Experimental studies of the physiologic properties of technetium-99m isonitriles. Recently, efforts have been directed at the development of technetium-99m (Tc-99m)-labeled isonitrile compounds for assessment of regional perfusion and viability after experimental myocardial infarction or ischemia. One of the most promising of these agents, Tc-99m sestamibi, has undergone rather extensive laboratory investigation. Like thallium-201 (Tl-201), the uptake of Tc-99m sestamibi in myocardial tissue is proportional to myocardial blood flow after intravenous injection. Similar to other diffusible indicators, Tc-99m sestamibi underestimates blood flow at high flow rates. In low flow regions, the myocardial uptake of this agent is higher relative to nonischemic uptake than is microsphere-determined blood flow. This is attributed to increased extraction at low flows. This first-pass myocardial extraction fraction for Tc-99m sestamibi is less than that for Tl-201. However, Tc-99m sestamibi has a higher parenchymal cell permeability and higher volume of distribution than T;-201. Tc-99m sestamibi shows minimal "delayed redistribution" after initial intravenous administration. Uptake of Tc-99m sestamibi is not altered by myocardial "stunning" or with ischemic dysfunction produced by sustained low coronary flow. The uptake of the isonitrile is still proportional to blood flow in these situations. In intact animal models, myocardial uptake of Tc-99m sestamibi during coronary occlusion delineates the in vivo area at risk. When Tc-99m sestamibi is administered after reperfusion following variable periods of preceding coronary occlusion, Tc-99m sestamibi uptake delineates the area of viable myocardium that is salvaged and not simply the degree of reflow. This suggests that serial Tc-99m sestamibi imaging might be useful in assessing the efficacy of coronary reperfusion after thrombolytic therapy. 