Nitric Oxide Releasing Extracorporeal Circuits: Assessment of NO Hyperacute Toxicity in an Ovine Model. – UROP Spring Symposium 2023

Nitric Oxide Releasing Extracorporeal Circuits: Assessment of NO Hyperacute Toxicity in an Ovine Model.

Rachel Toma

Rachel Toma photo

Pronouns: She/Her

Research Mentor(s): Alvaro Rojas-Peña
Research Mentor School/College/Department: Department of Surgery-Transplantation / Medicine
Program: UROP
Session: Session 1 (9:00am – 9:50am)
Authors: Rachel Toma, Jensyn VanZalen, Jamie Ho, Megan Stein, Gergely Lautner, Orsoyla Lautner-Csorba, Robert H. Bartlett , Alvaro Rojas-Pena

Abstract

Extracorporeal membrane oxygenation (ECMO) successfully supports severely ill patients during cardiac or pulmonary failure. Due to blood/artificial surface interaction, ECMO circuits will clot. Therefore, systemic anticoagulation is required, despite the potential risk of fatal bleeding. Local nitric oxide (NO) is a way to prevent thrombosis while avoiding severe bleeding. This study investigates the potential hyperacute cardiovascular toxicity of NO in an ovine model of ECMO. Methods: Eight sheep (40-50 kg) were anesthetized and instrumented for ECMO vascular access via the right internal jugular vein (drainage) and the right femoral vein (reinfusion). An arterial line was placed for hemodynamic monitoring. Four groups (n=2) with different ECMO circuits without systemic anticoagulation were studied: 1) Naïve uncoated circuit; 2) Carbosil coated circuit; 3) NO-releasing circuit+100ppm NO sweep; and 4) NO-releasing circuit+200ppm NO sweep. All animals remained under anesthesia until completion of the study (24hr) or circuit clotting. Data collected included: heart rate (HR), mean arterial pressure (MAP), fraction of inspired oxygen (FiO2), cardiac output (CO), P/F Ratio, and systemic vascular resistance (SVR). Methemoglobin (MetHb) levels to assess NO toxicity (>5%) with or without clinical signs. Results: During the first 4hr of ECMO support there is no depression in hemodynamics due to NO toxicity. Heart rate (HR) remained in normal values for all groups with a range of 90-213 bpm. Additionally, an absence of hemodynamic depression can be observed in MAP and SVR as no difference was observed between control groups (1 and 2) and NO groups (3 and 4) at 4hrs. There is also no difference between the groups for CO, and PF ratio data. MetHb, remained in the 1-1.8 g/dL range throughout the study. FiO2 was consistent throughout the groups (average 0.58), except in one animal in group 3 (0.24) due to anesthesia management. Conclusion: NO-releasing ECMO circuits appear to be a safe alternative to systemic anticoagulants when 100 and 200 ppm NO are used. Future directions include further investigation into the effect of NO at different concentrations to demonstrate the safety of this anticoagulation strategy.

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