CHARACTERIZATION OF IODOVINYLMISONIDAZOLE AS A MARKER FOR MYOCARDIAL HYPOXIA

Misonidazole and related compounds are metabolically trapped in viable cells as a function of reduced cellular pO2. [F-18]fluoromisonidazole has been used to detect hypoxia in the heart and in tumors noninvasiv ely with positron emission tomography. The purpose of this study was t o characterize the uptake of the iodinated misonidazole congener iodov inylmisonidazole (IVM) in ischemic myocardium. In six open chest dogs (Group 1), the left anterior descending (LAD) coronary artery was part ially occluded and in four dogs (Group 2), demand ischemia was produce d by the combination of atrial pacing and catecholamine infusion in th e presence of a LAD stenosis. [I-131]IVM (5-15 muCi/kg, i.v.) was give n following the onset of ischemia. Tracer deposition was measured by p ostmortem tissue sampling 4 hr postinjection and compared to microsphe re myocardial blood flow (MBF) measurements made at baseline and at 2 hr postinjection. In Group 1, regional IVM deposition in heart samples within the ischemic area was inversely related to MBF with maximum ti ssue:blood ratios of 3.2. For a given level of reduced blood flow, IVM uptake was higher in the subendocardium indicating a greater vulnerab ility of the subendocardium to reductions in oxygen delivery. In Group 2, enhanced IVM deposition was detected as a result of demand ischemi a, even in some regions where absolute flow was normal or increased fr om baseline, indicating that flow per se is not the principal determin ant of tracer uptake. We conclude that IVM is a promising marker for m yocardial hypoxia with potential clinical application using gamma came ra imaging.