Biomedical subjects

J P Simanis

Publications and source records attributed to J P Simanis.

4 recordsLinked to original sources

PubMed1995

Comparison of thallium-201 resting redistribution with technetium-99m-sestamibi uptake and functional response to dobutamine for assessment of myocardial viability.

BACKGROUND: 201Tl scintigraphy is useful for determination of viability in patients with coronary artery disease and depressed left ventricular function. Whether 99mTc sestamibi is adequate for viability detection remains controversial. The primary goal of this study was to compare 99mTc-sestamibi uptake with 201Tl uptake in canine models of sustained low flow and regional asynergy for determination of viability. A secondary objective was to compare myocardial uptake of these tracers with the functional response to low-dose dobutamine. METHODS AND RESULTS: In protocol 1, 14 open-chested, anesthetized dogs with a 50% reduction in resting left anterior descending coronary artery (LAD) flow underwent 1 hour of transient LAD occlusion followed by reperfusion through the severe stenosis. Then 1.0 mCi of 201Tl was injected, and serial imaging was performed 5 minutes and 2 hours later. After acquisition of the delayed 201Tl image, 10 mCi of 99mTc sestamibi was injected, and imaging was repeated 45 minutes later. No significant difference was seen between the 201Tl defect ratio (LAD/left circumflex coronary artery [LCx]) on redistribution images (0.62 +/- 0.02) and 99mTc-sestamibi defect ratio (0.60 +/- 0.02). Similarly, LAD/LCx activity ratios by gamma-well counting were comparable (0.62 +/- 0.02 versus 0.59 +/- 0.04) and reflected the flow decrement. Systolic thickening was -11 +/- 3% at the time of tracer injection. In protocol 2, 16 dogs underwent serial 201Tl and 99mTc-sestamibi imaging during a 50% reduction in LAD flow with no superimposed transient LAD occlusion. In this model, the 99mTc-sestamibi LAD/LCx image defect ratio (0.61 +/- 0.03) was significantly less than the 201Tl redistribution image defect ratio (0.66 +/- 0.03, P < .01). In 10 dogs, the stenosis was released, resulting in a significant increase in systolic thickening (P = .003), which increased further in response to 5 micrograms.kg-1.min-1 of dobutamine (P = .02). In contrast, thickening increased only from -7 +/- 3% to 2 +/- 4% (P = .004) in response to dobutamine infusion in the remaining 6 dogs with persistent severe LAD stenoses. In protocol 3, 5 dogs received both 201Tl and 99mTc sestamibi to compare the degree of delayed redistribution between tracers at 2 hours. The LAD/LCx microsphere flow ratios when 201Tl and 99mTc sestamibi were injected were 0.44 +/- 0.06 and 0.43 +/- 0.05 (P = NS), respectively. The LAD/LCx activity ratio by gamma-well counting was greater for 201Tl (0.56 +/- 0.08) than 99mTc sestamibi (0.50 +/- 0.07) at 2 hours of redistribution (P < .05), indicating greater redistribution for 201Tl. The LAD/LCx 99mTc-sestamibi defect ratios on serial imaging improved from 0.49 +/- 0.07 to 0.52 +/- 0.07 (P = .0005), consistent with a slight amount of 99mTc-sestamibi redistribution. In protocol 4, no difference between 201Tl and 99mTc-sestamibi defect magnitudes was seen in 4 dogs undergoing 3 hours of total LAD occlusion and ligation of visible coronary collaterals. Infarct size was 68 +/- 19% of the risk area. CONCLUSIONS: Although 99mTc-sestamibi and 201Tl defect magnitudes and regional activities were comparable in dogs with sustained low coronary flows and superimposed subendocardial infarctions and in dogs with large infarctions, approximately 5% more 201Tl than 99mTc-sestamibi uptake was observed in dogs with chronic low flow and severe systolic dysfunction. Substantial 99mTc-sestamibi uptake in asynergic zones was observed in this low-flow model, with some slight resting 99mTc-sestamibi redistribution observed on serial images. Systolic thickening was negligibly enhanced during dobutamine infusion in dogs with sustained low flow, whereas 201Tl uptake was only mildly reduced.

Animals↗

PubMed1995

Comparison between 201Tl and 99mTc sestamibi uptake during adenosine-induced vasodilation as a function of coronary stenosis severity.

BACKGROUND: Myocardial uptake of either 201Tl or 99mTc-sestamibi (sestamibi) is known to plateau at high coronary flow rates. However, few direct comparisons have been made between these tracers to determine what effect differences in the uptake plateau for the two tracers may have on the detection of coronary stenoses of various severities. METHODS AND RESULTS: Twenty-two dogs were instrumented with flow transducers on the left anterior descending (LAD) and circumflex (LCx) arteries. In 6 nonstenotic dogs, adenosine was infused directly into the LAD, whereas 16 dogs with either critical (n = 7) or mild (n = 9) LAD stenoses received an intravenous infusion. At peak flow, 201Tl (0.5 mCi), sestamibi (5 to 8 mCi), and radiolabeled microspheres were injected simultaneously. Five minutes later, dogs were killed, and ex vivo imaging of heart slices and gamma-well counting of multiple myocardial samples was performed. Neither 201Tl nor sestamibi uptake increased in direct proportion to flow. In the 6 nonstenotic dogs, a fivefold increase in LAD flow increased 201Tl and sestamibi uptake by only 202 +/- 6% and 138 +/- 4%, respectively (P < .0001). In the dogs with critical stenosis, the ratios of stenotic to normal activity by well counting for 201Tl (0.37 +/- 0.05) and sestamibi (0.53 +/- 0.06) underestimated the microsphere-determined flow disparity (0.17 +/- 0.03) (P < .005), but the degree of underestimation was greater for sestamibi (P = .001). Similarly, in the dogs with mild stenosis, the stenotic-to-normal ratio for 201Tl (0.62 +/- 0.04) approximated the flow ratio (0.43 +/- 0.04) better than sestamibi (0.79 +/- 0.03) (P < .0001). Sestamibi defects, however, were visually identifiable on the images of the myocardial slices. By image quantification, sestamibi defect magnitude (LAD-to-LCx count ratio) in the critical stenosis group (0.62 +/- 0.05) was significantly less than in the mild stenosis group (0.80 +/- 0.02) (P < .01). CONCLUSIONS: Thus, with adenosine-induced hyperemic flow, both 201Tl and sestamibi significantly underestimated the magnitude of the flow disparity between stenotic and normal perfusion beds. The degree of underestimation was greater for sestamibi. The clinical implication of these experimental findings for vasodilator perfusion imaging remains to be determined, since factors such as greater redistribution and scatter with 201Tl could offset its advantages.

Adenosine↗

PubMed1995

Myocardial technetium-99m-teboroxime uptake during adenosine-induced hyperemia in dogs with either a critical or mild coronary stenosis: comparison to thallium-201 and regional blood flow.

UNLABELLED: Experimental studies have shown 99mTc-teboroxime to have a higher first-pass myocardial extraction, exceeding that of 201Tl with nearly linear initial myocardial uptake over a wide range of coronary flows. The goal of this study was to quantitatively compare teboroxime with 201Tl for the assessment of a regional coronary flow imbalance when administered during adenosine vasodilation in dogs with either critical or mild LAD stenoses. METHODS: Twenty-four anesthetized dogs with either critical (n = 10) or mild (n = 14) LAD stenoses were given an i.v. infusion of adenosine (300 micrograms/kg/min). When LCx flow was maximal, 201Tl, teboroxime and microspheres were simultaneously injected and the dogs were killed either 2 or 4 min later. Regional 201Tl, teboroxime activities and myocardial blood flow were determined by gamma well counting and ex vivo imaging of 99mTc-teboroxime activity in myocardial heart slices was performed. RESULTS: In both the critical and mild stenosis groups, the LAD/LCx zone ratios in dogs killed 2 min after tracer injection for both 201Tl (0.31 +/- 0.07, 0.63 +/- 0.05) and teboroxime (0.38 +/- 0.09, 0.72 +/- 0.04) significantly underestimated the microsphere flow ratio (0.18 +/- 0.05, 0.43 +/- 0.05) (p < or = 0.01), but the degree of underestimation was greater for teboroxime compared with Tl (p < or = 0.05). CONCLUSION: In dogs with either critical or mild LAD stenoses, as early as 2 min after tracer injection, the 201Tl activity ratio more accurately assessed the adenosine-induced regional flow heterogeneity than did teboroxime. These results highlight the importance of an ultra-fast imaging protocol when using teboroxime with pharmacologic stress.

Adenosine↗

PubMed1993

99mTc-sestamibi uptake and retention during myocardial ischemia and reperfusion.

BACKGROUND: 99mTc-methoxyisobutyl isonitrile (Sestamibi) is a new perfusion agent that has shown promise for the noninvasive detection of myocardial salvage after coronary reperfusion in acute myocardial infarction. The objective of this study was to further validate that myocardial uptake and retention of Sestamibi after reperfusion in a canine myocardial infarction model are markers of tissue viability. The hypotheses tested were that if Sestamibi is given early after reperfusion and myocardial uptake is quantitated soon afterward, the degree of ultimate myocardial salvage will be overestimated, and that there will be continued loss of myocardial Sestamibi from ischemic tissue during 3 hours of reperfusion due to accelerated release of Sestamibi from cells already irreversibly injured during the phase of coronary occlusion, reperfusion injury to myocytes still viable early after reflow, or a combination of both mechanisms. METHODS AND RESULTS: In protocol 1, 8.0 mCi Sestamibi was injected intravenously in anesthetized dogs 2-5 minutes after reperfusion preceded by 3 hours of left anterior descending coronary artery (LAD) occlusion. Animals were killed either 5 minutes (n = 7) or 3 hours (n = 9) after Sestamibi administration. Mean endocardial Sestamibi activity was 74 +/- 3% of nonischemic activity in dogs killed early and 31 +/- 2% of nonischemic activity in dogs killed late after Sestamibi administration, indicating myocardial loss of Sestamibi during 3 hours of reflow. Regional flow (percent nonischemic) at the time of Sestamibi administration (2-5 minutes after reperfusion) was comparable in dogs killed early (144 +/- 23%) and dogs killed late (118 +/- 4%, p = NS). In protocol 2, Sestamibi was given intravenously at baseline under normal conditions followed by 3 hours of LAD occlusion and either 4 (n = 6), 30 (n = 9), or 180 minutes (n = 10) of reperfusion. At postmortem, myocardial slices were imaged for quantification of defect magnitude and regional flow (radiolabeled microspheres), and tissue Sestamibi activities were determined by gamma well counting. Coronary sinus Sestamibi activity was serially measured. In these dogs, which were preloaded with Sestamibi at baseline, 3 hours of LAD occlusion followed by 3 hours of reperfusion resulted in a loss of Sestamibi in the endocardial zone of the ischemic region to 40 +/- 6% of nonischemic levels (p < 0.0001). This loss corresponded to a sustained elevation of coronary sinus activity throughout the reflow period. The loss of myocardial Sestamibi was significantly greater than that observed in dogs killed 4 or 30 minutes after reflow. Defect magnitude also worsened over 3 hours of reperfusion as assessed by gamma camera imaging of slices of the excised hearts. CONCLUSIONS: These experimental data suggest that Sestamibi uptake and retention are dependent on myocardial viability as well as regional flow. If Sestamibi is administered early after reperfusion and imaging is performed soon afterward, the degree of myocardial salvage could be significantly overestimated.

Animals↗