Project Title

Metabolic Interventions in Cardiogenic Shock Complicating Acute Myocardial Infarction

Background

10 % of acute myocardial infarctions deteriorate to cardiogenic shock, a state still killing 40 to 60 % of patients despite standard treatment. The failing myocardium becomes metabolically inflexible, limiting fattyacid oxidation. Exogenous ketone bodies and lactate may circumvent this block, provide ATP with superior oxygen efficiency, and may improve contractility, tissue perfusion and ultimately reduce infarct size.

Aim

To determine whether exogenous 3-hydroxybutyrate or lactate, given intrevenously or intracoronarily, (i) enhance hemodynamics and curb reperfusion injury in a porcine AMI-cardiogenic-shock model, and (ii) clarify if these effects stem from direct myocardial contractile gain or secondary systemic vascular actions.

Methods

Randomised, blinded porcine trial. Severe AMI-CS is created by 90-min dual-coronary balloon occlusion followed by reperfusion. In one study animals receive intravenous 3-OHB, lactate or control. In the second study animals receive intracoronary 3-OHB, lactate or control. Pressure-volume loops, right-heart catheter, PET scan, cardiac MR, ultrasound and multi-omics track contractility, perfusion and infarct size over 4 h.

Preliminary results

In a model with lower grade ischemica cardiogenic shock, 3-OHB and lactate increased cardiac output and peripheral oxygenation. Both 3-OHB and lactate improved contractility and the mechanic properties of the heart and cardiovascular system. Endomyocardial mitochondrial respiration improved in biopsies, supporting safety, feasibility and the rationale for the present, more severe AMI-CS study.