Omega-halofatty acids: a probe for mitochondrial membrane integrity. In vitro investigations in normal and ischaemic...

Long-chain omega-halofatty acids, especially omega-123I-iodoheptadecanoic acid (IHA), are widely used clinically as radiopharmaceuticals for functional heart imaging. The metabolic interpretation of the various elimination rates, however, remains in dispute. It has been previously shown (Kloster and Stöcklin 1982) that in isolated perfused guinea-pig hearts halide diffusion from the mitochondrion to the blood is the rate-determining step of IHA pharmacokinetics in normal myocardium. We have now extended these in vitro experiments to normal and globally ischaemic isolated perfused rabbit hearts. Again, in normal hearts a single phase iodide elimination half-time (14.3 +/- 2.1 min) was observed. In hearts made globally ischaemic for 90 min, the iodide elimination was biphasic with a first fast phase (T 1/2 = 3.8 +/- 0.49 min) and a late slow phase (T 1/2 = 60.5 +/- 14.0 min). The first fast phase is attributed to iodide ion released by residual beta-oxidation (more rapid than in normal hearts due to damaged membranes in ischaemia), while the late slow phase is explained by beta-oxidation of IHA slowly released by hydrolysis of intracellular lipid stores. These data were compared with published data from investigations in patients which seem to support our interpretation.