Hemodynamic effects of the ketone body 3-hydroxybutyrate in a porcine acute pulmonary embolism model

Pulmonary embolism (PE) increases pulmonary vascular resistance (PVR) and mean pulmonary arterial pressure (mPAP) and may result in right ventricular (RV) failure due to an increase in afterload that exceeds RV compensatory capacity. The ketone body 3-hydroxybutyrate (3-OHB) has been shown to decrease PVR and increase cardiac output (CO) in heart failure and pulmonary hypertension. Effects of 3-OHB in a PE model are unknown.

To investigate the effects of intravenous 3-OHB on hemodynamic parameters in a porcine model of acute PE.

In an assessor-blinded crossover study, 16 pigs received 3-hour long infusions of 3-OHB and an isoosmolar sodium chloride control solution in randomized order. PE were induced by introducing large autologous blood clots into the pulmonary circulation until the predefined inclusion criterion, a 100% increase in mPAP, was met. Hemodynamic variables were measured hourly. A pulmonary artery catheter was used to measure CO as the primary endpoint using thermodilution, stroke volume (SV), right atrial pressure (RAP), mPAP and vascular resistance across both vascular beds. A pressure-volume catheter was used to measure RV parameters such as end-systolic volume (RVESV), maximal pressure generation rate (dP/dtmax) and end-systolic elastance (Ees). Results were analyzed using a linear mixed model.

Embolization of pulmonary arteries increased mPAP by 11 mmHg (P<0.001) and decreased arterial partial pressure of O2 by 4 kPa (P<0.001) with no significant effect on MAP or CO, thus corresponding to an intermediate risk stratum. Infusion of 3-OHB increased CO after 2 hours (1.0 L/min, 95% CI: 0.2 to 1.9 L/min, P=0.031). However, the increase was not significant after 3 hours (0.71 L/min, 95% CI: –0.15 to 1.6 L/min, P=0.13). 3-OHB increased mean systemic arterial pressure, heart rate, and dP/dtmax, compared with control, while significantly decreasing RAP, PVR/SVR-ratio, and RVESV. SV, mPAP and Ees were not significantly altered.

In this porcine model of acute PE, 3-OHB did not significantly increase cardiac output after 3 hours. However, RAP, PVR/SVR-ratio and RVESV were reduced, indicating increased contractile function of the RV. Effects on contractility were ambiguous with increased dP/dtmax and unaltered Ees.