A total closed chest swine model of acute myocardial infarction-related cardiogenic shock: A critical double coronary sub-occlusion approach

The management of acute myocardial infarction-related cardiogenic shock (AMICS) represents a significant challenge, with mortality rates remaining high (40–60%), despite recent advances. Current animal models of myocardial infarction are either associated with a very high rate of per-procedure malignant arrhythmia, or with very low impairment of hemodynamic parameters, or with the inability to have complete coronary reperfusion. We sought to develop a closed chest and clinically relevant large animal model of severe AMICS, with high survival rate. Adult pigs were anaesthetized and mechanically ventilated. Percutaneous cardiac catheterization was performed under fluoroscopy. Advanced left ventricular dysfunction was induced by 120 minutes of critical sub-occlusion of the proximal left anterior descending coronary artery and the mid circumflex artery. A thorough hemodynamic assessment was obtained by invasive and non-invasive monitoring devices. Repeated blood samples were obtained to determine blood gas parameters, lactate, and haemoglobin concentration. After death, the heart was retrieved for further histological analyses. All animals (n = 12) developed significant circulatory failure associated with AMICS upon reperfusion and beyond. No animal died during the ischemia process. However, all animals that did not benefited from vasopressor support (“sham” group, n = 4) spontaneously died within 30 minutes of reperfusion, confirming the severity of the model. Cardiogenic shock was characterized by a drop in mean arterial pressure below 60 mmHg (58 ± 5 mmHg at 120 min of ischemia), a significant decrease in mean cardiac output (−44% from 5.7 ± 0.4 at baseline to 3.2 ± 0.4 at 120 minutes of ischemia) and SvO2 (−32% from 57 ± 8 at baseline to 39 ± 6 at 120 minutes of ischemia) and a significant increase in left ventricle end-diastolic pressure (LVEDP) (+110% from 10 ± 3 at baseline to 21 ± 3 at 120 minutes of ischemia). CO2 gap and coronary sinus venous oxygen saturation increased significantly upon ischemia and reperfusion and remained elevated throughout (P ≤ 0.001 for all comparisons). Myocardial samples corroborated extensive cellular necrosis and inflammatory infiltrates. We present, for the first time, a stable and clinically relevant model of severe AMICS obtained by critical double coronary sub-occlusion. The greater severity of the model did not lead to an increase in the frequency of malignant arrythmias and per-procedure mortality.