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Biomedical subjects

G A Beller

Publications and source records attributed to G A Beller.

At least 19 recordsLinked to original sources
PubMed1999

Myocardial uptake of (99m)Tc-N-NOET and (201)Tl during dobutamine infusion. Comparison with adenosine stress.

BACKGROUND: The myocardial uptake of (99m)Tc-sestamibi is attenuated by dobutamine stress, resulting in underestimation of ischemia. N-Ethyl-N-ethoxy-dithiocarbamato-N-(99m)Tc ((99m)Tc-N-NOET) is a new (99m)Tc-labeled perfusion agent that is highly extracted by the myocardium by a mechanism different from that defined for (99m)Tc-sestamibi. We therefore hypothesized that (99m)Tc-N-NOET uptake would not be attenuated by dobutamine and that (99m)Tc-N-NOET uptake would be comparable to (201)Tl uptake during dobutamine stress. METHODS AND RESULTS: In 28 open-chest dogs, after placement of a stenosis in the left anterior descending coronary artery that reduced flow reserve by >50%, adenosine (300 microgram. kg(-1). min(-1); n=15) or dobutamine (2.5 to 30 microgram. kg(-1). min(-1); n=13) was infused. During adenosine stress, the stenotic-to-normal activity ratio for (99m)Tc-N-NOET was 0.55+/-0.05. The stenotic-to-normal flow ratio was 0.33+/-0.04 at the time of (99m)Tc-N-NOET injection. During dobutamine stress, the stenotic-to-normal (99m)Tc-N-NOET activity ratio was 0.63+/-0.04, comparable to the (201)Tl activity ratio of 0.59+/-0.04. The stenotic-to-normal flow ratio was 0.47+/-0.04 at the time of (99m)Tc-N-NOET and (201)Tl injection. The relationship between (99m)Tc-N-NOET uptake and blood flow was comparable for adenosine and dobutamine stress, with no evidence of attenuation of (99m)Tc-N-NOET extraction by dobutamine. Conclusions-In the presence of coronary stenoses that reduced regional flow reserve, the myocardial uptake of (99m)Tc-N-NOET and (201)Tl are closely proportional to blood flow during both adenosine and dobutamine stress, suggesting that the adverse effect of dobutamine on (99m)Tc-sestamibi uptake is a tracer-specific phenomenon rather than a generalized effect. The clinical implication of this finding is that (99m)Tc-N-NOET might be preferable to (99m)Tc-sestamibi when used with dobutamine stress for detection of coronary stenoses.

Adenosine↗
PubMed1999

Assessment of myocardial viability using 123I-labeled iodophenylpentadecanoic acid at sustained low flow or after acute infarction and reperfusion.

UNLABELLED: 123I-labeled iodophenylpentadecanoic acid (IPPA) is a synthetic fatty acid that may be useful for determination of myocardial viability. We investigated the uptake and clearance kinetics of this tracer in canine models of ischemia and infarction. METHODS: In protocol 1, 185 MBq (5 mCi) 123I-IPPA were injected intravenously in 19 dogs with 50% left anterior descending artery (LAD) flow reduction. In 9 dogs, 201TI was coinjected. In protocol 2, 5 dogs underwent LAD occlusion for 3 h, and 123I-IPPA was injected 60 min after reperfusion. All dogs had flow measured by microspheres, regional systolic thickening by ultrasonic crystals and measurements of postmortem risk area and infarct size. Tracer activities were quantified by gamma well counting and by serial imaging. RESULTS: In protocol 1 dogs with sustained low flow (50% +/- 4%) and absence of systolic thickening (-3.2% +/- 1%), 123I-IPPA defect magnitude (LAD/left circumflex artery [LCX] count ratios) decreased from 0.65 +/- 0.02 to 0.74 +/- 0.02 at 30 min and to 0.84 +/- 0.03 at 2 h (P < 0.01), indicative of rest redistribution. Final transmural 123I-IPPA LAD/LCX activity ratio (0.99 +/- 0.05) was significantly greater than the flow ratio (0.53 +/- 0.04) at injection, confirming complete rest redistribution. The final 123I-IPPA activity ratio was significantly greater than the 201TI ratio over the 2-h period (P < 0.01). In protocol 2 dogs that underwent 3 h of total LAD occlusion and reflow (infarct size = 51% +/- 13% of risk area), viability was overestimated with 123I-IPPA, because uptake averaged 64% of normal in the central necrotic region, where flow averaged < 10% of normal. CONCLUSION: These findings suggest that serial 123I-IPPA imaging may be useful for assessing myocardial viability under conditions of sustained low flow and myocardial asynergy, such as appears to exist in patients with chronic coronary artery disease and depressed left ventricular function. In contrast, 123I-IPPA given early after reperfusion following prolonged coronary occlusion overestimates the degree of viability and therefore may not provide useful information pertaining to the degree of myocardial salvage after reflow in the setting of acute myocardial infarction.

Animals↗
PubMed1999

99mTc-tetrofosmin assessment of myocardial perfusion and viability in canine models of coronary occlusion and reperfusion.

UNLABELLED: The goal of this study was to determine whether 99mTc-tetrofosmin can assess regional flow heterogeneity when injected during sustained coronary artery occlusion and to estimate the degree of myocardial salvage and viability during coronary reperfusion. METHODS: In protocol 1, 99mTc-tetrofosmin, 201 TI and microspheres were injected during total left anterior descending (LAD) coronary artery occlusion in five anesthetized open-chested dogs. Protocol 2 dogs underwent LAD occlusion for either 60 min (n = 7) or 180 min (n = 6) followed by 105 min of reperfusion. 99mTc-tetrofosmin (10 mCi), 201TI (1 mCi) and microspheres were injected 90 min after reflow. In both protocols, myocardial 99mTc-tetrofosmin and 201TI activities were quantified from regions of interest on ex vivo images and by in vitro well counting. RESULTS: In protocol 1, there was a linear relationship between 201TI (r = 0.96) and 99mTc-tetrofosmin (r 0.92) activities and microsphere flow during the occlusion. In protocol 2, the LAD/left circumflex (LCx) defect count ratios for 99mTc-tetrofosmin and 201TI from images of myocardial slices were comparable in dogs undergoing either 1 or 3 h of LAD occlusion and 105 min of reperfusion. Similarly, the LAD/LCx in vitro count ratios were comparable between 201TI and 99mTc-tetrofosmin in 1 and 3 h occluded dogs, and significantly lower than the reperfusion flow when these tracers were injected. Uptake of both tracers was depressed to a greater extent in areas of severe ischemic damage. CONCLUSION: These data suggest that administration of 99mTc-tetrofosmin during coronary occlusion accurately delineates the flow heterogeneity. When given after reperfusion, 99mTc-tetrofosmin uptake was significantly reduced in reperfused, infarcted areas and was reflective of viability and the degree of myocardial salvage in addition to reperfusion flow. These experimental studies validate the clinical use of 99mTc-tetrofosmin for assessing persistent coronary artery occlusion, and infarct size and myocardial viability after reperfusion.

Animals↗
PubMed1998

Postexercise systolic blood pressure response: clinical application to the assessment of ischemic heart disease.

Stress test parameters indicating the presence and extent of coronary artery disease have traditionally included such variables as exercise duration, and the blood pressure and ST-segment responses to exercise. The three-minute systolic blood pressure ratio, another important indicator of significant coronary artery disease, is a useful and readily obtainable measure that can be applied in all patients who are undergoing stress testing for the evaluation of known or suspected ischemic heart disease. The ratio is calculated by dividing the systolic blood pressure three minutes into the recovery phase of a treadmill exercise test by the systolic blood pressure at peak exercise. A three-minute systolic blood pressure ratio greater than 0.90 is considered abnormal and has a diagnostic accuracy of approximately 75 percent for the detection of coronary artery disease (i.e., an accuracy comparable to that of ST-segment depression). Higher values for the ratio are associated with more extensive coronary artery disease, as well as an adverse prognosis after myocardial infarction. Thus, the three-minute systolic blood pressure ratio provides information that is complementary to the traditional exercise test parameters for identifying high-risk ischemic heart disease.

Blood Pressure↗
PubMed1998

Are technetium-99m-labeled myocardial perfusion agents adequate for detection of myocardial viability?

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.

Animals↗
PubMed1998

Comparison of technetium-99m tetrofosmin and thallium-201 single-photon emission computed tomographic imaging for detection of myocardial perfusion defects in patients with coronary artery disease.

OBJECTIVES: We compared dipyridamole technetium-99m (Tc-99m) tetrofosmin and thallium-201 (Tl-201) single-photon emission computed tomographic (SPECT) imaging with respect to the detection rate of perfusion abnormalities in 26 patients with angiographic coronary artery disease (CAD). BACKGROUND: Experimental studies have shown that myocardial extraction of Tc-99m tetrofosmin is lower than that of Tl-201 at high flow rates, resulting in less severe defects with vasodilator stress. It is uncertain whether this results in a lower sensitivity than Tl-201 for detecting coronary stenoses with vasodilator stress in patients. METHODS: Twenty-six patients with CAD underwent both dipyridamole Tl-201 and Tc-99m tetrofosmin SPECT. Tomographic images were scored for initial defects and the presence of reversibility. Defect magnitude was computer quantitated. RESULTS: Of the 26 patients, 25 had defects on both Tl-201 and Tc-99m tetrofosmin SPECT images. Of 340 segments analyzed, 102 had defects by Tl-201 and 92 by Tc-99m tetrofosmin (p = NS). Whereas Tl-201 detected 27 fixed defects in 12 patients, Tc-99m tetrofosmin identified 37 fixed defects in 14 patients (p = NS). In contrast, Tl-201 identified more reversible and partially reversible defects than did Tc-99m tetrofosmin (89 vs. 55, p = 0.002). The average defect magnitude (percent normal) was similar for defects concordantly graded as fixed (38 +/- 3.0% for Tl-201 vs. 42 +/- 4% [mean +/- SEM] for Tc-99m tetrofosmin, p = NS). The average defect magnitude for defects concordantly graded as completely reversible was significantly more severe on Tl-201 than on Tc-99m tetrofosmin (49 +/- 3% vs. 58 +/- 3%) SPECT images. A significantly greater defect magnitude for Tl-201 was also found for defects concordantly classified as partly reversible (30 +/- 4% for Tl-201 vs. 45 +/- 5% for Tc-99m tetrofosmin). CONCLUSIONS: With dipyridamole stress, 1) at least one defect was seen on both Tl-201 and Tc-99m tetrofosmin SPECT images; 2) Tc-99m tetrofosmin SPECT identified fewer reversible defects than did Tl-201, but showed a similar number of fixed defects; 3) the magnitude of reversible defects seen on Tc-99m tetrofosmin images was less, whereas fixed defects were similar for both tracers; 4) reversible defects seen on Tl-201 and not on Tc-99m tetrofosmin SPECT images were predominantly regions perfused by mild coronary stenoses.

Adult↗
PubMed1997

Myocardial uptake and redistribution of 99mTc-N-NOET in dogs with either sustained coronary low flow or transient coronary occlusion: comparison with 201Tl and myocardial blood flow.

BACKGROUND: 99mTc-N-NOET (NOET) is a new myocardial perfusion imaging agent that redistributes over time. We sought to better define the redistribution kinetics of NOET using open-chest canine models of sustained low coronary flow (protocol 1) and transient coronary occlusion followed by reflow (protocol 2). METHODS AND RESULTS: In protocol 1 (n=10), NOET and 201Tl were injected during low flow in the left anterior descending coronary artery (LAD) that was sustained for 2 hours. Protocol 2 dogs (n=6) were injected with NOET during 20 minutes of LAD occlusion followed by 2 hours of reflow. In both protocols, serial NOET planar images were acquired, and myocardial flow and 2-hour tracer activities were determined by gamma-well counting. Defect resolution was observed on images in both protocols. Initial defect count ratios, reflecting flow disparity at injection (0.66+/-0.03 and 0.57+/-0.04, respectively), increased over 2 hours (0.73+/-0.02 and 0.75+/-0.04, respectively; P<.001 versus initial). Quantitative imaging showed that NOET redistribution resulted from greater clearance from normal areas versus low-flow or transiently occluded areas. In protocol 1, 2-hour NOET and 201Tl stenotic-to-normal tissue activity ratios were similar (0.76+/-0.06 versus 0.73+/-0.04, P=NS) and higher than injection flow ratios (0.52+/-0.06 and 0.56+/-0.07, respectively, P<.001), consistent with tracer redistribution. In protocol 2, NOET redistributed to an even greater extent (injection flow ratio, 0.27+/-0.04; 2-hour tissue activity ratio, 0.84+/-0.03, P<.001). CONCLUSIONS: NOET is the first 99mTc-labeled myocardial imaging agent with kinetics similar to 201Tl in experimental models, permitting redistribution imaging. NOET appears to be a promising agent for assessing patients with coronary artery disease.

Animals↗
PubMed1997

Myocardial 99mTc-tetrofosmin uptake during adenosine-induced vasodilatation with either a critical or mild coronary stenosis: comparison with 201Tl and regional myocardial blood flow.

BACKGROUND: Clinical studies have shown a comparable coronary stenosis detection rate between 99mTc-tetrofosmin and 201Tl but with smaller defect magnitudes for 99mTc-tetrofosmin. The goals of this study were to measure the first-pass extraction fraction (EF) of 99mTc-tetrofosmin in canine myocardium and to compare 99mTc-tetrofosmin with 201Tl uptake during adenosine-induced vasodilatation in dogs with various degrees of coronary stenosis. METHODS AND RESULTS: EF was calculated in 4 anesthetized, open-chest dogs after intracoronary administration of 125I-labeled albumin and 99mTc-tetrofosmin. In another 16 dogs with either critical (n=6) or mild (n= 10) left anterior descending coronary artery (LAD) stenoses, 201Tl and 99mTc-tetrofosmin were administered during adenosine infusion (250 microg x kg(-1) x min(-1)). Dogs were killed 5 minutes later, and tracer activities were determined by ex vivo imaging of heart slices and by well counting. Mean 99mTc-tetrofosmin EF was 54.0+/-3.7%. In the 6 critical-stenosis dogs, the LAD-to-left circumflex artery (LCx) microsphere flow ratio was 0.22+/-0.02 with adenosine. The LAD-to-LCx activity ratios were 0.37+/-0.04 for 201Tl and 0.67+/-0.05 for 99mTc-tetrofosmin (P<.01). For the 10 mild-stenosis dogs, the LAD-to-LCx flow ratio was 0.44+/-0.05. The 201Tl activity ratio was 0.58+/-0.04, compared with 0.81+/-0.04 for 99mTc-tetrofosmin (P<.01). Thus, in both groups, 99mTc-tetrofosmin uptake underestimated the flow disparity more than 201Tl. Similarly, magnitudes of ex vivo image defects were significantly greater for 201Tl than for 99mTc-tetrofosmin in both groups. CONCLUSIONS: In this canine model, relative underperfusion with adenosine stress is better resolved with 201Tl than with 99mTc-tetrofosmin and may be explained by the lower EF for 99mTc tetrofosmin. With clinical imaging, greater 201Tl attenuation and redistribution may lessen this advantage.

Adenosine↗
PubMed1997

Effects of dobutamine stress on myocardial blood flow, 99mTc sestamibi uptake, and systolic wall thickening in the presence of coronary artery stenoses: implications for dobutamine stress testing.

BACKGROUND: Although dobutamine stress is used with both 99mTc sestamibi (sestamibi) myocardial perfusion imaging and echocardiography for detecting coronary artery stenoses, the impact of stenosis severity on test end points (myocardial sestamibi uptake and systolic thickening, respectively) has not been clearly defined. METHODS AND RESULTS: In 15 open-chest dogs, dobutamine (2.5 to 30 microg x kg(-1) x min(-1)) was infused after placement of an LAD stenosis that reduced (n=8) or abolished (n=7) flow reserve. In dogs with reduced flow reserve, the stenotic-to-normal sestamibi activity ratio (0.86+/-0.03) significantly underestimated the approximately 2-to-1 dobutamine-induced flow disparity at the time of sestamibi injection (flow ratio, 0.53+/-0.04; P<.001). Stenotic-zone thickening increased at low but not at higher doses of dobutamine (2.9+/-0.4 versus 4.2+/-0.4 mm in normal zone at peak dobutamine; P=.055) but did not fall below baseline (2.7+/-0.3 mm). Similarly, in dogs with absent flow reserve, the sestamibi activity ratio (0.78+/-0.02) underestimated the approximately 2.5-to-1 dobutamine-induced flow disparity (flow ratio, 0.41+/-0.05; P<.001), and failure to increase systolic thickening was observed in the stenotic zone (2.7+/-0.4 versus 4.6+/-0.3 mm in the normal zone at peak stress, P<.01). In both groups of dogs, myocardial sestamibi uptake and image defect magnitudes were less than expected for the dobutamine-induced hyperemia, suggesting that dobutamine adversely affects myocardial sestamibi binding. Finally, a significant reduction in stenotic-zone thickening was seen during postdobutamine recovery, consistent with myocardial stunning. CONCLUSIONS: In the presence of stenoses that reduced or abolished regional flow reserve, (1) myocardial sestamibi uptake significantly underestimated the dobutamine-induced flow heterogeneity, (2) a "failure to increase systolic thickening" rather than a reduction in thickening was observed during dobutamine stress, and (3) myocardial stunning was observed during postdobutamine recovery.

Analysis of Variance↗
PubMed1997

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.

Aged↗
PubMed1997

Usefulness of preoperative noninvasive radionuclide testing for detecting coronary artery disease in candidates for liver transplantation.

This study, conducted in 87 candidates for liver transplantation, shows that neither stress perfusion imaging nor rest radionuclide ventriculography appear useful for preoperative cardiac risk assessment because most patients have normal studies and a favorable outcome. Routine myocardial function testing "to rule out cardiomyopathy" in asymptomatic (from a cardiac standpoint) patients with end-stage alcoholic liver disease should be abandoned.

Coronary Disease↗