Increased mitochondrial benzodiazepine receptors in inflamed lungs detected using multiple indicator dilution

We measured the pulmonary venous (isolated lungs), or systemic arterial (in vivo), concentration vs. time curves of ³H-diazepam and a vascular indicator following the injection of these indicators, with and without unlabelled PK11195, a potent mitochondrial benzodiazepine receptors ligand, into the pulmonary artery (isolated lungs), or a systemic vein (in vivo), of normal rabbits and rabbits with pulmonary inflammation induced by i.v. injection of complete Freund´s adjuvant. The data was analyzed using a kinetic model to estimate k_seq (m1/sec), which represents the rate of ³H-diazepam sequestration in lung tissue. The effect of pulmonary inflammation and PK11195 on k_seq, shown in the figure, demonstrate a large increase in MBR in inflamed lungs which are detectable by the multiple indicator dilution method both in isolated lungs and in vivo