TECHNETIUM-99M-NITROIMADAZOLE UPTAKE IN A SWINE MODEL OF DEMAND ISCHEMIA

Nitroheterocycles are electron affinic, lipophilic compounds that are retained in hypoxic tissue. This study was designed to test the hypoth esis that Tc-99m-5-oxa-amine-oxime nitroimadazole(BMS-194796) is retai ned in ischemic myocardial tissue in a swine model of demand ischemia and that the retained tracer can be imaged in vivo. Methods: Eighteen domestic swine were anesthetized, intubated and instrumented, includin g placement of a stenois (80% narrowing) mounted on a catheter into th e left anterior descending (LAD) coronary artery, Twelve experiments h ad complete sets of data for analysis. Each animal was paced at about 200 bpm for 4 min, and 28 mCi of Tc-99m BMS-194796 were injected durin g the last minute of pacing. Dynamic planar imaging was started after pacing and completed at 2.5 hr. In the last 8 experiments, SPECT imagi ng was performed after planar imaging and completed 3.5 hr after injec tion. Hemodynamic measurements were made continuously. Blood flow by m icrospheres and myocardial lactate extraction were measured at control , during pacing and after 2 hr of recovery. The animals were then kill ed; the risk region was delineated and the hearts were removed, sliced , imaged and stained with triphenyl tetrazolium chloride. Results: Nin e of the 12 animals became ischemic (net lactate production) during pa cing; 3 did not. None of the 3 nonischemic experiments showed focal up take on ex vivo or in vivo imaging. All 9 of the ischemic experiments showed focal EMS uptake in the risk region on ex vivo imaged slices; 6 of 9 had uptake in the risk region on in vivo imaging; and 4 of these 6 had small scattered areas of subendocardial necrosis in the risk re gion on triphenyl tetrazolium chloride staining, Four animals had smal l infarcts in the distribution of proximal LAD branch vessels occluded by the stenosis catheter. All animals with branch vessel infarcts had positive in vivo images. Overall, 8 of 9 ischemic experiments had pos itive in vivo images. Conclusion: These data support the conclusion th at focal myocardial retention of BMS-194796 can be visualized on in vi vo imaging in closed chest large animal model after intravenous inject ion.