Myocardial uptake of a (99m)Tc-nitroheterocycle in a swine model of occlusion and reperfusion.

UNLABELLED: The purpose of this study was to evaluate the window for scan positivity of the radiolabeled nitroheterocycle (99m)Tc-BRU-59-21 in the peri-ischemic period using a swine model of occlusion and reperfusion. METHODS: A balloon catheter was placed in the left anterior descending coronary artery in each of 19 domestic swine. Blood flow and hemodynamic measurements were made at baseline, during occlusion, and at 15 and 180 min after reperfusion. A dose of approximately 925 MBq (99m)Tc-BRU-59-21 was injected before a brief (6 min) period of coronary occlusion at the following times: 15 min (n = 2), 5 min (n = 2), and 2.2 min (n = 5). In 5 experiments the dose was injected 15 min after reperfusion. Animals underwent SPECT imaging 3 h later. Animals were then killed, and hearts were removed, sliced, stained with triphenyl tetrazolium chloride, and imaged on the detector. RESULTS: The risk region became ischemic during occlusion on the basis of severe reduction in blood flow and lactate production, but necrosis occurred in only 3 experiments. Focal tracer uptake was seen in the risk region in animals injected 5 and 2.2 min before occlusion but not in animals injected 15 min before occlusion and 15 min after reperfusion. CONCLUSION: The window for scan positivity for (99m)Tc-BRU-59-21 injected in the peri-ischemic period is short using this model of balloon occlusion and reperfusion in swine.

Technetium-99m glucarate uptake in a swine model of limited flow plus increased demand.

BACKGROUND: Glucarate is a 6-carbon dicarboxylic acid shown to be taken up by necrotic myocytes, binding to nuclear histones in animal models of coronary occlusion, resulting in infarction. This study investigated glucarate uptake in a model of severe ischemia. METHODS AND RESULTS: Thirty-five experiments were performed, in which a catheter-mounted stenosis (reducing lumen dimensions by 80%) was placed in the left anterior descending coronary artery (LAD) of an anesthetized, instrumented domestic swine and technetium-99m glucarate (GLU) was injected during the last minute of 5 minutes of pacing. Hemodynamic and blood flow measurements were performed at control, during pacing, and during recovery. The animals were killed; their hearts were stained with fluorescein dye and triphenyl tetrazolium chloride (TTC). Electron micography (EM; n = 6) and cell centrifugation (n = 7) were also performed. On the basis of net lactate production and severe blood flow reduction in the risk region (RR), ischemia with pacing developed in 25 animals. Fifteen of 25 animals showed tracer uptake in the RR on in vivo and ex vivo imaging (scan positive), and 10 were scan negative in the RR. Endocardial blood flow in the RR during pacing was 0.28+/-0.16 mL/g/min for scan-positive and 0.30+/-0.17 mL/g/min for scan-negative experiments (P = not significant [NS]). Transmyocardial net lactate extraction during pacing was -63%+/-44% for scan-positive and -53%+/-60% for scan-negative experiments (P = NS). Control and recovery heart rates were higher in scan-positive experiments (108+/-14 vs. 92+/-17, and 125+/-24 vs. 104+/-18, P<.02). Lactate extraction was lower during control and recovery in scan-positive animals (2+/-29 vs. 30+/-19, P = .03). Scan-positive animals had a more proximal stenosis position. Minimal necrosis was documented by means of TTC negative staining in 8 of 15 scan-positive experiments (comprising 10%+/-4.3% of RR area). EM or cell fractionation was performed in 5 of the 7 remaining scan-positive and TTC-positive hearts, and in those 5 experiments, necrosis was documented by means of EM in 2 and by means of cell fractionation in 3. CONCLUSIONS: Uptake of Tc-99m glucarate was seen in the RR in a swine model of ischemia severe enough to produce myocyte injury and early cell death.

Preconditioning myocardium with demand ischemia in the presence of a critical coronary artery stenosis.

The relative importance of adrenergic stimulation and demand ischemia as important preconditioning stimuli remains unclarified. The purpose of this investigation was to use a partial coronary stenosis to define the preconditioning role of demand ischemia. Dobutamine was infused intravenously before coronary occlusion in closed-chest swine with and without an artificial coronary stenosis in the mid-left anterior descending coronary artery. Control animals had no stenosis and did not receive dobutamine before occlusion. All three groups underwent 45 minutes of occlusion followed by 120 minutes of reperfusion. At baseline, regional myocardial blood flow in the area at risk was reduced in animals with a stenosis, but global left ventricular systolic function, measured by gated blood pool scan, was equivalent in all three groups. Animals with and without a stenosis received equivalent catecholamine stress with dobutamine, but only animals with a stenosis manifested ischemia during the infusion. At 2 hours after reperfusion, infarct size as a percentage of the area at risk was smaller in animals with a stenosis given dobutamine. Demand ischemia preconditions myocardium in closed-chest swine. Increased demand alone without ischemia had marginal preconditioning effects. This may have clinical relevance to patients with severe stenoses exposed to stressful stimuli before the development of myocardial infarction.

Technetium-99m-nitroimadazole uptake in a swine model of demand ischemia.

UNLABELLED: Nitroheterocycles are electron affinic, lipophilic compounds that are retained in hypoxic tissue. This study was designed to test the hypothesis that 99mTc-5-oxa-amine-oxime nitroimadazole (BMS-194796) is retained 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, including placement of a stenois (80% narrowing) mounted on a catheter into the left anterior descending (LAD) coronary artery. Twelve experiments had complete sets of data for analysis. Each animal was paced at about 200 bpm for 4 min, and 28 mCi of 99mTc BMS-194796 were injected during the last minute of pacing. Dynamic planar imaging was started after pacing and completed at 2.5 hr. In the last 8 experiments, SPECT imaging was performed after planar imaging and completed 3.5 hr after injection. Hemodynamic measurements were made continuously. Blood flow by microspheres and myocardial lactate extraction were measured at control, during pacing and after 2 hr of recovery. The animals were then killed; the risk region was delineated and the hearts were removed, sliced, imaged and stained with triphenyl tetrazolium chloride. RESULTS: Nine of the 12 animals became ischemic (net lactate production) during pacing; 3 did not. None of the 3 nonischemic experiments showed focal uptake on ex vivo or in vivo imaging. All 9 of the ischemic experiments showed focal BMS 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 region on triphenyl tetrazolium chloride staining. Four animals had small 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 positive in vivo images. CONCLUSION: These data support the conclusion that focal myocardial retention of BMS-194796 can be visualized on in vivo imaging in closed chest large animal model after intravenous injection.