Development of a reproducible large-animal model of cardiogenic shock mimicking human pathophysiology

Cardiogenic shock (CS) remains a clinical condition with exceptionally high morbidity and mortality. The critical status of affected patients and associated ethical constraints limit the feasibility of randomised clinical trials. Consequently, translational large-animal models are essential to deepen our understanding of CS pathophysiology and to evaluate potential therapeutic strategies. However, establishing a rapid-onset yet hemodynamically stable animal model of CS that ensures short-term survival remains a major experimental challenge.

To develop and validate a reproducible porcine model of CS induced by sequential acute myocardial infarctions, allowing for comprehensive haemodynamic and metabolic characterization.

Female Large White pigs (60–70 kg) were included. Under general anaesthesia, mechanical ventilation and invasive monitoring, a balloon occlusion of the mid-left anterior descending artery (distal to the first diagonal branch) was performed during 100 minutes. After 20 minutes of reperfusion, the proximal circumflex artery was occluded with a coronary balloon during additional 100 minutes. Continuous monitoring included systemic and pulmonary pressures, cardiac output (CO), and arterial and mixed venous blood gases. Norepinephrine was administered as needed to maintain a mean arterial pressure >50 mmHg, and amiodarone was used to prevent refractory arrhythmias. CS was defined as mixed venous oxygen saturation (SvO₂) <30 %, or a ≥50 % decrease from baseline SvO₂, and/or cardiac index < 1.5 L/min/m² sustained for ≥ 10 minutes. The experimental workflow and CS criteria are summarized in Figure 1. The study was approved by the relevant Animal Experimentation Ethics Committee (PROEX 051.3/25).

Of the fourteen animals included (mean weight 66.6±6.5 kg), ten (71%) fulfilled the predefined criteria for CS. One animal showed baseline haemodynamic impairment prior to coronary occlusion and was thus excluded, and three died from refractory ventricular arrhythmias. In the animals that developed CS, all haemodynamic and metabolic parameters worsened significantly from baseline to the time of shock diagnosis (Figure 2), including a mean 39% decrease in mean arterial pressure, a 44% reduction in cardiac index, and a 24-point drop in mixed venous oxygen saturation (p < 0.001 for all). Lactate levels increased by an average of 3.2±2.0-fold (range 1.5–7.3) from individual minimum to the peak values. In parallel, biochemical markers of liver, renal, and myocardial injury increased significantly.

This sequential two-territory infarction model reliably reproduces the haemodynamic, metabolic, and clinical features of CS. It offers a robust and clinically relevant translational platform for investigating pathophysiological mechanisms and evaluating novel therapeutic strategies in CS.

Experimental workflow