Quantitative analysis of 123I-meta-iodobenzylguanidine (MIBG) uptake in hypertrophic cardiomyopathy

Myocardial scintigraphy with 123I-meta-iodobenzylguanidine (MIBG) and thallium-201 (201Tl) was performed in 29 patients with hypertrophic cardiomyopathy (HCM) using whole-body scintigraphy and single-photon emission computed tomography (SPECT). Nonhypertensive patients were classified into three groups according to the septal thickness determined by ultrasonography; group 1 (wall thickness less than 16 mm, n = 5), group 2 (from 16 to 20 mm, n = 12) and group 3 (greater than 20 mm, n = 4). The regional myocardial uptakes of both 201Tl and 123I-MIBG (percent of injected dose/cm3 myocardium) were higher in the more hypertrophic septa. However, when regional MIBG uptake at 3 hours was divided by the 201Tl uptake to calculate the MIBG uptake per unit of blood flow, the hypertrophic septa showed lower mean values--0.39 +/- 0.23 and 0.50 +/- 0.10 in groups 3 and 2, respectively (p less than 0.1 compared with 0.69 +/- 0.20 in group 1). The regional MIBG clearance rate in the septum was significantly higher in group 3 compared with group 1 (13.4 +/- 8.0%/hr versus 1.5 +/- 6.2%/hr, p less than 0.05). The uptake and 123I-MIBG clearance rate in the lateral wall showed a similar tendency. Myocardial uptake determined by whole-body scintigraphy was slightly increased in group 2 (3.5 +/- 0.6%, p less than 0.05) compared with group 1 (2.7 +/- 0.8%); however, it was lower in group 3 (2.7 +/- 0.4%). Myocardial 123I-MIBG distribution demonstrated various patterns in comparison with 201Tl distribution, suggesting that flow-independent changes in sympathetic innervation or activity may exist in patients with HCM.(ABSTRACT TRUNCATED AT 250 WORDS)     

Coronary collateral vessels in patients with previous myocardial infarction

To assess the degree of collateral vessels after myocardial infarction, coronary angiograms, left ventriculograms, and exercise thallium-201 myocardial scintigrams of 36 patients with previous myocardial infarction were reviewed. All 36 patients had total occlusion of infarct-related coronary artery and no more than 70% stenosis in other coronary arteries. In 19 of 36 patients with transient reduction of thallium-201 uptake in the infarcted area during exercise (Group A), good collaterals were observed in 10 patients, intermediate collaterals in 7 patients, and poor collaterals in 2 patients. In 17 of 36 patients without transient reduction of thallium-201 uptake in the infarcted area during exercise (Group B), good collaterals were seen in 2 patients, intermediate collaterals in 7 patients, and poor collaterals in 8 patients (p less than 0.025). Left ventricular contractions in the infarcted area were normal or hypokinetic in 10 patients and akinetic or dyskinetic in 9 patients in Group A. In Group B, 1 patient had hypokinetic contraction and 16 patients had akinetic or dyskinetic contraction (p less than 0.005). Thus, patients with transient reduction of thallium-201 uptake in the infarcted area during exercise had well developed collaterals and preserved left ventricular contraction, compared to those in patients without transient reduction of thallium-201 uptake in the infarcted area during exercise. These results suggest that the presence of viable myocardium in the infarcted area might be related to the degree of collateral vessels.     

Fatty acid analogue accumulation: a marker of myocyte viability in ischemic-reperfused myocardium

A 3-methyl substituted radioiodinated long chain fatty acid analogue was evaluated as an agent for the noninvasive detection of altered fatty acid uptake in reperfused, postischemic myocardium. This iodinated fatty acid analogue, 15-(para-iodophenyl)-3-methyl pentadecanoic acid, was given intravenously at 3 hours of reperfusion following 15 minutes (Group 1, n = 5 dogs) or 60 minutes (Group 2, n = 5 dogs) of left anterior descending coronary artery occlusion. Myocardial blood flow (MBF) was measured during occlusion and reperfusion with radiolabeled microspheres administered via the left atrium. Paired ultrasonic subendocardial crystals were placed in the ischemic perfusion bed to assess regional left ventricular systolic function at baseline, during ischemia and reperfusion. Electron microscopic analysis and staining with triphenyltetrazolium chloride (TTC) was performed. Groups 1 and 2 dogs had similar (p = NS) myocardial blood flows during occlusion. TTC positive 1 g endocardial segments from Group 1 (n = 98) and Group 2 (n = 71) had 37% greater fatty acid analogue activity (0.26 +/- 0.04 vs. 0.19 +/- 0.09 percent injected dose per gram; p less than 0.05) compared with TTC negative segments from Group 2 dogs (n = 37). When fatty acid analogue activity was related to near simultaneous reperfusion blood flow, this ratio was 27% greater (p less than 0.05) in TTC positive segments (0.38 +/- 0.1) compared with TTC negative (0.30 +/- 0.16) segments, and 9% greater than normal (0.35 +/- 0.09; p less than 0.05). While ischemic regions from both Groups 1 and 2 dogs became similarly dyskinetic during occlusion (systolic shortening, -11 +/- 6 vs. -11 +/- 2%; p = NS), TTC negative segments remained akinetic (= 1 +/- 7%) at 3 hours of reperfusion while TTC positive zones had recovered partial systolic function (8 +/- 22%). Electron microscopy confirmed the presence of reversible ultrastructural changes in TTC positive regions. A 60-minute occlusion, 3-hour reperfusion model adapted for in vivo single photon emission computed tomography showed a similar excess of 123I fatty acid activity over flow when compared to perfusion (as measured with 201Tl) in the ischemic border zone of 4/4 canine myocardial infarcts. We conclude that the accumulation of this non-beta-oxidized fatty acid analogue noninvasively identifies zones of discordance between fatty acid and flow distribution that are characteristic of ischemically "stunned" but viable myocardium.     

Myocardial viability: nuclear medicine versus stress echocardiography

The failure of nonimaging techniques in the identification of myocardial viability has promoted the clinical application of radioisotopic and echocardiographic methods. Unfortunately, none of these techniques provides, per se, a 100% predictive accuracy and only few studies have been based on the postoperative improvement in regional wall motion, the absolute "gold standard" for myocardial viability. The recent thallium-201 protocols (reinjection, late redistribution, rest studies) have provided nuclear cardiology with a cell membrane integrity image able to unmask viable myocardium in more than 85% of viable segments. Sestamibi has been introduced as a nonrecirculating flow tracer able to detect transient ischemia as well as thallium-201. Its main limit, a high sensitivity to intermediate reductions in coronary blood flow, determines a high incidence of false positive studies. Positron emission tomography allows the evaluation of regional myocardial blood flow and metabolism. The marker of viable myocardium is the mismatch between reduced blood flow and normal or increased uptake of 18-F fluorodeoxyglucose. This technique allows the detection of viable tissue in most segments showing improved postoperative function. In our experience, applying a multiparametric approach, rest thallium-201 scan, rest sestamibi, dobutamine, and dipyridamole echocardiography showed a sensitivity and a specificity of 86%, 75%, 82%, 75% and 92%, 84%, 92%, and 89%, respectively, in the detection of residual viability. The main advantages of thallium-201 are reproducibility and standardization; those of stress echo are low cost and availability. In patients with severely depressed ventricular function, positron emission tomography retains a primary role when compared to thallium-201 and stress echocardiography.     

Myocardial viability in patients with Q wave myocardial infarction and no residual ischemia.

BACKGROUND. Coronary revascularization in patients with persistent angina after myocardial infarction reduces the incidence of recurrent angina pectoris and myocardial infarction and improves left ventricular function. The results of revascularization after a Q wave myocardial infarction when there is no residual ischemia may depend on myocardial viability. METHODS AND RESULTS. To determine whether there was viable myocardium in the infarct area in the absence of clinical and scintigraphic evidence of myocardial ischemia, 15 asymptomatic patients with a Q wave myocardial infarction, no redistribution on stress 201Tl test, and single-vessel disease (greater than 70% stenosis) with persistent anterograde blood flow were randomized to percutaneous transluminal coronary artery angioplasty (PTCA) or conservative medical treatment. After 2 months of follow-up, mean coronary blood flow measured by Doppler catheter in the infarct-related artery was higher in the PTCA treatment group (33 +/- 6 ml/min, n = 8) than in the conservative treatment group (16 +/- 4 ml/min, n = 7; p less than 0.05 between groups). The 201Tl pathological-to-normal ratios measured on postexercise images did not change in patients treated conservatively during the follow-up period (delta = +1.1 +/- 2.2%; NS from baseline) but increased significantly in patients treated by PTCA (delta = +8.5 +/- 2.3%; p less than 0.01 from baseline; p less than 0.05 between groups). Segmental wall motion improved on left ventricular angiography 2 months after PTCA (delta = +11.5 +/- 2.2%; p less than 0.001 from baseline) significantly more than in the conservative treatment group (delta = +4.1 +/- 1.4%; p less than 0.05 between both groups). Improvements of 201Tl ratios and segmental wall motion indexes correlated significantly (r = 0.73, p = 0.002). The mild improvement of global left ventricular ejection fraction measured in the PTCA treatment group did not differ significantly from changes in the conservative treatment group. CONCLUSIONS. Successful angioplasty of the stenotic infarct artery in patients with a Q wave myocardial infarction and no residual ischemia improved coronary flow, 201Tl uptake in the infarct area, and regional wall motion. Therefore, myocardial viability may last several weeks, as long as residual blood flow persists in the infarct-related artery. Optimal assessment of viability by imaging techniques should identify patients who are most likely to benefit from revascularization.     

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.     

Regional myocardial nitrogen-13 glutamate uptake in patients with coronary artery disease: inverse post-stress relation to thallium-201 uptake in ischemia

The purpose of the present study was to evaluate the clinical significance of myocardial scintigraphy with nitrogen-13 (N-13) glutamate as a marker of myocardial metabolism. Within 2 weeks after cardiac catheterization, 25 patients with single vessel left anterior descending coronary artery disease underwent thallium-201 imaging (5 min and 3 h after injection) and N-13 glutamate scintigraphy (10 min after injection). Radionuclide studies were performed in the 30 degrees left anterior oblique projection after symptom-limited bicycle exercise, and regional tracer uptake was quantified by computer-assisted placement of regions of interest within the regions of myocardial activity. Poststenotic tracer uptake in the perfusion bed of the left anterior descending coronary artery (septum) was then normalized to the tracer uptake in the nondiseased left circumflex territory (posterolateral segments = 100%). In 14 patients with a history of previous myocardial infarction (Subgroup A), deficient poststenotic N-13 uptake correlated closely with thallium-201 uptake in both initial (r = 0.82, p less than 0.001) and redistribution (r = 0.74, p less than 0.01) scintigrams. By contrast, in 11 patients with no previous myocardial infarction and normal left ventricular function at rest (Subgroup B), initial uptake of both tracers was inverse: poststenotic N-13 glutamate uptake increased with decreasing thallium-201 uptake during exercise-induced ischemia (r = -0.64, p less than 0.05) and was closely correlated with the percent thallium-201 redistribution (r = 0.74, p less than 0.01). Thus, augmented accumulation of N-13 glutamate in reversibly ischemic (that is, viable) myocardium, and decreased uptake in myocardial scar tissue suggest the clinical usefulness of this metabolic tracer in the differentiation between viable (metabolically active) and irreversibly damaged myocardium.     

Relation between regional distribution of thallium-201 and myocardial blood flow in normal,acutely ischemic,and infarcted myocardium

Myocardial localization of thallium-201 was compared with direct measurements of myocardial perfusion in normal, acutely ischemic, and recently infarcted myocardium. Studies were performed in 6 chronically instrumented dogs that were subjected to myocardial infarction by occlusion of the proximal left circumflex coronary artery. Four days after myocardial infarction, thallium-201 and 9 ± 1 μm niobium-95-labelled microspheres were injected simultaneously after acute left anterior descending coronary arterial occlusion; the animals were killed 5 minutes later and the entire left ventricle was sectioned into 1 to 2 g samples. Regression analyses between thallium-201 activity and regional myocardial blood flow using all myocardial samples demonstrated a very close linear relation in each dog; r values were 0.98 or greater, indicating that the initial localization of thallium-201 in acutely ischemic and recently infarcted myocardium as a function of regional blood flow was essentially identical. Consequently, in each dog the regional distribution of thallium-201 closely approximated myocardial perfusion over a wide range of blood flow and potentially different local metabolic conditions that may be encountered in the clinical use of the isotope.     

Beta-methyl-15-P-[123I] iodophenyl-pentadecanoic acid and thallium-201 in the assessment of myocardial perfusion defects

The purpose of this investigation was to examine the ability of beta-methyl-15-P-[123I]-iodophenyl-pentadecanoic acid (beta 123IPPA) and thallium-201 to assess the ischemic risk zone associated with myocardial infarction. The hearts of mongrel dogs were infarcted by ligating the left anterior descending coronary artery and at 6 h post infarction injected with thallium-201 (2 mCi; scanning time 30 mins) followed by beta 123IPPA (3 to 5 mCi; scanning time 30 mins). Scintigraphic assessment of the perfusion defect yielded perfusion defect size (percentage of whole slice), which was then compared to the defect when assessed by tetrazolium staining. Myocardial ratios were calculated to assess differences in localization between tracers. Any differences noted may affect identification of the area at risk following acute myocardial infarction. A slice-by-slice comparison of perfusion defect size for scintigraphic methods and histochemical method showed no significant difference between beta 123IPPA and thallium-201. The mean ratio for myocardial defect size expressed as beta 123IPPA/thallium-201 was 1.03 +/- 1.29. Enzymatic analysis demonstrated significant increases in creatine kinase (160.33 +/- 46.44 to 5030.6 +/- 2238 U) and creatine kinase-MB% (31.85 +/- 15.11 to 82.99 +/- 8.14%) post infarction (P less than 0.05 in both cases). Elevated ST segments were also seen in all dogs post infarction. It can be concluded that the combined use of beta 123IPPA and thallium-201 does not allow the identification of the ischemic risk zone (percentage area at risk) often associated with myocardial perfusion defects. Problems continue to exist with image resolution and border demarcation.     

Relationship between Tl-201, Tc-99m (Sn) pyrophosphate and F-18 2-deoxyglucose uptake in ischemically injured dog myocardium

We have previously demonstrated that enhanced glucose utilization in reperfused myocardium as assessed by F-18 2-deoxyglucose (FDG) and positron tomography predicts functional recovery. In this study, we compared segmental uptake of F-18 FDG with that of Tl-201 and Tc-99m (Sn) pyrophosphate (Tc-99m PPi) as conventional markers of tissue viability in seven dogs after a 3-hour intracoronary balloon occlusion and 20 hours of reperfusion. Myocardial blood flow was determined with microspheres. Regional retention fractions were calculated from tracer tissue concentrations, the arterial input function, and blood flow. Ischemic injury was assessed by triphenyltetrazolium chloride (TTC) staining and histologic analysis. At 24 hours, blood flow was 22% lower in reperfused than in control myocardium (p less than 0.05). Uptake of Tl-201 was related linearly to blood flow (r = 0.92), while glucose utilization and Tc-99m PPi were 2.9 (p less than 0.01) and 4.7 (p less than 0.05) times higher in reperfused than in control myocardium. Retention fractions of Tc-99m PPi increased with the degree of ischemic injury, while F-18 FDG uptake was highest in segments with mild cell injury. Thus, in ischemically injured myocardium, Tl-201 primarily reflects blood flow. F-18 FDG as a marker of glucose utilization identifies ischemically injured but viable tissue. The admixture of necrotic cells can be determined with Tc-99m PPi. Our results indicate that a dual tracer approach might best characterize the presence and extent of reversibly and of irreversibly injured tissue in a given myocardial region.     

Role of myocardial perfusion imaging in evaluating thrombolytic therapy for acute myocardial infarction

Myocardial thallium-201 scintigraphy is being increasingly employed as a method for assessing the efficacy of coronary reperfusion in acute myocardial infarction. New thallium uptake after intracoronary tracer administration after successful recanalization indicates that nutrient blood flow has been successfully restored. One may also presume that some myocardial salvage occurred if thallium administered in this manner is transported intracellularly by myocytes with intact sarcolemmal membranes. However, if one injects thallium by way of the intracoronary route immediately after reperfusion, the initial uptake of thallium in reperfused myocardium may predominantly represent hyperemic flow and regional thallium counts measured may not be proportional to the mass of viable myocytes. When thallium is injected intravenously during the occlusion phase the degree of redistribution after thrombolysis is proportional to the degree of flow restoration and myocardial viability. When thallium is injected for the first time intravenously immediately after reperfusion, an overestimation of myocardial salvage may occur because of "excess" thallium uptake in the infarct zone consequent to significant hyperemia. Another approach to myocardial thallium scintigraphy in patients undergoing thrombolytic therapy is to administer two separate intravenous injections before and 24 hours or later after treatment. Clinical studies have demonstrated that the improvement in defect size on serial images predicts improvement in regional function and patency of the infarct-related vessel. Finally, patients with acute myocardial infarction who receive intravenous thrombolytic therapy are candidates for predischarge exercise thallium-201 scintigraphy for risk stratification and detection of residual ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)     

A study of the variations in myocardial perfusion induced by systemic thrombolysis in acute myocardial infarct using sequential scintigraphy with 201-thallium

To assess scintigraphic changes induced by intravenous streptokinase therapy, serial rest redistribution thallium-201 perfusion imaging was performed in 62 patients with acute myocardial infarction lasting less than 6 hours. Twenty-seven patients randomized to treatment with intravenous streptokinase (group A) and 35 to conventional therapy (group B) underwent thallium-201 scintigraphy as soon as possible after admission to the coronary care unit (early study). Regional myocardial perfusion was assessed using thallium-201 scintigraphy 7-9 days later in each patient (late study). The size of the perfusion defect was evaluated using a semi-quantitative score. The size of the perfusion defect decreased in serial scans in both group A (preintervention score: 12.1 +/- 6.8; redistribution score: 11.4 +/- 6.8; late study: 8.8 +/- 7.0) and group B (12.8 +/- 6.5; 12.3 +/- 6.7; 10.6 +/- 7.5, respectively). No statistical difference in myocardial perfusion was found between the two groups, on late study. Peak serum creatine kinase MB (CKMB) was earlier in group A than in group B (1030.8 +/- 326.6 vs 1361.0 +/- 271.1: p less than 0.001). The fast CKMB release group (onset of symptoms-peak of CKBM less than or equal to 900 minutes) exhibited higher thallium-201 uptake when compared to the slow CKMB release group, at the time of late study (perfusion defect score: 6.1 +/- 5.7 vs 10.7 +/- 7.3: p = 0.03). Reversibility was observed in 21/62 patients (34%). Reversibility corresponded to unchanged or improved perfusion defect score on late study in 18/21 patients (86%). Nevertheless 20/41 (49%) patients not showing redistribution of thallium-201 within pre-treatment defect had an improvement in regional perfusion on late study. Reversibility was observed in 9/14 (64%) patients with fast CKMB release and in 12/47 (26%) patients with slow CKMB release. We conclude that the early peak of CKMB is associated with a higher uptake of thallium-201 on late study. Furthermore, the reversibility of perfusion defect on redistribution imaging forecasts evolution of scintigraphic perfusion, but, when this is not present, it doesn't rule out late improvement of thallium-201 myocardial uptake. The low sensitivity and specificity of redistribution imaging and the procedure related delay in instituting therapy make thallium-201 scintigraphy unreliable in the evaluation of myocardial reperfusion following thrombolysis.     

Prognostic value and limitation of doughnut pattern of technetium-99m pyrophosphate myocardial uptake in acute anterior infarction

The prognostic significance of the doughnut pattern of technetium-99m pyrophosphate myocardial uptake was evaluated in 140 patients with acute anterior infarction. There were significantly higher early complications, greater mortality and more severe hemodynamic abnormalities in the doughnut pattern group than in the non-doughnut pattern group. The former had a more depressed left ventricular ejection fraction and larger thallium-201 defect size (27.6 +/- 10.4 versus 40.0 +/- 13.5%, p less than 0.001 and 9.9 +/- 3.6 versus 5.6 +/- 3.3, p less than 0.001, respectively). There was, however, considerable overlap of the ranges of these variables for both groups. The patency rate of the infarct vessel during the acute phase of infarct in each group was similar (54.8 versus 45.2%). It is concluded that the prognostic value of the doughnut pattern may be limited to some extent by this overlapping and the presence of this pattern does not appear to correlate with the lack of residual blood flow to the infarcted area.     

Value of low-dose dobutamine addition to routine dual isotope gated SPECT myocardial imaging in patients with healed myocardial infarction or abnormal wall thickening by echocardiogram

There is overlap in myocardial viability detection by thallium-201 uptake and contractile reserve (CR) using low-dose dobutamine (LDD). The dual isotope protocol was modified in this study by acquiring thallium-201 images using LDD to enhance viability detection in addition to coronary flow reserve assessment. One hundred twenty-four patients with coronary disease underwent gated single-photon emission computed tomographic thallium-201 imaging at rest with LDD (10 microg/kg/min) during acquisition followed by stress technetium-99m sestamibi myocardial perfusion (MP) imaging with dobutamine, adenosine, or treadmill exercise. F-18-fluorodeoxyglucose (FDG) positron emission tomography was obtained in 41 patients. Myocardial perfusion (MP) imaging was divided into normal, fixed, and ischemic segments, and subclassified by wall motion and/or thickening changes between 1-hour poststress and LDD into normal, fixed, or improved dysfunctional segments (CR present). Mean left ventricular ejection fraction was 39% at 1 hour after stress and 47% with LDD (p <0.001). In dysfunctional myocardium, CR was significantly higher (p <0.001) in ischemic (233 of 368) and fixed segments (150 of 335) than in normal MP segments (43 of 220). Combined MP and CR analysis showed higher accuracy and negative predictive value in identifying FDG-viable myocardium than either method alone, whereas a high positive predictive value was maintained, similar to both markers. Quantitative analysis showed significant increased wall motion and thickening with LDD compared with 1 hour after stress, which was highest in ischemic segments and lowest in fixed segments. Thus, LDD dual isotope is a practical protocol that improves viability detection by simultaneous MP and CR analysis in addition to coronary flow reserve assessment in 1 study. Moreover, it requires no extra imaging time or radioactivity than the routine protocol.     

Relation of left ventricular perfusion and wall motion with metabolic activity in persistent defects on thallium-201 tomography in healed myocardial infarction

Myocardial viability in persistent thallium (TI)-201 defect is a controversial subject. To assess metabolic activity in segments with persistent defect, stress TI-201 tomography and positron emission tomography using nitrogen-13 ammonia and fluorine-18 2-fluoro-deoxyglucose (FDG) were performed in 28 patients with healed myocardial infarction. The segments with TI-201 perfusion defect in electrocardiogram-determined infarcted areas were selected for assessment. Stress perfusion defect was detected in 61 segments by TI-201 tomography. Twenty-two patients (36%) showed transient defects with redistribution (group 1) and 39 showed persistent defects (group 2). Increase in FDG uptake was observed in 95% in group 1. Among group 2 patients, 15 segments (38%) showed an increase in FDG uptake (group 2A) while the remaining 24 (62%) did not have an increased uptake (group 2B). The decrease in nitrogen-13 ammonia perfusion was more severe in group 2B (-23 +/- 7%) than in group 2A (-13 +/- 9%) (p less than 0.005) and group 1 (-10 +/- 4%) (p less than 0.001). In addition, wall motion scores tended to be lower in group 2B (0.21 +/- 0.71), compared with group 2A (0.67 +/- 0.70) (p = 0.05) and group 1 (0.77 +/- 0.60) (p less than 0.01). These data indicate that metabolic viability was observed in approximately 40% of the segments with persistent TI-201 defect. Preservation of regional perfusion and wall motion in these areas was similar to that in areas with transient TI-201 defect.     

Experimental studies of the physiologic properties of technetium-99m isonitriles

Recently, efforts have been directed at the development of technetium-99m (Tc-99m)-labeled isonitrile compounds for assessment of regional perfusion and viability after experimental myocardial infarction or ischemia. One of the most promising of these agents, Tc-99m sestamibi, has undergone rather extensive laboratory investigation. Like thallium-201 (Tl-201), the uptake of Tc-99m sestamibi in myocardial tissue is proportional to myocardial blood flow after intravenous injection. Similar to other diffusible indicators, Tc-99m sestamibi underestimates blood flow at high flow rates. In low flow regions, the myocardial uptake of this agent is higher relative to nonischemic uptake than is microsphere-determined blood flow. This is attributed to increased extraction at low flows. This first-pass myocardial extraction fraction for Tc-99m sestamibi is less than that for Tl-201. However, Tc-99m sestamibi has a higher parenchymal cell permeability and higher volume of distribution than T;-201. Tc-99m sestamibi shows minimal "delayed redistribution" after initial intravenous administration. Uptake of Tc-99m sestamibi is not altered by myocardial "stunning" or with ischemic dysfunction produced by sustained low coronary flow. The uptake of the isonitrile is still proportional to blood flow in these situations. In intact animal models, myocardial uptake of Tc-99m sestamibi during coronary occlusion delineates the in vivo area at risk. When Tc-99m sestamibi is administered after reperfusion following variable periods of preceding coronary occlusion, Tc-99m sestamibi uptake delineates the area of viable myocardium that is salvaged and not simply the degree of reflow. This suggests that serial Tc-99m sestamibi imaging might be useful in assessing the efficacy of coronary reperfusion after thrombolytic therapy.     

Demonstration of myocardial reperfusion injury in humans: results of a pilot study utilizing acute coronary angioplasty with perfluorochemical in anterior myocardial infarction

Reperfusion may limit the amount of potentially salvageable myocardium through the introduction of cellular elements into previously ischemic but viable myocardium (reperfusion injury). It has been demonstrated that intracoronary infusion of a 20% intravascular perfluorochemical emulsion (Fluosol) significantly reduces infarct size and results in improved left ventricular function in the canine model. This pilot study was performed to explore the existence of myocardial reperfusion injury in humans. Utilizing Fluosol as a probe in conjunction with emergency coronary angioplasty, 26 patients presenting within 4 h with a first anterior myocardial infarction were randomized to emergency angioplasty or angioplasty followed by a 30-min intracoronary infusion of Fluosol at 40 ml/min. Global and regional ventricular function were assessed immediately and a mean of 12 days after successful angioplasty with contrast ventriculography. Infarct size was semiquantitated with thallium-201 single-photon emission computed tomography (SPECT) images before discharge. Twelve patients (six undergoing angioplasty alone, six treated with angioplasty and Fluosol) had an occluded infarct-related vessel (Thrombolysis in Myocardial Infarction [TIMI] grade 0 to 1) at the time of emergency catheterization and were included in the final analysis. At 12 days after successful angioplasty, the improvement in regional ventricular function was greater in patients receiving adjunctive therapy with intracoronary Fluosol versus those undergoing angioplasty alone utilizing both the radial shortening and centerline method, respectively (23 +/- 3.1% vs. 8 +/- 2.3%, p less than 0.02; and -1.6 +/- 0.4 vs. -2.9 +/- 0.2 SD/chord, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Myocardial uptake and clearance of thallium-201 in normal subjects: comparison of dipyridamole-induced hyperemia with exercise stress

Thallium-201 uptake and clearance after dipyridamole infusion may differ from that after exercise stress because the hemodynamic effects of these two interventions are different. In this study of normal volunteers, thallium kinetics after dipyridamole (n = 13) were determined from three serial image sets (early, intermediate and delayed) and from serial blood samples and compared with thallium kinetics after exercise (n = 15). Absolute myocardial thallium uptake was greater after dipyridamole compared with exercise (p less than 0.0001), although the relative myocardial distribution was similar. The myocardial clearance (%/h) of thallium was slower after dipyridamole than it was after exercise. Comparing dipyridamole and exercise, the differences in clearance were large from the early to the intermediate image (anterior, -11 +/- 17 versus 24 +/- 5, p = 0.0005; 50 degrees left anterior oblique, -7 +/- 11 versus 15 +/- 8, p = 0.004; 70 degrees left anterior oblique, 3 +/- 9 versus 21 +/- 6, p = 0.001). In contrast, the differences in clearance were small from the intermediate to the delayed image (anterior, 15 +/- 4 versus 20 +/- 2, p = 0.025; 50 degrees left anterior oblique, 15 +/- 4 versus 19 +/- 3, p = 0.13; 70 degrees left anterior oblique, 15 +/- 3 versus 18 +/- 2, p = 0.047). Thallium uptake and clearance in the liver, splanchnic region and spleen were greater after dipyridamole (p less than 0.001). Blood thallium levels were greater after dipyridamole (p less than 0.05) and cleared more slowly (p = 0.07). Thus, myocardial thallium-201 uptake and clearance after dipyridamole infusion differ from thallium kinetics after exercise. This difference is, in part, related to associated differences in extracardiac and blood kinetics. Diagnostic criteria for the detection of abnormal thallium-201 clearance must be specific for the type of intervention.     

Identification of viable myocardium in patients with chronic coronary artery disease and left ventricular dysfunction. Comparison of thallium scintigraphy with reinjection and PET imaging with 18F-fluorodeoxyglucose

In patients with chronic coronary artery disease and left ventricular dysfunction, the distinction between ventricular dysfunction arising from myocardial fibrosis and ischemic, but viable, myocardium has important clinical implications. By positron emission tomography (PET), enhanced fluorine-18-labeled fluorodeoxyglucose (FDG) uptake in myocardial segments with impaired function and reduced blood flow is evidence of myocardial viability. Reinjection of thallium-201 at rest immediately after stress-redistribution imaging may also provide evidence of myocardial viability by demonstrating thallium uptake in regions with apparently "irreversible" defects. To compare these two methods, we studied 16 patients with chronic coronary artery disease and left ventricular dysfunction (ejection fraction, 27 +/- 9%), all of whom had irreversible defects on standard exercise-redistribution thallium single-photon emission computed tomography (SPECT) imaging. Thallium was reinjected immediately after the redistribution study, and SPECT images were reacquired. The patients also underwent PET imaging with FDG and oxygen-15-labeled water. A total of 432 myocardial segments were analyzed from comparable transaxial tomograms, of which 166 (38%) had irreversible thallium defects on redistribution images before reinjection. FDG uptake was demonstrated in 121 (73%) of these irreversible defects. Irreversible defects were then subgrouped according to the degree of thallium activity, relative to peak activity in normal regions. Irreversible defects with only mild (60-85% of peak activity) or moderate (50-59% of peak) reduction in thallium activity were considered viable on the basis of FDG uptake in 91% and 84% of these segments, respectively. In contrast, in irreversible defects with severe reduction in thallium activity (less than 50% of peak), FDG uptake was present in 51% of segments. In such severe defects, an identical number of segments (51%) demonstrated enhanced uptake of thallium after reinjection. In these severe "irreversible" defects, data on myocardial viability were concordant by the two techniques in 88% of segments, with 45% identified as viable and 43% identified as scar on both PET and thallium reinjection studies. These observations suggest that thallium imaging can be used to identify viable myocardium in patients with chronic coronary artery disease and left ventricular dysfunction. Most irreversible defects with only mild or moderate reduction in thallium activity represent viable myocardium as confirmed by FDG uptake.(ABSTRACT TRUNCATED AT 400 WORDS)     

Myocardial reperfusion imaging: basic principals and clinical applications

In recent years, radionuclide imaging techniques have gained increasing popularity in clinical practice to evaluate regional myocardial perfusion and viability in patients with acute myocardial infarction who have undergone reperfusion therapy. Myocardial thallium-201 (Tl-201) or technetium-99m methoxyisobutyl isonitrile (Tc-99m Sestamibi) scintigraphy can be used for detecting and localizing areas of necrosis when injected at rest and can be used in conjunction with exercise or pharmacological stress testing for predischarge risk stratification and determining prognosis. In the presence of residual blood flow, uptake of Tl-201 by myocardial cells is not altered unless irreversible membrane injury is present. Postischemic myocardial "stunning" alone does not affect Tl-201 extraction. Tl-201 administered very soon after reperfusion is established may reflect more the hyperemic flow state rather than the degree of myocardial salvage. Initial myocardial uptake of Tc-99m Sestamibi after intravenous injection is also proportional to blood flow. When injected during coronary occlusion, the pattern of uptake of Tc-99m Sestamibi accurately delineates the "area of risk." When injected several hours after coronary reperfusion, the uptake pattern accurately reflects the degree of residual myocardial viability. Serial Tc-99m Sestamibi imaging in patients with myocardial infarction receiving thrombolytic therapy showed that patients with a patent infarct vessel had a significant reduction in defect size compared with prethrombolysis images.