The hemodynamic and cardiometabolic effects of butyrate infusion in ischemic cardiogenic shock

Background Cardiogenic shock (CS) is a condition caused by insufficient cardiac output (CO) which results in end-organ hypoperfusion. CS frequently presents as a complication of left ventricle (LV) failure caused acute myocardial infarction (AMI-CS). In spite of early initiation of treatment, CS in hospital-mortality remains high. Therefore, alternative treatment approaches are needed to improve CO and improve organ perfusion without the associated detrimental effects such as ischemia, cardiac dysfunction and death. Purpose In this study, we aimed to investigate the acute cardiovascular effects of butyrate in a porcine CS model. Methods With a randomized, controlled, assessor-blinded design, we studied 22 59±8kg Danish Landrace pigs. A well-established method was employed to induce cardiogenic shock (CS) via repeated slow injections of 1 to 1.5 mL of microspheres into the left main coronary artery. Hemodynamic parameters were allowed to stabilize for three minutes following each injection before subsequent injections were administered. Inclusion criterium was a 30% reduction in either CO or mixed venous oxygen saturation (SvO2) relative to baseline measurements prior to embolization. Injections of microspheres were repeated until this criterium was obtained. Following onset of CS, the pigs were randomized to receive either 600 mM butyrate (intervention group) or isovolumic, equimolar 600 mM saline (control group) at a rate of 2.5 mL/kg/h for three hours. Hemodynamic measurements were conducted hourly using a LV pressure-volume catheter to generate pressure-volume (PV)-loops, and blood samples were drawn from femoral- and pulmonary arteries. Endomyocardial biopsies were taken at three specific time stamps Results Cardiogenic shock was obtained in a total of 27 pigs. During the no-touch period but before the infusion period 5 pigs died due to cardiac arrest. The pigs were replaced 1:1. 22 pigs were included in the final analysis. After the induction of CS followed by one hour no-touch period, CO was decreased from 3.96±1.08 L/min at baseline to 2.67±0.58 L/min (33% reduction, P<0.001) and SvO2 was decreased from 59.8±9.71% at baseline to 36.4±8.83% (39% reduction, P<0.001). Significant decreases in MAP, CPO, SV and LVEF, CPP, LVEDP and LVESP and significant increases in HR, PAWP and P(v-a) CO2, LVEDV and LVESV were observed After three hours of butyrate infusion plasma levels increased from <0.025 mmol/L (i.e. detection threshold) to 0.58 mmol/L (95% CI: 0.51 to 0.64 mmol/L) compared to control infusion. Butyrate infusion increased CO 0.55 L/min (95% CI: 0.01 to 1.09 L/min, P=0.046) compared to control infusion. Conclusion In a randomized, controlled, assessor-blinded study of 22 pigs with CS, we found butyrate increased CO with 0.55 L/min without observing indices of increased myocardial oxygen consumption or a decline in mitochondrial function.