Pia Ryhammer

Normothermic regional perfusion (NRP) allows assessment of therapeutic interventions prior to donation after circulatory death transplantation. Sodium-3-hydroxybutyrate (3-OHB) increases cardiac output in heart failure patients and diminishes ischemia–reperfusion injury, presumably by improving mitochondrial metabolism. We investigated effects of 3-OHB on cardiac and mitochondrial function in transplanted hearts and in cardiac organoids. Donor pigs (n = 14) underwent circulatory death followed by NRP. Following static cold storage, hearts were transplanted into recipient pigs. 3-OHB or Ringer’s acetate infusions were initiated during NRP and after transplantation. We evaluated hemodynamics and mitochondrial function. 3-OHB mediated effects on contractility, relaxation, calcium, and conduction were tested in cardiac organoids from human pluripotent stem cells. Following NRP, 3-OHB increased cardiac output (P < 0.0001) by increasing stroke volume (P = 0.006), dP/dt (P = 0.02) and reducing arterial elastance (P = 0.02). Following transplantation, infusion of 3-OHB maintained mitochondrial respiration (P = 0.009) but caused inotropy-resistant vasoplegia that prevented weaning. In cardiac organoids, 3-OHB increased contraction amplitude (P = 0.002) and shortened contraction duration (P = 0.013) without affecting calcium handling or conduction velocity. 3-OHB had beneficial cardiac effects and may have a potential to secure cardiac function during heart transplantation. Further studies are needed to optimize administration practice in donors and recipients and to validate the effect on mitochondrial function.

Purpose To investigate if dynamic contrast-enhanced MRI in lungs could add new information to pulmonary hypertension in a newborn piglet model. Materials and Methods Six newborn piglets were subjected to instillation of meconium following treatment with sildenafil. Before and after both of these events, dynamic contrast-enhanced MRI was performed to determine pulmonary blood flow (PBF) using a model-free deconvolution of the dynamic signal-time curve, together with invasive measurements of mean airway pressure (PAW), cardiac output (CO), and oxygenation index (OI). Results Meconium instillation caused a significant increase in PAW (P < 0.05) accompanied by a marked increase in OI, the average PBF in the four lung regions (apical-anterior, apical-posterior, distal-anterior, and distal-posterior) decreased significantly by 33% (P < 0.001), but it did not significantly affect CO. On the other hand, infusion of sildenafil caused a significant increase in CO (P < 0.01), and administration resulted mainly in an increased PBF in the distal parts of the lungs. Conclusion By using dynamic contrast-enhanced MRI, we demonstrated a marked decrease in PBF following instillation of meconium, which was not followed by an equivalent decrease in CO, suggesting that measurements of CO inadequately reflect the intrapulmonary changes in the blood circulation. J. Magn. Reson. Imaging 2007;26:296–303.