Butyrate increases cardiac output and causes vasorelaxation in a healthy porcine model

Butyrate, a short-chain fatty acid, has shown potential to improve left ventricular (LV) function and induce vasorelaxation in rodents. Butyrate may either be produced by the microbiome in the colon, be ingested or administered intravenously. This study aimed to evaluate effects of butyrate on cardiac output (CO) and associated hemodynamic variables in a porcine model.

In a randomized, blinded crossover study, ten healthy 60-kg pigs were given three-hour infusions of 600 mM butyrate and equimolar sodium chloride (control). CO was measured by thermodilution via a pulmonary artery catheter. LV contractility was assessed using pressure-volume admittance catheterization. Additionally, isolated porcine coronary arteries were exposed to butyrate in a wire myograph to evaluate vasorelaxation.

Butyrate infusion increased plasma butyrate concentration to 0.53 mM (95% confidence interval (CI): 0.49 to 0.58 mM, P<0.001) and CO by 1.6 L/min (95% CI: 1.0 to 2.1 L/min, P<0.001) compared with the control. Heart rate, LV ejection fraction, cardiac efficiency and dP/dtmax rose, while systemic vascular resistance, arterial elastance, mean arterial pressure and LV ends-systolic volume decreased. Load-independent LV contractility and stroke volume did not significantly differ. In the myograph, porcine coronary arteries relaxed in response to butyrate in a concentration-dependent manner.

Butyrate increased CO by lowering systemic vascular tone and raising heart rate. Although load-independent contractility remained stable, increased dP/dtmax and ejection fraction, preserved stroke volume and decreased LV end-systolic volume indicated an enhanced cardiac contractile performance. These cardiovascular effects of butyrate warrant further clinical investigation.