Evaluation of flow-modulation approaches in ventricular assist devices using an in-vitro endothelial cell culture model

Haglund, Thomas A.; Rajasekaran, Namakkal S.; Smood, Benjamin; Giridharan, Guruprasad A.; Hoopes, Charles W.; Holman, William L.; Mauchley, David C.; Prabhu, Sumanth D.; Pamboukian, Salpy V.; Tallaj, José; Rajapreyar, Indranee; Kirklin, James K.; Sethu, Palaniappan

doi:10.1016/j.healun.2018.10.007

Cited by 17 publications

(22 citation statements)

References 49 publications

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“…Partial LVAD support devices did not reduce the incidence of GIB despite sufficient preservation of arterial pulsatility. On the contrary, reduced arterial pulsatility (for example due to incremental LVAD speed) increased the level of angiopoietin‐2 in other studies, which might result in the occurrence of GIB.…”

Section: Discussionmentioning

confidence: 70%

Omega‐3 and hemocompatibility‐related adverse events

et al. 2019

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Background: Hemocompatibility-related clinical adverse events (HRAEs) are major causes of readmission in patients with left ventricular assist devices (LVADs). Omega-3 is an unsaturated fatty acid that possesses anti-inflammatory and antiangiogenic properties. We aimed to investigate the impact of omega-3 therapy on HRAEs during LVAD support.Methods: Consecutive LVAD patients who were followed for 6 months were enrolled, and stratified by the use of omega-3. Freedom from any HRAEs and net burden of HRAEs, which was calculated by using a hemocompatibility score (using 4 escalating tiers of hierarchal severity to derive a total score for events), were compared between those with and without omega-3 therapy.Results: Among 169 LVAD patients (57 years old and 124 males), 31 patients received 4 g/d of omega-3 therapy and 138 patients were in the control group. During the 6-month observational period, freedom from any HRAEs was 90% in the omega-3 group compared with 70% in the control group with a hazard ratio of 0.35 (95% confidence interval 0.11-0.87 and P = .042). The average hemocompatibility score in the omega-3 group was significantly lower compared with the control group (0.23 vs 0.91; P = .042), due to reduced Tier I scores (mild HRAE; P = .003) andTier IIIB scores (severe HRAE; P < .001). The similar trends remained at propensitymatched populations.Conclusions: Omega-3 therapy was associated with reduced HRAEs including both bleeding and thromboembolic events in LVAD patients.

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Section: Discussionmentioning

confidence: 70%

Omega‐3 and hemocompatibility‐related adverse events

et al. 2019

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“…By incorporating the compliance element, pulse pressure was reduced to about 7 mmHg (peak systolic/diastolic pressures of 99/92 mmHg), while stretch and mean flow rate matched that of the pulsatile model. In 2019, Haglund and others from our group also demonstrated that synchronous and asynchronous flow profiles similar to those of popular CF-VAD models could be replicated, with the synchronous flow requiring some alteration of the compliance element, and the asynchronous flow necessitating the addition of a second pulsatile pump [84]. In a recently accepted but not yet published study of ours, physiologic arterial flow parameters of 120/80 mmHg pressure, 6-10% EC strain, 15 dynes/cm 2 average shear stress, and 10-12 mL/min flow rate at 60-80 beats/min was achieved [85].…”

Section: Examples Of Vascular Tissue Chipsmentioning

confidence: 76%

“…Disturbed flow, similar to the infrarenal segment of an atherosclerotic abdominal aorta, was generated in this model by removing the one-way valve (thus allowing retrograde flow) and lowering the flow rate to mimic the flow velocity and shear stress experienced by the aortic ECs in vivo. In addition to modeling disturbed flow profiles, our lab group has used the ECCM in two studies to compare the effects of arterial physiologic pulsatile fluid flow on arterial ECs to those of continuous flow, as seen in patients with a continuous-flow ventricular assist device (CF-VAD) (Figure 3b) [83,84]. We replicated physiologic arterial flow in vitro by tuning the pump settings and resistance and bypassing the compliance element, generating peak systolic/diastolic pressures of approximately 120/80 mmHg, 6-8% stretch, and a 9 mL/min flow rate at a pump frequency of 80 beats/min.…”

Section: Examples Of Vascular Tissue Chipsmentioning

confidence: 99%

Tissue Chips and Microphysiological Systems for Disease Modeling and Drug Testing

et al. 2021

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Tissue chips (TCs) and microphysiological systems (MPSs) that incorporate human cells are novel platforms to model disease and screen drugs and provide an alternative to traditional animal studies. This review highlights the basic definitions of TCs and MPSs, examines four major organs/tissues, identifies critical parameters for organization and function (tissue organization, blood flow, and physical stresses), reviews current microfluidic approaches to recreate tissues, and discusses current shortcomings and future directions for the development and application of these technologies. The organs emphasized are those involved in the metabolism or excretion of drugs (hepatic and renal systems) and organs sensitive to drug toxicity (cardiovascular system). This article examines the microfluidic/microfabrication approaches for each organ individually and identifies specific examples of TCs. This review will provide an excellent starting point for understanding, designing, and constructing novel TCs for possible integration within MPS.

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“…This group also showed that the pulsatility created by modulating the speed of CF pumps can potentially minimize those effects. 39 This vascular remodeling might be partially responsible for the postsuegical bleeding observed with CF support. Weber et al 40 showed that the reduced pulsatility index in patients supported with a CF LVAD was associated with an increased risk of nonsurgical bleeding.…”

Section: Continuous-flow Supportmentioning

confidence: 99%

“…These results suggest that chronic exposure to reduced pulsatility may lead to endothelial cell dysfunction and vascular clinical complications. This group also showed that the pulsatility created by modulating the speed of CF pumps can potentially minimize those effects …”

Section: Chronic Effects Of Continuous‐flow Supportmentioning

confidence: 99%