An innovative ovine model of severe cardiopulmonary failure supported by veno-arterial extracorporeal membrane oxygenation

Abstract

Refractory cardiogenic shock (CS) often requires veno-arterial extracorporeal membrane oxygenation (VA-ECMO) to sustain end-organ perfusion. Current animal models result in heterogenous cardiac injury and frequent episodes of refractory ventricular fibrillation. Thus, we aimed to develop an innovative, clinically relevant, and titratable model of severe cardiopulmonary failure. Six sheep (60 ± 6 kg) were anaesthetized and mechanically ventilated. VA-ECMO was commenced and CS was induced through intramyocardial injections of ethanol. Then, hypoxemic/hypercapnic pulmonary failure was achieved, through substantial decrease in ventilatory support. Echocardiography was used to compute left ventricular fractional area change (LVFAC) and cardiac Troponin I (cTnI) was quantified. After 5 h, the animals were euthanised and the heart was retrieved for histological evaluations. Ethanol (58 ± 23 mL) successfully induced CS in all animals. cTnI levels increased near 5000-fold. CS was confirmed by a drop in systolic blood pressure to 67 ± 14 mmHg, while lactate increased to 4.7 ± 0.9 mmol/L and LVFAC decreased to 16 ± 7%. Myocardial samples corroborated extensive cellular necrosis and inflammatory infiltrates. In conclusion, we present an innovative ovine model of severe cardiopulmonary failure in animals on VA-ECMO. This model could be essential to further characterize CS and develop future treatments.

Effect of flow change on brain injury during an experimental model of differential hypoxaemia in cardiogenic shock supported by extracorporeal membrane oxygenation

“…This is the first experiment assessing the effect of the V-A ECMO flow consequences on the brain in a context of DH. We used a cardiogenic shock model developed specifically for this study 7 , allowing us to keep native LV output constant-where other CS models (especially acute myocardial infarction models) suffer from a decrease in LV cardiac output over time 34 . We confirmed arterial cannula tip position and mixing zone location for each animal using fluoroscopy which allowed our results to be consistent and robust.…”

“…Instrumentation, cardio-pulmonary failure and ECMO canulation. The experimental set-up used in this study has been published previously 7 and details are available in Supplementary Materials. In summary, animals underwent general anaesthesia using propofol for induction and were placed on mechanical ventilation with the following settings: tidal volume (VT) of 8 mL kg −1 , positive end-expiratory pressure (PEEP) of 5 cmH 2 O, respiratory rate (RR) and inspiratory fraction of oxygen (FiO 2 ) adjusted to maintain an arterial partial pressure of oxygen (PaO 2 ) between 60 and 100 mmHg, and an arterial partial pressure of carbon dioxide (PaCO 2 ) between 35 and 45 mmHg.…”

“…A detailed description of the ECMO equipment and set-up has been previously reported 7 and is detailed in Supplementary Materials. Animals were cannulated using a 19-Fr right jugular venous access and a 15-Fr femoral arterial return cannula, the positions of which were assessed using fluoroscopy to obtain the tip of the access cannula in the inferior vena cava and the return cannula in the abdominal aorta below the renal arteries.…”

Effectiveness and Safety of a Prolonged Hemodynamic Support by the IVAC2L System in Healthy and Cardiogenic Shock Pigs

“…Our invasive open chest model was associated with bleeding and a systemic inflammatory response syndrome that may explain the relative instability of our hemodynamic results over time. Recently, a model of total percutaneous ischemic CS has been described based on an intracoronary ethanol injection titration under the fluoroscopic guidance ( 20 , 21 ). It is possible that this model initially made it possible to visualize a more stable hemodynamic effect over time, by limiting the hypovolemia and vasoplegia secondary to bleeding.…”

A clinically relevant sheep model of orthotopic heart transplantation 24 h after donor brainstem death

“…The concentrations of EDTA plasma interleukin (IL)-6, IL-8, IL-10, and IL-1β were quantified using in-house developed ELISAs according to previously published methods [ 25 ]. Tumour necrosis factor alpha (TNFα; Cat# EBTNF, Invitrogen), big endothelin-1 (BET-1; Cat# BI-20082H, United Bioresearch) and high sensitivity cardiac troponin I (cTnI; Cat# CTNI-9-HSP, Life Diagnostics) levels were determined in plasma using commercial kits as per manufacturer’s instructions [ 14 , 26 ]. Accuracy of all ELISA assays were confirmed using quality control samples, with inter-and intra-plate variability < 10%.…”