Combination of polycarboxybetaine coating and factor XII inhibitor reduces clot formation while preserving normal tissue coagulation during extracorporeal life support.

Blood contact with high surface area medical devices, such as dialysis and extracorporeal life support (ECLS), induces rapid surface coagulation. Systemic anticoagulation, such as heparin, is thus necessary to slow clot formation, but some patients suffer from bleeding complications. Both problems might be reduced by 1) replacing heparin anticoagulation with artificial surface inhibition of the protein adsorption that initiates coagulation and 2) selective inhibition of the intrinsic branch of the coagulation cascade. This approach was evaluated by comparing clot formation and bleeding times during short-term ECLS using zwitterionic polycarboxybetaine (PCB) surface coatings combined with either a potent, selective, bicyclic peptide inhibitor of activated Factor XII (FXII900) or standard heparin anticoagulation. Rabbits underwent venovenous ECLS with small sham oxygenators for 60 min using three means of anticoagulation (n = 4 ea): (1) PCB coating + FXII900 infusion, (2) PCB coating + heparin infusion with an activated clotting time of 220-300s, and (3) heparin infusion alone. Sham oxygenator blood clot weights in the PCB + FXII900 and PCB + heparin groups were 4% and 25% of that in the heparin group (p < 10-6 and p < 10-5), respectively. At the same time, the bleeding time remained normal in the PCB + FXII900 group (2.4 ± 0.2 min) but increased to 4.8 ± 0.5 and 5.1 ± 0.7 min in the PCB + heparin and heparin alone groups (p < 10-4 and 0.01). Sham oxygenator blood flow resistance was significantly lower in the PCB + FXII900 and PCB + heparin groups than in the heparin only group (p < 10-6 and 10-5). These results were confirmed by gross and scanning electron microscopy (SEM) images and fibrinopeptide A (FPA) concentrations. Thus, the combined use of PCB coating and FXII900 markedly reduced sham oxygenator coagulation and tissue bleeding times versus the clinical standard of heparin anticoagulation and is a promising anticoagulation method for clinical ECLS.

Flexions of the Popliteal Artery and the Culture Could Challenge the Outcomes of the Endovascular Procedures.

Recently a hinge point or the maximum bending stress point of the popliteal artery was identified when the knee bends using a lateral view dynamic angiography and a correlation between the lateral view angiography with the extended limb angiography to predict the potential location of the hinge point was defined. A hinge point has been correlated to stent fracture. These findings allowed us to develop a dynamic classification of the popliteal artery. The dynamic classification is useful for endovascular procedures in the popliteal artery. Cultural aspects of our patient population must be considered previous to the endovascular treatment of the popliteal artery, especially to the Japanese culture, which is commonly observed sitting posture such as "seiza ()."

A Dual-Lumen Bicaval Cannula for Venovenous Extracorporeal Membrane Oxygenation.

BACKGROUND: Single-site, dual-lumen venovenous extracorporeal membrane oxygenation ECMO) facilitates mobilization, reduces recirculation, and mitigates insertion and infectious risks of an additional access site. This study reports the experience with a bicaval dual-lumen cannula that comprises a robust physical design allowing for easy and safe cannulation, precise positioning and monitoring, and appropriate physiologic support for patients with acute respiratory failure. METHODS: Statistical analysis was performed from data gathered retrospectively from the electronic medical records of 20 adult patients who were cannulated for ECMO with this bicaval dual-lumen cannula from August 2018 through May 2019. RESULTS: Gas exchange and blood flow were optimized in all patients after cannulation (median pH, 7.42 [interquartile range {IQR}, 7.39, 7.44], ratio of arterial partial pressure of oxygen to fraction of inspired oxygen, 186.5 [Pao2:Fio2, 116.5, 247.0]; pump flow, 3.9 L/min [IQR, 3.1, 4.3]). Eleven patients (55%) were able to be freed from mechanical ventilation after cannulation, 9 (45%) patients underwent a tracheostomy procedure while undergoing ECMO, and no patients required reintubation. No morbidity or mortality was related to the cannulation strategy or the catheter. Two patients required cannula repositioning. Survival to decannulation was 90%, and survival to hospital discharge was 80%. CONCLUSIONS: The bicaval dual-lumen cannula maintains the advantages of upper body single-site configuration to provide the adjunctive respiratory support necessary to facilitate awakening and rehabilitation while minimizing the use of invasive mechanical ventilation. This cannula introduces design qualities that may offer advantages for acute respiratory failure requiring venovenous ECMO.

Zwitterionic poly-carboxybetaine coating reduces artificial lung thrombosis in sheep and rabbits.

Current artificial lungs fail in 1-4 weeks due to surface-induced thrombosis. Biomaterial coatings may be applied to anticoagulate artificial surfaces, but none have shown marked long-term effectiveness. Poly-carboxybetaine (pCB) coatings have shown promising results in reducing protein and platelet-fouling in vitro. However, in vivo hemocompatibility remains to be investigated. Thus, three different pCB-grafting approaches to artificial lung surfaces were first investigated: 1) graft-to approach using 3,4-dihydroxyphenylalanine (DOPA) conjugated with pCB (DOPA-pCB); 2) graft-from approach using the Activators ReGenerated by Electron Transfer method of atom transfer radical polymerization (ARGET-ATRP); and 3) graft-to approach using pCB randomly copolymerized with hydrophobic moieties. One device coated with each of these methods and one uncoated device were attached in parallel within a veno-venous sheep extracorporeal circuit with no continuous anticoagulation (N = 5 circuits). The DOPA-pCB approach showed the least increase in blood flow resistance and the lowest incidence of device failure over 36-hours. Next, we further investigated the impact of tip-to-tip DOPA-pCB coating in a 4-hour rabbit study with veno-venous micro-artificial lung circuit at a higher activated clotting time of 220-300 s (N ≥ 5). Here, DOPA-pCB reduced fibrin formation (p = 0.06) and gross thrombus formation by 59% (p < 0.05). Therefore, DOPA-pCB is a promising material for improving the anticoagulation of artificial lungs. STATEMENT OF SIGNIFICANCE: Chronic lung diseases lead to 168,000 deaths each year in America, but only 2300 lung transplantations happen each year. Hollow fiber membrane oxygenators are clinically used as artificial lungs to provide respiratory support for patients, but their long-term viability is hindered by surface-induced clot formation that leads to premature device failure. Among different coatings investigated for blood-contacting applications, poly-carboxybetaine (pCB) coatings have shown remarkable reduction in protein adsorption in vitro. However, their efficacy in vivo remains unclear. This is the first work that investigates various pCB-coating methods on artificial lung surfaces and their biocompatibility in sheep and rabbit studies. This work highlights the promise of applying pCB coatings on artificial lungs to extend its durability and enable long-term respiratory support for lung disease patients.

72-Hour in vivo evaluation of nitric oxide generating artificial lung gas exchange fibers in sheep.

The large, densely packed artificial surface area of artificial lungs results in rapid clotting and device failure. Surface generated nitric oxide (NO) can be used to reduce platelet activation and coagulation on gas exchange fibers, while not inducing patient bleeding due to its short half-life in blood. To generate NO, artificial lungs can be manufactured with PDMS hollow fibers embedded with copper nanoparticles (Cu NP) and supplied with an infusion of the NO donor S-nitroso-N-acetyl-penicillamine (SNAP). The SNAP reacts with Cu NP to generate NO. This study investigates clot formation and gas exchange performance of artificial lungs with either NO-generating Cu-PDMS or standard polymethylpentene (PMP) fibers. One miniature artificial lung (MAL) made with 10 wt% Cu-PDMS hollow fibers and one PMP control MAL were attached to sheep in parallel in a veno-venous extracorporeal membrane oxygenation circuit (n = 8). Blood flow through each device was set at 300 mL/min, and each device received a SNAP infusion of 0.12 µmol/min. The ACT was between 110 and 180 s in all cases. Blood flow resistance was calculated as a measure of clot formation on the fiber bundle. Gas exchange experiments comparing the two groups were conducted every 24 h at blood flow rates of 300 and 600 mL/min. Devices were removed once the resistance reached 3x baseline (failure) or following 72 h. All devices were imaged using scanning electron microscopy (SEM) at the inlet, outlet, and middle of the fiber bundle. The Cu-PDMS NO generating MALs had a significantly smaller increase in resistance compared to the control devices. Resistance rose from 26 ±â€¯8 and 23 ±â€¯5 in the control and Cu-PDMS devices, respectively, to 35 ±â€¯8 mmHg/(mL/min) and 72 ±â€¯23 mmHg/(mL/min) at the end of each experiment. The resistance and SEM imaging of fiber surfaces demonstrate lower clot formation on Cu-PDMS fibers. Although not statistically significant, oxygen transfer for the Cu-PDMS MALs was 13.3% less than the control at 600 mL/min blood flow rate. Future in vivo studies with larger Cu-PDMS devices are needed to define gas exchange capabilities and anticoagulant activity over a long-term study at clinically relevant ACTs. STATEMENT OF SIGNIFICANCE: In artificial lungs, the large, densely-packed blood contacting surface area of the hollow fiber bundle is critical for gas exchange but also creates rapid, surface-generated clot requiring significant anticoagulation. Monitoring of anticoagulation, thrombosis, and resultant complications has kept permanent respiratory support from becoming a clinical reality. In this study, we use a hollow fiber material that generates nitric oxide (NO) to prevent platelet activation at the blood contacting surface. This material is tested in vivo in a miniature artificial lung and compared against the clinical standard. Results indicated significantly reduced clot formation. Surface-focused anticoagulation like this should reduce complication rates and allow for permanent respiratory support by extending the functional lifespan of artificial lungs and can further be applied to other medical devices.