Archive | 2021
An innovative ovine model of severe cardiopulmonary failure supported by veno-arterial extracorporeal membrane oxygenation
Abstract
\n Background\n\nRefractory cardiogenic shock (CS), frequently complicated by pulmonary failure, often requires veno-arterial extracorporeal membrane oxygenation (VA-ECMO) to sustain end-organ perfusion. Currently available animal models, such as the coronary ligation model, result in highly variable injury profiles and unacceptably high levels of subsequent ventricular fibrillation, cardiac arrest, and death. As the use of ECMO increases, there is a growing need for a clinically relevant, robust, and titratable model of severe cardiopulmonary failure supported by VA-ECMO.\nMethods\n\nSix sheep (60\u2009±\u20096 kg) were anaesthetized, intubated and mechanically ventilated. VA-ECMO was initially carried out at a flow rate of 1 L/min. CS was induced through 1-mL left ventricle myocardial injections of 96% ethanol and confirmed when systolic blood pressure (SBP) was <\u200990 mmHg and lactate\u2009>\u20094 mmol/L. Then, pulmonary failure was confirmed when PaO2 was <\u200960 mmHg through substantial decrease in the ventilatory support. Thereafter, VA-ECMO support was increased to obtain a mean arterial pressure of 65 mmHg. Echocardiography and cardiac Troponin I (cTnI) analysis were performed at baseline, upon CS confirmation, establishment of pulmonary failure and hourly thereafter. After 5h, the animals were euthanised and the heart collected for histological and macroscopic assessment.\nResults\n\nEthanol (58\u2009±\u200923 mL) rapidly induced CS in all animals. cTnI levels increased near 5000-fold. SBP decreased from 97\u2009±\u200918 mmHg at baseline to 67\u2009±\u200914 mmHg upon CS, and lactate from 1.4\u2009±\u20090.8 to 4.7\u2009±\u20090.9 mmol/L, respectively. Echocardiography studies demonstrated a decrease in the left ventricular fractional area change from 34\u2009±\u20099% upon baseline to 16\u2009±\u20097% after CS. Analysis of myocardial tissue samples corroborated extensive cellular necrosis and inflammatory infiltrates.\nConclusions\n\nWe present a novel titratable model of severe cardiopulmonary failure in animal on VA-ECMO, through intramyocardial ethanol injections and reduction in ventilatory support. This model could be essential to further characterize left-sided heart failure and develop future treatments.