Impairment of regional fatty acid uptake in relation to wall motion and thallium-201 uptake in ischaemic but viable myocardium: assessment with iodine-123-labelled beta-methyl-branched fatty acid

In coronary artery disease, discrepancy in the uptake of thallium-201 and of methyl-branched fatty acid at rest has been described. The purpose of this study was to evaluate iodine-123 labelled beta-methyl-branched fatty acid (BMIPP) myocardial uptake and wall motion at rest in segments with stress-induced ischaemia identified by stress 201Tl tomography in patients with chronic coronary artery disease. 123I-BMIPP myocardial tomography was performed at rest and was compared with the findings of exercise-reinjection 201Tl tomography in 45 patients with chronic coronary artery disease. Regional wall motion was evaluated by contrast left ventriculography in 36 patients. Among 237 segments with reversible 201Tl defects, equally decreased uptake on both reinjection 201Tl and BMIPP images was observed in 93 (39%), more severely decreased uptake of BMIPP in 118 (50%) and more severely decreased uptake of reinjection 201Tl in 26 (11%). On the other hand, among 90 segments with non-reversible 201Tl defects, each pattern was observed in 71 (79%), 6 (7%) and 13 (14%) segments, respectively. When comparing the ischaemic segments with and without more severely reduced uptake of BMIPP than of reinjection 201Tl, wall motion was impaired to a greater extent in the segments with more severely reduced uptake of BMIPP than of reinjection 201Tl [severe hypo- or dyskinesis was present in 64 (70%) of 91 segments and in 24 (22%) of 110 segments, respectively, P<0.005]. In patients with chronic coronary artery disease, resting fatty acid uptake was frequently more reduced than reinjection 201Tl in the segments with stress-induced ischaemia, while in most of the fixed perfusion defects BMIPP and reinjection 201Tl uptake decreased concordantly. In ischaemic myocardium, wall motion was impaired to a greater extent in those segments which showed more severely reduced uptake of BMIPP than of reinjection 201Tl. In ischaemic but viable myocardium, discordant BMIPP uptake less than reinjection 201Tl uptake may indicate metabolic alterations and wall motion abnormality at rest independent of perfusion abnormalities. In conclusion, the combination of resting BMIPP and stress-reinjection 201Tl imaging may provide information on metabolic alterations and wall motion abnormality at rest independent of perfusion abnormalities.     

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The noninvasive assessment of myocardial viability in patients with coronary artery disease and depressed left ventricular function has proven clinically useful for identifying those patients with ischemic cardiomyopathy who benefit most from coronary revascularization. Thallium-201 (201Tl) imaging at rest has been the radionuclide imaging technique most often utilized for distinguishing viable myocardium from scar. However, new technetium-99m (99mTc) perfusion agents such as 99mTc-sestamibi and 99mTc-tetrofosmin have emerged as alternatives to 201Tl for imaging of regional myocardial perfusion. Whether these new agents, which have better physical properties for imaging with a gamma camera than 201Tl, are valid for use in assessing myocardial viability is still uncertain. Recent clinical studies have demonstrated that these agents, when imaged using quantitative SPECT, can identify patients with myocardial hibernation who exhibit improved regional systolic function following revascularization. Experimental laboratory studies have shown that the uptake of 99mTc-sestamibi and 99mTc-tetrofosmin in ischemic myocardium is only slightly lower than the uptake of 201Tl. These 99mTc-labeled agents remain bound intracellularly in mitochondria of viable myocytes under conditions of myocardial stunning and short-term hibernation, producing severe myocardial asynergy. With respect to determination of viability, the inferior wall region is at times problematic since attenuation of 99mTc-sestamibi and 99mTc-tetrofosmin is greatest in this area. Demonstration of preserved systolic thickening on ECG-gated SPECT images is indicative of viability in the instance of decreased regional 99mTc counts due to attenuation and not scar. Administration of nitrates prior to tracer injection improves the sensitivity for identifying viable myocardial segments using rest imaging with 99mTc-sestamibi or 99mTc-tetrofosmin. Thus, it appears that the new 99mTc perfusion imaging agents can be successfully employed for the determination of myocardial viability in the setting of severe regional dysfunction and chronic coronary artery disease. The greater the myocardial uptake of these agents in the resting state, the greater the probability of improved systolic function after coronary revascularization.     

Effect of human pancreastatin peptide (hP-16) on oral glucose tolerance in man

Thallium-201 (201Tl) late reinjection after stress-redistribution imaging improves the detection of viable myocardium. Recently, early reinjection of 201Tl immediately after stress imaging was proposed as a new method for distinguishing ischemic myocardium, hibernating myocardium, and myocardial scar. However, there are no data on the influence of the timing of reinjection on "fill-in." This study was designed to assess whether the reinjection time influences "fill-in" in chronic coronary artery disease. Thirty-three patients with chronic coronary artery disease were studied. All patients underwent exercise 201Tl tomography. Immediately after stress imaging, 37 MBq of thallium was reinjected earlier than usual and early reinjection delayed image (ERDI) was acquired 3 h later. With the same protocol, all patients also underwent a second study involving late reinjection of 201Tl within 1 week. An additional 37 MBq of thallium was reinjected 3 h after stress imaging, and late reinjection delayed image (LRDI) was obtained 10 min later. All images were analyzed qualitatively using a 4-point grading uptake score. Of the 72 hypoperfused segments on stress images, 66 segments showed fill-in and 6 showed persistent defects on ERDI, and of the same 72 segments 55 segments displayed fill-in and the remaining 17 showed persistent defects on LRDI (p<0.05). The delta uptake score (the uptake score of the delayed image minus that of stress image) in early reinjection was 1.60+/-0.80, which was significantly higher than that in late reinjection (1.24+/-0.94, p<0.01). A small dose of thallium reinjected immediately after stress imaging with delayed images obtained 3 h later is convenient and might provide another technique for determining myocardial viability.     

Evaluation of myocardial damage using 123I-BMIPP imaging in patients with vasospastic angina

The purpose of this study is to determine whether left ventricular dysfunction following coronary artery spasm by 123I-BMIPP myocardial imaging. To reveal the clinical efficacy of 123I-BMIPP SPECT, 20 patients with vasospastic angina were studied using resting, 3-hour delayed image with 123I-BMIPP and exercise, 3-hour delayed image with 201Tl SPECT. 123I-BMIPP uptake was decreased compared to 201Tl (discordant) in 12 patients (60%) and in 49/100 myocardial segments (49%). The extent and severity score in resting image with 123I-BMIPP were significantly larger than that in delayed image with 201Tl (p < 0.01). In 123I-BMIPP SPECT, the severity score in the latest ischemia were significantly larger than that in others. The incidence of a complete agreement of decreased 123I-BMIPP uptake and coronary artery spasm was significantly higher (75%) than that in 201Tl (28%, p < 0.01). Furthermore, compared to 201Tl uptake, decreased 123I-BMIPP uptake much more corresponded to reduced wall motion in 9 of patients with mismatching. The severity of regional wall motion abnormality was significantly correlated with severity score of 123I-BMIPP. Late redistribution in delayed image with 123I-BMIPP was seen in 6 patients. The regional washout rate and the severity of regional wall motion abnormality in 6 patients was significantly lower than that in others (p < 0.05). Thus, metabolic abnormality assessed by 123I-BMIPP is well associated with left ventricular asynergy and spastic region in patients with vasospastic angina. In conclusion, 123I-BMIPP SPECT may sensitively delineate the impaired myocardium following coronary artery spasm, and it is very useful in diagnosing and estimating the severity of vasospastic angina.     

Comparison of rest/exercise ECG, thallium-201 scans and radionuclide angiography in patients with suspected coronary artery disease

The results of rest and exercise ECG, 201Tl myocardial perfusion imaging and equilibrium radionuclide angiography were analyzed in 71 consecutive patients referred for diagnosis or evaluation of coronary artery disease (CAD). In 45 patients the diagnosis was established either by catheterization or typical history. In this group the overall sensitivity for rest/exercise ECG was 66%, for 201Tl scans 74%, for both combined 79% and for the ejection fraction response to exercise determined by radionuclide angiography 97%. If only the exercise response was considered, the corresponding sensitivity values were 58% (ECG), 50% (201Tl scans), 71% (ECG + 201Tl) and 97% (radionuclide angiography). The specificity for coronary artery disease was determined to be 71% for ECG, 86% for 201Tl scans and 42% for radionuclide angiography. All patients with false-positive results by radionuclide angiography had cardiomyopathies, thus this test has a high specificity for left ventricular dysfunction rather than for CAD alone. Criteria developed from the analysis of the test results in the 45 patients with definite diagnoses were then applied to the evaluation of 26 additional patients with atypical chest pain. A diagnosis could be made in all but 5 of them and radionuclide angiography was again the single most reliable test. Based on this study a new approach for the noninvasive evaluation of patients with suspected coronary artery disease is proposed.     

Myocardial perfusion SPET in the detection of coronary artery disease in orthotopic heart transplantation

BACKGROUND: Thallium-201 (201Tl) reinjection after conventional redistribution imaging is a standard procedure, resulting in enhanced 201Tl redistribution which is compatible with viable myocardium. Although this method significantly improves identification of viable myocardium, it increases the investigation time by approximately 1 h. Thus, this technique is suboptimal from the standpoint of patient convenience, since its routine performance may be impractical in a high-volume nuclear medicine laboratory. HYPOTHESIS: This study was undertaken to evaluate the efficacy of an early 201Tl reinjection and imaging protocol in combination with sublingual nitroglycerin, to detect myocardial ischemia and/or viability, and to reduce the need for conventional (4 h) redistribution imaging. MATERIALS AND METHODS: In this study, 62 consecutive coronary patients, referred for the detection of possible myocardial ischemia and/or viability, were involved (mean age 55 years, range 41-70). Of those, 50 had previous angina attacks, with 42 having a history of previous myocardial infarction; 10 patients had coronary artery bypass grafting; and the remaining 2 had atypical chest pain. Immediately after the completion of the initial postexer-cise imaging, 0.3 mg sublingual nitroglycerin followed by the reinjection of 1 m Ci of 201Tl were administered, and two further sets of images were acquired 1 h and 4 h later. RESULTS: In each set of images, a total of 496 segments were analyzed. On postexercise imaging, 305 (61%) segments demonstrated defects of which 198 (65%) showed enhanced thallium uptake, 97 (32%) did not change, and 10 (3%) showed reverse redistribution on 1 h reinjection imaging (IRI). Of the 97 persistent defects, only 17 (6%) showed fill-in of 201Tl on 4 h redistribution imaging (CRI), while 12 (4%) segments showed reverse redistribution. On the other hand, after analyzing the 62 patients of the 1 h IRI, 17 (27%) remained unchanged while in only 1 patient (6%) of 17 the diagnosis changed from myocardial necrosis to ischemia after analysis of the 4 h CRI. CONCLUSION: These results indicate that early postexercise reinjection of 201Tl in combination with sublingual nitroglycerin followed by 1 h image acquisition may prove useful for a comprehensive and convenient assessment of myocardial ischemia and/or viability.     

Improved outcome after coronary bypass surgery in patients with ischemic cardiomyopathy and residual myocardial viability

BACKGROUND: Although residual myocardial viability in patients with coronary artery disease and extensive regional asynergy is associated with improved ventricular function after coronary bypass surgery, the relationship between viability and clinical outcome after surgery is unclear. We hypothesized that patients with poor ventricular function and predominantly viable myocardium have a better outcome after bypass surgery compared with those with less viability. METHODS AND RESULTS: Seventy patients with multivessel coronary artery disease and left ventricular ejection fractions < 40% who underwent preoperative quantitative 201Tl scintigraphy before coronary bypass surgery were analyzed retrospectively. 201Tl scintigrams were reviewed blindly, and each segment was assigned a score based on defect magnitude. Segmental viability scores were summed and divided by the number of segments visualized to determine a viability index. The viability index was significantly related to 3-year survival free of cardiac event (cardiac death or heart transplant) after bypass surgery (P=.011) and was independent of age, ejection fraction, and number of diseased coronary vessels. Patients with greater viability (group 1; viability index > 0.67; n=33) were similar to patients with less viability (group 2; viability index < or = 0.67; n=37) with respect to age, comorbidities, and extent of coronary artery disease. There were 6 cardiac deaths and no heart transplants in group 1 patients and 15 cardiac deaths and two transplants in group 2 patients. Survival free of cardiac death or transplantation was significantly better in group 1 patients on Kaplan-Meier analysis (P=.018). CONCLUSIONS: We conclude that resting 201Tl scintigraphy may be useful in preoperative risk stratification for identification of patients more likely to benefit from surgical revascularization.     

Myocardial uptake of 99mTc-tetrofosmin, sestamibi, and 201Tl in a model of acute coronary reperfusion

BACKGROUND: To investigate whether tetrofosmin uptake is affected by myocardial viability as has been noted for 201Tl and sestamibi, we analyzed the initial and delayed distribution patterns of tetrofosmin in a rat coronary artery occlusion-reperfusion model. METHODS AND RESULTS: Animals were intubated and ventilated, and their arterial pressures were monitored. A left thoracotomy was performed. After 1-hour occlusion and 1-hour reperfusion of a major branch of the circumflex artery, 201Tl and either tetrofosmin or sestamibi were injected intravenously. Radiolabeled microspheres were used to document the area at risk and reperfusion. Five minutes or 1 hour after administration of the diffusible tracers, the animals were killed. Tracer distribution was determined by use of segmental tissue analysis, and tissue viability was determined by use of histochemical staining. Both the initial and delayed retention of tetrofosmin were sensitive to myocardial viability, as shown by significantly lower uptake (30 +/- 14%) and retention (24 +/- 12%) of tetrofosmin in the nonviable segments compared with the viable segments. In addition, the initial myocardial distribution of tetrofosmin was similar to that noted for 201Tl, but after 1 hour of tracer circulation, the tetrofosmin tissue distribution appeared unchanged compared with the initial regional blood flow distribution. This is in direct contrast to our present observations of significant 201Tl redistribution and some changes in sestamibi distribution as well. CONCLUSIONS: The clinical implication of these observations suggests that initial and delayed imaging after tetrofosmin administration would reflect both the initial regional blood flow pattern and myocardial viability.     

Clinical value of triple-energy window scatter correction in simultaneous dual-isotope single-photon emission tomography with 123I-BMIPP and 201Tl

To improve the image quality in simultaneous dual-isotope single-photon emission tomography (SPET) with iodine-123 labelled 15-(p-iodophenyl)-3-methylpentadecanoic acid (BMIPP) and thallium-201, we applied the triple-energy window method (TEW) for correction of the cross-talk and scatter artifact. Seventy-one patients with coronary artery disease were included. 201Tl cross-talk into the 123I acquisition window (group 1, n = 30) and 123I cross-talk into the 201Tl window (group 2, n = 41) were studied. In group 1, 123I images were first obtained (single-isotope images), followed by 201Tl injection and SPET acquisition using dual-isotope windows (dual-isotope images). In group 2, the order was reversed. The dual-isotope SPET images with and without TEW were compared with the single-isotope images. Qualitative evaluation was performed by scoring the segmental defect pattern. Detectability of the mismatched fatty acid metabolism on dual-isotope SPET was evaluated by receiver operating characteristic (ROC) curve analysis. Segmental defect pattern agreement between dual and corrected single images was significantly improved by TEW correction (P<0.01). The agreement was particularly improved in segments with absence of uptake. There was no significant difference between TEW-corrected dual-isotope SPET and corresponding single-isotope SPET with regard to either % defect count or background activity. Mismatched fatty acid metabolism depicted by dual-isotope SPET predicted abnormal wall motion more accurately with TEW than without TEW. With TEW, a practical method for scatter and cross-talk correction in clinical settings, simultaneous dual 123I-BMIPP/201Tl SPET is feasible for the assessment of myocardial perfusion/metabolism mismatch.     

Large-scale expression of recombinant sialyltransferases and comparison of their kinetic properties with native enzymes

The purpose of the present study is to assess the effect of nicorandil, a coronary vasodilator with a mechanism of potassium channel opening, on the abnormal myocardial 201Tl perfusion evoked by exercise. Eleven patients who had a history of typical angina, positive exercise electrocardiograms, positive 201Tl scintigraphy, nearly normal coronary arteriograms, and negative coronary vasospasm underwent exercise 201Tl scintigraphies under no medication (baseline test) and administration of nicorandil (nicorandil test). 201Tl was injected at a matched workload in both tests. Nicorandil did not alter heart rate, blood pressure, or the rate-pressure product at the end of the exercise, but it significantly improved the extent score from 0.37 +/- 0.22 to 0.20 +/- 0.15 (p < 0.05) and the severity score from 33.9 +/- 32.2 to 13.5 +/- 16.4 (p < 0.05), and also significantly hastened the 201Tl mean washout rate from 30.5 +/- 14.8% to 37.4 +/- 13.1% (p < 0.05). Anginal symptoms disappeared in 3 of 5 cases and ST depression improved in 5 of 7 cases after nicorandil. We conclude that nicorandil augments coronary flow reserve, possibly due to a reduction of vasotone in the small coronary arteries.     

Acute functional consequences of left ventriculotomy

To investigate whether Q12 uptake is affected by myocardial viability, as has been noted for 201Tl and sestamibi, we analyzed the initial and delayed distribution patterns of Q12 in a rat coronary artery occlusion-reperfusion model. METHODS: Animals were intubated and ventilated, and their arterial pressures were monitored. A left thoracotomy was performed. After a 1-hr occlusion and a 1-hr reperfusion of a major branch of the circumflex artery, 201Tl and Q12 were injected intravenously. Radiolabeled microspheres were used to document the areas of risk and reperfusion. The animals were killed at 5 min or 1 hr after administration of the diffusible tracers. Tracer distribution was determined by segmental tissue analysis, and tissue viability was determined by histochemical staining. RESULTS: Both the initial uptake and delayed retention of Q12 are sensitive to myocardial viability as shown by significantly lower uptake (28% +/- 8%) and retention (41% +/- 13%) of Q12 in the nonviable as compared to the viable segments (p < 0.001). In addition, the myocardial retention of Q12 was significantly less in the nonviable tissue when compared to the initial uptake (p < 0.01). CONCLUSION: The clinical implication of these observations suggests that initial and delayed imaging after Q12 administration would reflect both the initial regional blood flow pattern and myocardial viability. Also, delayed imaging of Q12 may reflect viability better than the initial imaging.     

Race and serum prostate-specific antigen levels: current status and future directions

The usefulness of thallium-201 (201Tl) myocardial scintigraphy was studied in 109 patients with vasospastic angina who had nearly normal coronary arteries (degree of stenosis < 50%). Coronary spasm was confirmed by pharmacologic agents in all 109 patients from January 1991 to June 1996. The appearance rate of visual redistribution on 201Tl myocardial scintigraphy was compared between four groups, 34 patients performing graded bicycle ergometer exercise starting at a work load of 50 W with increments of 25 W every 3 min [Ergo (3) group], 14 patients performing hyperventilation for 5 min [HV (5) group], 31 patients performing bicycle ergometer exercise with increments of 25 W every 1 min after 5 min hyperventilation [HV (5) + Ergo (1) group], and 30 patients at rest (Rest group). The value of the visual redistribution rate on 201Tl myocardial scintigrams in the HV(5) + Ergo (1) group (65%) was higher than that in the patients of other groups [Ergo (3) 41%, HV (5) 43%, Rest 33%]. However, there were no significant differences between the four groups. Stress 201Tl imaging after hyperventilation and accelerated exercise is useful to disclose ischemic evidence in about two thirds of patients with vasospastic angina and nearly normal coronary arteries, whereas about 40% of patients had visual redistribution on 201Tl myocardial scintigrams by performing standard procedures.     

One-year effect of myocardial revascularization on resting left ventricular function and regional thallium uptake in chronic CAD

It is still unclear whether in patients with chronic coronary artery disease (CAD) the improvements in myocardial perfusion and left ventricular (LV) function induced by revascularization persist in the long run. This study was planned to evaluate the 1-yr effects of successful revascularization on myocardial perfusion and LV function in patients with CAD and to assess the accuracy of thallium imaging in the prediction of functional recovery 1 yr after revascularization. METHODS: Thirty-eight patients with chronic CAD who were revascularized (experimental group) underwent, while off drugs, 201Tl tomography, two-dimensional echocardiography and radionuclide angiography before and after a 1-yr follow-up. Twenty-nine patients with similar characteristics who were not revascularized (control group) and completed the 1-yr follow-up were also studied. Regional thallium activity was quantitatively measured in 13 segments per patient. Systolic function was assessed by echocardiography in corresponding segments. RESULTS: In the experimental group, at baseline, on the basis of regional LV function and thallium uptake, 276 segments were normal, 169 dysfunctional-viable and 49 nonviable. After revascularization, the majority (75%) of the dysfunctional-viable segments at baseline showed functional recovery at follow-up, whereas the majority (81%) of the nonviable segments at baseline did not. Simultaneously, LV ejection fraction increased 4 wk after revascularization (from 39% +/- 9% to 42% +/- 10%, p < 0.01) and remained unchanged after 1-yr (43% +/- 8%, p < 0.01 versus baseline study). LV wall-motion score index after 1 yr was reduced (from 1.68 +/- 0.4 to 1.42 +/- 0.3, p < 0.001) as compared with baseline. On the contrary, in the control group, no change in myocardial perfusion and LV function was detected after the 1-yr follow-up. CONCLUSION: In patients with chronic CAD, successful coronary revascularization induces a stable improvement in myocardial perfusion and LV function, which is still detectable after a 1-yr follow-up. Furthermore, preserved thallium uptake in dysfunctional regions is predictive of functional recovery after revascularization.     

Molecular biology of iron and zinc uptake in eukaryotes

This study was designed to evaluate the feasibility of assessing myocardial viability using glucose loading followed by 201Tl SPECT. METHODS: First, the effect of insulin on the kinetics of 201Tl uptake was evaluated in isolated perfused rat hearts. Second, glucose-loading 201Tl myocardial SPECT was performed in 13 nondiabetic patients with histories of anterior myocardial infarction. Thirty minutes before acquiring rest 201Tl SPECT, 20 g of glucose were intravenously injected into the fasting subjects. Thallium perfusion defects were compared to those of conventional rest-redistribution SPECT images obtained within a 2-wk interval. SPECT images were divided into 21 segments, and a defect score in 17 segments was calculated as a sum of the semiquantitative defect scores (0 = normal; 1 = mildly decreased uptake; 2 = severely decreased uptake; 3 = absence of uptake). RESULTS: Thallium-201 uptake in isolated hearts showed a significant increase of 26% after insulin loading. Eleven (24%) of 45 segments showing perfusion defects on the conventional rest SPECT images demonstrated 201Tl uptake on glucose-loading SPECT imaging. Defect scores decreased significantly on the glucose-loading SPECT images (9.9 +/- 2.2 in early images; mean +/- s.e.) compared with the conventional rest-redistribution SPECT images (12.6 +/- 6.9 in delayed images, p < 0.05). CONCLUSION: Glucose-loading SPECT represents a superior method for assessing myocardial viability using 201Tl.     

Myocardial perfusion reserve studied by single-photon emission-computed tomography with thallium-201 and a drug stress test with adenosine triphosphate in patients with cardiovascular risk factors

INTRODUCTION AND OBJECTIVE: Recent studies have suggested that the evaluation of coronary reserve is a sensitive method in the early detection of vascular alterations before plaques exist, and certainly before clinical detection of atherosclerotic lesions. Single-photon emission-computed tomography (SPECT) with thallium-201 (201Tl) provides a noninvasive tool for evaluating myocardial perfusion reserve. The objective of this study was to measure the myocardial perfusion reserve in two groups of subjects, some with and some without cardiovascular risk factors and in a group of patients with coronary artery disease. METHODS: Seventy-four subjects, divided into three groups, were recruited to assess regional and global myocardial perfusion reserve. The control group consisted of 11 asymptomatic individuals without cardiovascular risk factors. The second group was composed of 49 patients with one or more risk factors. Finally, the third group included 14 patients with coronary artery disease. 201Tl-SPECT at rest and after pharmacological stress with a 7 minute adenosine triphosphate (ATP) infusion (140 micrograms/kg/min) was performed in all patients. ATP minus rest value subtraction was applied in order to obtain the stress data. Relative myocardial perfusion reserve indices were calculated as the ratio between stress and rest values. RESULTS: Global and regional myocardial perfusion reserves of the vascular territories were significantly lower in patients with cardiovascular risk factors than in control subjects (Global: 1.48 +/- 0.19 vs 1.81 +/- 0.08, LAD: 1.52 +/- 0.21 vs 1.85 +/- 0.09, CX: 1.45 +/- 0.2 vs 1.79 +/- 0.86, RCA: 1.47 +/- 0.2 vs 1.79 +/- 0.86) and higher than in patients with coronary artery disease (Global: 1.48 +/- 0.19 vs 1.31 +/- 0.14, LAD: 1.52 +/- 0.21 vs 1.35 +/- 0.15, CX: 1.45 +/- 0.2 vs 1.2 +/- 0.24). Univariate linear regression analysis in a group of 40 patients with high risk lipid profiles revealed a significant negative correlation between myocardial perfusion reserve and total cholesterol (r = -0.35; p = 0.01), LDL-cholesterol (r = -0.38; p = 0.036) and LDL/HDL ratio (r = -0.39; p = 0.029). CONCLUSION: Determination of myocardial perfusion reserve with 201Tl-SPECT allows the detection of abnormal vasodilatory response to intravenous ATP in patients with cardiovascular risk factors. These patients have higher reserves than patients with coronary disease, which might suggest an early phase of atherosclerosis.     

The distribution of Nematospiroides dubius within the small intestine of laboratory mice

Recent reports have suggested the use of intravenous 201T1 (thallium-201) for myocardial imaging with the gamma scintillation camera. In order to better appreciate the possible utility of this agent in humans we examined its distribution and kinetics in 13 patients and in six mongrel dogs, three with experimental coronary artery occlusion. In addition, 201T1 was compared to 86Rb (rubidium-86) in 84 rats. In the rat heart, the concentration of 201T1 was 30% higher than that of 86Rb ten minutes after injection. Moreover, myocardium-to-blood ratios for 201T1 averaged 51:1, but only 32:1 for 86Rb ten minutes after administration. In the dog heart, the distribution of 201T1 paralleled that of radioiodinated (131I) albumin particles injected into the left atrium and, thus, appears to be related to regional blood flow. Its concentration in ischemic regions decreased to 32.3% of the normally perfused myocardium. In the patients with a recent or old myocardial infarction, areas of decreased 201T1 uptake were easily identified and corresponded in location to that by ECG. Repeat scans 24 hours after the initial injection showed a significant retention of 201T1 by the myocardium. 201T1 blood levels in humans 15 minutes after injection were low (averaging 1.06% +/- 0.41% SD of the total dose per liter) and these levels decreased with a biological half-life of 3.1 +/- 0.7 days. Twenty-four hour urinary excretion rates ranged from 0.6 to 6.5% of the total dose and appeared related to urinary flow and the concentation of 201T1 in blood. Because of the higher target to background ratios, 201T1 compares favorably with radioactive rubidium. 201T1 in diagnostic doses remained without detectable adverse effects and appears promising as an agent for visualizing abnormal regional myocardial perfusion in patients with coronary artery disease.     

Effect of cigarette smoke on CYP1A1, CYP1A2 and CYP2B1/2 of nasal mucosae in F344 rats

BACKGROUND: Dobutamine stress echocardiography (DSE) is sensitive and specific in detecting myocardial ischemia of male patients. However, there have been few reports about the use of DSE for the detection of coronary artery disease (CAD) in women. METHODS: DSE was evaluated in 51 consecutive women who underwent concomitant quantitative coronary angiography. Forty-four of the 51 patients received stress thallium-201 single-photon emission computed tomography (SPECT), and 30 of the 51 patients had interpretable results (exercise level > or = 85% of age-predicted maximal heart rate) of treadmill exercise. Twenty-nine patients had angiographically documented CAD defined as > or = 50% diameter stenosis. RESULTS: The overall sensitivity of DSE and stress 201Tl SPECT in detecting CAD was 93% and 79% (p = nonsignificant), and the specificity was 82% and 75% (p = nonsignificant), respectively. A combination of both tests increased the sensitivity (96%) at the expense of some decrease in specificity (60%). The agreement of DSE and 201Tl SPECT was 68% (30 of 44; kappa statistic = 0.35; p < 0.0001). The overall sensitivity, specificity, and accuracy in detecting CAD by treadmill exercise test and DSE were 71% vs 93% (p = nonsignificant), 44% vs 82% (p = 0.036), and 57% vs 88% (p = 0.003). In patients with abnormal results of treadmill exercise testing, the false-positive rate in detecting CAD was 2 (18%) of 11 in patients with abnormal results of DSE and 7 (88%) of 8 in those with normal results of DSE (p = 0.005). In patients with normal results of treadmill exercise testing, the false-negative rate in detecting CAD was 4 (100%) of 4 in patients with abnormal results of DSE and 0 (0%) of 7 in those with normal results of DSE (p = 0.003). CONCLUSION: The diagnostic accuracy of DSE was similar to that of stress 201Tl SPECT in women. DSE was able to stratify female patients with either abnormal or normal results of treadmill exercise testing and to avoid unnecessary cardiac catheterization.     

Nitrate-augmented myocardial imaging for assessment of myocardial viability

201Tl myocardial perfusion imaging is presently done by several possible strategies. Stress/delayed redistribution, stress/redistribution/reinjection, and rest/redistribution imaging can be useful in the clinical assessment of myocardial viability. Unfortunately, the extent of myocardial viability may still be underestimated even by 201Tl reinjection imaging, compared with 18F-fluorodeoxyglucose positron emission tomography. 99mTc-labeled sestamibi imaging provides results similar to those of 201Tl imaging in the detection of coronary artery disease, but several previous studies suggest that stress/rest 99mTc-labeled sestamibi imaging significantly underestimates myocardial viability. Recently it has been reported that the administration of nitrates, before 201Tl reinjection, improves detection of defect reversibility. Several studies also suggested that administration of nitrates before the injection of 99mTc-labeled sestamibi significantly improved detection of reversibility with this agent, whereas additional studies showed further that this combination improves the predictive accuracy for recovery of left ventricular function and perfusion after coronary revascularization, compared with a standard rest 99mTc-labeled sestamibi study. Nitrate administration before the injection of 201Tl and 99mTc-labeled sestamibi may thus be a potentially attractive alternative for the evaluation of myocardial viability. Although the available results are encouraging, further studies are needed to evaluate the clinical value of 201Tl and 99mTc-labeled sestamibi imaging, in combination with nitrates, for predicting recovery of left ventricular dysfunction.     

Comparison between thallium-201 and technetium-99m-tetrofosmin uptake with sustained low flow and profound systolic dysfunction

Technetium-99m-tetrofosmin uptake was compared to that of 201Tl in the setting of low flow and systolic dysfunction. METHODS: In nine open-chested dogs, a severe left anterior descending (LAD) coronary artery stenosis resulted in a 54.3% mean flow reduction and decreased left ventricular thickening from 21% +/- 1% to -3 +/- 2%. After 30 min, 37 MBq (1 mCi) of 201Tl and microspheres were injected and initial and 2-hr redistribution images acquired. Two hours later, 370 MBq (10 mCi) of 99mTc-tetrofosmin and microspheres were injected and an image was obtained. LAD: left circumflex (LCX) count ratios for both tracers and flows were calculated by well counting postmortem, and 201Tl and 99mTc-tetrofosmin defect magnitudes were determined by quantitative image analysis. RESULTS: LAD:LCx flow ratios were similar during 201Tl and 99mTc-tetrofosmin injections (0.48 +/- 0.04 versus 0.49 +/- 0.05, p = n.s.). Final 201Tl activity (0.66 +/- 0.04) was significantly higher than 99mTc-tetrofosmin (0.55 +/- 0.05; p < 0.05). LAD/LCx 99mTc-tetrofosmin image defect count ratio was similar to 201Tl defect count ratio on the initial rest 201Tl scan (0.57 +/- 0.03 versus 0.56 +/- 0.02, p = ns), but significantly less than 201Tl defect count ratio at 2 hr (0.57 +/- 0.03 versus 0.65 +/- 0.02, p < 0.05). CONCLUSION: In a low-flow model with profound systolic dysfunction, myocardial 99mTc-tetrofosmin uptake ( > 50%) reflective of viability was observed in the asynergic zone perfused by the stenotic LAD.     

Assessment of myocardial viability: Dobutamine echocardiography and thallium-201 single-photon emission computed tomographic imaging predict the postoperative improvement of left ventricular function after bypass surgery

The aim of this study was to evaluate the usefulness of dobutamine echocardiography and quantitative thallium-201 single photon emission computed tomography myocardial scintigraphy with reinjection in the detection of viable myocardium in patients with coronary artery disease and reduced left ventricular function, which will improve after aortocoronary bypass surgery. Forty-eight patients (47 men, aged 61 +/- 6 years) with angiographically documented reduced left ventricular function (ejection fraction 35 +/- 14, 63% with chronic transmural myocardial infarction) were examined by dobutamine two-dimensional echocardiography (before and during low dosage), 201Tl, and gated radionuclide ventriculography before and 3 +/- 2 months after aortocoronary bypass surgery. Four of 55 areas classified viable before operation were revascularized inadequately and discarded. Global left ventricular ejection fraction at rest rose from 35% +/- 14% before operation to 40% +/- 13% (p < 0.05) after operation. Stress-induced perfusion defects involved 40% +/- 19% of the left ventricle circumference after stress and showed a significant reduction of size to 23% +/- 14% (p < 0.01) at rest, 4 hours later, and after reinjection. This value fell to 16% +/- 12% (p < 0.05) 3 months after aortocoronary bypass surgery. We conclude that both dobutamine echocardiography (sensitivity 95%, specificity 80%, positive predictive value 87%, negative predictive value 88%) and 201Tl studies (sensitivity 87%, specificity 98%, positive predictive value 97%, negative predictive value 93%) are suitable and comparable accurate methods for predicting improvement in systolic function 3 months after revascularization in a selected population with a high prevalence of viable but hypokinetic or akinetic myocardium.