Mirta Ruiz - Academia.edu (original) (raw)
Papers by Mirta Ruiz
Circulation, May 1, 1994
Background SsmTc-labeled methoxyisobutyl isonitrile (9'Tc-sestamibi) is a myocardial perfusion ag... more Background SsmTc-labeled methoxyisobutyl isonitrile (9'Tc-sestamibi) is a myocardial perfusion agent that clears slowly from the myocardium. This study evaluates the early and late myocardial distributions of 9Tc-sestamibi and 11fl in the presence of low-flow ischemia to determine whether 99'Tc-sestamibi demonstrates rest "redistribution." Methods and Res Low-flow ischemia was produced in 18 anesthetized, open-chest dogs by partial occlusion of the left anterior descending coronary artery. Dogs were injected intravenously with 9'Tc-sestamibi, "' Tl, and radiolabeled microspheres during sustained low-flow ischemia. The hearts were excised either 20 minutes (group 1, 10 dogs) or 2.5 hours (group 2, 8 dogs) after injection for gamma well counting to evaluate the early and late myocardial distributions of these radiotracers, relative to microsphere flow. The early myocardial distributions of 9Tc-sestamibi and 'Tl were comparable and correlated with the flow deficit (group 1). We observed a significant difference in myocardial flT (P=.005) and 'Tcsestamibi (P<.0001) activities between groups 1 and 2 dogs relative to flow, suggesting some redistribution of both tracers. Myocardial slices were imaged postmortem with a gamma camera, and 9"'Tc-sestamibi defect intensity was quantified. There was excellent correlation (r=.97) between the early relative 99mTc-sestamibi defect intensity on postmortem images and the flow deficit (group 1). Among group 2 dogs, the correlation was good (r=.87), but the 99'Tc-sestamibi defect was less severe than the flow deficit, again suggesting redistribution. Conclsions The myocardial distributions of ITc-sestamibi and 17Tl early after injection are comparable and proportional to flow. Under conditions of sustained low flow, there was detectable rest "redistribution" of 99'Tc-sestamibi verified by both gamma well counting and high-resolution postmortem imaging of myocardial slices. Whether this degree of 9"'Tcsestamibi rest redistribution will be detectable by serial clinical imaging remains uncertain. Nevertheless, these data suggest that imaging should be delayed after the resting injection of 9'Tc-sestamibi when assessing myocardial viability in the presence of a critical stenosis. (Circulaion. 1994;89:2332-2341.) Key Words * ischemia * myocardium * radionuclides. imaging M yocardial perfusion imaging with 20`T1 has been used extensively for the assessment of myocardial viability.1-13 Evaluation of`1TI "redistribution" with serial imaging after the intravenous injection of`'Tl either at rest or after stress permits the distinction of myocardial ischemia and infarction in patients with coronary artery disease.1,14-18 20`T1 redistribution, which is characterized by the filling in of a perfusion defect, may occur in the presence of a fixed coronary stenosis despite persistent low flow.14'19'20 The resolution of perfusion defects with resting`'TI scintigraphy is attributed to the increase in activity in the ischemic region relative to the nonischemic region.21 The phenomenon of`1Tl redistribution is dependent on the severity of a stenosis in addition to circulating levels
This article and updated information are available at:
Circulation Journal Official Journal of the Japanese Circulation Society, Mar 31, 2002
Reperfusion is often incomplete after recanalization therapy because of the presence of residual ... more Reperfusion is often incomplete after recanalization therapy because of the presence of residual coronary stenoses. Detecting mild to moderate stenoses requires assessing coronary flow reserve with vasodilator stress. 99m Tc-(N-ethoxy-N-ethyl-dithiocarbamato)nitrido (N-NOET) is a viability-independent flow tracer and thus may be well suited for assessing coronary flow reserve in the acute phase of reperfusion. Methods: Twelve open-chest dogs underwent 60 min of total left anterior descending artery (LAD) occlusion followed by either full reperfusion (group 1; n ϭ 4) or reperfusion through a residual critical stenosis (group 2; n ϭ 8). 99m Tc-N-NOET was given during peak vasodilator stress 165 min after reperfusion, and initial and 60-min delayed images were acquired. Regional blood flow was assessed with radiolabeled microspheres. Results: Infarct size was similar in both groups (9% Ϯ 2% vs. 8% Ϯ 2% of left ventricle). Both initial (0.61 Ϯ 0.02 vs. 0.73 Ϯ 0.01; P Ͻ 0.01) and 60-min (0.67 Ϯ 0.02 vs. 0.80 Ϯ 0.01; P Ͻ 0.01) defect count ratios (LAD/left circumflex coronary artery [LCx]) differentiated between the 2 groups, reflecting the greater diminution in coronary flow reserve in group 2 dogs (LAD/LCx flow ratios ϭ 0.37 Ϯ 0.04 vs. 0.57 Ϯ 0.09; P Ͻ 0.01). Interestingly, coronary flow reserve in the reperfused zone of group 1 was diminished despite the absence of a stenosis. Thus, the difference in 99m Tc-N-NOET uptake between the 2 groups was less than expected. Conclusion: In this canine myocardial infarction model with some coronary flow reserve preservation, 99m Tc-N-NOET imaging can detect residual coronary stenoses. However, with more prolonged occlusion resulting in more severe endothelial or microvascular dysfunction, it may be difficult to distinguish varying degrees of vessel patency using any coronary flow reserve technique.
Circulation Journal Official Journal of the Japanese Circulation Society, Mar 1, 2005
Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 1995
N6-endonorboman-2-yl-9-methyladenine (N-0861) is a drug which inhibits the A1 adenosine receptor ... more N6-endonorboman-2-yl-9-methyladenine (N-0861) is a drug which inhibits the A1 adenosine receptor subtype. One proposed use for N-0861 is to eliminate A1 receptor-mediated side effects such as A-V heart block and possibly angina in patients undergoing pharmacologic stress with adenosine. The goal of this study was to determine whether N-0861 has any crossover effect on the A2 vasodilatory action of adenosine or on 201TI uptake which would adversely affect imaging of coronary stenoses. In eight dogs with critical left anterior descending (LAD) stenoses, we compared the hemodynamic response to intravenous adenosine (250 micrograms/kg/min) before and after N-0861 administration. LAD and left circumflex (LCx) coronary flows were measured ultrasonically and regional blood flow was assessed using microspheres. Thallium-201 (18.5-37.0 MBq) was injected during adenosine hyperemia while N-0861 was present. Imaging of heart slices was performed and defect magnitude was calculated as LAD:LCx co...
Journal of the American College of Cardiology, 1995
may be an important contributor to improved peak aerobic capacity. Thus, low level training produ... more may be an important contributor to improved peak aerobic capacity. Thus, low level training produces benefits similar to high level training with only a moderate rise in PCWP, and may therefore provide less of a stimulus for ventricular dilatation.
Journal of Nuclear Cardiology, 2001
Journal of Nuclear Cardiology, 2000
Bis (N-ethoxy, N-ethyl dithiocarbamato) nitrido technetium-99m (V) (Tc-99m-N-NOET) is a new Tc-99... more Bis (N-ethoxy, N-ethyl dithiocarbamato) nitrido technetium-99m (V) (Tc-99m-N-NOET) is a new Tc-99m-labeled myocardial perfusion imaging agent that redistributes. We sought to determine the optimal timing for acquiring initial and delayed images to maximize sensitivity for the detection of coronary stenoses. Twelve anesthetized dogs with critical stenoses of the left anterior descending coronary artery were infused with adenosine (250 microg/kg/min) or MRE-0470, an adenosine A2a agonist (0.6 microg/kg/min x 10 minutes), and Tc-99m-N-NOET (8 mCi; 296 MBq) was injected intravenously at peak flow. Myocardial and lung Tc-99m-N-NOET activities were determined by serial quantitative imaging and arterial blood sampling was performed over 2 hours. Left anterior descending/left circumflex artery defect count ratios showed rapid redistribution during the first 10 minutes after Tc-99m-N-NOET injection (0.66 +/- 0.02 at 2 minutes to 0.73 +/- 0.01 at 10 minutes; P < .01). Redistribution was nearly complete by 120 minutes (defect ratio = 0.87 +/- 0.03; P < or = .01 vs 2 minutes). Lung activity fell significantly during the first 10 minutes from a heart/lung activity ratio of 1.07 +/- 0.05 (2 minutes) to 1.44 +/- 0.09 (10 minutes; P < or = .01). Initial stress Tc-99m-N-NOET images should be acquired within 10 minutes after injection, whereas delayed images can be obtained as early as 2 hours later. Lung activity clears rapidly, permitting acquisition of good-quality poststress cardiac images. These Tc-99m-N-NOET uptake and redistribution kinetics after vasodilator stress provide important information for designing clinical imaging protocols for optimal identification of inducible ischemia.
Journal of Nuclear Cardiology, 2003
We sought to determine whether a dual-isotope imaging strategy (rest thallium 201/stress techneti... more We sought to determine whether a dual-isotope imaging strategy (rest thallium 201/stress technetium 99m sestamibi) might be useful for assessing myocardial viability and residual ischemia in the infarct zone very early after reperfusion. Fifteen open-chest dogs had left anterior descending coronary artery occlusion for 60 minutes, followed by full reperfusion (group 1, n = 8) or reperfusion through a residual critical stenosis (group 2, n = 7). Tl-201 was injected at rest 45 minutes after reperfusion, and initial and 2-hour redistribution images were acquired. Tc-99m sestamibi was then injected during vasodilator stress, followed by imaging. Infarct size was similar in both groups (risk area, 21% +/- 4% vs 22% +/- 3%). Rest Tl-201 defect count ratios (left anterior descending coronary artery/left circumflex artery) were comparable (0.71 +/- 0.03 vs 0.74 +/- 0.02) and reflected infarct size. With vasodilation, Tc-99m sestamibi defect count ratio in group 1 (0.71 +/- 0.02) was comparable to rest Tl-201 and was significantly greater than in group 2 (0.62 +/- 0.02) with residual stenoses (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;.01). Although vasodilator Tc-99m sestamibi imaging unmasked the presence of residual stenoses, Tc-99m sestamibi uptake underestimated their functional severity (flow ratio, 0.38 +/- 0.03). Dual-isotope imaging very early after reperfusion may have limited utility for detecting residual stenoses in the infarct zone. Underestimation of the flow disparity by Tc-99m sestamibi may make the detection of stenoses more difficult, and impaired flow reserve after ischemic insult may complicate the detection of fully reperfused segments.
Journal of Cardiovascular Magnetic Resonance, 2009
Introduction: Prophylactic implantation of a cardioverter/ defibrillator (ICD) has been shown to ... more Introduction: Prophylactic implantation of a cardioverter/ defibrillator (ICD) has been shown to reduce mortality in patients with chronic myocardial infarction (CMI) and an increased risk for life threatening ventricular arrhythmia (VA). The use of ICDs in this large patient population is still limited by high costs and possible adverse events including inappropriate discharges and progression of heart failure. VA is related to infarct size and seems to be related to infarct morphology. Contrast enhanced cardiovascular magnetic resonance imaging (ceCMR) can detect and quantify myocardial fibrosis in the setting of CMI and might therefore be a valuable tool for a more accurate risk stratification in this setting. Hypothesis: ceCMR can identify the subgroup developing VA in patients with prophylactic ICD implantation following MADIT criteria. Methods: We prospectively enrolled 52 patients (49 males, age 69 ± 10 years) with CMI and clinical indication for ICD therapy following MADIT criteria. Prior to implantation (36 ± 78 days) patients were investigated on a 1.5 T clinical scanner (Siemens Avanto © , Germany) to assess left ventricular function (LVEF), LV end-diastolic volume (LVEDV) and LV mass (sequence parameters: GRE SSFP, matrix 256 × 192, short axis stack; full LV coverage, no gap; slice thickness 6 mm). For quantitative assessment of infarct morphology late gadolinium enhancement (LGE) was performed including measurement of total and relative infarct mass (related to LV mass) and the degree of transmurality (DT) as defined by the percentage of transmurality in each scar. (sequence parameters: inversion recovery gradient echo; matrix 256 × 148, imaging 10 min after 0.2 μg/kg gadolinium DTPA; slice orientation equal to SSFP). MRI images were analysed using dedicated software (MASS © , Medis, Netherlands). LGE was defined as myocardial areas with signal intensity above the average plus 5 SD of the remote myocardium. After implantation, patients were followed up including ICD readout after 3 and than every 6 months for a mean of 945 ± 344 days. ICD data were evaluated by an experienced electrophysiologist. Primary endpoint was the occurrence of an appropriate discharge (DC), antitachycard pacing (ATP) or death from cardiac cause. Results: The endpoint occurred in 10 patients (3 DC, 6 ATP, 1 death). These patients had a higher relative infarct mass (28 ± 7% vs. 22 ± 11%, p = 0.03) as well as high degree of transmurality (64 ± 22% vs. 44 ± 25%, p = 0.05). Their LVEF (29 ± 8% vs. 30 ± 4%, p = 0.75), LV mass (148 ± 29 g vs. 154 ± 42 g, p = 0.60), LVEDV (270 ± 133 ml vs. 275 ± 83 ml, p = 0.90) or total infarct mass (43 ± 19 g vs. 37 ± 21 g, p = 0.43) were however not significant from the group with no events. In a cox proportional hazards regression model including LVEF, LVEDV, LV mass, DT and age, only degree of transmurality and relative infarct mass emerged as independent predictors of the primary end point (p = 0.009). Conclusion: In CMI-patients fulfilling MADIT criteria ceCMR could show that the extent and transmurality of myocardial scarring are independent predictors for life threatening ventricular arrhythmia or death. This additional information could lead to more precise risk stratification and might reduce adverse events and cost of ICD therapy in this patient population. Larger trials are needed to confirm this finding.
Clinical Nuclear Medicine, 1992
Circulation, 2002
Background — 99m Tc-RP517 is a new leukotriene B 4 (LTB4) receptor antagonist developed for imagi... more Background — 99m Tc-RP517 is a new leukotriene B 4 (LTB4) receptor antagonist developed for imaging acute inflammation or infection. A unique property of 99m Tc-RP517 is its ability to label white blood cells in vivo after intravenous injection. The goals of this study were to determine relative 99m Tc-RP517 binding to human leukocyte subtypes and the 99m Tc-RP517 uptake pattern in canine myocardium where inflammation was induced by either coronary occlusion and reperfusion or tumor necrosis factor α (TNFα) injection. Methods and Results — Fluorescence-activated cell sorter analysis was performed on whole human blood (n=2) and isolated neutrophils (n= 4) with a fluorescent analog of 99m Tc-RP517, [F]-RP517. In whole blood, [F]-RP517 (500 nmol/L) preferentially labeled neutrophils. On isolated neutrophils, [F]-RP517 (10 nmol/L) binding was inhibited by 44% when LTB4 (400 nmol/L) was added. 99m Tc-RP517 was injected intravenously in anesthetized, open-chest dogs before coronary occlus...
Circulation, 1997
Background Although dobutamine stress is used with both 99m Tc sestamibi (sestamibi) myocardial p... more Background Although dobutamine stress is used with both 99m Tc 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 μg · kg −1 · 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 ≈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...
Circulation, 1999
Background —The myocardial uptake of 99m Tc-sestamibi is attenuated by dobutamine stress, resulti... more 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 μg · kg −1 · min −1 ; n=15) or dobutamine (2.5 to 30 μg · 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 dobutamin...
Circulation, 2001
Background — Adenosine (Ado) and dipyridamole are alternatives to exercise stress for myocardial ... more Background — Adenosine (Ado) and dipyridamole are alternatives to exercise stress for myocardial perfusion imaging. Though generally safe, side effects frequently occur that cause patient discomfort and sometimes lead to premature termination of the study or require aminophylline administration. Recently, a new class of A 2A Ado receptor agonists was synthesized. ATL193 and ATL146e are 2-propynylcyclohexyl-5′- N -ethylcarboxamido derivatives of Ado. The study goals were to evaluate the potency and selectivity of these new compounds on recombinant canine Ado receptors and to evaluate their hemodynamic properties in dogs to assess their usefulness as vasodilators for myocardial perfusion imaging. Methods and Results — In assays of recombinant canine Ado receptors, ATL-193 and ATL-146e were highly selective for the A 2A over the A 1 and A 3 receptors and were more potent than MRE-0470 and CGS-21680. In 16 anesthetized dogs, the agonists were administered by infusion (ATL-193; n=7 norma...
Circulation, 1995
Background 201 Tl scintigraphy is useful for determination of viability in patients with coronary... more Background 201 Tl scintigraphy is useful for determination of viability in patients with coronary artery disease and depressed left ventricular function. Whether 99m Tc sestamibi is adequate for viability detection remains controversial. The primary goal of this study was to compare 99m Tc-sestamibi uptake with 201 Tl uptake in canine models of sustained low flow and regional asynergy for determination of viability. A secondary objective was to compare myocardial uptake of these tracers with the functional response to low-dose dobutamine. Methods and Results In protocol 1, 14 open-chested, anesthetized dogs with a 50% reduction in resting left anterior descending coronary artery (LAD) flow underwent 1 hour of transient LAD occlusion followed by reperfusion through the severe stenosis. Then 1.0 mCi of 201 Tl was injected, and serial imaging was performed 5 minutes and 2 hours later. After acquisition of the delayed 201 Tl image, 10 mCi of 99m Tc sestamibi was injected, and imaging wa...
Circulation, 1996
Background Pharmacological stress imaging with adenosine or dipyridamole is associated with a hig... more Background Pharmacological stress imaging with adenosine or dipyridamole is associated with a high incidence of side effects, including hypotension, chest pain, AV conduction abnormalities, and bronchospasm. Although the desired coronary vasodilatory response is mediated primarily by the adenosine A 2A receptors, these side effects result from stimulation of the A 1 , A 2B , or A 3 adenosine receptors. We hypothesized that a selective adenosine A 2A receptor agonist would induce coronary vasodilatation appropriate for pharmacological stress imaging, without evoking adenosine receptor–mediated side effects. Methods and Results Infusions of a potent and selective A 2A adenosine receptor agonist, WRC-0470 (0.1 to 3 μg · kg −1 ·min −1 for 10 minutes), to five open-chest dogs produced dose-related left anterior descending (LAD) and left circumflex (LCx) coronary artery vasodilatation without altering mean arterial pressure, heart rate, left atrial pressure, or left ventricular dP/dt. In ...
Circulation, 1997
Background 99m Tc-N-NOET (NOET) is a new myocardial perfusion imaging agent that redistributes ov... more Background 99m Tc-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 201 Tl 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 in...
American Journal of Physiology-Heart and Circulatory Physiology, 2004
Adenosine and adenosine A2Areceptor agonists have been shown to limit myocardial infarct size whe... more Adenosine and adenosine A2Areceptor agonists have been shown to limit myocardial infarct size when given at vasodilatory doses during reperfusion. This beneficial effect is thought to be due, in part, to stimulation of adenosine A2Areceptors on inflammatory cells. The specific aims of this study were to determine whether the anti-inflammatory and cardioprotective properties of a novel adenosine A2Areceptor agonist, ATL-146e (ATL), alone or in combination with the phosphodiesterase IV inhibitor rolipram would occur using very low, nonvasodilating doses. In a canine model of reperfused myocardial infarction, low-dose ATL given alone reduced infarct size by 45% ( P < 0.05 vs. control). When ATL was combined with a very low dose of rolipram (0.001 μg·kg−1·min−1), a marked reduction in P-selectin expression and neutrophil infiltration (51% lower; P < 0.001 vs. control) was seen and the infarct size reduction (58% lower; P < 0.01 vs. control) was greater than observed with ATL (4...
Circulation, May 1, 1994
Background SsmTc-labeled methoxyisobutyl isonitrile (9'Tc-sestamibi) is a myocardial perfusion ag... more Background SsmTc-labeled methoxyisobutyl isonitrile (9'Tc-sestamibi) is a myocardial perfusion agent that clears slowly from the myocardium. This study evaluates the early and late myocardial distributions of 9Tc-sestamibi and 11fl in the presence of low-flow ischemia to determine whether 99'Tc-sestamibi demonstrates rest "redistribution." Methods and Res Low-flow ischemia was produced in 18 anesthetized, open-chest dogs by partial occlusion of the left anterior descending coronary artery. Dogs were injected intravenously with 9'Tc-sestamibi, "' Tl, and radiolabeled microspheres during sustained low-flow ischemia. The hearts were excised either 20 minutes (group 1, 10 dogs) or 2.5 hours (group 2, 8 dogs) after injection for gamma well counting to evaluate the early and late myocardial distributions of these radiotracers, relative to microsphere flow. The early myocardial distributions of 9Tc-sestamibi and 'Tl were comparable and correlated with the flow deficit (group 1). We observed a significant difference in myocardial flT (P=.005) and 'Tcsestamibi (P<.0001) activities between groups 1 and 2 dogs relative to flow, suggesting some redistribution of both tracers. Myocardial slices were imaged postmortem with a gamma camera, and 9"'Tc-sestamibi defect intensity was quantified. There was excellent correlation (r=.97) between the early relative 99mTc-sestamibi defect intensity on postmortem images and the flow deficit (group 1). Among group 2 dogs, the correlation was good (r=.87), but the 99'Tc-sestamibi defect was less severe than the flow deficit, again suggesting redistribution. Conclsions The myocardial distributions of ITc-sestamibi and 17Tl early after injection are comparable and proportional to flow. Under conditions of sustained low flow, there was detectable rest "redistribution" of 99'Tc-sestamibi verified by both gamma well counting and high-resolution postmortem imaging of myocardial slices. Whether this degree of 9"'Tcsestamibi rest redistribution will be detectable by serial clinical imaging remains uncertain. Nevertheless, these data suggest that imaging should be delayed after the resting injection of 9'Tc-sestamibi when assessing myocardial viability in the presence of a critical stenosis. (Circulaion. 1994;89:2332-2341.) Key Words * ischemia * myocardium * radionuclides. imaging M yocardial perfusion imaging with 20`T1 has been used extensively for the assessment of myocardial viability.1-13 Evaluation of`1TI "redistribution" with serial imaging after the intravenous injection of`'Tl either at rest or after stress permits the distinction of myocardial ischemia and infarction in patients with coronary artery disease.1,14-18 20`T1 redistribution, which is characterized by the filling in of a perfusion defect, may occur in the presence of a fixed coronary stenosis despite persistent low flow.14'19'20 The resolution of perfusion defects with resting`'TI scintigraphy is attributed to the increase in activity in the ischemic region relative to the nonischemic region.21 The phenomenon of`1Tl redistribution is dependent on the severity of a stenosis in addition to circulating levels
This article and updated information are available at:
Circulation Journal Official Journal of the Japanese Circulation Society, Mar 31, 2002
Reperfusion is often incomplete after recanalization therapy because of the presence of residual ... more Reperfusion is often incomplete after recanalization therapy because of the presence of residual coronary stenoses. Detecting mild to moderate stenoses requires assessing coronary flow reserve with vasodilator stress. 99m Tc-(N-ethoxy-N-ethyl-dithiocarbamato)nitrido (N-NOET) is a viability-independent flow tracer and thus may be well suited for assessing coronary flow reserve in the acute phase of reperfusion. Methods: Twelve open-chest dogs underwent 60 min of total left anterior descending artery (LAD) occlusion followed by either full reperfusion (group 1; n ϭ 4) or reperfusion through a residual critical stenosis (group 2; n ϭ 8). 99m Tc-N-NOET was given during peak vasodilator stress 165 min after reperfusion, and initial and 60-min delayed images were acquired. Regional blood flow was assessed with radiolabeled microspheres. Results: Infarct size was similar in both groups (9% Ϯ 2% vs. 8% Ϯ 2% of left ventricle). Both initial (0.61 Ϯ 0.02 vs. 0.73 Ϯ 0.01; P Ͻ 0.01) and 60-min (0.67 Ϯ 0.02 vs. 0.80 Ϯ 0.01; P Ͻ 0.01) defect count ratios (LAD/left circumflex coronary artery [LCx]) differentiated between the 2 groups, reflecting the greater diminution in coronary flow reserve in group 2 dogs (LAD/LCx flow ratios ϭ 0.37 Ϯ 0.04 vs. 0.57 Ϯ 0.09; P Ͻ 0.01). Interestingly, coronary flow reserve in the reperfused zone of group 1 was diminished despite the absence of a stenosis. Thus, the difference in 99m Tc-N-NOET uptake between the 2 groups was less than expected. Conclusion: In this canine myocardial infarction model with some coronary flow reserve preservation, 99m Tc-N-NOET imaging can detect residual coronary stenoses. However, with more prolonged occlusion resulting in more severe endothelial or microvascular dysfunction, it may be difficult to distinguish varying degrees of vessel patency using any coronary flow reserve technique.
Circulation Journal Official Journal of the Japanese Circulation Society, Mar 1, 2005
Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 1995
N6-endonorboman-2-yl-9-methyladenine (N-0861) is a drug which inhibits the A1 adenosine receptor ... more N6-endonorboman-2-yl-9-methyladenine (N-0861) is a drug which inhibits the A1 adenosine receptor subtype. One proposed use for N-0861 is to eliminate A1 receptor-mediated side effects such as A-V heart block and possibly angina in patients undergoing pharmacologic stress with adenosine. The goal of this study was to determine whether N-0861 has any crossover effect on the A2 vasodilatory action of adenosine or on 201TI uptake which would adversely affect imaging of coronary stenoses. In eight dogs with critical left anterior descending (LAD) stenoses, we compared the hemodynamic response to intravenous adenosine (250 micrograms/kg/min) before and after N-0861 administration. LAD and left circumflex (LCx) coronary flows were measured ultrasonically and regional blood flow was assessed using microspheres. Thallium-201 (18.5-37.0 MBq) was injected during adenosine hyperemia while N-0861 was present. Imaging of heart slices was performed and defect magnitude was calculated as LAD:LCx co...
Journal of the American College of Cardiology, 1995
may be an important contributor to improved peak aerobic capacity. Thus, low level training produ... more may be an important contributor to improved peak aerobic capacity. Thus, low level training produces benefits similar to high level training with only a moderate rise in PCWP, and may therefore provide less of a stimulus for ventricular dilatation.
Journal of Nuclear Cardiology, 2001
Journal of Nuclear Cardiology, 2000
Bis (N-ethoxy, N-ethyl dithiocarbamato) nitrido technetium-99m (V) (Tc-99m-N-NOET) is a new Tc-99... more Bis (N-ethoxy, N-ethyl dithiocarbamato) nitrido technetium-99m (V) (Tc-99m-N-NOET) is a new Tc-99m-labeled myocardial perfusion imaging agent that redistributes. We sought to determine the optimal timing for acquiring initial and delayed images to maximize sensitivity for the detection of coronary stenoses. Twelve anesthetized dogs with critical stenoses of the left anterior descending coronary artery were infused with adenosine (250 microg/kg/min) or MRE-0470, an adenosine A2a agonist (0.6 microg/kg/min x 10 minutes), and Tc-99m-N-NOET (8 mCi; 296 MBq) was injected intravenously at peak flow. Myocardial and lung Tc-99m-N-NOET activities were determined by serial quantitative imaging and arterial blood sampling was performed over 2 hours. Left anterior descending/left circumflex artery defect count ratios showed rapid redistribution during the first 10 minutes after Tc-99m-N-NOET injection (0.66 +/- 0.02 at 2 minutes to 0.73 +/- 0.01 at 10 minutes; P < .01). Redistribution was nearly complete by 120 minutes (defect ratio = 0.87 +/- 0.03; P < or = .01 vs 2 minutes). Lung activity fell significantly during the first 10 minutes from a heart/lung activity ratio of 1.07 +/- 0.05 (2 minutes) to 1.44 +/- 0.09 (10 minutes; P < or = .01). Initial stress Tc-99m-N-NOET images should be acquired within 10 minutes after injection, whereas delayed images can be obtained as early as 2 hours later. Lung activity clears rapidly, permitting acquisition of good-quality poststress cardiac images. These Tc-99m-N-NOET uptake and redistribution kinetics after vasodilator stress provide important information for designing clinical imaging protocols for optimal identification of inducible ischemia.
Journal of Nuclear Cardiology, 2003
We sought to determine whether a dual-isotope imaging strategy (rest thallium 201/stress techneti... more We sought to determine whether a dual-isotope imaging strategy (rest thallium 201/stress technetium 99m sestamibi) might be useful for assessing myocardial viability and residual ischemia in the infarct zone very early after reperfusion. Fifteen open-chest dogs had left anterior descending coronary artery occlusion for 60 minutes, followed by full reperfusion (group 1, n = 8) or reperfusion through a residual critical stenosis (group 2, n = 7). Tl-201 was injected at rest 45 minutes after reperfusion, and initial and 2-hour redistribution images were acquired. Tc-99m sestamibi was then injected during vasodilator stress, followed by imaging. Infarct size was similar in both groups (risk area, 21% +/- 4% vs 22% +/- 3%). Rest Tl-201 defect count ratios (left anterior descending coronary artery/left circumflex artery) were comparable (0.71 +/- 0.03 vs 0.74 +/- 0.02) and reflected infarct size. With vasodilation, Tc-99m sestamibi defect count ratio in group 1 (0.71 +/- 0.02) was comparable to rest Tl-201 and was significantly greater than in group 2 (0.62 +/- 0.02) with residual stenoses (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;.01). Although vasodilator Tc-99m sestamibi imaging unmasked the presence of residual stenoses, Tc-99m sestamibi uptake underestimated their functional severity (flow ratio, 0.38 +/- 0.03). Dual-isotope imaging very early after reperfusion may have limited utility for detecting residual stenoses in the infarct zone. Underestimation of the flow disparity by Tc-99m sestamibi may make the detection of stenoses more difficult, and impaired flow reserve after ischemic insult may complicate the detection of fully reperfused segments.
Journal of Cardiovascular Magnetic Resonance, 2009
Introduction: Prophylactic implantation of a cardioverter/ defibrillator (ICD) has been shown to ... more Introduction: Prophylactic implantation of a cardioverter/ defibrillator (ICD) has been shown to reduce mortality in patients with chronic myocardial infarction (CMI) and an increased risk for life threatening ventricular arrhythmia (VA). The use of ICDs in this large patient population is still limited by high costs and possible adverse events including inappropriate discharges and progression of heart failure. VA is related to infarct size and seems to be related to infarct morphology. Contrast enhanced cardiovascular magnetic resonance imaging (ceCMR) can detect and quantify myocardial fibrosis in the setting of CMI and might therefore be a valuable tool for a more accurate risk stratification in this setting. Hypothesis: ceCMR can identify the subgroup developing VA in patients with prophylactic ICD implantation following MADIT criteria. Methods: We prospectively enrolled 52 patients (49 males, age 69 ± 10 years) with CMI and clinical indication for ICD therapy following MADIT criteria. Prior to implantation (36 ± 78 days) patients were investigated on a 1.5 T clinical scanner (Siemens Avanto © , Germany) to assess left ventricular function (LVEF), LV end-diastolic volume (LVEDV) and LV mass (sequence parameters: GRE SSFP, matrix 256 × 192, short axis stack; full LV coverage, no gap; slice thickness 6 mm). For quantitative assessment of infarct morphology late gadolinium enhancement (LGE) was performed including measurement of total and relative infarct mass (related to LV mass) and the degree of transmurality (DT) as defined by the percentage of transmurality in each scar. (sequence parameters: inversion recovery gradient echo; matrix 256 × 148, imaging 10 min after 0.2 μg/kg gadolinium DTPA; slice orientation equal to SSFP). MRI images were analysed using dedicated software (MASS © , Medis, Netherlands). LGE was defined as myocardial areas with signal intensity above the average plus 5 SD of the remote myocardium. After implantation, patients were followed up including ICD readout after 3 and than every 6 months for a mean of 945 ± 344 days. ICD data were evaluated by an experienced electrophysiologist. Primary endpoint was the occurrence of an appropriate discharge (DC), antitachycard pacing (ATP) or death from cardiac cause. Results: The endpoint occurred in 10 patients (3 DC, 6 ATP, 1 death). These patients had a higher relative infarct mass (28 ± 7% vs. 22 ± 11%, p = 0.03) as well as high degree of transmurality (64 ± 22% vs. 44 ± 25%, p = 0.05). Their LVEF (29 ± 8% vs. 30 ± 4%, p = 0.75), LV mass (148 ± 29 g vs. 154 ± 42 g, p = 0.60), LVEDV (270 ± 133 ml vs. 275 ± 83 ml, p = 0.90) or total infarct mass (43 ± 19 g vs. 37 ± 21 g, p = 0.43) were however not significant from the group with no events. In a cox proportional hazards regression model including LVEF, LVEDV, LV mass, DT and age, only degree of transmurality and relative infarct mass emerged as independent predictors of the primary end point (p = 0.009). Conclusion: In CMI-patients fulfilling MADIT criteria ceCMR could show that the extent and transmurality of myocardial scarring are independent predictors for life threatening ventricular arrhythmia or death. This additional information could lead to more precise risk stratification and might reduce adverse events and cost of ICD therapy in this patient population. Larger trials are needed to confirm this finding.
Clinical Nuclear Medicine, 1992
Circulation, 2002
Background — 99m Tc-RP517 is a new leukotriene B 4 (LTB4) receptor antagonist developed for imagi... more Background — 99m Tc-RP517 is a new leukotriene B 4 (LTB4) receptor antagonist developed for imaging acute inflammation or infection. A unique property of 99m Tc-RP517 is its ability to label white blood cells in vivo after intravenous injection. The goals of this study were to determine relative 99m Tc-RP517 binding to human leukocyte subtypes and the 99m Tc-RP517 uptake pattern in canine myocardium where inflammation was induced by either coronary occlusion and reperfusion or tumor necrosis factor α (TNFα) injection. Methods and Results — Fluorescence-activated cell sorter analysis was performed on whole human blood (n=2) and isolated neutrophils (n= 4) with a fluorescent analog of 99m Tc-RP517, [F]-RP517. In whole blood, [F]-RP517 (500 nmol/L) preferentially labeled neutrophils. On isolated neutrophils, [F]-RP517 (10 nmol/L) binding was inhibited by 44% when LTB4 (400 nmol/L) was added. 99m Tc-RP517 was injected intravenously in anesthetized, open-chest dogs before coronary occlus...
Circulation, 1997
Background Although dobutamine stress is used with both 99m Tc sestamibi (sestamibi) myocardial p... more Background Although dobutamine stress is used with both 99m Tc 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 μg · kg −1 · 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 ≈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...
Circulation, 1999
Background —The myocardial uptake of 99m Tc-sestamibi is attenuated by dobutamine stress, resulti... more 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 μg · kg −1 · min −1 ; n=15) or dobutamine (2.5 to 30 μg · 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 dobutamin...
Circulation, 2001
Background — Adenosine (Ado) and dipyridamole are alternatives to exercise stress for myocardial ... more Background — Adenosine (Ado) and dipyridamole are alternatives to exercise stress for myocardial perfusion imaging. Though generally safe, side effects frequently occur that cause patient discomfort and sometimes lead to premature termination of the study or require aminophylline administration. Recently, a new class of A 2A Ado receptor agonists was synthesized. ATL193 and ATL146e are 2-propynylcyclohexyl-5′- N -ethylcarboxamido derivatives of Ado. The study goals were to evaluate the potency and selectivity of these new compounds on recombinant canine Ado receptors and to evaluate their hemodynamic properties in dogs to assess their usefulness as vasodilators for myocardial perfusion imaging. Methods and Results — In assays of recombinant canine Ado receptors, ATL-193 and ATL-146e were highly selective for the A 2A over the A 1 and A 3 receptors and were more potent than MRE-0470 and CGS-21680. In 16 anesthetized dogs, the agonists were administered by infusion (ATL-193; n=7 norma...
Circulation, 1995
Background 201 Tl scintigraphy is useful for determination of viability in patients with coronary... more Background 201 Tl scintigraphy is useful for determination of viability in patients with coronary artery disease and depressed left ventricular function. Whether 99m Tc sestamibi is adequate for viability detection remains controversial. The primary goal of this study was to compare 99m Tc-sestamibi uptake with 201 Tl uptake in canine models of sustained low flow and regional asynergy for determination of viability. A secondary objective was to compare myocardial uptake of these tracers with the functional response to low-dose dobutamine. Methods and Results In protocol 1, 14 open-chested, anesthetized dogs with a 50% reduction in resting left anterior descending coronary artery (LAD) flow underwent 1 hour of transient LAD occlusion followed by reperfusion through the severe stenosis. Then 1.0 mCi of 201 Tl was injected, and serial imaging was performed 5 minutes and 2 hours later. After acquisition of the delayed 201 Tl image, 10 mCi of 99m Tc sestamibi was injected, and imaging wa...
Circulation, 1996
Background Pharmacological stress imaging with adenosine or dipyridamole is associated with a hig... more Background Pharmacological stress imaging with adenosine or dipyridamole is associated with a high incidence of side effects, including hypotension, chest pain, AV conduction abnormalities, and bronchospasm. Although the desired coronary vasodilatory response is mediated primarily by the adenosine A 2A receptors, these side effects result from stimulation of the A 1 , A 2B , or A 3 adenosine receptors. We hypothesized that a selective adenosine A 2A receptor agonist would induce coronary vasodilatation appropriate for pharmacological stress imaging, without evoking adenosine receptor–mediated side effects. Methods and Results Infusions of a potent and selective A 2A adenosine receptor agonist, WRC-0470 (0.1 to 3 μg · kg −1 ·min −1 for 10 minutes), to five open-chest dogs produced dose-related left anterior descending (LAD) and left circumflex (LCx) coronary artery vasodilatation without altering mean arterial pressure, heart rate, left atrial pressure, or left ventricular dP/dt. In ...
Circulation, 1997
Background 99m Tc-N-NOET (NOET) is a new myocardial perfusion imaging agent that redistributes ov... more Background 99m Tc-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 201 Tl 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 in...
American Journal of Physiology-Heart and Circulatory Physiology, 2004
Adenosine and adenosine A2Areceptor agonists have been shown to limit myocardial infarct size whe... more Adenosine and adenosine A2Areceptor agonists have been shown to limit myocardial infarct size when given at vasodilatory doses during reperfusion. This beneficial effect is thought to be due, in part, to stimulation of adenosine A2Areceptors on inflammatory cells. The specific aims of this study were to determine whether the anti-inflammatory and cardioprotective properties of a novel adenosine A2Areceptor agonist, ATL-146e (ATL), alone or in combination with the phosphodiesterase IV inhibitor rolipram would occur using very low, nonvasodilating doses. In a canine model of reperfused myocardial infarction, low-dose ATL given alone reduced infarct size by 45% ( P < 0.05 vs. control). When ATL was combined with a very low dose of rolipram (0.001 μg·kg−1·min−1), a marked reduction in P-selectin expression and neutrophil infiltration (51% lower; P < 0.001 vs. control) was seen and the infarct size reduction (58% lower; P < 0.01 vs. control) was greater than observed with ATL (4...