella Quality (IQ) database for those supported with a BBPS and clinically suspected or confirmed HIT. Purge pressures and purge flows were evaluated from the Automated Impella Controller (AIC). Results: Ten patients were supported with a BBPS during this period. Impella support was begun either with no anticoagulant (n=5), DTI (n=2), or heparin (n=3) and then switched to BBPS. Impella run time using a BBPS ranged from 1-14 days; five pumps had a run time with a BBPS \u3e 10 days (Figure 1). Systemic DTI use was used in five cases along with a BBPS. No purge pathway thrombosis or bleeding events were observed, along with no changes in purge flow or purge pressures observed. In conclusion, preliminary experience suggests the use of BBPS in the setting suspected or confirmed HIT patients supported with an Impella is safe and effective and may provide a useful therapeutic option for heparin intolerant patients. Future work should investigate mechanisms and purge reliability of BBPS in this setting

Tubulin tyrosination is a major factor affecting the recruitment of CAP-Gly proteins at microtubule plus ends

Tubulin-tyrosine ligase (TTL), the enzyme that catalyzes the addition of a C-terminal tyrosine residue to α-tubulin in the tubulin tyrosination cycle, is involved in tumor progression and has a vital role in neuronal organization. We show that in mammalian fibroblasts, cytoplasmic linker protein (CLIP) 170 and other microtubule plus-end tracking proteins comprising a cytoskeleton-associated protein glycine-rich (CAP-Gly) microtubule binding domain such as CLIP-115 and p150 Glued, localize to the ends of tyrosinated microtubules but not to the ends of detyrosinated microtubules. In vitro, the head domains of CLIP-170 and of p150 Glued bind more efficiently to tyrosinated microtubules than to detyrosinated polymers. In TTL-null fibroblasts, tubulin detyrosination and CAP-Gly protein mislocalization correlate with defects in both spindle positioning during mitosis and cell morphology during interphase. These results indicate that tubulin tyrosination regulates microtubule interactions with CAP-Gly microtubule plus-end tracking proteins and provide explanations for the involvement of TTL in tumor progression and in neuronal organization

The nature of slow dynamics in a minimal model of frustration-limited domains

We present simulation results for the dynamics of a schematic model based on the frustration-limited domain picture of glass-forming liquids. These results are compared with approximate theoretical predictions analogous to those commonly used for supercooled liquid dynamics. Although model relaxation times increase by several orders of magnitude in a non-Arrhenius manner as a microphase separation transition is approached, the slow relaxation is in many ways dissimilar to that of a liquid. In particular, structural relaxation is nearly exponential in time at each wave vector, indicating that the mode coupling effects dominating liquid relaxation are comparatively weak within this model. Relaxation properties of the model are instead well reproduced by the simplest dynamical extension of a static Hartree approximation. This approach is qualitatively accurate even for temperatures at which the mode coupling approximation predicts loss of ergodicity. These results suggest that the thermodynamically disordered phase of such a minimal model poorly caricatures the slow dynamics of a liquid near its glass transition

Angiotensin Inhibition and Gastrointestinal Bleeding Prevention in Patients with Left Ventricular Assist Devices

Gastrointestinal bleeding remains a common complication in advanced heart failure patients following implantation of continuous-flow left ventricular assist devices. While the cause is likely multifactorial, development of arterial venous malformations in the gastrointestinal mucosa are a key factor. Inhibition of angiotensin II activity has been postulated to disrupt the signaling that promotes angiogenesis in these patients. We aim to review the theoretical basis for angiotensin receptor blockade, which has been proposed and explore the published evidence regarding this therapy and gastrointestinal bleeding in LVAD patients

Cytoskeletal dynamics in growth-cone steering

Interactions between dynamic microtubules and actin filaments are essential to a wide range of cell biological processes including cell division, motility and morphogenesis. In neuronal growth cones, interactions between microtubules and actin filaments in filopodia are necessary for growth cones to make a turn. Growth-cone turning is a fundamental behaviour during axon guidance, as correct navigation of the growth cone through the embryo is required for it to locate an appropriate synaptic partner. Microtubule-actin filament interactions also occur in the transition zone and central domain of the growth cone, where actin arcs exert compressive forces to corral microtubules into the core of the growth cone and thereby facilitate microtubule bundling, a requirement for axon formation. We now have a fairly comprehensive understanding of the dynamic behaviour of the cytoskeleton in growth cones, and the stage is set for discovering the molecular machinery that enables microtubule-actin filament coupling in growth cones, as well as the intracellular signalling pathways that regulate these interactions. Furthermore, recent experiments suggest that microtubule-actin filament interactions might also be important for the formation of dendritic spines from filopodia in mature neurons. Therefore, the mechanisms coupling microtubules to actin filaments in growth-cone turning and dendritic-spine maturation might be conserved