An experimental model of veno-venous arterial extracorporeal membrane oxygenation

Introduction: Veno-venous arterial extracorporeal membrane oxygenation is a hybrid-modality of extracorporeal membrane oxygenation combining veno-venous and veno-arterial extracorporeal membrane oxygenation. It may be applied to patients with both respiratory and cardio-circulatory failure. Aim: To describe a computational spreadsheet regarding an ex vivo experimental model of veno-venous arterial extracorporeal membrane oxygenation to determine the return of cannula pairs in a single pump–driven circuit. Methods: We developed an ex vivo model of veno-venous arterial extracorporeal membrane oxygenation with a single pump and two outflow cannulas, and a glucose solution was used to mimic the features of blood. We maintained a fixed aortic impedance and physiological pulmonary resistance. Both flow and pressure data were collected while testing different pairs of outflow cannulas. Six simulations of different cannula pairs were performed, and data were analysed by a custom-made spreadsheet, which was able to predict the flow partition at different flow levels. Results: In all simulations, the flow in the arterial cannula gradually increased differently depending on the cannula pair. The best cannula pair was a 19-Fr/18-cm arterial with a 17-Fr/50-cm venous cannula, where we observed an equal flow split and acceptable flow into the arterial cannula at a lower flow rate of 4 L/min. Conclusion: Our computational spreadsheet identifies the suitable cannula pairing set for correctly splitting the outlet blood flow into the arterial and venous return cannulas in a veno-venous arterial extracorporeal membrane oxygenation configuration without the use of external throttles. Several limitations were reported regarding fixed aortic impedance, central venous pressure and the types of cannulas tested; therefore, further studies are mandatory to confirm our findings

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Effect of ex vivo extracorporeal membrane oxygenation flow dynamics on immune response

Perfusion ◽

10.1177/0267659119830012 ◽

2019 ◽

Vol 34 (1_suppl) ◽

pp. 5-14 ◽

Cited By ~ 4

Author(s):

Katrina K Ki ◽

Margaret R Passmore ◽

Chris Hoi Houng Chan ◽

Maximillian V Malfertheiner ◽

Mahe Bouquet ◽

...

Keyword(s):

Inflammatory Response ◽

Extracorporeal Membrane Oxygenation ◽

Ex Vivo ◽

Antigen Expression ◽

High Flow ◽

Flow Dynamics ◽

Low Flow ◽

Technological Advancement ◽

Ex Vivo Model ◽

Membrane Oxygenation

Background: Extracorporeal membrane oxygenation is a life-saving support for heart and/or lung failure patients. Despite technological advancement, abnormal physiology persists and has been associated with subsequent adverse events. These include thrombosis, bleeding, systemic inflammatory response syndrome and infection. However, the underlying mechanisms are yet to be elucidated. We aimed to investigate whether the different flow dynamics of extracorporeal membrane oxygenation would alter immune responses, specifically the overall inflammatory response, leukocyte numbers and activation/adhesion surface antigen expression. Methods: An ex vivo model was used with human whole blood circulating at 37°C for 6 hours at high (4 L/minute) or low (1.5 L/minute) flow dynamics, with serial blood samples taken for analysis. Results: During high flow, production of interleukin-1β (p < 0.0001), interleukin-6 (p = 0.0075), tumour necrosis factor-α (p = 0.0013), myeloperoxidase (p < 0.0001) and neutrophil elastase (p < 0.0001) were significantly elevated over time compared to low flow, in particular at 6 hours. While the remaining assessments exhibited minute changes between flow dynamics, a consistent trend of modulation in leukocyte subset numbers and phenotype was observed at 6 hours. Conclusion: We conclude that prolonged circulation at high flow triggers a prominent pro-inflammatory cytokine response and activates neutrophil granule release, but further research is needed to better characterize the effect of flow during extracorporeal membrane oxygenation.

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Macro- and micronutrient disposition in an ex vivo model of extracorporeal membrane oxygenation

Intensive Care Medicine Experimental ◽

10.1186/s40635-014-0029-7 ◽

2014 ◽

Vol 2 (1) ◽

Cited By ~ 7

Author(s):

Kristine Estensen ◽

Kiran Shekar ◽

Elissa Robins ◽

Charles McDonald ◽

Adrian G Barnett ◽

...

Keyword(s):

Extracorporeal Membrane Oxygenation ◽

Ex Vivo ◽

Ex Vivo Model ◽

Membrane Oxygenation

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Ex Vivo Model to Decipher the Impact of Extracorporeal Membrane Oxygenation on Beta-lactam Degradation Kinetics

Therapeutic Drug Monitoring ◽

10.1097/ftd.0000000000000369 ◽

2017 ◽

Vol 39 (2) ◽

pp. 180-184 ◽

Cited By ~ 12

Author(s):

Cyril Leven ◽

Pierre Fillâtre ◽

Antoine Petitcollin ◽

Marie-Clémence Verdier ◽

Jérôme Laurent ◽

...

Keyword(s):

Extracorporeal Membrane Oxygenation ◽

Ex Vivo ◽

Degradation Kinetics ◽

Beta Lactam ◽

Ex Vivo Model ◽

Membrane Oxygenation ◽

The Impact

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Isolated superfused rats atrial model for the investigation of atrial fibrillation mechanisms and treatment

European Heart Journal ◽

10.1093/eurheartj/ehab724.3321 ◽

2021 ◽

Vol 42 (Supplement_1) ◽

Author(s):

S Glatstein ◽

M Ghiringhelli ◽

L Maizels ◽

E Heller ◽

E Maor ◽

...

Keyword(s):

Atrial Fibrillation ◽

High Resolution ◽

Sinus Rhythm ◽

Optical Mapping ◽

Ex Vivo ◽

Anatomical Landmarks ◽

Ex Vivo Model ◽

Electrophysiological Properties ◽

Custom Made ◽

Isolated Atria

Abstract Background One of the major barriers to an improved mechanistic understanding of atrial fibrillation (AF), and thus in the pipeline of drug development, has been a lack of appropriate tissue models, especially in small animals. Aim We propose an advanced anatomical ex-vivo model based on rat atria for acute assessment of AF susceptibility. This novel model could yield a better understanding of arrhythmia mechanisms as well as the development of potential therapeutic strategies for the prevention or termination of atrial arrhythmias. Methods Wistar rats atria (N=25) were isolated, flattened and pinned to a custom-made silicon plate. Atria were superfused with an oxygenized Tyrode's solution. Tissues were then loaded with a voltage-sensitive dye and mapped using a high-resolution optical mapping system. AF was induced with 1uM carbamylcholine (N=23) coupled with pacing maneuvers and treated with 30uM Vernakalant (N=10) or 10uM Flecainide (N=10). Finally, the feasibility of a new ablation technique (electroporation) was evaluated. Results Optical mapping results suggested that the superfusion procedure led to a fast atrial recovery. Sinus activity was conserved for all atria for a long period. All the anatomical landmarks were clearly visualized. The acquired optical signals were analyzed during sinus rhythm and pacing, which allowed the creation of detailed activation maps and measurements of action potential duration (APD) and conduction velocity (CV) at different pacing rates. The resulting APD restitution curves revealed electrical excitation at high pacing rates (cycle length between 50ms and 300ms) with a relatively flattened curve. AF was successfully induced and optically mapping confirmed the presence of reentrant activity. AF was successfully treated using Vernacalant and Flecainide. Finally, we demonstrated the feasibility of a new ablation approach (electroporation) for creation of a continuous linear lesion serving as a functional block. Conclusion The isolated superfused atria model, coupled with voltage-sensitive dyes, can be utilized for long-term high-resolution functional imaging of the atria during sinus rhythm, pacing and arrhythmogenic activity. This allows the study of the atrial electrophysiological properties, the mechanisms involved in AF initiation, perpetuation, and termination as well as the study of drug and new ablation modalities. FUNDunding Acknowledgement Type of funding sources: Public grant(s) – EU funding. Main funding source(s): European Research Council (ERC) Spontaneous activation of isolated atria

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Effects of an Ex Vivo Pediatric Extracorporeal Membrane Oxygenation Circuit on the Sequestration of Mycophenolate Mofetil, Tacrolimus, Hydromorphone, and Fentanyl

The Journal of Pediatric Pharmacology and Therapeutics ◽

10.5863/1551-6776-24.4.290 ◽

2019 ◽

Vol 24 (4) ◽

pp. 290-295

Author(s):

Catherine S. Heith ◽

Lizbeth A. Hansen ◽

Rhonda M. Bakken ◽

Sharon L. Ritter ◽

Breeanna R. Long ◽

...

Keyword(s):

Mycophenolate Mofetil ◽

Extracorporeal Membrane Oxygenation ◽

Mycophenolic Acid ◽

Pediatric Patients ◽

Ex Vivo ◽

Centrifugal Pumps ◽

Ecmo Circuit ◽

Binding Characteristics ◽

Membrane Oxygenation ◽

Set Up

OBJECTIVES With the expanding use of extracorporeal membrane oxygenation (ECMO), understanding drug pharmacokinetics has become increasingly important, particularly in pediatric patients. This ex vivo study examines the effect of a pediatric Quadrox-iD ECMO circuit on the sequestration and binding of mycophenolate mofetil (MMF), tacrolimus, and hydromorphone hydrochloride, which have not been extensively studied to date in pediatric ECMO circuits. Fentanyl, which has been well studied, was used as a comparator. METHODS ECMO circuits were set up using Quadrox-iD pediatric oxygenators and centrifugal pumps. The circuit was primed with whole blood and a reservoir was attached to represent a 5-kg patient. Fourteen French venous and 12 French arterial ECMO cannulas were inserted into the sealed reservoir. Temperature, pH, PO2, and PCO2 were monitored and corrected. MMF, tacrolimus, hydromorphone, and fentanyl were injected into the ECMO circuit. Serial blood samples were taken from a postoxygenator site at intervals over 12 hours, and levels were measured. RESULTS Hydromorphone hydrochloride was not as significantly sequestered by the ex vivo pediatric ECMO circuit when compared with fentanyl. Both mycophenolic acid and tacrolimus serum concentrations were stable in the circuit over 12 hours. CONCLUSIONS Hydromorphone may represent a useful medication for pain control for pediatric patients on ECMO due to its minimal sequestration. Mycophenolic acid and tacrolimus also did not show significant sequestration in the circuit, which was unexpected given their lipophilicity and protein-binding characteristics, but may provide insight into unexplored pharmacokinetics of particular medications in ECMO circuits.

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Impact of arterial and venous cannula diameter in venoarterial extracorporeal membrane oxygenation (VA-ECMO)

Resuscitation ◽

10.1016/j.resuscitation.2018.07.053 ◽

2018 ◽

Vol 130 ◽

pp. e32

Author(s):

Alex Supady ◽

Tobias Wengenmayer ◽

Florentine Schroth ◽

Daniel Duerschmied ◽

Christoph Benk ◽

...

Keyword(s):

Extracorporeal Membrane Oxygenation ◽

Membrane Oxygenation ◽

Venoarterial Extracorporeal Membrane Oxygenation ◽

Venous Cannula ◽

Va Ecmo

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A simulation study of left ventricular decompression using a double lumen arterial cannula prototype during a veno-arterial extracorporeal membrane oxygenation

The International Journal of Artificial Organs ◽

10.1177/0391398819858084 ◽

2019 ◽

Vol 42 (12) ◽

pp. 748-756

Author(s):

Filip Ježek ◽

Svitlana Strunina ◽

Brian E Carlson ◽

Jiří Hozman

Keyword(s):

Extracorporeal Membrane Oxygenation ◽

Cardiogenic Shock ◽

Cardiovascular System ◽

Diastolic Pressure ◽

Systolic Pressure ◽

Left Ventricular ◽

Ventricular Contractility ◽

Double Lumen ◽

Membrane Oxygenation ◽

Arterial Cannula

Background: Veno-arterial extracorporeal membrane oxygenation can be vital to support patients in severe or rapidly progressing cardiogenic shock. In cases of left ventricular distension, left ventricular decompression during veno-arterial extracorporeal membrane oxygenation may be a crucial factor influencing the patient outcome. Application of a double lumen arterial cannula for a left ventricular unloading is an alternative, straightforward method for left ventricular decompression during extracorporeal membrane oxygenation in a veno-arterial configuration. Objectives: The purpose of this article is to use a mathematical model of the human adult cardiovascular system to analyze the left ventricular function of a patient in cardiogenic shock supported by veno-arterial extracorporeal membrane oxygenation with and without the application of left ventricular unloading using a novel double lumen arterial cannula. Methods: A lumped model of cardiovascular system hydraulics has been coupled with models of non-pulsatile veno-arterial extracorporeal membrane oxygenation, a standard venous cannula, and a drainage lumen of a double lumen arterial cannula. Cardiogenic shock has been induced by decreasing left ventricular contractility to 10% of baseline normal value. Results: The simulation results indicate that applying double lumen arterial cannula during veno-arterial extracorporeal membrane oxygenation is associated with reduction of left ventricular end-systolic volume, end-diastolic volume, end-systolic pressure, and end-diastolic pressure. Conclusions: A double lumen arterial cannula is a viable alternative less invasive method for left ventricular decompression during veno-arterial extracorporeal membrane oxygenation. However, to allow for satisfactory extracorporeal membrane oxygenation flow, the cannula design has to be revisited.

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