Myocardial clearance of technetium-99m-teboroxime in reperfused injured canine myocardium.

BACKGROUND: Recent technical developments using solid-state technology have enabled rapid image acquisition with single photon emission computed tomography (SPECT) and have led to a renewed interest in technetium-99m-teboroxime (Tc-99m-teboroxime) as a myocardial imaging agent. Tc-99m-teboroxime has demonstrated high myocardial extraction, linear myocardial uptake relative to flow even at high flow rates, rapid uptake and clearance kinetics, and differential clearance in the setting of ischemia. However, the myocardial clearance kinetics of Tc-99m-teboroxime in a model of myocardial injury has not been previously reported. Thus, the purposes of this study were to use a canine model of ischemia-reperfusion to (1) compare Tc-99m-teboroxime clearance kinetics in normal and ischemic-reperfused myocardium and (2) assess the utility of Tc-99m-teboroxime clearance kinetics in determining the severity of injury following ischemia-reperfusion. METHODS: Thirteen dogs underwent left circumflex coronary artery (LCx) occlusion for either 30 min (IR30, n = 6) or 120 min (IR120, n = 7), followed by reperfusion, and finally Tc-99m-teboroxime administration 120 min after reperfusion. Microsphere blood flows were determined at baseline, during occlusion, after reperfusion, and before euthanasia. Post-mortem, area at risk was determined using Evans blue dye, and viability was determined using triphenytetrazolium chloride (TTC) staining. The hearts were then subdivided into 24 pieces and Tc-99m activity was measured in a well counter. RESULTS: TTC-determined infarct area as a percentage of total left ventricular myocardium was 1.1% ± 0.3% for the IR30 group and 7.5% ± 2.9% for the IR120 group (p < 0.05). During coronary occlusion, both the IR30 and IR120 groups demonstrated decreases in percent wall thickening in the ischemia-reperfusion zone (IRZ) as compared with the normal zone (NZ). In the IR30 group, percent wall thickening in the IRZ recovered during the reperfusion phase as compared with the NZ. In the IR120 group, percent wall thickening in the IRZ remained depressed during the reperfusion phase and through the end of the experiment as compared with the NZ. Final Tc-99m-teboroxime myocardial IRZ/NZ activity ratio was 0.94 ± 0.01 for the IR30 group, compared to 0.80 ± 0.01 for the IR120 group (p < 0.05). CONCLUSIONS: Tc-99m-teboroxime demonstrates moderate differential clearance in a model of severe injury with 120 min of ischemia-reperfusion, but only minimal differential clearance in a model of mild injury with 30 min of ischemia-reperfusion. Thus, Tc-99m-teboroxime clearance kinetics may be helpful in differentiating normal and minimally injured from severely injured myocardium.

Beta adrenergic receptor blockade causing severe left ventricular systolic dysfunction during dobutamine stress echocardiography in a patient with no structural heart disease.

A 41-year-old woman with a history of neurocardiogenic syncope treated with beta-blockers was admitted with chest pain. Dobutamine echocardiogram images demonstrated decreased global LV systolic wall motion and thickening. Coronary angiograms were normal. Beta-blockers were stopped and dobutamine stress echocardiogram (DSE) was repeated. Dobutamine images demonstrated increased global LV systolic wall motion and thickening. Beta-blockers were restarted and again dobutamine produced global LV dysfunction. This case suggests that DSE wall motion response may be falsely abnormal in a patient on beta-blockers. Physicians should be aware of this possibility when interpreting dobutamine echocardiography in patients taking beta-blockers.

99mTc-glucarate kinetics differentiate normal, stunned, hibernating, and nonviable myocardium in a perfused rat heart model.

PURPOSE: (99m)Tc-glucarate is an infarct-avid imaging agent. However, patients may have mixtures of normal, irreversibly injured, stunned, and hibernating myocardium. The purposes were to determine (99m)Tc-glucarate uptake and clearance kinetics in these four conditions, and its ability to determine the extent of injury. METHODS: Twenty-two perfused rat hearts were studied: controls (n = 5), stunned (n = 5; 20-min no-flow followed by 5-min reflow), hibernating (n = 6; 120-min low flow at 4 ml/min), and ischemic-reperfused (n = 6; 120-min no-flow followed by reflow). (99m)Tc-glucarate was then infused. Tracer activity was monitored using a NaI scintillation detector and a multichannel analyzer. Creatine kinase, electron microscopy, and triphenyltetrazolium chloride determined viability. RESULTS: (99m)Tc-glucarate 10-min myocardial uptake was significantly greater in ischemic-reperfused (2.50 +/- 0.09) (cpm, SEM) than in control (1.74 +/- 0.07), stunned (1.68 +/- 0.11), and hibernating (1.59 +/- 0.11) (p < 0.05). Tracer retention curves for ischemic-reperfused were elevated at all time points as compared with the other groups. (99m)Tc-glucarate 60-min myocardial uptake was significantly greater in ischemic-reperfused (7.60 +/- 0.63) than in control (1.98 +/- 0.15), stunned (1.79 +/- 0.08), and hibernating (2.33 +/- 0.15) (p < 0.05). The 60-min well-counted tracer activity ratio of ischemic-reperfused to control was 9:1 and corroborated the NaI detector results. Creatine kinase, triphenyltetrazolium chloride, and electron microscopy all demonstrated significantly greater injury in ischemic-reperfused compared to the other groups. An excellent correlation was observed between viability markers and tracer activity (r = 0.99 triphenyltetrazolium chloride; r = 0.90 creatine kinase). CONCLUSION: (99m)Tc-glucarate activity continually and progressively increased in irreversibly injured myocardium. (99m)Tc-glucarate uptake was strongly correlated with myocardial necrosis as determined by three independent assessments of viability. There were minimal and similar (99m)Tc-glucarate uptakes in control, stunned, and hibernating myocardium.

Monocationic radiotracer kinetics and myocardial infarct size: a perfused rat heart study.

OBJECTIVE: To compare the myocardial kinetics of three (99m)technetium-labeled monocationic tracers [methoxy-isobutylisonitrile (MIBI), tetrofosmin, and Q12] in a model of ischemia-reperfusion (IR) to determine their abilities to assess myocardial viability. METHODS: Isolated perfused rat hearts (n = 30) were studied in control and IR groups for each tracer. IR hearts were treated with 120 min global no-flow followed by 5 min reflow, then 60 min tracer uptake/clearance. Tracer kinetics were monitored using a scintillation detector. RESULTS: This model produced significant myocardial injury, without significant differences in the percentage of injured myocardium by triphenyltetrazolium chloride (TTC) staining and creatine kinase (CK) assay. Transmission electron microscopy analysis also confirmed necrosis with abundant mitochondrial damage in the IR hearts. All three IR groups exhibited significantly less mean (+/-standard error of the mean) tracer retention than matched controls (MIBI 73.4 +/- 4.9% vs. 96.9 +/- 1.76%, tetrofosmin 38.7 +/- 4.6% vs. 82.2 +/- 3.5%, and Q12 23.0 +/- 2.5% vs. 43.8 +/- 1.8%, respectively; P < 0.05). Tetrofosmin IR hearts exhibited 54 +/- 9% of control myocardial retention, which was significantly less than either MIBI (86 +/- 5%, P < 0.05) or Q12 (63 +/- 6%, P < 0.05); thus, tetrofosmin provided the best differentiation between nonviable and normal myocardium. Furthermore, tetrofosmin end activity (%id/g) in controls was significantly higher than Q12 (4.09 +/- 0.04 vs. 1.71 +/- 0.06, respectively, P < 0.05), and tetrofosmin end activity (%id/g) in IR hearts was significantly higher than Q12 (2.19 +/- 0.37 vs. 1.06 +/- 0.12, respectively, P < 0.05). The correlation between end activity and viable myocardium determined by TTC staining was r = 0.66 (P < 0.05) for MIBI, r = 0.94 (P < 0.05) for tetrofosmin, and r = 0.91 (P < 0.05) for Q12. The correlation between myocardial end activity and myocardial CK leak was r = -0.62 (P < 0.05) for MIBI, r = -0.87 (P < 0.05) for tetrofosmin, and r = -0.89 (P < 0.05) for Q12. CONCLUSIONS: Nonviable myocardium can be distinguished from normal myocardium by the retention kinetics of all three monocationic tracers studied. Tetrofosmin and Q12 end activities demonstrate the best correlation with infarct size. However, tetrofosmin kinetics may combine the greatest differentiation between nonviable and normal myocardium, while still retaining adequate activity for imaging.

99mTc-sestamibi kinetics predict myocardial viability in a perfused rat heart model.

INTRODUCTION: (99m)Tc-sestamibi has been proposed as a viability imaging agent. The purposes of this study were: (1) to determine the relationship between myocardial viability and (99m)Tc-sestamibi kinetics using perfused rat heart models across a full spectrum of viability, (2) to do so under conditions where myocardial flow was controlled and held constant, and (3) to do so using multiple quantitative methods to assess myocardial viability. METHODS: Twenty-three isolated rat hearts were perfused retrogradely with a modified Krebs-Henseleit (KH) solution. Four groups were studied: controls (C, n = 6), stunned (S, n = 6), ischemic-reperfused (IR, n = 6), and calcium injured (CAL, n = 5). Following a 20-min baseline and subsequent treatment phase, (99m)Tc-sestamibi was infused over 60 min (uptake) followed by 60 min clearance. Treatment phases consisted of 20 min no flow for S, 60 min no flow followed by 60 min reflow for IR, and 10 min infusion of KH solution without calcium followed by 20 min infusion of KH solution with 2 times normal calcium for CAL hearts. Creatine kinase (CK) assay, triphenyltetrazolium chloride (TTC) staining, and transmission electron microscopic (TEM) analysis were used to determine tissue viability. RESULTS: Myocardial peak (99m)Tc-sestamibi uptake (%id) was significantly decreased in IR (4.11 +/- 0.22 SEM; p < 0.05) and CAL (1.07 +/- 0.13; p < 0.05), but not in S (4.88 +/- 0.17) as compared with C (5.99 +/- 0.50). One hour fractional retention was 79.3 +/- 1.9% for C, 80.3 +/- 1.3% for S (p = n.s.), 79.1 +/- 1.8% for IR (p = n.s.), and 14.9 +/- 4.3% for CAL (p < 0.05 compared to all other groups). (99m)Tc-sestamibi absolute retention (%id) 1 h after the end of tracer administration was significantly decreased in IR (3.26 +/- 0.23) and CAL (0.15 +/- 0.02) as compared with both S (3.92 +/- 0.16) and C (4.52 +/- 0.32) (p < 0.05). CK increased significantly from baseline in the IR and CAL hearts. TTC determined percent viability was 100 +/- 0% for C, 98.3 +/- 1.1% for S, 82.8 +/- 2.6% for IR, and 0.0 +/- 0% for CAL. TEM analysis supported these findings. End tracer activity was significantly correlated with TTC determined percentage viable myocardium (r = 0.93, p < 0.05) and CK leak (r = -0.90, p < 0.05). CONCLUSION: (99m)Tc-sestamibi myocardial activity is significantly reduced in areas of nonviability after 1 h of tracer uptake and 1 h of tracer clearance. There is a linear correlation between myocardial viability, as determined by three independent methods, and tracer activity.

(99m)Tc-glucarate imaging for the early detection of infarct in partially reperfused canine myocardium.

PURPOSE: (99m)Tc-glucarate is an imaging agent developed for the detection of acutely infarcted myocardium. The purposes of the current study were to (1) determine whether (99m)Tc-glucarate can detect acute infarct in the setting of only partial minimal reperfusion, (2) study the persistence and time course of scan positivity following coronary occlusion and intravenous tracer injection, (3) assess the ability of (99m)Tc-glucarate to determine infarct size, and (4) compare these data with previous results obtained using a 100% reperfusion model. METHODS: Six dogs underwent left circumflex (LCx) coronary occlusion for 90 min, followed by 10% epicardial blood flow reperfusion. Fifteen mCi (555 MBq) (99m)Tc-glucarate was injected intravenously 30 min later. Serial gamma camera images were acquired over 240 min. Microsphere blood flow determinations were performed at baseline, during occlusion, during tracer administration, and just before euthanasia. Ex vivo gamma camera images were obtained. Triphenyltetrazolium chloride (TTC) staining was performed to assess infarct size. RESULTS: Qualitatively, (99m)Tc-glucarate images showed a well-defined "hot spot" in all six dogs by 30 min after tracer injection (150 min following coronary occlusion), which persisted for 240 min following tracer administration. Quantitatively, there was a significant increase in the LCx/LAD (left anterior descending) counts ratio beginning 10 min after tracer administration (130 min after occlusion), and continuing to 240 min after tracer administration. Tracer retention was 12.0+/-0.9% for the LAD and 39.0+/-4.1% for the LCx hot spot zone (p<0.05) at 240 min after (99m)Tc-glucarate injection. The correlation coefficient was 0.90 for infarct size by TTC versus (99m)Tc-glucarate. CONCLUSION: In the setting of only partial minimal coronary reperfusion following infarction, (99m)Tc-glucarate myocardial uptake is delayed and less intense compared with the setting of complete reperfusion. Nevertheless, infarcts can still be reliably detected in dogs using qualitative in vivo imaging, and significant abnormalities in quantitative parameters are observed. Thus, (99m)Tc-glucarate imaging may be useful for the clinical detection and relative sizing of acute myocardial infarction, even in the setting of only minimal coronary reperfusion.

Early detection of infarct in reperfused canine myocardium using 99mTc-glucarate.

UNLABELLED: 99mTc-Glucarate is an infarct-avid imaging agent with the potential for very early detection of myocardial infarction. The purposes of this study using a canine model were to determine (a) the time course of (99m)Tc-glucarate uptake and clearance from necrotic and normal myocardium; (b) the (99m)Tc-glucarate necrotic-to-normal activity ratio over time; (c) the time course of detectable scan positivity after intravenous administration of the tracer; and (d) the relationship of infarct size determined by triphenyltetrazolium chloride (TTC) staining versus (99m)Tc-glucarate imaging ex vivo. METHODS: A 90-min left circumflex coronary artery (LCx) occlusion was followed by 270 min of reperfusion at 100% baseline flow in 6 open-chest, anesthetized dogs. (99m)Tc-Glucarate (555 MBq [15 mCi]) was injected 30 min after reperfusion and was followed by 240 min of gamma-camera serial imaging. Microspheres were injected during baseline, occlusion, tracer injection, and before the dogs were euthanized. Creatine kinase assays were performed to assess developing injury. Ex vivo gamma-camera imaging was performed. Blood flow and tracer activity were determined by well counting. TTC stain was used to mark infarct areas, which were sized using computerized digital planimetry. RESULTS: Hemodynamics demonstrated no significant change from baseline at any time for any parameter except LCx flow, which was significantly depressed during occlusion. The mean infarct size +/- SEM was 10.7% +/- 2% of total left ventricle. Blood (99m)Tc-glucarate clearance was triexponential and rapid. Qualitative image analysis revealed a well defined hot spot after 30 min, which remained well defined through 240 min after injection (150 and 360 min after occlusion, respectively). Images were quantitatively abnormal with hot spot-to-normal zone activity ratios of >/=2:1 within 10 min of tracer administration (130 min after occlusion), reaching 8:1 at 240 min after tracer administration (360 min after occlusion). There was a linear correlation between infarct size determined by (99m)Tc-glucarate and TTC staining (r = 0.96; slope = 0.87). CONCLUSION: (99m)Tc-Glucarate marks acute myocardial infarct very early after occlusion and appears to accurately assess infarct size when compared with TTC staining.