Butyrate infusion improves cardiac performance without aggravating myocardial injury in a porcine model of myocardial ischemic reperfusion

Background Ischemia-reperfusion injury (IRI) contributes to myocardial damage and adverse left ventricular (LV) remodelling following acute coronary occlusion. Thus, novel therapeutic strategies to mitigate IRI are needed. Butyrate, a short-chain fatty acid, normally produced in small amounts by colonic microbial fermentation of dietary fibres, improves cardiac function in healthy pigs and mitigates IRI in isolated rat hearts. Purpose To investigate the effect of intravenous butyrate infusion during reperfusion on LV function and myocardial injury in a porcine model of myocardial ischemic reperfusion. Methods In a randomised, assessor-blinded study, 18 anaesthetised pigs (≈80 kg) underwent 75 minutes of left anterior descending artery occlusion followed by 120 minutes of reperfusion. The animals were randomised (1:1) to receive Na‑butyrate (1.5 mmol/kg/h) or equimolar saline (control) during reperfusion. Hemodynamic parameters and LV function were continuously assessed using right heart catheterization and pressure–volume conductance analysis. Myocardial injury was quantified by Evans blue staining to delineate the area at risk (AAR) and by triphenyltetrazolium chloride (TTC) staining to determine infarct (IS). Salvage index (SI) was calculated as SI=(AAR-IS)/AAR. Results Butyrate infusion increased plasma butyrate concentrations from <0.02 mmol/L to 0.35 mmol/L (p < 0.001). LV end-systolic volume was 14 mL (95% CI: 2 to 26 mL; p=0.028) lower during butyrate vs. control infusion, and there was a trend towards higher LV ejection fraction (mean difference: 11 percentage points; 95% CI: -1 to 24 percentage points; p=0.077). Na-butyrate infusion reduced systemic vascular resistance by 2.4 Wood units (95% CI: 0.6 to 4.2 WU; p=0.012) and mean arterial pressure (difference: 10 mmHg; 95% CI: 2 to 18 mmHg; p=0.021), compared with control. Cardiac output (p=0.63), or myocardial SI (p=0.81) did not differ between groups. Load-independent contractility (end-systolic elastance, Ees) was comparable between groups, whereas diastolic relaxation parameter (dP/dt min) improved during butyrate vs. control infusion (p=0.05). Conclusion Butyrate infusion during reperfusion enhanced LV systolic and diastolic performance and reduced systemic resistance without altering infarct size. The findings suggest that butyrate confers beneficial hemodynamic and potentially anti-remodelling effects during myocardial reperfusion, independent of direct myocardial salvage.