3-DIMENSIONAL CARDIOGENIC SHOCK SIMULATOR PHASE I: SUCCESSFUL DEVELOPMENT OF A LARGE ANIMAL CARDIOGENIC SHOCK MODEL

Abstract

<h3>BACKGROUND</h3> Post-myocardial infarction (Post-MI) cardiogenic shock (CS) is a serious life-threatening condition that requires complex coordinated care. Despite this, early mortality remains as high as 50%, likely owing to still inadequate understanding of pathophysiology and the potential benefits of percutaneous ventricular assist devices (pVADs). Although all pVADs increase circulatory flow, they vary in their ability to help restore cardiac pump function. Additionally, shortcomings in terms of our understanding of the optimal timing of such devices in STEMI and shock algorithms likely contributes to the high mortality. Currently, preclinical pVAD evaluation is limited by the need for animal research where the induction of CS is often lethal before devices can be tested. We therefore plan to develop a high-fidelity simulator to facilitate device evaluation and help train clinical teams. The first phase to this program requires the elaboration of a stable animal post-MI CS model that can generate the physiologic data necessary for simulator validation. <h3>METHODS AND RESULTS</h3> Using 10 anesthetized 65-75kg female pigs, we sought to induce a large anterior infarct by percutaneous balloon occlusion of the left anterior descending artery with a provision for ethanol injection if CS was not observed within 2 hours of balloon occlusion. Continuous physiologic monitoring was ensured in order to record right and left heart and arterial pressures, mixed venous oxygen saturation, cardiac output, and serum lactate levels. Indices of myocardial contractility and relaxation were calculated at regular intervals. At the end of the experiment, Evans Blue was injected into the coronary circulation in order to determine the size of the myocardium at risk. The explanted heart was then stained with TTC mitochondrial stain and fixed with formaldehyde to determine the size of the infarct. A rate of survival of the anterior infarct of ≥50% and a rate of induction of CS in at least 50% of the survivors was considered necessary for the viability of the program. We successfully induced myocardial infarction in all 10 pigs and 5 pigs survived to develop cardiogenic shock. <h3>CONCLUSION</h3> While challenging, we successfully demonstrated that a large animal model of cardiogenic shock is possible and stable enough to generate the physiologic data necessary for the development of a CS simulator. The second phase will consist of the collection of detailed physiological data in a CS state with and without different pVAD support.