MD. Lyhne, N. Gopalasingam, K. Berg-Hansen, SJ. Dragsbaek, C. Homilius, J. Seefeldt, JV. Hansen, AD. Kramer, LJ. Christensen, MS. Ellegaard, OK. Hørsdal, A. Overgaard, AM. Larsen, E. Boedtkjer, A. Andersen, et al. (2025). Ketone bodies for hemodynamic support in acute pulmonary embolism: a randomized, blinded, controlled animal study. Intensive care medicine experimental, 13(1), 133. https://doi.org/10.1186/s40635-025-00844-7

PubMed 41420069

[Abstract]
BACKGROUND: Acute pulmonary embolism (PE) is a leading cause of cardiovascular death, primarily due to abrupt increased pulmonary vascular resistance (PVR) leading to acute right ventricular (RV) failure. Ketone bodies, especially 3-hydroxybutyrate (3-OHB), have shown potential to increase cardiac output (CO) and reduce PVR in pulmonary hypertension, suggesting possible benefits in PE. We hypothesized that 3-OHB would induce pulmonary vasorelaxation and increase CO in a porcine model of acute PE.

METHODS: We conducted a randomized, controlled, assessor-blinded study in a porcine model of acute PE. Acute PE was induced, followed by a 3-h infusion of 3-OHB (0.22 g/kg/h, n = 8) or control (isovolumic saline of equimolar tonicity) (n = 8). Hemodynamic parameters were monitored hourly including right heart catheterization and RV pressure-volume loop acquisition. Primary outcome was the difference in CO during 3 h. Ex vivo effects on isolated pulmonary arteries were tested using wire myography.

RESULTS: Compared with control infusion, 3-OHB did not increase CO significantly (between-group difference: 0.7 [-0.2 to 1.6] L/min, p = 0.131). However, 3-OHB treatment lowered the PVR/systemic vascular resistance (SVR) ratio (-0.05 [-0.09; -0.01], p = 0.046) and increased pulmonary artery pulsatility index (5 [2-8], p = 0.006). Ex vivo, 3-OHB caused vasorelaxation in pre-contracted pulmonary arteries (p < 0.0001).

CONCLUSIONS: 3-OHB reduced PVR/SVR ratio, while CO was not significantly increased in a porcine model of acute PE. The present findings demonstrated potential hemodynamic effects in PE. Further studies are needed to explore the translational potential of ketone body therapy in humans with PE.