Inotropic effects of 3-hydroxybutyrate in a rodent heart: pressure-volume and isolated rat ventricular trabeculae analysis

A study on a rodent heart examined the inotropic effects of 3-hydroxybutyrate (3-OHB) by analyzing pressure-volume and isolated ventricular trabeculae. Administering 3-OHB to experimental rats led to an increase in cardiac output, but it was unclear if this benefit came from direct myocardial inotropy or heart unloading through peripheral vasodilation.

To determine these factors, the researchers examined the integrated cardiovascular response using pressure-volume analysis of the left ventricle and isolated left ventricular trabeculae from normotensive male HanSD rats after 3-OHB administration and drugs targeting adrenergic and cAMP-dependent signaling.

Pressure-volume analysis revealed a 34% increase in left ventricular end-systolic elastance, a 65% improvement in ventriculo-arterial coupling, and a 28% increase in LV efficiency, indicating a direct inotropic effect of 3-OHB. In isolated LV trabeculae, 3-OHB increased twitch force in both healthy and heart failure (HF) groups, but the increase was greater in healthy hearts (+55.8%) than in HF hearts (+35.6%) (p = 0.014).

The inotropic effect of 3-OHB was not further enhanced by coadministration of isoprenaline and was not reduced by beta-1 adrenergic blockade or cAMP inhibition. The results suggest that 3-OHB directly improves LV inotropy through a mechanism independent of receptor-mediated beta-adrenergic signaling, most likely due to a direct bioenergetic pathway.

These findings support 3-OHB as a potential candidate for an inotropic agent with a distinct mechanistic profile compared to conventional cAMP-dependent inotropes.