Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is a commonly used in refractory cardiogenic shock (CS) but may exacerbate left ventricular (LV) loading conditions and impair cardiac energetics. Adjunctive LV unloading strategies are frequently combined with VA-ECMO to counteract these effects and potentially enhance myocardial recovery through activation of cardioprotective pathways. We hypothesized that adding an intra-aortic balloon pump (IABP) or Impella to VA-ECMO would alleviate LV overload, improve cardiac energetics, and modulate RISK/SAFE pathways.

Severe CS was induced in sheep through coronary artery alcoholization. Animals were then randomly assigned to VA-ECMO alone, VA-ECMO with IABP, or VA-ECMO with Impella. ECMO blood flow was progressively increased from 25% to 100% of the baseline cardiac output (CO).

Twenty-four animals were analyzed. CS was characterized by a 37% ± 2% decrease in CO, 52% ± 10% increase in LV end-diastolic pressure (LVEDP), and lactate rising from 1.6 ± 0.1 to 3.8 ± 0.3 mmol/L (p < 0.0001 for all). Both unloading strategies reduced LVEDP compared to VA-ECMO alone (−51% ± 6% with IABP, −58% ± 6% with Impella; p < 0.001), while only Impella reduced LV volumes and improved cardiac energetics. Phosphorylation of extracellular signal–regulated kinase and Akt in LV myocardium from the peri-infarcted area was significantly higher in both combined strategy groups. However, infarct size and apoptotic signaling did not differ between the groups.

Adding LV active unloading to VA-ECMO reduces LV overload, improves cardiac energetics, and positively modulates cardioprotective signaling pathways. These findings enhance our understanding of myocardial recovery in patients treated with combined VA-ECMO and LV unloading strategies.