Maleah Grover-McKay

Positron emission tomography detects tissue metabolic activity in myocardial segments with persistent thallium perfusion defects

Positron emission tomography with 13N-ammonia and 18F-2-deoxyglucose was used to assess myocardial perfusion and glucose utilization in 51 myocardial segments with a stress thallium defect in 12 patients. Myocardial infarction was defined by a concordant reduction in segmental perfusion and glucose utilization, and myocardial ischemia was identified by preservation of glucose utilization in segments with rest hypoperfusion. Of the 51 segments studied, 36 had a fixed thallium defect, 11 had a partially reversible defect and 4 had a completely reversible defect. Only 15 (42%) of the 36 segments with a fixed defect and 4 (36%) of the 11 segments with a partially reversible defect exhibited myocardial infarction on study with positron tomography. In contrast, residual myocardial glucose utilization was identified in the majority of segments with a fixed (58%) or a partially reversible (64%) thallium defect. All of the segments with a completely reversible defect appeared normal on positron tomography. Apparent improvement in the thallium defect on delayed images did not distinguish segments with ischemia from infarction. Thus, positron emission tomography reveals evidence of persistent tissue metabolism in the majority of segments with a fixed or partially resolving stress thallium defect, implying that markers of perfusion alone may underestimate the extent of viable tissue in hypoperfused myocardial segments.

Regional myocardial metabolism in patients with acute myocardial infarction assessed by positron emission tomography

Positron emission tomography has been shown to distinguish between reversible and irreversible ischemic tissue injury. Using this technique, 13 patients with acute myocardial infarction were studied within 72 hours of onset of symptoms to evaluate regional blood flow and glucose metabolism with nitrogen (N)-13 ammonia and fluorine (F)-18 deoxyglucose, respectively. Serial noninvasive assessment of wall motion was performed to determine the prognostic value of metabolic indexes for functional tissue recovery. Segmental blood flow and glucose utilization were evaluated using a circumferential profile technique and compared with previously established semiquantitative criteria. Relative N-13 ammonia uptake was depressed in 32 left ventricular segments. Sixteen segments demonstrated a concordant decrease in flow and glucose metabolism. Regional function did not change over time in these segments. In contrast, 16 other segments with reduced blood flow revealed maintained F-18 deoxyglucose uptake consistent with remaining viable tissue. The average wall motion score improved significantly in these segments (p less than 0.01), yet the degree of recovery varied considerably among patients. Coronary anatomy was defined in 9 of 13 patients: patent infarct vessels supplied 8 of 10 segments with F-18 deoxyglucose uptake, while 10 of 13 segments in the territory of an occluded vessel showed concordant decreases in flow and metabolism (p less than 0.01). Thus, positron emission tomography reveals a high incidence of residual tissue viability in ventricular segments with reduced flow and impaired function during the subacute phase of myocardial infarction. Absence of residual tissue metabolism is associated with irreversible injury, while preservation of metabolic activity identifies segments with a variable outcome.(ABSTRACT TRUNCATED AT 250 WORDS)

Role for Glucose Transporter 1 Protein in Human Breast Cancer

Glycolysis is increased in cancer cells compared with normal cells. It has been shown that glucose enters cells via a family of five functional glucose transporters (GLUT). However, GLUT expression appears to be altered in human breast cancer, which may serve as a selective advantage and facilitate the metastatic potential of these cells. The relationship of GLUT isoform expression and breast cancer cell invasiveness has not been adequately addressed. Thus, the purpose of this study was to investigate whether an association exists between GLUT expression and human breast cancer cell invasiveness. Invasiveness of the human breast cancer lines MCF-7, MDA-MB-435 and MDA-MB-231 was measured using anin vitro assay and compared with cellular GLUT isoform expression, assessed by Western blot analysis and verified by immunohistochemistry in a poorly differentiated human ductal breast cancer. Cell surface GLUT-1 expression was associated with the invasive ability of MCF-7 (2.0 ± 0.02%), MDA-MB-435 (6.4 ±0.4%), and MDA-MB-231 (19.3 ± 2.0%). However, GLUT-2 and GLUT-5 were inversely associated with invasiveness; GLUT-3 expression was variable; and GLUT-4 was undetected. In a poorly differentiated human ductal breast cancer,in situ GLUT-1 staining was intense. GLUT-1 expression was associated with the in vitro invasive ability of human breast cancer cells which was validatedin situ. If this relationship is found to exist in a larger number of human breast cancer tissues, it may be possible to develop diagnostic and therapeutic strategies based on targeted GLUT isoform expression.

Coronary artery disease and cardiac events with asymptomatic and symptomatic cerebrovascular disease.

Background and Purpose The purpose of this study was to evaluate the prevalence of coronary artery disease and coronary events during follow-up in patients with asymptomatic carotid stenosis, transient ischemic attacks, or small strokes. Methods We prospectively studied 60 consecutive patients with thallium-201 scintigraphy followed by coronary arteriography according to an established protocol. Results The 201TI testing was abnormal in seven of 15 patients (47%) with asymptomatic carotid stenosis and in 19 of 44 patients (43%) with transient ischemic attacks or small strokes (p>0.05). In 33 patients with no history of coronary artery disease, 11 (33%) had reversible 201TI defects. In 26 patients with a history of coronary artery disease, 15 (58%) had reversible and/or fixed defects (p=0.054 compared with patients with no history). A history of peripheral vascular disease was the only risk factor significantly associated with an abnormal 201TI test (p=0.032). Coronary artery stenosis of greater than 50% was identified in one or more vessels in 14 of 15 patients undergoing coronary arteriography. Over a mean follow-up period of 311 days, four patients (7%) developed new onset of angina. There were four coronary events among 14 patients (29%) with both a reversible area on the 201TI and abnormal coronary arteriography. In comparison, there were only four coronary events among 46 patients (9%) without reversible defects on the 201TI studies (p=0.055). Conclusions Our study demonstrates that one third of patients with no history of coronary artery disease had an abnormal 201TI test and that nearly one half of patients with either symptomatic or asymptomatic cerebrovascular disease had abnormal 201TI tests. Patients with a reversible 201TI defect and significant stenosis by coronary arteriography were at higher risk for subsequent cardiac events. These findings demonstrate the utility of screening patients with asymptomatic and symptomatic cerebrovascular disease for cardiac disease.

Evaluation Of Diabetic Patients For Renal And Pancreas Transplantation: Noninvasive Screening for Coronary Artery Disease Using Radionuclide Methods

Pharmacologic stress thallium scintigraphy is commonly performed in the risk assessment of diabetic patients with nephropathy before kidney and/or pancreas transplantation; however, controversy exists regarding the tests accuracy in detecting coronary artery disease. Our purpose was to compare pharmacologic stress thallium scintigraphy and also exercise radionuclide ventriculography with coronary angiography in diabetic patients undergoing evaluation for transplantation. In addition, we also determined the association of the test results with outcome after transplantation. The medical records of 47 patients (mean age, 37+/-9 years) without clinical evidence of coronary artery disease were reviewed. Forty-one patients had pharmacologic stress thallium scintigraphy performed during their evaluation. Sensitivity was 62% and specificity was 76% for detecting > or = 75% coronary artery stenosis (sensitivity was 53% and specificity was 73% for > or = 50% stenosis). Thirty-five patients had exercise radionuclide ventriculography performed. Sensitivity was 50% and specificity was 67% for detecting > or = 75% coronary artery stenosis (sensitivity was 44% and specificity was 63% for > or = 50% stenosis). Thirty patients had both pharmacologic stress thallium scintigraphy and exercise radionuclide ventriculography performed; when either test was abnormal, sensitivity in the detection of > or = 50% or > or = 75% stenosis tended to increase compared with pharmacologic stress thallium scintigraphy alone (0.05<P<0.10), whereas specificity decreased (P<0.01). The incidence of adverse cardiac outcomes was identical for patients with abnormal thallium scintigrams and undergoing transplantation (2/11) compared with patients with normal scintigrams and undergoing transplantation (4/22). We conclude that: (1) pharmacologic stress thallium scintigraphy and exercise radionuclide ventriculography are suboptimal screening tests for coronary artery disease in diabetic patients awaiting kidney and/or pancreas transplantation; (2) using the two radionuclide tests in combination results in a decrease in specificity; and (3) patients with abnormal thallium scintigrams can receive transplants with outcomes similar to those for patients with normal thallium scintigrams.

Myocardial collagen concentration and nuclear magnetic resonance relaxation times in the spontaneously hypertensive rat.

In order to test the hypothesis that the increased myocardial collagen concentration in the older, spontaneously hypertensive (SH) rat is associated with altered T2 and T1, we performed in vitro studies of 70 left ventricles from 8-, 22-, and 33-week-old SH and Wistar-Kyoto (WKY) rats. We also measured the left ventricle/body weight (LV/BW) ratio (as a measure of hypertrophy), left ventricular water and fat content, and hydroxyproline concentration (as a measure of collagen). The LV/BW ration was not significantly different between 8-week-old SH rats and WKY rats but was significantly greater in SH rats than in WKY rats at 22 and 33 weeks of age. Comparing SH rats with WKY rats at 22 weeks of age, no significant difference existed in T1, T2, water content, or hydroxyproline concentration. However, at 33 weeks of age in SH rats compared with WKY rats, hydroxyproline concentration was significantly greater (4.3 +/- 0.6 mg/g, respectively; P less than .0005), water content was significantly greater (77.1% +/- 0.3% vs. 76.2% +/- 0.3%, respectively; P less than .0001), and T2 and T1 were significantly longer (T2: 52.6 +/- 2.1 msec vs. 48.6 +/- 2.2 msec, respectively; P less than .0001; T1: 656 +/- 14 msec vs. 619 +/- 12 msec, respectively; P less than .0001). In all SH rats combined, T2 and hydroxyproline concentration were significantly correlated (r = .63; P less than .0001). Thus, in SH rats, myocardial hypertrophy precedes increased collagen deposition. These data suggest that estimation of magnetic resonance relaxation times may permit noninvasive identification of increased myocardial collagen deposition independent from changes in myocardial hypertrophy.

GLUCOSE TRANSPORTER 3 (GLUT3) PROTEIN IS PRESENT IN HUMAN MYOCARDIUM

Glucose and fructose enter mammalian cells via facilitated diffusion, a process regulated by five glucose transporter isoforms (GLUT1-5) at the plasma membrane. The tissue-specific pattern of GLUT isoform expression likely reflects differing needs for glucose transport by various tissues. Myocytes must respond expeditiously to increased metabolic demand. A basal isoform, GLUT1, and the insulin-regulatable glucose transporter, GLUT4, have been demonstrated in human myocytes. GLUT3 has a high affinity for glucose, but its presence in human myocardium has not been clearly established. The purpose of this study was to determine whether GLUT3 protein is present in human cardiac myocytes. We examined rapidly frozen myocardial tissue from the explanted heart of seven patients undergoing cardiac transplantation, from the heart of a young, previously healthy male organ donor, from the heart of a 67-year-old woman without known cardiac disease who had a fatal stroke, and from the heart of six human fetuses. GLUT3 protein was detected by immunoblots and localized by light and electron microscopy immunohistochemistry. The presence of GLUT3 protein was verified in myocardial tissue by both immunoblots and immunohistochemistry. Light and electron microscopy confirmed that GLUT3 was in cardiac myocytes. GLUT3 was also demonstrated as a 48 kDa protein in fetal myocardium, which was present at 10 weeks, increased at 15 weeks, then decreased at 20 weeks of gestation. GLUT3 is present in human adult and fetal myocardium. Human myocardial GLUT3 regulation and its role in myocardial glucose uptake remain to be elucidated.

Dissociation between regional myocardial dysfunction and subendocardial ST segment elevation during and after exercise-induced ischemia in dogs

The onset and resolution of electrical and functional measures of regional myocardial ischemia were examined in nine conscious dogs during control exercise and exercise after beta-receptor blockade. The dogs had been instrumented with an ameroid constrictor and were studied when no regional dysfunction was evident at rest, although severe coronary stenosis or coronary occlusion with collateral circulation development was present. ST segment elevation was measured on subendocardial electrograms, and regional wall motion was studied by sonomicrometry. During control exercise, subendocardial myocardial blood flow in the ischemic zone, normalized to blood flow in the nonischemic zone, decreased. Subendocardial ST elevation increased slowly, was significantly different from control standing values by 2.5 minutes of exercise and returned quickly to control values within 5 minutes after exercise. Percent systolic wall thickening decreased rapidly, was significantly depressed by 1 minute of exercise and did not return to control values until 30 minutes after exercise. A second, identical exercise stress was performed on the same day after a single oral dose (1 mg/kg body weight) of atenolol. In the ischemic zone during exercise after atenolol compared with control exercise, normalized subendocardial myocardial blood flow was improved and significantly less ST elevation occurred, but the onset and resolution of ST elevation were not altered. Systolic wall dysfunction during exercise was significantly less after atenolol, and function returned toward preexercise values by 1 minute after exercise, even more rapidly than ST segment resolution.(ABSTRACT TRUNCATED AT 250 WORDS)

Thrombolytic‐Associated Cholesterol Emboli Syndrome: Case Report and Literature Review

Thrombolytics can cause cholesterol embolization syndrome (CES). This adverse effect has received less attention than other risks of thrombolytic therapy, such as systemic bleeding and hemorrhage, with only sporadic reports of CES in the literature. Risk factors have not been consistently identified and emphasized; therefore, occurrence of CES after thrombolysis remains difficult to predict, it results in substantial morbidity and mortality, and it lacks effective pharmacologic treatment. Heightened awareness of the disorder can aid in its correct identification and reporting.

Emission-based attenuation correction of myocardial perfusion studies

BackgroundNonuniform attenuation in the thorax can generate artifacts in single-photon emission computed tomographic myocardial perfusion studies that mimic coronary artery disease. In this article we present both phantom and simulation data, as well as clinical data, in support of an emission-based method that provides reliable correction for attenuation effects without the need for a transmission measurement.Methods and ResultsThe attenuation map is derived from the measured distribution of 99mTc-labeled macroaggregated albumin in the lungs and a radioactive binder wrapped about the thorax. This information is acquired as part of a dual-isotope acquisition during the rest 201TI study. Segmentation is used to define the interiors of lung and body compartments, which are assigned a single attenuation coefficient for each of the two tissue types. The appropriateness of this approach was investigated by examining the measured attenuation coefficients in a group of 80 individuals (40 male, 40 female) from positron emission tomographic transmission studies. The correction technique was evaluated with computer simulations, a physical phantom, and clinical data acquired from 20 patients. Analysis of the positron emission tomographic data found a small SD in the mean attenuation coefficients for the body (<5%) and lungs (<15%). The application of emission-based attenuation-correction technique produced a substantial reduction in the magnitude of the attenuation artifact in images obtained from both the phantom and the simulation studies. The emission-based attenuation-correction technique was easily applied to myocardial perfusion studies, where it had a significant effect, resulting in changes in interpretation for nine of 20 patients.ConclusionsThe results of this study provide strong support for the concept that an attenuation map can be generated with fixed attenuation values in place of those that are directly measured. Thus the emission-based attenuation-correction technique can be considered an inexpensive alternative to transmission-based correction methods. Because the emission-based correction technique does not require any additional hardware, it has the major advantage of being applicable to all single-photon emission computed tomographic systems.