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Biomedical subjects

D D Watson

Publications and source records attributed to D D Watson.

At least 19 recordsLinked to original sources
PubMed1992

Myocardial thallium-201 scintigraphy for assessment of viability in patients with severe left ventricular dysfunction.

Many patients with ischemic heart disease and depressed left ventricular (LV) function have asynergic zones with sustained microcirculatory perfusion and myocardial metabolic activity that exhibit improved systolic function after coronary revascularization. The 2 predominant noninvasive techniques used to determine myocardial viability in patients with severely depressed LV function are thallium-201 (201Tl) scintigraphy and positron emission tomography (PET). Myocardial extraction of 201Tl is unaltered under experimental conditions of myocardial stunning or short-term hibernation (characterized by decreased flow and ischemic dysfunction). Akinetic or dyskinetic LV wall segments can exhibit normal or near normal 201Tl uptake as long as some residual flow is present. 201Tl scintigraphy can identify viable asynergic segments when performed on patients with severe coronary artery disease who are in the resting state. Many of these patients have initial resting defects that demonstrate delayed redistribution, or mild persistent defects that show improved perfusion and function after revascularization. There is a direct correlation between the extent of 201Tl uptake in zones of severe regional myocardial asynergy and the magnitude of improvement in resting LV ejection fraction after coronary bypass surgery. Rest 201Tl scintigraphy may help in the selection of patients with coronary artery disease and severely depressed LV function who would benefit the most from revascularization.

Animals↗
PubMed1992

ST-segment depression during dipyridamole infusion, and its clinical, scintigraphic and hemodynamic correlates.

The goal of this study was to determine whether dipyridamole-induced ST-segment depression reflects more severe or extensive myocardial hypoperfusion than the absence of this electrocardiographic finding. The clinical, hemodynamic and scintigraphic correlates of ST-segment depression during intravenous dipyridamole infusion were studied in 204 consecutive patients undergoing dipyridamole stress thallium-201 (Tl-201) imaging for evaluation of coronary artery disease. Of 182 patients with a diagnostic baseline electrocardiogram, 28 (15%) developed ST depression after dipyridamole. Patients with ST depression, compared with those without, were older (64 +/- 1 vs 60 +/- 1 years; p less than 0.03) and had a higher frequency of chest pain (57 vs 23%; p less than 0.001) and a higher heart rate-blood pressure product (12.7 +/- 0.6 vs 11.2 +/- 0.2 x 10(3); p less than 0.008) after dipyridamole. Patients with ST depression were more likely to have Tl-201 redistribution (64 vs 38%; p less than 0.02) and a greater number of redistribution defects (2.3 +/- 0.04 vs 0.9 +/- 0.1, p less than 0.001) than were those without ST depression. By multivariate logistic regression analysis, the most powerful correlate of ST depression was the number of segments having Tl-201 redistribution (p less than 0.001). Other independent correlates were presence of chest pain, heart rate at Tl-201 injection, and age. Thus, the determinants of dipyridamole-induced ST-segment depression include the scintigraphic extent of reversible hypoperfusion, as well as indexes of myocardial oxygen demand.

Aged↗
PubMed1992

Effects of intracoronary dipyridamole infusion on regional myocardial blood flow and intrinsic thallium-201 washout in dogs with a critical coronary stenosis.

Intravenous dipyridamole (DP) infusion produces a significant endocardial-to-epicardial flow gradient distal to a critical coronary stenosis, resulting in diminished regional thallium-201 (Tl-201) uptake and washout. Intravenous DP can also produce a significant decrease in arterial blood pressure and therefore in coronary perfusion pressure. We determined to further clarify the mechanism of this transmural coronary "steal" employing intracoronary DP administration, thereby avoiding systemic hypotension. In five of eight dogs with a critical left anterior descending (LAD) stenosis, intracoronary DP caused no significant fall in systemic arterial pressure, a rise in epicardial flow from 1.15 +/- 0.2 to 1.75 +/- 0.2 ml/min/gm, and a slight fall in subendocardial flow from 1.15 +/- 0.2 to 1.03 +/- 0.5 ml/min/gm. Intracoronary DP caused no prolongation of the intrinsic Tl-201 washout rate. In three dogs that developed systemic hypotension after intracoronary DP, endocardial flow fell from 1.14 to 0.63 ml/min/gm, the epicardial/endocardial flow ratio fell to 0.35, and Tl-201 washout became more prolonged. Thus intracoronary DP in the setting of a critical LAD stenosis caused minimal endocardial-to-epicardial steal and had no effect on the intrinsic Tl-201 washout rate unless it was accompanied by a fall in systemic arterial pressure. The magnitude of the transmural steal was substantially less than reported in our previous experiments utilizing intravenous DP infusion. This study provides a further insight into the mechanism of DP-induced subendocardial ischemia and suggests that systemic hemodynamic alterations play an important role in the effects of the vasodilator on myocardial blood flow and Tl-201 kinetics.

Animals↗
PubMed1992

Influence of subendocardial ischemia on transmural myocardial function.

The relationship between regional myocardial perfusion and function under ischemic conditions was examined by using a nontraumatic single-crystal pulsed Doppler system that permits complete transmural assessment of myocardial thickening. Sixteen open-chest dogs underwent either 50 (n = 4) or 180 (n = 12) min of partial coronary artery occlusion. Simultaneous measurements of myocardial thickening fraction (TF) and microsphere-determined blood flow (BF) were taken in the subepicardial, midwall, and subendocardial thirds of the left ventricular wall. During ischemia, there was an excellent correlation between BF and TF in the subendocardium. Mean subendocardial BF was reduced to 0.45 +/- 0.3 ml.min-1.g-1, resulting in a subendocardial TF of 0.8 +/- 19%. Although subepicardial BF was relatively preserved at 1.03 +/- 0.4 ml.min-1.g-1, subepicardial TF was diminished markedly and not significantly different from subendocardial TF. Subepicardial and midwall TF were highly dependent on subendocardial flow rather than on the actual flow in these areas. Hence these studies show a marked dependence of transmural myocardial function on subendocardial blood flow. Outer wall function is more dependent on subendocardial than subepicardial blood flow.

Animals↗
PubMed1992

Blinded evaluation of planar technetium-99m-sestamibi myocardial perfusion studies.

Sestamibi planar myocardial perfusion studies were performed at Hotel-Dieu de Montreal on 28 patients with documented coronary artery disease and 16 normal subjects. Stress and rest studies were performed on separate days. These studies were sent to Virginia for interpretation while blinded as to age, sex, and other clinical information. Studies were quantitated independently by two operators (using a computer program modified for Sestamibi), and interpreted independently by two experienced interpreters. Computer quantitation of 2816 segments gave an average interoperator deviation of 2.2%. Pure quantitative criteria were applied for computer interpretation. By varying the detection threshold, we produced the entire ROC curve relating sensitivity and specificity as a function of detection threshold. Using only computer criteria for normal or abnormal, interoperator agreement by patient was 98% and 93% by view. The computer could achieve equal positive and negative predictive accuracy of 87%. Interpreters, allowed both quantitative and subjective judgment, agreed on 91% of 44 patients, 90% of 132 views, and 92% of 660 segments. Interpreters averaged 94% positive and 86% negative predictive accuracy.

Adult↗
PubMed1991

Physiological basis of myocardial perfusion imaging with the technetium 99m agents.

In recent years, several technetium 99m-labeled myocardial perfusion agents have been under investigation to determine their utility in assessing regional myocardial blood flow and cellular viability. 99mTc sestamibi (2-methoxyisobutyl isonitrile), one of the most promising of these agents, is a lipophilic cation that is sequestered largely within mitochondria by the large negative transmembrane potential. Experimental studies have shown that this agent is taken up in the myocardium in proportion to blood flow, but like other diffusible radionuclides underestimates flow at high flow rates. Fractional extraction (Emax) for 99mTc sestamibi is lower than that for thallium 201, but net myocardial uptake is comparable between the two radionuclides. Compared with 201Tl, 99mTc sestamibi does not significantly redistribute. Studies have shown that 99mTc sestamibi uptake after reperfusion, preceded by varying periods of coronary occlusion, reflects the degree of myocardial salvage and viability. 99mTc teboroxime, another promising new perfusion agent, is a boronic acid adduct of technetium dioxime complexes. Emax of 99mTc teboroxime is higher than Emax for 201Tl, but myocardial washout is very rapid (half-life = 21 minutes). Myocardial uptake is proportional to regional flow as found with 99mTc sestamibi and 201Tl.

Coronary Circulation↗
PubMed1991

Value of planar 201Tl imaging in risk stratification of patients recovering from acute myocardial infarction.

Although exercise ECG testing has been shown to have important prognostic value after acute myocardial infarction, exercise 201Tl scintigraphy offers several potential advantages, including: 1) increased sensitivity for detecting residual myocardial ischemia; 2) the ability to localize ischemia to a specific area or areas subtended by a specific coronary artery; 3) the ability to identify exercise-induced left ventricular dysfunction, which is manifested by increased lung uptake or transient left ventricular dilation; and 4) more reliable risk stratification of individual patients. The more optimal prognostic efficiency of 201Tl scintigraphy partially results from the fact that the error rate in falsely classifying patients as low risk is significantly smaller with 201Tl scintigraphy than with stress ECG. Because of these substantial advantages, there seems to be adequate rationale for recommending exercise perfusion imaging rather than exercise ECG alone as the preferred method for evaluating mortality and morbidity risks after acute myocardial infarction.

Angiography↗
PubMed1991

A model to predict multivessel coronary artery disease from the exercise thallium-201 stress test.

PURPOSE: The aim of this study was to (1) determine whether nonimaging variables add to the diagnostic information available from exercise thallium-201 images for the detection of multivessel coronary artery disease; and (2) to develop a model based on the exercise thallium-201 stress test to predict the presence of multivessel disease. PATIENTS AND METHODS: The study populations included 383 patients referred to the University of Virginia and 325 patients referred to the Massachusetts General Hospital for evaluation of chest pain. All patients underwent both cardiac catheterization and exercise thallium-201 stress testing between 1978 and 1981. RESULTS: In the University of Virginia cohort, at each level of thallium-201 abnormality (no defects, one defect, more than one defect), ST depression and patient age added significantly in the detection of multivessel disease. Logistic regression analysis using data from these patients identified three independent predictors of multivessel disease: initial thallium-201 defects, ST depression, and age. A model was developed to predict multivessel disease based on these variables. As might be expected, the risk of multivessel disease predicted by the model was similar to that actually observed in the University of Virginia population. More importantly, however, the model was accurate in predicting the occurrence of multivessel disease in the unrelated population studied at the Massachusetts General Hospital. CONCLUSION: It is, therefore, concluded that (1) nonimaging variables (age and exercise-induced ST depression) add independent information to thallium-201 imaging data in the detection of multivessel disease; and (2) a model has been developed based on the exercise thallium-201 stress test that can accurately predict the probability of multivessel disease in other populations.

Arrhythmias, Cardiac↗
PubMed1991

Childhood retroperitoneal fibrosis associated with a horseshoe kidney: a case report.

The case of a 12-year-old girl with retroperitoneal fibrosis and a horseshoe kidney is presented. This is a relationship that has not previously been described. An in-depth review of the literature of childhood retroperitoneal fibrosis is undertaken with accompanying discussion on the etiology, symptoms, pathology, radiographic findings, treatments and prognosis of the disease.

Child↗
PubMed1991

Assessment of myocardial perfusion and viability with technetium-99m methoxyisobutyl isonitrile.

The clinical application of Tc-99m Sestamibi imaging in acute myocardial infarction should be most useful. The capability of assessing risk area during acute coronary occlusion and degree of myocardial salvage after reperfusion offers a noninvasive means to assess the benefit of therapeutic interventions aimed at reducing myocardial ischemic injury. Further studies in larger numbers of patients appear warranted to identify the precise worth of this new imaging technique relative to other existing noninvasive imaging methodologies in clinical practice.

Animals↗
PubMed1990

Prevalence and correlates of increased lung/heart ratio of thallium-201 during dipyridamole stress imaging for suspected coronary artery disease.

There is little information concerning the prevalence and clinical correlates of increased pulmonary thallium-201 uptake during dipyridamole thallium-201 stress imaging. Accordingly, the clinical characteristics and quantitative thallium-201 findings were correlated with quantitative lung/heart thallium-201 ratio in 87 patients undergoing dipyridamole thallium-201 stress testing. Nineteen patients (22%) had an elevated ratio (greater than 0.51). These patients were more likely to have had an infarction, to be taking beta blockers, and have a lower rate-pressure product after dipyridamole administration than those with a normal ratio (p less than 0.03). An elevated ratio was associated with a greater likelihood of initial, redistribution and persistent defects, as well as left ventricular cavity dilatation on thallium-201 imaging (p less than 0.05). In addition, the number of myocardial segments demonstrating initial, redistribution and persistent defects was also greater in patients with increased ratios (p less than 0.03). Multivariate analysis demonstrated that the presence of redistribution and left ventricular cavity dilatation were the most significant correlates of lung/heart thallium-201 ratio. It is concluded that the prevalence of increased lung/heart thallium-201 ratio with dipyridamole thallium-201 stress imaging is similar to that seen with exercise stress imaging. As with exercise thallium-201 imaging, increased pulmonary thallium-201 uptake may be a marker of functionally more significant coronary artery disease.

Adult↗
PubMed1990

Technical aspects of myocardial planar imaging with technetium-99m sestamibi.

Fundamental quantitative planar imaging techniques, evolved over the years, have been adapted to maximize the efficiency and clinical effectiveness of technetium-99m (Tc-99m) sestamibi imaging. To ensure reproducible image interpretation, the Society for Motion Picture and Television Engineers test pattern is used to obtain the necessary standardization of video and hard copy images. A standardized intensity scale intuitively relates count density to perceived brightness. Data are accumulated via standard 16-frame multiple gated acquisition and can be viewed in cine mode to assess wall motion. The images are then automatically summed for quantitative analysis of myocardial perfusion. Excessive extracardiac Tc-99m activity is automatically suppressed by the computer program to prevent suboptimal display of the heart. Due to the difference in heart background ratio and shape of the extracardiac background between resting and exercise Tc-99m sestamibi images, a modified interpolative background subtraction algorithm was developed. Image registration is necessary for accurate comparison of the rest and exercise images to detect redistribution. This is automatically accomplished by adjusting the position of the background-subtracted and centered images so as to maximize the cross-correlation coefficient. Profiles are generated to sample the myocardial count distribution and can be compared to a normal database, subject to confirmation by a competent interpreter. Rest redistribution is defined by a change in the myocardial distribution of Tc-99m sestamibi between exercise and rest images. Flashback display is used to identify subtle regions of redistribution that often signify residual viability within an infarct zone.(ABSTRACT TRUNCATED AT 250 WORDS)

Heart↗
PubMed1990

Effects of dipyridamole and aminophylline on hemodynamics, regional myocardial blood flow and thallium-201 washout in the setting of a critical coronary stenosis.

Experiments were performed to characterize the interaction of intravenous dipyridamole and aminophylline on thallium-201 transport kinetics, regional myocardial blood flow and systemic hemodynamics in the presence of a critical coronary artery stenosis. In 12 dogs with a critical left anterior descending coronary artery stenosis, arterial pressure decreased from a mean value (+/- SEM) of 107 +/- 6 to 94 +/- 3 mm Hg (p less than 0.05) and distal left anterior descending artery pressure decreased from 70 +/- 7 to 55 +/- 4 mm Hg (p less than 0.05) after intravenous administration of dipyridamole (0.25 mg/kg body weight). In the left anterior descending perfusion zone, the endocardial/epicardial flow ratio decreased from 0.70 to 0.36 and the intrinsic thallium washout rate was significantly prolonged. Intravenous aminophylline (5 mg/kg) reversed the dipyridamole-induced systemic hypotension and transmural coronary steal and restored the thallium washout rate to baseline values. In six other dogs, aminophylline alone resulted in no alterations in systemic and coronary hemodynamics or regional myocardial blood flow. As expected, dipyridamole-induced vasodilation and coronary steal were prevented by aminophylline pretreatment. These data show that in a canine model of partial coronary stenosis, systemic hypotension, adverse regional flow effects (coronary steal) and prolonged thallium-201 washout consequent to intravenously administered dipyridamole are promptly reversed by intravenous aminophylline administration. Aminophylline alone had no significant hemodynamic and coronary flow effects. This study provides further insight into the altered thallium kinetics occurring as a consequence of dipyridamole-induced vasodilation and suggests that the prompt reversal of symptoms and signs of ischemia with aminophylline in patients receiving intravenous dipyridamole for clinical imaging studies probably reflects the reversal of transmural coronary steal.

Aminophylline↗
PubMed1990

Intraoperative assessment of regional myocardial perfusion using quantitative myocardial contrast echocardiography: an experimental evaluation.

To test the hypothesis that myocardial contrast echocardiography can be used to quantitate regional myocardial flow in the arrested heart at the time of delivery of cardioplegic solution, data were acquired in 13 dogs on cardiopulmonary bypass. Different degrees of stenosis were placed in random order on the left anterior descending coronary artery. For each stenosis, myocardial contrast echocardiography was performed by injecting sonicated albumin microbubbles into the cross-clamped aortic root at the time of delivery of cardioplegic solution. The resultant echocardiographic images were analyzed on an off-line computer. Background-subtracted time-intensity plots were generated, and an exponential function, f(t) = Ce-alpha t + De- beta t, was applied to each plot. Variables that reflected the total number of microbubbles entering the coronary artery bed, such as the area under the curve and the peak height of the curve, correlated best with radiolabeled microsphere-measured myocardial flow (r = 0.92 and r = 0.91, respectively). Variables that reflected the appearance of contrast microbubbles in the myocardium, such as the initial slope and the slope at 1 s, also had a good correlation with myocardial flow (r = 0.84 and r = 0.89, respectively). Variables that reflected the washout of contrast medium from the myocardium, such as the slope of the descending portion of the curve, had only a fair correlation with myocardial flow (r = 0.65). In six dogs, the technique of injecting contrast medium into the cross-clamped aortic root was also examined. Although continuous infusion of contrast medium produced smaller perturbations in mean aortic and distal left anterior descending artery pressures compared with a bolus injection (p less than 0.01), the correlation between the variables of the time-intensity curves and flow was equally close with both techniques. It is concluded that it is possible to quantitate myocardial flow by using myocardial contrast echocardiography at the time of delivery of cardioplegic solution in dogs on cardiopulmonary bypass. The implementation of this technique in humans might be useful in guiding the sequence of graft placement and thereby improving myocardial preservation during coronary artery bypass operations.

Animals↗
PubMed1990

Cardiac imaging with technetium 99m-labeled isonitriles.

The 99mTc-labeled isonitriles are a new class of myocardial imaging agents that, because of superior physical characteristics, may be better for myocardial perfusion imaging than 201Tl, particularly with SPECT imaging modalities. The initial experimental and clinical experience with one of these radiotracers, 99mTc-MIBI, suggests that this radiotracer may be promising for the assessment of myocardial ischemia and infarction. The capability of assessing risk area during acute coronary occlusion and extent of myocardial salvage after reperfusion offers a noninvasive means to evaluate the efficacy of therapeutic interventions aimed at reducing ischemic myocardial injury. 99mTc-MIBI will provide a unique noninvasive means of simultaneously assessing myocardial perfusion and function, ultimately permitting a better understanding of ischemic-induced myocardial dysfunction. The analysis of the myocardial perfusion and function relationship may possibly provide a method of discriminating reversible myocardial ischemia from irreversible myocardial injury. Algorithms will need to be developed for the optimal quantification of 99mTc-MIBI images. Additionally, single-day protocols using split doses of 99mTc-MIBI will need to be further developed before 99mTc-MIBI imaging can be widely employed. Although further clinical studies are necessary in larger numbers of patients before the full clinical implications of this radiotracer are known, the initial experience is encouraging.

Angina, Unstable↗
PubMed1990

Thallium 201 kinetics in stunned myocardium characterized by severe postischemic systolic dysfunction.

The hypothesis tested in this study was that despite the presence of severe postischemic myocardial dysfunction ("stunning"), the extraction and subsequent intracellular washout of thallium 201 should be preserved as long as irreversible sarcolemmal membrane injury was avoided. To produce myocardial stunning, 19 open-chested dogs with a critical left anterior descending coronary artery (LAD) stenosis underwent 10 5-minute periods of total LAD occlusion, each interspersed by 10 minutes of reperfusion by reflow through the critical stenosis. In another 12 control dogs observed for the same time period, no LAD occlusions were performed after placement of the critical stenosis. Hemodynamics, regional myocardial thickening by quantitative two-dimensional echocardiography, and microsphere-determined regional blood flows were serially measured. In 18 stunned dogs, systolic thickening in the LAD zone was markedly reduced to 0.4 +/- 2.4% at 40 minutes after the 10th reperfusion period compared with 32.5 +/- 2.2% thickening (p less than 0.001) in 12 control dogs at a matched time. The 201Tl first-pass extraction fraction determined by a double-isotope method using intracoronary 201Tl administration was comparable after the 10th reflow in a subgroup of 13 stunned (0.78) and six control (0.79) dogs. The T1/2 for the intracellular washout rate was also not significantly different in another group of six stunned (60 +/- 13 minutes) and six control (53 +/- 14 minutes) dogs, nor was the percentage of the 201Tl dose initially distributed in the interstitial compartment (11 +/- 3% vs. 7 +/- 2%). Systemic hemodynamics and regional flows were comparable in the two groups at 40 minutes after the 10th reflow. No dog had evidence of myocardial necrosis by triphenyl tetrazolium chloride staining. Thus, normal myocardial 201Tl extraction and washout kinetics are observed in a canine model of severe postischemic dysfunction (stunning) produced by repetitive brief LAD occlusions. These findings might have important clinical implications concerning the application of rest 201Tl scintigraphy for evaluation of perfusion and viability in patients with coronary artery disease and regional myocardial asynergy that is ultimately reversible.

Animals↗
PubMed1990

Quantification of area at risk during coronary occlusion and degree of myocardial salvage after reperfusion with technetium-99m methoxyisobutyl isonitrile.

Serial myocardial imaging with technetium-99m methoxyisobutyl isonitrile (99mTc-MIBI) has been proposed for evaluating myocardial salvage after reperfusion. To define 99mTc-MIBI uptake before and after reperfusion, 17 open-chest dogs underwent 3 hours of left anterior descending artery occlusion and 3 hours of reperfusion. 99mTc-MIBI was injected during occlusion (group 1) or after 90 minutes of reperfusion (group 2). Myocardial 99mTc-MIBI activity was correlated with microsphere flow during occlusion and reperfusion. Anatomic risk area and infarct area were defined by postmortem vital staining and correlated with the perfusion defects defined by analysis of 99mTc-MIBI macroautoradiographs and gamma camera images of myocardial slices. The left ventricle was divided into 96 segments for gamma well counting. Flow and 99mTc-MIBI activity were normalized to nonischemic values. Myocardial segments were grouped, based on occlusion flow, into zones: severely ischemic (less than or equal to 30% nonischemic), moderately ischemic (greater than 30%, less than or equal to 60% nonischemic), mildly ischemic (greater than 60%, less than or equal to 90% nonischemic), and nonischemic (greater than 90%, less than or equal to 120% nonischemic). Among dogs injected with 99mTc-MIBI during coronary occlusion (group 1), myocardial 99mTc-MIBI activity correlated linearly with occlusion flow for both endocardial (r = 0.91) and transmural (r = 0.91) segments. The risk area defined by 99mTc-MIBI autoradiography (group 1) correlated with the postmortem risk area (rho = 0.94) but was 29% smaller than the anatomic risk area (p = 0.03), reflecting the contribution of collateral flow. Among dogs injected with 99mTc-MIBI after reperfusion (group 2), myocardial 99mTc-MIBI did not correlate with reperfusion flow in either endocardial or transmural segments. Among group 2 dogs, myocardial 99mTc-MIBI activity was significantly less than reperfusion flow at the time of injection in the severely ischemic (25 +/- 5% versus 74 +/- 24% nonischemic, p = 0.002), moderately ischemic (54 +/- 12% versus 96 +/- 15% nonischemic, p = 0.001), and mildly ischemic (84 +/- 6% versus 93 +/- 3% nonischemic, p = 0.002) zones. The defect area defined by 99mTc-MIBI autoradiography (group 2) correlated very closely with the postmortem infarct area (rho = 0.98). Thus, the myocardial uptake of 99mTc-MIBI during coronary occlusion correlates with occlusion flow and reflects the "area at risk." When 99mTc-MIBI was given after 90 minutes of reperfusion following 3 hours of coronary occlusion, the myocardial activity was significantly reduced compared with reperfusion flow in both necrotic and perinecrotic regions, reflecting myocardial viability more than the degree of reperfusion.

Animals↗