Relationship between regional myocardial blood flow and the distribution of 99mTc-sestamibi in the presence of total coronary artery occlusion

This study was designed to assess the relationship between the distribution of the monocationic 99mTc-hexakis-2-methoxy, 2-methylpropylisonitrile (99mTc-sestamibi) and regional myocardial blood flow (RMBF) in swine. The left anterior descending coronary artery (LAD) was totally occluded and dipyridamole (0.4 mg/kg) was intravenously infused over 4 minutes. 99mTc-sestamibi and 201Tl were coinjected intravenously and a set of microspheres (15 microns) labelled with 113Sn or 55Nb was injected via a left atrial cannula. Animals were put to death at different times after injection of 99mTc-sestamibi/201Tl and the left ventricle was sectioned for gamma spectroscopy. Regression analysis of regional myocardial distribution of 99mTc-sestamibi or 201Tl versus microsphere-determined RMBF demonstrated a linear relationship with flow up to 2.5 ml/min/gm. The myocardial uptake for both 99mTc-sestamibi and 201Tl at higher flow levels was shown not to follow a linear relationship to microsphere-determined RMBF. The first-pass myocardial extraction fractions (%EF) of 99mTc-sestamibi and 201Tl in dogs were 65.5 +/- 2.5% and 82 +/- 3%, respectively (p less than 0.001), at resting flow. At flow levels above the resting flow, a significant decrease in the first-pass extraction fraction for both tracers was shown. At hyperemic flow levels (two to three times the resting flow), the %EF for both tracers are not significantly different. These data provide a basic validation for the utility of 99mTc-sestamibi as a reliable myocardial perfusion imaging agent.     

Effects of dipyridamole-induced vasodilation on myocardial uptake and clearance kinetics of thallium-201

Myocardial thallium-201 (201Tl) uptake and clearance after intravenous administration of dipyridamole (150 micrograms/kg) were determined in 12 open-chest anesthetized dogs with a partial coronary artery stenosis. 201Tl (1.5 mCi) was injected intravenously and myocardial biopsy specimens were obtained 10 min, 60 min, and 2 hr after injection. Serial changes in 201Tl activity in the normal zone and in the zone of partial stenosis were correlated with microsphere-determined regional blood flow and distal coronary pressure. Another nine dogs with equivalent stenosis not given dipyridamole before 201Tl served as controls. In the 12 dogs given dipyridamole, 201Tl activity at 10 min in the zone of stenosis was reduced to 42 +/- 5% of initial normal zone activity (p less than .001) and remained at 44 +/- 3% of initial normal zone activity at 2 hr. There was a good correlation (.81) between the percent reduction in myocardial 201Tl activity and the percent reduction of peak hyperemic flow as determined by measuring the percentage difference in peak coronary flow after a transient 10 sec occlusion under control and stenotic conditions. In contrast, 201Tl clearance was rapid in the normal zone, with 201Tl activity decreasing to 55 +/- 3% of initial normal zone activity by 2 hr. A redistribution pattern was produced because of the disparate clearance rates from hyperperfused and relatively hypoperfused myocardial regions. The relative 201Tl defect decreased from 58% to 11% from 10 min to 2 hr. In the normal zone dipyridamole increased epicardial flow from 1.03 +/- 0.09 (SEM) to 3.52 +/- 0.36 ml/min/g (p less than .0001) and endocardial flow from 1.19 +/- 0.09 to 2.96 +/- 0.20 ml/min/g (p = .0001). In the zone of partial stenosis the increase in epicardial flow after dipyridamole was less marked (1.01 +/- 0.10 to 1.55 +/- 0.15 ml/min/g; p = .009) and endocardial flow decreased (0.84 +/- 0.11 to 0.64 +/- 0.15 ml/min/g; p = .04). Coronary perfusion pressure distal to the stenotic zone fell from 65 +/- 3 to 50 +/- 3 mm Hg after dipyridamole. In the nine control dogs with equivalent stenosis, 201Tl uptake and washout were not significantly different in the stenotic zone compared with the normal zone. These data indicate that dipyridamole-induced vasodilation in the presence of a partial stenosis results in diminished uptake and delayed clearance compared with increased uptake and more rapid clearance in normally perfused myocardium producing an initial 201Tl defect with delayed redistribution.(ABSTRACT TRUNCATED AT 400 WORDS)     

Thallium 201 kinetics in stunned myocardium characterized by severe postischemic systolic dysfunction

The hypothesis tested in this study was that despite the presence of severe postischemic myocardial dysfunction ("stunning"), the extraction and subsequent intracellular washout of thallium 201 should be preserved as long as irreversible sarcolemmal membrane injury was avoided. To produce myocardial stunning, 19 open-chested dogs with a critical left anterior descending coronary artery (LAD) stenosis underwent 10 5-minute periods of total LAD occlusion, each interspersed by 10 minutes of reperfusion by reflow through the critical stenosis. In another 12 control dogs observed for the same time period, no LAD occlusions were performed after placement of the critical stenosis. Hemodynamics, regional myocardial thickening by quantitative two-dimensional echocardiography, and microsphere-determined regional blood flows were serially measured. In 18 stunned dogs, systolic thickening in the LAD zone was markedly reduced to 0.4 +/- 2.4% at 40 minutes after the 10th reperfusion period compared with 32.5 +/- 2.2% thickening (p less than 0.001) in 12 control dogs at a matched time. The 201Tl first-pass extraction fraction determined by a double-isotope method using intracoronary 201Tl administration was comparable after the 10th reflow in a subgroup of 13 stunned (0.78) and six control (0.79) dogs. The T1/2 for the intracellular washout rate was also not significantly different in another group of six stunned (60 +/- 13 minutes) and six control (53 +/- 14 minutes) dogs, nor was the percentage of the 201Tl dose initially distributed in the interstitial compartment (11 +/- 3% vs. 7 +/- 2%). Systemic hemodynamics and regional flows were comparable in the two groups at 40 minutes after the 10th reflow. No dog had evidence of myocardial necrosis by triphenyl tetrazolium chloride staining. Thus, normal myocardial 201Tl extraction and washout kinetics are observed in a canine model of severe postischemic dysfunction (stunning) produced by repetitive brief LAD occlusions. These findings might have important clinical implications concerning the application of rest 201Tl scintigraphy for evaluation of perfusion and viability in patients with coronary artery disease and regional myocardial asynergy that is ultimately reversible.     

Quantitative rotational tomography with 201Tl and 99mTc 2-methoxy-isobutyl-isonitrile. A direct comparison in normal individuals and patients with coronary artery disease

We tested the hypothesis that 99mTc 2-methoxy-isobutyl-isonitrile (99mTc MIBI), a new radiopharmaceutical for myocardial perfusion imaging, provides accurate noninvasive detection of coronary artery disease (CAD). Imaging in patients after exercise and at rest with 99mTc MIBI was compared with imaging after exercise and redistribution with 201Tl in 12 normal subjects and 38 patients with angiographic documentation of CAD (greater than or equal to 50% diameter stenosis). We used single-photon emission computed tomography (SPECT) and computer quantitation of regional tracer distribution. The quality of reconstructed images with 99mTc MIBI judged visually was superior to that of 201Tl in 88% of all studies performed and was comparable in the others. With the limits of normal as 2.5 SD below the mean of gender-matched normal volunteers, 201Tl SPECT identified 32 and 99mTc MIBI identified 36 patients with CAD (p = 0.2). 201Tl SPECT identified 45 of 75 (60%) and 99mTc MIBI identified 59 of 75 (79%) stenosed coronary arteries (p less than 0.05). The quantitative severity of perfusion defects was similar for the two tracers. 201Tl SPECT identified 104 reversibly ischemic myocardial segments compared with 134 with 99mTc MIBI (p less than 0.05). Thus, SPECT myocardial perfusion imaging with 99mTc MIBI and computer quantitation provides an accurate method for the noninvasive detection of significant coronary artery disease. Furthermore, image quality is generally superior to 201Tl, and reversibly ischemic myocardial segments may be better identified with 99mTc MIBI.     

Effects of intracoronary dipyridamole infusion on regional myocardial blood flow and intrinsic thallium-201 washout in dogs with a critical coronary stenosis.

Intravenous dipyridamole (DP) infusion produces a significant endocardial-to-epicardial flow gradient distal to a critical coronary stenosis, resulting in diminished regional thallium-201 (Tl-201) uptake and washout. Intravenous DP can also produce a significant decrease in arterial blood pressure and therefore in coronary perfusion pressure. We determined to further clarify the mechanism of this transmural coronary "steal" employing intracoronary DP administration, thereby avoiding systemic hypotension. In five of eight dogs with a critical left anterior descending (LAD) stenosis, intracoronary DP caused no significant fall in systemic arterial pressure, a rise in epicardial flow from 1.15 +/- 0.2 to 1.75 +/- 0.2 ml/min/gm, and a slight fall in subendocardial flow from 1.15 +/- 0.2 to 1.03 +/- 0.5 ml/min/gm. Intracoronary DP caused no prolongation of the intrinsic Tl-201 washout rate. In three dogs that developed systemic hypotension after intracoronary DP, endocardial flow fell from 1.14 to 0.63 ml/min/gm, the epicardial/endocardial flow ratio fell to 0.35, and Tl-201 washout became more prolonged. Thus intracoronary DP in the setting of a critical LAD stenosis caused minimal endocardial-to-epicardial steal and had no effect on the intrinsic Tl-201 washout rate unless it was accompanied by a fall in systemic arterial pressure. The magnitude of the transmural steal was substantially less than reported in our previous experiments utilizing intravenous DP infusion. This study provides a further insight into the mechanism of DP-induced subendocardial ischemia and suggests that systemic hemodynamic alterations play an important role in the effects of the vasodilator on myocardial blood flow and Tl-201 kinetics.     

Intrinsic washout rates of thallium-201 in normal and ischemic myocardium after dipyridamole-induced vasodilation

Infusion of dipyridamole has been suggested as an alternative to exercise stress for myocardial perfusion imaging for detection of ischemia, but the mechanism and significance of thallium-201 (201Tl) redistribution after administration of dipyridamole are uncertain. If disparate intrinsic cellular efflux rates of 201Tl from normal and relatively underperfused myocardium in response to dipyridamole-induced vasodilation were observed, this could explain delayed 201Tl redistribution. We investigated eht effect of an intravenous infusion of 0.15 mg/kg dipyridamole on the intrinsic myocardial washout rate of 201Tl as measured with a gamma-detector probe after intracoronary injection (50 muCi) of the radionuclide in open-chested anesthetized dogs. In six normal dogs the t 1/2 for intrinsic 201Tl washout from the myocardium was 89 +/- 11 min (SE) at control conditions and became more rapid at 59 +/- 10 min (p = .0001) after dipyridamole. This corresponded to a significant increase in microsphere-determined epicardial (0.95 +/- 0.11 to 2.23 +/- 0.46 ml/min/g; p = .01) and endocardial (0.86 +/- 0.10 to 1.53 +/- 0.27; p = .029) flows. In 12 dogs with a critical coronary stenosis, the 201Tl intrinsic washout rate slowed from 70 +/- 5 to 104 +/- 6 min (p = .0001) after production of the stenosis and slowed even further to 169 +/- 21 min (p = .003) after dipyridamole.(ABSTRACT TRUNCATED AT 250 WORDS)     

Correlation between myocardial uptake of technetium-99m-sestamibi and pressure-derived myocardial fractional flow reserve

OBJECTIVES: Development of the coronary pressure wire has facilitated the measurement of fractional flow reserve (FFR) to assess the functional severity of coronary artery stenoses. METHODS: This study evaluated the correlations between FFR and myocardial direct counts of technetium-99m(99mTc)-sestamibi in 20 patients (16 men, 4 women, mean age 66 +/- 8 years) who underwent 99mTc-sestamibi single-photon emission computed tomography (SPECT) with the 2-day protocol using 740 MBq of 99mTc-sestamibi each day. Visual assessment of myocardial imaging and quantitative analysis with the measurement of percent uptake and direct count of 99mTc-sestamibi were performed. RESULTS: Visual assessment of myocardial imaging revealed that reversibility of 99mTc-sestamibi perfusion defects was correlated with FFR of < 0.75, which is regarded as functionally important stenosis (17/20 vs 3/20, kappa = 0.71, p < 0.002). Regional reversibility score did not correlate with FFR (r = -0.40, p = NS). Quantitative analysis revealed that the change in 99mTc-sestamibi percent uptake with pharmacologic stress using adenosine triphosphate disodium (ATP) also did not correlate with FFR (r = 0.35, p = NS). In contrast, percent increase in 99mTc direct counts with ATP was lower in patients with FFR of < 0.75 than in those with FFR of > = 0.75 (-4 +/- 16% vs 24 +/- 30%, p < 0.01). In addition, a significant correlation (r = 0.70, p < 0.001) was observed between percent increase in 99mTc direct counts with ATP and FFR. CONCLUSIONS: These results suggest that quantitative analysis of 99mTc-sestamibi scintigraphy enables the assessment of the magnitude of functional significance of coronary stenosis.     

Comparison of thallium-201 and technetium-99m methoxyisobutyl isonitrile.

Thallium-201 (201Tl) is a well-established radionuclide used in myocardial perfusion imaging for assessing the presence and prognostic significance of coronary artery disease. Recently, technetium-99m hexakis-2-methoxyisobutyl isonitrile (99mTc-sestamibi) has become available for the same diagnostic and prognostic procedures. This discussion compares the imaging characteristics and clinical applications of 201Tl with those of 99mTc-sestamibi. There is a strong diagnostic concordance between the 2 agents in symptomatic patients. Various comparative clinical trials have shown in numerous patients that both agents have a similar diagnostic yield in both planar and single-photon emission computed tomography (SPECT) imaging. Because of better image quality of the 99mTc agent, there is a trend toward better specificity and normalcy rate, in comparison to 201Tl. However, when using reinjection imaging protocols, 201Tl retains a unique place as an imaging agent to identify viable myocardium.     

Kinetics of technetium-99m-Sestamibi and thallium-201 in a transient ischemic myocardium animal model: insight into the 'redistribution' phenomenon.

This study was designed to determine the redistribution potential for technetium-99m (99mTc)-hexakis-2-methoxy isobutyl isonitrile (99mTc-Sestamibi) as compared to thallium-201 (201Tl) in a transiently ischemic swine heart model. The left anterior descending coronary artery (LAD) was totally occluded for 10 min. One minute prior to the release of the LAD, 99mTc-Sestamibi, 201Tl and a set of 95Nb-radiolabeled microspheres (15 microns) were injected. A second set of 51Cr-radiolabeled microspheres was injected prior to sacrifice in order to document reflow. Animals were sacrificed at different times post-LAD release (ranging from 1 min to 4 h). The left ventricle was sectioned into 0.2- to 0.5-gram pieces for the gamma spectroscopic counting of the 99mTc-Sestamibi, 201Tl and radiolabeled microspheres. Linear regression analysis of radiotracer localization versus microsphere-determined regional myocardial blood flow (rMBF) demonstrates an initial slight filling in of 99mTc-Sestamibi into transiently ischemic zones, with subsequent stable kinetics up to 4 h (i.e., it does not further redistribute). In comparison, the ischemic to normal ratios for 201Tl activity increase progressively in a time-dependent manner. These differences between 99mTc-Sestamibi and 201Tl might be explained on the basis of their blood clearance kinetics and/or their net clearance from normal and ischemic zones of the heart. It is concluded that 99mTc-Sestamibi is a stable and reliable indicator for rMBF over time, and that the lack of normalization of 99mTc-Sestamibi into transient ischemic zones will necessitate two separate injections for differentiation between ischemia and persistent defects.     

Technetium-99m-labeled myocardial perfusion agents: Are they better than thallium-201?

Currently, thallium-201 (201Tl)- and technetium-99m (99mTc)-labeled tracers are used interchangeably for the detection of coronary artery disease, the assessment of myocardial viability, and risk stratification. This article reviews some of the potential advantages and disadvantages of the 99mTc-labeled tracers relative to 201Tl. The basic myocardial kinetic properties and biodistribution of the commonly used 99mTc-labeled perfusion tracers are compared with those of 201Tl. The clinical value of the 99mTc-labeled perfusion tracers is then compared with that of 201Tl imaging. With regard to imaging physics and radiation safety, the 99mTc-labeled tracers are superior to 201Tl. Cost and tracer availability also may favor 99mTc-labeled perfusion tracers rather than 201Tl imaging. However, the most widely used 99mTc-labeled perfusion tracers currently approved for clinical use-99mTc-sestamibi and 99mTc-tetrofosmin-do not track myocardial flow as well as 201Tl does. This shortcoming of 99mTc-labeled perfusion tracers may reduce the sensitivity of these agents in detecting subcritical coronary artery disease. The most notable new perfusion agent is 99mTc-labeled bis(N-ethoxy, N-ethyl dithiocarbamato) nitrido technetium(v), which is considered to be the 99mTc-labeled equivalent of 201Tl. However, 99mTc-labeled bis(N-ethoxy, N-ethyl dithiocarbamato) nitrido technetium(v) is a neutral compound with kinetic properties that are very different from those of 201Tl. Myocardial perfusion imaging is often conducted in conjunction with exercise or with different pharmacologic stressors, both of which augment regional flow heterogeneity. Each of these stressors has unique effects on the coronary vasculature and influences the behavior of the radiolabeled perfusion agents. The substantial differences in myocardial uptake, clearance kinetics, and biodistribution between each of the 99mTc-labeled perfusion tracers and 201Tl should be considered in the clinical application of perfusion imaging. The myocardial retention of all of the agents is affected by myocardial viability. However, 201Tl demonstrates greater differential clearance from normal and ischemic regions (redistribution), making 201Tl a better agent for assessment of viability, particularly in patients with extremely low flow. In contrast, agents that do not redistribute, such as 99mTc-tetrofosmin, might be better for acute assessment of "risk areas" or of chest pain. Each of the available perfusion tracers has unique advantages and disadvantages that must be considered to ensure its optimal application.     

Myocardial thallium-201 kinetics during coronary occlusion and reperfusion: influence of method of reflow and timing of thallium-201 administration

Thallium-201 (201Tl) uptake and redistribution kinetics were examined in an open-chest canine preparation of occlusion and reperfusion. Seven dogs (group I) underwent 3 hr of sustained occlusion and received 1.5 mCi of 201Tl after 40 min of occlusion of the left anterior descending coronary artery (LAD). Group II (n = 18) underwent 60 min of LAD occlusion followed by sudden and total release of the ligature. Group IIa (n = 8) received intravenous 201Tl during occlusion of the LAD, whereas group IIb (n = 10) received intravenous 201Tl at the time of peak reflow. Group III dogs (n = 26) also underwent 60 min of LAD occlusion that was followed by gradual reflow through a residual critical stenosis. Animals in this group also received 201Tl either before (IIIa; n = 16) or after reflow was established (IIIb; n = 10). In group I, the relative 201Tl gradient (nonischemic minus ischemic activity) decreased from 88 +/- 8% (mean +/- SEM) to 59 +/- 6% during 3 hr of coronary occlusion (p = .034). After rapid and total reperfusion (group IIa), this gradient decreased from 71 +/- 6% during occlusion to 26 +/- 5% after reflow (p less than .001). After slow reperfusion through a residual stenosis (group IIIa), the gradient decreased from 81 +/- 5% to 31 +/- 5% (p less than .001) (p = .56 compared with group IIa). In rapidly reperfused dogs receiving intravenous thallium during peak reflow (IIb), initial 201Tl activity in the ischemic zone was 155 +/- 20% of initial normal activity and fell to 93 +/- 13% of normal after 2 hr of reperfusion. Similarly, in dogs reperfused slowly through a critical stenosis (IIIb), which received 201Tl during reflow, 201Tl activity soon after reflow was 94 +/- 4% of initial normal and decreased to 80 +/- 6% at 2 hr of reperfusion (p = .10). Histochemical evidence of necrosis was present in the biopsy region in 80% of the 20 dogs subjected to triphenyl tetrazolium chloride (TTC) staining. Microsphere-determined transmural blood flow was similar in all groups during LAD occlusion and final flows after 2 hr were comparable in all subgroups undergoing reflow. Ischemic zone flow (% normal) was significantly higher at the time of 201Tl administration in groups IIb (192 +/- 25%) and IIIb (110 +/- 5%), which received 201Tl during reflow, than in groups IIa (31 +/- 9%) and IIIa (22 +/- 5%), which received 201Tl during occlusion.(ABSTRACT TRUNCATED AT 400 WORDS)     

Assessment of left ventricular function using radionuclide angiography after dipyridamole infusion

Thirty-six patients with significant coronary artery stenosis and no previous myocardial infarction and 25 subjects with normal coronary arteries underwent 99mTc RNV before and after coronary vasodilatation induced by dipyridamole, 0.75 mg/kg, given IV over 10 min. In subjects with normal coronary arteries, dipyridamole induced an increase in LVEF (from 66 +/- 8 to 76 +/- 8 percent; mean +/- SD; p less than 0.001); in patients with significant coronary artery stenosis (greater than or equal to 75 percent narrowing of at least one major vessel), dipyridamole injection did not affect LVEF (from 63 +/- 12 to 62 +/- 12 percent). In ten patients a complete, successful PTCA was performed and the RNV with the dipyridamole test repeated. The EF did not change with the dipyridamole test before PTCA (63 +/- 7 to 65 +/- 9 percent), but increased significantly after PTCA (62 +/- 11 to 70 +/- 9 percent; p less than 0.01). Sensitivity and specificity of EF changes after dipyridamole infusion were 75 and 76 percent, respectively. The test produced no major side effects or complications. Radionuclide angiography with dipyridamole helps to detect coronary artery stenosis and might be used to assess the effects of angioplasty on coronary flow reserve.     

Myocardial perfusion in patients with permanent ventricular pacing and normal coronary arteries

OBJECTIVES: The purposes of this study were to test the specificity of dipyridamole myocardial perfusion scintigraphy in patients with permanent ventricular pacing (PVP) and to evaluate coronary blood flow and reserve in these patients. BACKGROUND: Permanent ventricular pacing is associated with exercise perfusion defects on myocardial scintigraphy in the absence of coronary artery disease (CAD). On the basis of studies in patients with left bundle brunch block, coronary vasodilation with dipyridamole has been proposed as an alternative to exercise testing for detecting CAD in paced patients, but this approach has never been tested. METHODS: Fourteen patients with a PVP and normal coronary arteries underwent stress thallium-201 scintigraphy and cardiac catheterization. In these patients and in eight control subjects, coronary flow velocities were measured in the left anterior descending coronary artery (LAD) and in the dominant coronary artery before and after adenosine administration. RESULTS: In the paced patients, coronary flow velocities in the LAD and in the dominant coronary artery were significantly lower than those in the control subjects. In addition, seven patients showed perfusion defects on dipyridamole thallium-201 single-photon emission computed tomography, with a specificity of 50% for this test. The defect-related artery in these patients had lower coronary flow reserve (2.6 +/- 0.5) as compared with those without perfusion defects (3.9 +/- 1.0, p < 0.05) or the control group (3.5 +/- 0.5, p < 0.05). CONCLUSIONS: Permanent ventricular pacing is associated with alterations in regional myocardial perfusion. Furthermore, abnormalities of microvascular flow, as indicated by reduced coronary flow reserve in the defect-related artery, are at least partially responsible for the uncertain specificity of dipyridamole myocardial perfusion scintigraphy.     

Relations of the myocardial imaging agents 99mTc-MIBI and 201T1 to myocardial blood flow in a canine model of myocardial ischemic insult

Myocardial imaging with thallium 201 has proven to be an important clinical procedure to assess the severity of the myocardial ischemic insult. Uptake of 201Tl is related to perfusion to and extraction by intact myocardium. Recently, a newer group of agents based on 99mTc alkyl isonitriles has been developed and appears promising for myocardial imaging. Although the distribution of this new agent has been shown to be related to myocardial perfusion, its dependence on myocardial integrity has not been established. This study compared the distribution of 99mTc-2-methoxy-isobutyl-isonitrile (99mTc-MIBI) with that of 201Tl in a clinically relevant canine model of ischemic insult. Fifteen adult dogs underwent 2 hours of occlusion by left anterior descending coronary artery ligation followed by reperfusion. In one group of dogs, 201Tl and 99mTc-MIBI were administered 5 minutes before 35 minutes of reflow (group 1, n = 5). In the other animals, the agents were given 5 minutes after onset of reflow, and dogs were killed after 10 (group 2, n = 5) and 35 minutes of reperfusion (group 3, n = 5). 99mTc-MIBI activity was significantly correlated with 201Tl activity (r = 0.91, 0.77, and 0.92, for groups 1, 2, and 3, respectively). Both 201Tl and 99mTc-MIBI activities were correlated similarly with blood flow in all models. In groups 1 and 2, 201Tl and 99mTc-MIBI activities correlated directly with microsphere-determined blood flow, whereas in group 3, they correlated inversely. The present study shows that in these models of myocardial ischemic insult, 99mTc-MIBI distribution is closely related to that of 201Tl.     

Effects of acute left anterior descending occlusion on regional myocardial blood flow and wall thickening in the presence of a circumflex stenosis in dogs

In this study, 2 hypotheses were tested: (1) Myocardium supplied by a stenosed circumflex coronary artery (LC) does not demonstrate compensatory increases in regional blood flow and systolic thickening when the left anterior descending coronary artery (LAD) is acutely occluded. (2) Blood flow to myocardium in the distribution of an acutely occluded LAD is lower in the presence of a stenosed than in the presence of an unstenosed LC. Fifty-three open-chest, anesthetized dogs were studied. Regional coronary blood flow (8 to 10-mu microspheres) and wall thickening (sonomicrometer crystals) were measured before and after LAD occlusion in the presence of an unstenosed LC artery, and a moderate and severe LC stenosis. Acute LAD occlusion in the presence of an unstenosed LAD was not accompanied by a significant increase in regional blood flow to the remote LC bed; posterior myocardial wall thickening, however, increased from 0.22 +/- 0.02% to 0.24 +/- 0.02% (p = 0.04). In the presence of a moderate LC stenosis (gradient 29 +/- 1 mm Hg), LAD occlusion was associated with a 9% (p = 0.02) decrease in endocardial flow and an 11% decrease in the endocardial/epicardial flow ratio (p = 0.002). Transmural flow was unchanged and there was no compensatory increase in posterior wall thickening. In the presence of a more severe LC stenosis (gradient 49 +/- 1 mm Hg), central LC endocardial flow decreased by 32% (p = 0.0008) at the time of LAD occlusion. Similar alterations were noted in the peripheral LC region.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of ischemia on thallium-201 clearance from the myocardium

To determine the effect of ischemia on myocardial clearance of thallium-201 (201Tl), we studied 12 dogs with ischemia produced after the injection of Tl. Tl was given I.V. 10 minutes before left anterior descending (LAD) coronary artery ligation. 85Sr-microspheres (MS) were administered 5 minutes later, and control biopsies were obtained from the myocardium. The LAD was tied and repeat biopsies obtained from the ischemic zone (IZ) and normal zone (NZ) 15 minures and 2 hours later. 46Sc-MS were given just before the final giopsy. Tl activity in the IZ was not significantly different from that in the NZ either before LAD occlusion or 15 minutes and 2 hours later. Tl clearance at the end of 2 hours was not significantly different (27 +/- 5% vs 28 +/- 5%, IZ vs NZ respectively) between the two zones. The half-time of Tl clearance from both the IZ and NZ was calculated at 4.5 hours (consistent with previously reported normal values). This occurred despite a decrease in regional myocardial blood flow to 24 +/- 6% of control (P less than 0.01) in the IZ and an increase to 47 +/- 14% of control (P less than 0.01) in the NZ during the study. We conclude that myocardial ischemia does not alter the normal rate of Tl clearance from the myocardium.     

Evaluation and clinical use of early washout ratio of thallium-201 in normal and ischemic myocardium after dipyridamole-induced vasodilation using ring-type emission computed tomography

Using newly developed ring-type emission computed tomography (SPECT), we investigated the washout ratio (WR) of T1-201 in the myocardium quantitatively with fast dynamic scanning after infusion of dipyridamole (0.57 mg/kg), and assessed the feasibility of early WR as a marker to detect coronary artery disease. Twenty-three patients with and 8 patients without coronary artery disease had serial SPECT images obtained every 5 min for 45 min and at 180 min after dipyridamole and subsequent T1-201 injection. The best appropriate transaxial slice was selected for WR analysis. Most appropriate diagnostic time was 25 min after infusion of T1-201 (WR-25). Normal WR-25 was 7.1 +/- 4.0%, 5.9 +/- 3.1% and 7.1 +/- 2.3% at the septum, anterior and lateral wall, respectively. Sensitivity, specificity and accuracy to identify coronary stenosis greater than 50% with a usage of abnormal WR-25, defined as WR-25 less than (mean of normals--1SD) in each region of inferest of the left ventricle (LV), were 96%, 100% and 97%, respectively. These results were better than those achieved by visual analysis (sensitivity 78%, specificity 100%, accuracy 84%). In patients with single as well as multivessel disease, the regional accuracy in assessing stenosis of more than 50% in the left anterior descending artery (LAD) and left circumflex artery (LCX) by WR-25 was 94% and 83%, respectively, which was significantly better than using visual methods (LAD 72% and LCX 50%; p less than 0.05). Thus, evaluation of early washout ratios (WR-25) after dipyridamole injection is a valuable method to increase sensitivity in assessing regional myocardial perfusion abnormality and is helpful in detection of ischemic heart disease, even with multivessel disease.     

Myocardial thallium-201 kinetics and regional flow alterations with 3 hours of coronary occlusion and either rapid reperfusion through a totally patent vessel or slow reperfusion through a critical stenosis

Myocardial thallium-201 kinetics and regional blood flow alterations were examined in a canine model using 3 hours of coronary occlusion and different methods of reperfusion. Group I comprised 10 dogs undergoing a 3 hour left anterior descending artery occlusion and no reperfusion. Group II comprised seven dogs undergoing 3 hours of left anterior descending artery occlusion and rapid reperfusion through a totally patent vessel. Group III comprised 10 dogs undergoing 3 hours of left anterior descending artery occlusion and slow reperfusion through a residual stenosis. All dogs received 1.5 mCi of thallium-201 after 40 minutes of coronary occlusion. During occlusion and 2 hours of reperfusion, serial hemodynamic, blood flow and myocardial thallium-201 activity measurements were made. The relative thallium-201 gradient (normal zone minus ischemic zone activity when initial normal activity is expressed as 100%) during left anterior descending coronary occlusion was similar in all groups. Group I, 87 +/- 3%; Group II, 78 +/- 6%; Group III, 83 +/- 6% (p = NS). After 2 hours of either method of reperfusion, the final relative gradient had decreased to a similar level (Group II, 51 +/- 9%; Group III, 42 +/- 6%). These values were not significantly different from the final relative thallium-201 gradient seen in dogs undergoing a sustained 3 hour occlusion (Group I, 55 +/- 5%). After 2 hours of reperfusion, both methods of reflow were associated with similar degrees of "no reflow." Transmural flows in the central ischemic zone were 89 +/- 10% of normal in Group II and 71 +/- 6% of normal in Group III after reperfusion, with both flows substantially higher than the relative thallium-201 activities in these dogs. Infarct size (percent of left ventricle) determined with triphenyltetrazolium chloride was similar in all groups (Group I, 24 +/- 4%; Group II, 29 +/- 4%; Group III, 25 +/- 4%). Thus, in this experimental canine model, 3 hours of coronary occlusion followed by either rapid reperfusion through a totally patent vessel or slow reperfusion through a critical stenosis resulted in little delayed thallium-201 redistribution or myocardial salvage as assessed histologically, despite significant recovery of regional flow.     

The physiologic basis of dobutamine as compared with dipyridamole stress interventions in the assessment of critical coronary stenosis

Noninvasive cardiac imaging with echocardiography or thallium-201 scintigraphy utilizing pharmacologic agents as alternatives to exercise is gaining popularity. We investigated the physiologic rationale underlying the optimal choice of pharmacologic stress for functional versus perfusion imaging. With the use of an open-chest dog model, a critical stenosis of the left circumflex coronary artery was produced with total ablation of hyperemic response to a 15 sec period of complete occlusion. Regional left ventricular wall thickening was assessed by quantitative two-dimensional echocardiography. Regional myocardial blood flow was determined by microspheres in both the flow-restricted left circumflex area and the control area supplied by the left anterior descending artery. Eight dogs received 15 micrograms/kg/min dobutamine intravenously for 10 min, and nine dogs received 0.14 mg/kg/min dipyridamole intravenously for 4 min. Dobutamine induced wall thickening abnormalities in all dogs while dipyridamole induced dysfunction in only 55% of the animals studied (p less than .01). Subendocardial blood flow to the left circumflex area was unchanged after both dobutamine and dipyridamole when compared with baseline blood flow. However, subendocardial blood flow increased markedly after dipyridamole in the control area. Regional subendocardial blood flow ratio (left anterior descending/left circumflex) was 3.74 +/- 0.09 (mean +/- SEM) after dipyridamole versus 1.27 +/- 0.09 after dobutamine (p less than .001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of transesophageal doppler coronary flow reserve measurements with thallium-201 single-photon emission computed tomography imaging in assessment of left anterior descending artery stenoses

Background and hypothesis: Recent studies demonstrate the feasibility of coronary flow reserve measurements by transesophageal echocardiographic (TEE) Doppler recordings of coronary sinus or left anterior descending (LAD) coronary artery flow velocity for detecting stenoses of the LAD artery. This study compares coronary flow reserve measurements by Doppler TEE with thallium-201 (²⁰¹T1) single-photon emission computed tomography (SPECT) in patients with proximal single-vessel LAD stenosis. Methods: Nineteen patients with various degrees of LAD stenosis (mean area stenosis 71 ± 24%; range 24-96%) were studied. Area stenosis by quantitative coronary angiography was < 75% in 7 patients and > 75% in 12 patients. Transesophageal LAD and coronary sinus Doppler measurements were performed at baseline and after intravenous dipyridamole. Coronary flow reserve was calculated as the ratio of hyperemic to baseline average peak velocities. Predefined coronary flow reserve cut-off values of 1.8 for the coronary sinus method and of 2.0 for the LAD method were used for diagnosis of significant LAD stenosis. Results were compared with qualitative ²⁰¹T1 dipyridamole SPECT. Results: Overall predictive accuracy for diagnosis of > 75% LAD stenosis was 79% for ²⁰¹T1 SPECT, 77% for the transesophageal LAD and 79% for the transesophageal coronary sinus technique. Concordant results between ²⁰¹T1 SPECT and the LAD and coronary sinus Doppler methods were observed in 79% and 71% of patients, respectively. Conclusions: Thallium-201 SPECT and transesophageal Doppler assessment of coronary flow reserve have similar accuracy for diagnosing significant proximal LAD stenosis. Therefore, both transesophageal Doppler techniques might constitute another widely available, noninvasive method for assessment of left coronary artery disease, if disease location is proximal.