Biomedical subjects

D K Glover

Publications and source records attributed to D K Glover.

29 records · Page 2Linked to original sources

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

Myocardial technetium 99m sestamibi kinetics after reperfusion in a canine model.

Clinical sestamibi imaging protocols after reperfusion therapy are based on the premise that redistribution does not occur. However, animal studies that use punch biopsies or imaging have variably reported either some or no redistribution. This study was designed to (1) utilize implantable radiation detectors to determine whether sestamibi is redistributed after reperfusion, (2) accurately determine the time course, extent, and kinetics of the redistribution, and (3) determine whether sestamibi kinetics can be used to document reperfusion and salvage after a single dose of sestamibi. Twenty-five dogs were injected with 5.0 mCi of technetium 99m sestamibi and microspheres during circumflex occlusion, and reperfusion occurred within 5 minutes in group 1 (15-minute occlusion) and group 2 (1-hour occlusion). Group 3 was not reperfused. Sestamibi activities in the normal and occluded zones were monitored with radiation detectors for 2 hours, and serial gamma camera imaging and arterial blood sampling was begun. No dogs in group 1 and all dogs in groups 2 and 3 had infarcts as shown by triphenyltetrazolium chloride stain. The final occluded/normal zone technetium 99m activity ratio was significantly higher than the flow ratio at the time of sestamibi injection only in the group 1 dogs (0.51 +/- 0.05 vs 0.38 +/- 0.06, p = < 0.0001). In addition, the mean 2-hour fractional sestamibi clearance from the occluded/reperfused zone (0.03 +/- 0.02) was significantly slower in the group 1 dogs compared with normal zone clearance (0.09 +/- 0.01, p = 0.03). Gamma camera images demonstrated large posterior wall perfusion defects initially, which persisted 2 hours later with no visual evidence of redistribution in any of the reperfused dogs in groups 1 and 2. Thus in an experimental animal model under ideal conditions, sestambi is redistributed into reperfused viable myocardium; however, the amount of this redistribution is small and could not be perceived by visual image analysis. Sestamibi is not redistributed into reperfused nonviable myocardium or into nonreperfused myocardium. Therefore sestamibi kinetics after a single dose of tracer in an experimental animal model can be used to document reperfusion of viable myocardium but cannot differentiate reperfusion of the infarcted territory from nonreperfused infarcted myocardium.

Animals↗

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↗

PubMed1993

Early myocardial clearance kinetics of technetium-99m-teboroxime differentiate normal and flow-restricted canine myocardium at rest.

Technetium-99m-teboroxime (CardioTec) is a promising new myocardial perfusion imaging agent. The purposes of this study were to define teboroxime clearance kinetics in normal and flow-restricted myocardium over a 1-hr period and to determine whether teboroxime kinetics are useful in detecting myocardial hyperperfusion. Accordingly, the circumflex arteries of 23 dogs were stenosed. By using miniature cadmium-telluride radiation detectors, myocardial teboroxime activities were continuously monitored in both the control and the stenosed zones. Myocardial clearance of teboroxime was modeled and found to be biexponential over 1 hr. A significant difference in myocardial clearance between the normal and stenosed zones (t1/2 = 4.5 +/- 0.9 min versus 10.2 +/- 2.6 min, respectively; p < 0.05) was observed for the first exponential phase (the first 5 min following initial uptake), but not for the second exponential phase (t1/2 = 160.7 +/- 35.9 min versus 140.4 +/- 27.4 min, respectively; p = ns). One hour fractional teboroxime blood clearance was 0.95 +/- 0.03, with most of the clearance occurring during the first 4 min. Gamma camera images of excellent quality demonstrated an initial defect with significant quantitative differential clearance over 1 hr. Thus, there are two phases of myocardial teboroxime clearance. During the early exponential clearance phase, teboroxime kinetics at rest may be able to differentiate between normal and hypoperfused myocardium.

Animals↗

PubMed1991

Dipyridamole 201Tl scintigraphy in the evaluation of prognosis after myocardial infarction.

Dipyridamole 201Tl imaging has been proposed as an alternative to exercise ECG testing for the prehospital discharge evaluation of patients recovering from myocardial infarction. The rationale is that many postinfarction patients with exercise-induced ischemia experience later cardiac events, and the sensitivity of predischarge exercise ECG testing in patients with multivessel disease ranges from only 45% to 62%. In addition, several groups of investigators have shown the sensitivity of submaximum exercise 201Tl imaging to be less than ideal. This report summarizes the current status of dipyridamole 201Tl imaging in the period of 1-13 days after myocardial infarction. Although the number of studies performed to date is limited, the following conclusions can be drawn: dipyridamole 201Tl imaging after myocardial infarction was associated with no serious side effects, and those present could be quickly reversed with aminophylline; redistribution with dipyridamole 201Tl images definitely correlates with prognosis after uncomplicated myocardial infarction; dipyridamole 201Tl imaging is definitely useful in patients unable to exercise for a variety of reasons; and future studies are definitely indicated to further define the role of dipyridamole 201Tl imaging for assessing prognosis, especially in those patients undergoing interventional therapy after acute myocardial infarction.

Aged↗

PubMed1990

Serial evaluation of right ventricular dysfunction associated with acute inferior myocardial infarction.

Right ventricular (RV) function was evaluated serially by multigated blood pool imaging in 18 patients with RV dysfunction associated with acute inferior myocardial infarction. Radionuclide ventriculograms were performed on all patients within 18 hours of chest pain and again at 10 days. In addition, 15 of 18 patients had rest and exercise radionuclide ventriculograms at 3 months. The mean resting right ventricular ejection fractions (RVEF) at admission, 10 days, and 3 months in these patients was 31.8 +/- 12.6% (SD), 46.9 +/- 11.2% (p less than 0.05), and 44.5 +/- 10.2% (p less than 0.05), while the left ventricular ejection fractions were 55.9 +/- 10.6%, 57.9 +/- 13.3%, and 53.1 +/- 11.2% (p = ns). The 3-month exercise radionuclide ventriculogram demonstrated an increase in RVEF greater than 5% in 6 of 15 patients. In eight catheterized patients, neither the location nor the severity of coronary artery narrowing nor the presence of collaterals correlated with the RV exercise response. Improvement in RV function over a 10-day interval following acute inferior myocardial infarction suggests the presence of significant reversible right ventricular dysfunction during the acute phase.

Cardiac Catheterization↗

PubMed1990

Myocardial kinetics of Tc-MIBI in canine myocardium after dipyridamole.

Technetium 99m-hexakis-2-methoxy-2-methylpropyl-isonitrile (Tc-MIBI) is a promising new myocardial perfusion imaging agent producing excellent rest images. Imaging, however, will need to be performed with exercise or dipyridamole to detect ischemia and to differentiate salvaged but still ischemic myocardium from scar. Accordingly, 12 dogs were given mild-to-moderate left circumflex coronary stenoses (group 2), and 10 dogs were given severe stenoses (group 3). In five control dogs (group 1), there was no stenosis. After an intravenous infusion of dipyridamole (0.08 mg/kg/min for 4 minutes), Tc-MIBI was injected into the right atrium. Over the next 4-hour study period, myocardial Tc-MIBI activities were continuously monitored in both the left anterior descending (LAD) (normal) and left circumflex (LCx) (ischemic) coronary artery (ischemic) zones using miniature cadmium telluride radiation detectors and serial gamma camera images were acquired when necessary. Tc-MIBI was rapidly taken up by nonischemic, mild-to-moderate, and severe ischemic myocardium. The initial myocardial uptake of Tc-MIBI was linearly related (r = 0.97) to regional myocardial blood flow at rates up to 2.0 ml/min/g. After the initial uptake, the mean 4-hour fractional myocardial clearance was similar between the control (0.09 +/- 0.03 [+/- SEM]) and group 2 (0.07 +/- 0.03) and group 3 (0.09 +/- 0.03) ischemic zones. Tc-MIBI blood clearance was rapid and biexponential with an initial fast clearance phase followed by a slow clearance phase.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1988

Cardiac imaging and myocardial kinetics of technetium-tertiary butyl-isonitrile during dipyridamole-induced hyperemia.

UNLABELLED: To determine the myocardial kinetics of technetium-tertiary-butyl-isonitrile (Tc-TBI) during dipyridamole-induced hyperemia, the circumflex coronary arteries (LCX) of 15 dogs were partially occluded. Dipyridamole was then infused intravenously over 4 minutes, creating hyperemic flows in the anterior descending (LAD) coronary system. Tc-TBI was administered, then LAD and LCX regional myocardial Tc-TBI activities were continuously monitored with miniature detectors and gamma camera imaging over 3 hours. Microsphere-determined regional myocardial blood flows demonstrated an LCX/LAD flow ratio of 0.81 +/- 0.21 at rest and 0.45 +/- 0.24 (SD) during dipyridamole infusion. Three-hour fractional Tc-TBI clearance rates were minimal and were equal in the LAD (0.14 +/- 0.11) and LCX (0.13 +/- 0.12) zones (p = ns). Excellent gamma camera images, demonstrating the LCX defect, were obtained in all dogs. The correlation coefficient was 0.98 for regional myocardial blood flow vs initial Tc-TBI distribution. IN CONCLUSION: (1) Dipyridamole vasodilation unmasked coronary stenoses despite no flow disparities at rest. (2) The initial distribution of Tc-TBI is proportional to regional myocardial blood flow. (3) There is minimal washout and no redistribution into the initial defect over time, and thus image quality is stable over time. (4) Tc-TBI myocardial kinetics may be applicable to closely related agents currently being developed.

Animals↗

PubMedDate not supplied

Myocardial technetium 99m-labeled teboroxime clearance derived from canine scans differentiates severity of stenosis after dipyridamole.

BACKGROUND: The purposes of this study were to determine (1) whether perfusion defects and differential teboroxime clearance observed on serial postdipyridamole planar gamma camera images have utility in differentiating severity of coronary stenosis in canine myocardium and (2) whether single-zone (99mTc activity in one zone over time) or dual-zone (99mTc activity ratio in two zones over time) quantitative analysis provides the most useful characterization of teboroxime clearance kinetics. METHODS AND RESULTS: Accordingly, eight dogs received a mild coronary stenosis (microsphere-determined, post-dipyridamole flow > or = 0.4 ml/min/gm) and 10 dogs received a severe coronary stenosis (flow < or = 0.3 ml/min/gm). In three control dogs there was no coronary stenosis. Teboroxime (5 mCi) was injected after dipyridamole (0.8 mg/kg/min), and gamma camera imaging was begun immediately and continued for 60 minutes. Quantitative analysis of single-zone clearance curves indicated that teboroxime retention for both zones of stenosis (mild = 66.3% +/- 2.8%, SEM; severe = 69.5% +/- 3.7%) was significantly greater than control zone retention (54.5% +/- 3.0%; p < 0.05) at 10 minutes. Retention in mild (37.2% +/- 1.9%, SEM) and severe (42.3% +/- 1.5%) zones of stenosis was significantly different from each other at 60 minutes (p < 0.05). There was a significant direct, linear correlation of flow with teboroxime clearance at 20 minutes (r = +0.74, normal and ischemic zones). Quantitative analysis with dual-zone count ratios (stenosed/normal) demonstrated significant differences among control (0.93 +/- 0.04, SEM), mild stenoses (0.54 +/- 0.04), and severe stenoses (0.39 +/- 0.03) as early as 2 minutes after administration of 99mTc-labeled teboroxime. The correlation coefficient for flow ratio versus dual-zone counts/pixel ratio at 20 minutes was r = +0.74. CONCLUSION: Thus in this canine stenosis model with dipyridamole, gamma camera imaging could distinguish mild from severe coronary stenoses by either single- or dual-zone analysis.

Animals↗

PubMedDate not supplied

Optimal timing for initial and redistribution technetium 99m-N-NOET image acquisition.

BACKGROUND: Bis (N-ethoxy, N-ethyl dithiocarbamato) nitrido technetium-99m (V) (Tc-99m-N-NOET) is a new Tc-99m-labeled myocardial perfusion imaging agent that redistributes. We sought to determine the optimal timing for acquiring initial and delayed images to maximize sensitivity for the detection of coronary stenoses. METHODS: Twelve anesthetized dogs with critical stenoses of the left anterior descending coronary artery were infused with adenosine (250 microg/kg/min) or MRE-0470, an adenosine A2a agonist (0.6 microg/kg/min x 10 minutes), and Tc-99m-N-NOET (8 mCi; 296 MBq) was injected intravenously at peak flow. Myocardial and lung Tc-99m-N-NOET activities were determined by serial quantitative imaging and arterial blood sampling was performed over 2 hours. RESULTS: Left anterior descending/left circumflex artery defect count ratios showed rapid redistribution during the first 10 minutes after Tc-99m-N-NOET injection (0.66 +/- 0.02 at 2 minutes to 0.73 +/- 0.01 at 10 minutes; P < .01). Redistribution was nearly complete by 120 minutes (defect ratio = 0.87 +/- 0.03; P < or = .01 vs 2 minutes). Lung activity fell significantly during the first 10 minutes from a heart/lung activity ratio of 1.07 +/- 0.05 (2 minutes) to 1.44 +/- 0.09 (10 minutes; P < or = .01). CONCLUSION: Initial stress Tc-99m-N-NOET images should be acquired within 10 minutes after injection, whereas delayed images can be obtained as early as 2 hours later. Lung activity clears rapidly, permitting acquisition of good-quality poststress cardiac images. These Tc-99m-N-NOET uptake and redistribution kinetics after vasodilator stress provide important information for designing clinical imaging protocols for optimal identification of inducible ischemia.

Animals↗

PubMedDate not supplied

Tc-99m sestamibi defect magnitude predicts the amount of viable myocardium after coronary reperfusion despite the presence of severe residual stenosis.

BACKGROUND: Whether technetium-99m-labeled methoxyisobutyl isonitrile (Tc-99m sestamibi) imaging early after reperfusion can detect the amount of salvaged viable myocardium in the presence of a severe residual stenosis remains controversial. METHODS AND RESULTS: Nine dogs underwent total left anterior descending coronary artery (LAD) occlusion for 40 to 180 minutes followed by reperfusion through a flow-limiting stenosis. They were divided into 2 groups based on infarct size (group 1, <15% of risk area; group 2, > or =15%). Triphenyl tetrazolium chloride infarct size was measured by planimetry, and regional flow was quantified by radiolabeled microspheres. Mean infarct size was 9.3% +/- 3.0% of risk area in group 1 versus 51.1% +/- 4.8% in group 2 (P <.01). Tc-99m sestamibi was injected 30 minutes after reperfusion, when the LAD flows were comparable for group 1 (9 +/- 2 mL. min(-1)) and group 2 (9 +/- 1 mL. min(-1)). Left circumflex coronary artery flows were 33 +/- 5 and 32 +/- 9 mL. min(-1) for groups 1 and 2, respectively. Despite administration of Tc-99m sestamibi during diminished residual LAD flow after reperfusion, defect magnitude on ex vivo images in group 1 was significantly less severe than that in group 2, which had larger infarcts (0.71 +/- 0.02 vs 0.42 +/- 0.05, P <.01). This reflects greater salvage and more viability in group 1. CONCLUSION: Resting perfusion imaging with Tc-99m sestamibi accurately determined viability of the infarct zone despite reperfusion through a residual stenosis. Tc-99m sestamibi imaging may prove useful in the clinical setting for the prediction of the amount of salvaged myocardium.

Animals↗