The effects of nitric oxide on coagulation and inflammation in ex vivo models of extracorporeal membrane oxygenation and cardiopulmonary bypass.

BACKGROUND: Extracorporeal life support (ECLS) has extensive applications in managing patients with acute cardiac and pulmonary failure. Two primary modalities of ECLS, cardiopulmonary bypass (CPB) and extracorporeal membrane oxygenation (ECMO), include several similarities in their composition, complications, and patient outcomes. Both CPB and ECMO pose a high risk of thrombus formation and platelet activation due to the large surface area of the devices and bleeding due to system anticoagulation. Therefore, novel methods of anticoagulation are needed to reduce the morbidity and mortality associated with extracorporeal support. Nitric oxide (NO) has potent antiplatelet properties and presents a promising alternative or addition to anticoagulation with heparin during extracorporeal support. METHODS: We developed two ex vivo models of CPB and ECMO to investigate NO effects on anticoagulation and inflammation in these systems. RESULTS: Sole addition of NO as an anticoagulant was not successful in preventing thrombus formation in the ex vivo setups, therefore a combination of low-level heparin with NO was used. Antiplatelet effects were observed in the ex vivo ECMO model when NO was delivered at 80 ppm. Platelet count was preserved after 480 min when NO was delivered at 30 ppm. CONCLUSION: Combined delivery of NO and heparin did not improve haemocompatibility in either ex vivo model of CPB and ECMO. Anti-inflammatory effects of NO in ECMO systems have to be evaluated further.

Anti-thrombogenic Surface Coatings for Extracorporeal Membrane Oxygenation: A Narrative Review.

Extracorporeal membrane oxygenation (ECMO) is used in critical care to manage patients with severe respiratory and cardiac failure. ECMO brings blood from a critically ill patient into contact with a non-endothelialized circuit which can cause clotting and bleeding simultaneously in this population. Continuous systemic anticoagulation is needed during ECMO. The membrane oxygenator, which is a critical component of the extracorporeal circuit, is prone to significant thrombus formation due to its large surface area and areas of low, turbulent, and stagnant flow. Various surface coatings, including but not limited to heparin, albumin, poly(ethylene glycol), phosphorylcholine, and poly(2-methoxyethyl acrylate), have been developed to reduce thrombus formation during ECMO. The present work provides an up-to-date overview of anti-thrombogenic surface coatings for ECMO, including both commercial coatings and those under development. The focus is placed on the coatings being developed for oxygenators. Overall, zwitterionic polymer coatings, nitric oxide (NO)-releasing coatings, and lubricant-infused coatings have attracted more attention than other coatings and showed some improvement in in vitro and in vivo anti-thrombogenic effects. However, most studies lacked standard hemocompatibility assessment and comparison studies with current clinically used coatings, either heparin coatings or nonheparin coatings. Moreover, this review identifies that further investigation on the thrombo-resistance, stability and durability of coatings under rated flow conditions and the effects of coatings on the function of oxygenators (pressure drop and gas transfer) are needed. Therefore, extensive further development is required before these new coatings can be used in the clinic.

Five-Year Survival of Transcatheter Aortic Valve Implantation in High-Risk Patients.

BACKGROUND: Although transcatheter aortic valve implantation (TAVI) has become the standard treatment for severe aortic stenosis in high-risk patients in Australia, there is still limited data on long term survival. METHODS: All patients undergoing TAVI at a single tertiary institution between September 2009 and December 2015 were included. The primary outcome was survival, by linkage of patients with the National Death Index of the Australian Institute of Health and Welfare. Post-procedure data and echocardiographic measurements were retrospectively analysed for all patients. RESULTS: A total of 186 patients were included. It was a high-risk patient population (mean EuroSCORE 31.5±20.5, mean age 83.0±8.2 years). Valve prostheses used were Edwards SAPIEN (ES) (Edwards, Irvine, CA, USA) in 16.1%, Edwards SAPIEN XT (ESXT) in 74.2%, and Medtronic CoreValve (MCV) (Medtronic, Minneapolis, MN, USA) in 9.7%. Median survival time for the entire cohort was 68.2 months (95% Confidence Interval [CI]; Lower Limit [LL] 58.0 months, Upper Limit [UL] not defined). The 2- and 5-year estimates of survival were 85% (LL 80%, UL 90%) and 56% (LL 48%, UL 66%), respectively. There was no statistically significant difference in median survival between the ES and ESXT valves, or implantation approach. Survival was greater in patients with creatinine <200 µmol/L compared to >200 µmol/L (68.8 months [LL 61.4, UL n/a] vs 48.0 months [LL 25.5, UL n/a]). Over the study period, there was a statistically significant trend in increasing mean transvalvular gradient (ES: 1.66 mmHg/yr, p=0.0058; ESXT: 2.50 mmHg/yr, p≤0.001) and maximum velocity (ESXT: 0.16 m/s/yr, p=0.004) and decreasing valve area (ESXT: -0.07 cm2/yr, p<0.001). There was substantial attrition of patient echocardiographic follow-up (number of echocardiograms followed up at 5 years=6, number at risk=41). CONCLUSIONS: This study has demonstrated acceptable survival in a high-risk cohort of patients undergoing TAVI, with comparable results to larger international experiences. There was a trend for worsening haemodynamics that needs to be monitored. Future studies need to examine patient quality of life and the performance of newer generation prostheses.

Studying the Endothelial Glycocalyx in vitro: What Is Missing?

All human cells are coated by a surface layer of proteoglycans, glycosaminoglycans (GAGs) and plasma proteins, called the glycocalyx. The glycocalyx transmits shear stress to the cytoskeleton of endothelial cells, maintains a selective permeability barrier, and modulates adhesion of blood leukocytes and platelets. Major components of the glycocalyx, including syndecans, heparan sulfate, and hyaluronan, are shed from the endothelial surface layer during conditions including ischaemia and hypoxia, sepsis, atherosclerosis, diabetes, renal disease, and some viral infections. Studying mechanisms of glycocalyx damage in vivo can be challenging due to the complexity of immuno-inflammatory responses which are inextricably involved. Previously, both static as well as perfused in vitro models have studied the glycocalyx, and have reported either imaging data, assessment of barrier function, or interactions of blood components with the endothelial monolayer. To date, no model has simultaneously incorporated all these features at once, however such a model would arguably enhance the study of vasculopathic processes. This review compiles a series of current in vitro models described in the literature that have targeted the glycocalyx layer, their limitations, and potential opportunities for further developments in this field.

Assessing potential for aortoiliac vascular injury from venoarterial extracorporeal membrane oxygenation cannulae: An in vitro particle image velocimetry study.

Limb ischemia is a major complication associated with peripheral venoarterial extracorporeal membrane oxygenation (VA-ECMO). The high velocity jet from arterial cannulae can cause "sandblasting" injuries to the arterial endothelium, with the potential risk of distal embolization and end organ damage. The aim of this study was to identify, for a range of clinically relevant VA-ECMO cannulae and flow rates, any regions of peak flow velocity on the aortic wall which may predispose to vascular injury, and any regions of low-velocity flow which may predispose to thrombus formation. A silicone model of the aortic and iliac vessels was sourced and the right external iliac artery was cannulated. Cannulae ranged from 15 to 21 Fr in size. Simulated steady state ECMO flow rates were instituted using a magnetically levitated pump (CentriMag pump). Adaptive particle image velocimetry was performed for each cannula at 3, 3.5, 4, and 4.5 L/min. For all cannulae, in both horizontal and vertical side hole orientations, the peak velocity on the aortic wall ranged from 0.3 to 0.45 m/s, and the regions of lowest velocity flow were 0.05 m/s. The magnitude of peak velocity flow on the aortic wall was not different between a single pair versus multiple pairs of side holes. Maximum velocity flow on the aortic wall occurred earlier at a lower pump flow rate in the vertical orientation of distal side holes compared to a horizontal position. The presence of multiple paired side holes was associated with fewer low-velocity flow regions, and some retrograde flow, in the distal abdominal aorta compared to cannulae with a single pair of side holes. From this in vitro visualization study, the selection of a cannula design with multiple versus single pairs of side holes did not change the magnitude of peak velocity flow delivered to the vessel wall. Cannulae with multiple side holes were associated with fewer regions of low-velocity flow in the distal abdominal aorta. Further in vivo studies, and ideally clinical data would be required to assess any correlation of peak velocity flows with incidence of vascular injury, and any low-velocity flow regions with incidence of thrombosis.

When the Conventional Treatment Fails: A Rare Approach to Superior Mesenteric Arterial Embolization.

Retroperitoneal haemorrhage is a rare but potentially life-threatening event. It may occur either spontaneously or secondary to percutaneous vascular access procedures, trauma, or ruptured aortic, iliac, or mesenteric aneurysms. As a result, the clinical presentation is variable. Computed tomography and/or angiography are vital for diagnosis. Management may range from conservative treatment for stable patients to emergency laparotomy or embolization for catastrophic haemorrhage. Direct percutaneous puncture of a deep intra-abdominal pseudoaneurysm is an accepted but infrequently performed technique due to a number of diagnostic and technical challenges. We describe the successful percutaneous transabdominal angioembolization of a superior mesenteric artery rupture in a 77-year-old woman with a large retroperitoneal haematoma. This was performed after a conventional femoral transarterial approach was unsuccessful.