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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 an in 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 validated in 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.

A patient with diabetes mellitus and coronary artery disease presented with recurring episodes of worsening angina not associated with angiographic changes. Correlation with blood sugars demonstrated that angina would occur during episodes of hyperglycemia. During cardiac catheterization, coronary vascular responses including coronary flow reserve and responses to atrial pacing were measured with a Doppler flow wire before and following a glucose challenge. Coronary microvascular responses were impaired by hyperglycemia.

Purpose: This study evaluated the value of preoperative cardiac screening with dipyridamole thallium scintigraphy and radionuclide ventriculography in vascular surgery patients., Methods: From July 1, 1989, to Dec. 31, 1991, we routinely (irrespective of the patient's cardiac history or symptomatology) performed dipyridamole thallium scintigraphy (DTS) and radionuclide ventriculography (RVG) in 394 patients being considered for an elective vascular operation. Patients with reversible defects on DTS underwent coronary arteriography., Results: DTS results were normal in 146 patients (37%), showed a fixed defect in 75 (19%), and showed a reversible defect in 173 (44%). Patients with and without a history of angina or myocardial infarction had identical rates of reversible defects. Normal left ventricular function (> 50%) was noted in 76% of the patients; 17% had moderate dysfunction (35% to 50%) and 7% had a low ejection fraction (< 35%). The finding of severe coronary artery disease led to cardiac revascularization in 17 patients who had no prior history of cardiac disease and in 13 patients with a history of angina or myocardial infarction. Two deaths and nine major complications were associated with coronary arteriography and cardiac revascularization. Vascular procedures (144 aortic, 53 carotid, 146 infrainguinal) were ultimately performed in 343 patients, with a mortality rate of 1.7% (3.5% aortic, 0% carotid, and 0.7% infrainguinal bypass). The nonfatal perioperative myocardial infarction rate was 2.0%. We monitored all 394 patients for cardiovascular events, with a mean follow-up of 40 months. Patients who underwent cardiac revascularization had a 4-year survival rate of 75%, which was similar to those with a normal DTS. Late cardiac events were significantly more frequent in patients who had either a reversible DTS or RVG < 35%., Conclusions: Routine cardiac screening of vascular surgery patients had similar impact on patients irrespective of their prior history or current symptoms suggesting coronary artery disease. Routine screening did not result in substantial benefit. Screening studies such as DTS or RVG may be most useful as part of an overall risk versus benefit assessment in patients without active symptoms of coronary artery disease who have less compelling indications for vascular intervention (claudication, moderate-sized aortic aneurysms, or asymptomatic carotid disease).

Objectives: The purpose of this study was to determine the accuracy of cine computed tomography in the diagnosis of constrictive pericarditis., Background: Constrictive pericarditis is characterized by abnormalities of both cardiac structure and function. Accurate diagnosis requires detection of both a thickened pericardium and abnormal ventricular diastolic filling. At present, no one diagnostic technique has demonstrated sufficient accuracy in this setting. Cine computed tomography is a relatively new cardiac imaging mode with very high time and spatial resolution that has the potential to accurately diagnose constrictive pericarditis., Methods: Twelve consecutive patients were retrospectively identified who had catheterization findings suggestive of constrictive physiology, had undergone a cine computed tomographic examination and had pathologic data that delineated the status of the pericardium. Group 1 (with constrictive pericarditis; n = 5) had surgical confirmation of thickened pericardium and improved clinically after pericardiectomy. Group 2 (no constrictive pericarditis; n = 7) had cardiomyopathy with normal pericardium. Seven normal volunteers (Group 3) were also studied. Cine computed tomograms were obtained for the entire heart (8-mm slices, 17 frames/s, nonionic contrast medium). Pericardial thickness was measured at 10 degrees intervals at three ventricular levels in each subject. The rapidity of diastolic filling was assessed by calculating the percent filling fraction in early diastole., Results: Pericardial thickness was 10 +/- 2 mm (mean +/- SD) in Group 1, 2 +/- 1 mm in Group 2 and 1 +/- 1 mm in Group 3 (p < 0.05, constrictive pericarditis vs. no constrictive pericarditis). Left ventricular filling fraction was 83 +/- 6% in Group 1, 62 +/- 9% in Group 2 and 44 +/- 5% in Group 3. Right ventricular filling fraction was 93 +/- 5% in Group 1, 62 +/- 14% in Group 2 and 35 +/- 6% in Group 3 (p < 0.05, Group 1 vs. Groups 2 and 3). Both indexes provided a clear-cut distinction between patients with and without constriction., Conclusions: Cine computed tomography simultaneously provides both anatomic and physiologic data that allow accurate preoperative diagnosis of pericardial constriction.

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 201Tl 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 greater than 0.05). In 33 patients with no history of coronary artery disease, 11 (33%) had reversible 201Tl 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 201Tl 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 201Tl and abnormal coronary arteriography. In comparison, there were only four coronary events among 46 patients (9%) without reversible defects on the 201Tl studies (p = 0.055)., Conclusions: Our study demonstrates that one third of patients with no history of coronary artery disease had an abnormal 201Tl test and that nearly one half of patients with either symptomatic or asymptomatic cerebrovascular disease had abnormal 201Tl tests. Patients with a reversible 201Tl 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.

Phosphorus-31 nuclear magnetic resonance (P-31 NMR) spectroscopy is able to identify alterations in myocardial high energy phosphate metabolism associated with acute infarction. It was hypothesized that the extent of acute myocardial infarction could be quantitated from changes in the tissue content of inorganic phosphate (Pi), phosphocreatine (PCr) and adenosine triphosphate (ATP) derived from P-31 NMR spectra. Nine isolated, perfused rat hearts were studied at 121.5 MHz. After baseline spectra were obtained, varying locations of either the right or the left coronary artery were occluded without removing the heart from the spectrometer. Spectra were then collected during regional ischemia at 15 and 45 min after occlusion. Phosphate metabolites were quantitated from the baseline and 45-min regional ischemia spectra, times at which the metabolites are at steady state for the normal and ischemic conditions. The heart was removed from the spectrometer, perfused for a total duration of 2 h and sectioned into 2-mm thick slices for triphenyltetrazolium chloride staining. Percent infarct was determined by manual tracing of magnified, digitized images of the stained sections. Coronary blood flow, heart rate and blood pressure were monitored throughout the experiment. Significant linear relations were found between percent infarct (by triphenyltetrazolium chloride staining) and the percent change of beta-ATP (r = -0.74), Pi (r = 0.83) and the PCr/Pi ratio (r = -0.71) at 45 min after coronary occlusion. Coronary flow was also found to correlate significantly with percent infarct (r = -0.70). These results are applicable to in vivo P-31 NMR studies of acute infarction where the volume of interest may include both normal and acutely infarcted myocardium.(ABSTRACT TRUNCATED AT 250 WORDS)

We have investigated a technique for quantifying QP/QS in left-to-right cardiac shunts. In this method, the gamma variate, which is fitted to the first-pass portion of the lung curve, is used to generate a curve, which simulates the response of a normal lung curve with systemic recirculation. The difference between this curve and the observed lung curve is then used to calculate QP/QS. This method was evaluated on a set of simulated lung time-activity curves with precisely known QP/QS values on a group of 11 patients with no clinical suspicion of cardiac shunt and on a group of 30 patients referred for cardiac shunt studies. The QP/QS in each of these studies was determined by three individuals using both the Maltz-Treves method and the new method. This method yielded QP/QS values that were more accurate on the simulated lung data and had less interobserver variation on all the studies than those obtained from the Maltz-Treves method.

In advanced heart failure, mitral regurgitation increases the burden of the failing ventricle and decreases effective stroke volume. Although tailored afterload reduction decreases mitral regurgitation at rest, it is not known if this benefit is maintained during upright exercise. Simultaneous radionuclide ventriculography and thermodilution stroke volumes were compared to measure the forward ejection fraction in 10 patients during upright bicycle exercise before and after therapy with vasodilators and diuretics tailored to decrease pulmonary capillary wedge pressure and systemic vascular resistance. Ventricular volumes, total ejection fraction and the forward ejection fraction did not change during exercise at baseline. At rest, tailored therapy decreased average pulmonary capillary wedge pressure from 36 to 19 mm Hg (p less than 0.01), systemic vascular resistance from 1,570 to 1,210 dynes.s.cm-5 (p less than 0.05), and left ventricular volume index from 251 to 177 ml/m2 (p less than 0.01), while increasing the forward ejection fraction from 0.53 to 0.85 (p less than 0.01) without change in total ejection fraction (0.18 from 0.17). During steady state exercise at low work load, tailored therapy decreased left ventricular volume index from 279 to 213 (p less than 0.05) and increased forward ejection fraction from 0.52 to 0.79 (p less than 0.01) without change in total ejection fraction (0.20 from 0.19). The total stroke volume during exercise was not increased after therapy; the increase in forward stroke volume after therapy appeared to result instead from the decrease in mitral regurgitant flow. The benefits of tailored afterload reduction are maintained throughout upright exercise.

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)

Previous observations and clinical manifestations suggest the presence of ischemia in the disproportionately thickened septum of patients with hypertrophic cardiomyopathy. Metabolic consequences of ischemia can be demonstrated with positron emission tomography. Therefore, 10 patients with hypertrophic cardiomyopathy and an echocardiographic septum to posterior wall thickness ratio of 1.8 +/- 0.4 cm (range 1.3 to 2.5) were studied with the use of nitrogen (N)-13 ammonia, carbon (C)-11 palmitate and fluoro (F)-18 2-deoxyglucose as tracers of myocardial blood flow, fatty acid metabolism and exogenous glucose utilization. The results of positron emission tomography in 9 patients with hypertrophic cardiomyopathy were compared with those in 10 normal volunteers. In the hypertrophic cardiomyopathy group, observed myocardial activity of N-13 ammonia and C-11 palmitate in the septum was similar to that in the lateral wall. Septum to lateral wall tissue activity ratios averaged 1.04 +/- 0.15 for N-13 ammonia and 1.04 +/- 0.18 for C-11 palmitate, and were similar to those in the normal volunteers (0.98 +/- 0.07 and 0.98 +/- 0.03, respectively; p = NS). Myocardial clearance half-time and residual fraction of C-11 palmitate did not differ significantly between the septum and lateral wall. However, F-18 2-deoxyglucose uptake was significantly lower in the septum than in the lateral wall (15,768 +/- 4,314 versus 19,818 +/- 5,234 counts/pixel; p less than 0.003). The mean septum to lateral wall activity ratio of 0.83 +/- 0.21 was less than that observed in normal volunteers (0.92 +/- 0.07; p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

We investigated myocardial 11C-palmitate clearance kinetics at a resting heart rate (control) and during pacing using positron-emission tomography in 10 patients with significant coronary artery stenosis (greater than 70%) and evidence of exercise-induced ischemia. Serial 11C-palmitate images acquired at control and during pacing revealed biexponential myocardial 11C clearance both in myocardium supplied by a stenotic coronary artery (myocardium "at risk") and in myocardium supplied by a normal coronary artery (normal myocardium). At control, the average rate of myocardial 11C clearance from the early rapid curve component (the clearance half-time) was similar in normal myocardium and in that at risk (22.2 +/- 5.2 vs 21.0 +/- 5.4 min, NS), as was the amount of myocardial 11C activity at the end of the early rapid phase (residual fraction 56.3 +/- 7.2% vs 54.7 +/- 7.3%, NS). Thus, myocardial clearance was homogeneous at control, suggesting a similar rate and amount of 11C-palmitate oxidation in normal myocardium and in that at risk. Pacing shortened clearance half-times and decreased residual fraction in both normal myocardium and that at risk compared with control. However, clearance half-times were 17% longer and residual fractions 14% higher in myocardium at risk compared with normal myocardium (p less than .005 and p less than .01, respectively). Therefore, during pacing myocardial 11C clearance became heterogeneous, suggesting impaired 11C-palmitate oxidation in myocardium at risk compared with normal myocardium. Increased substrate utilization in response to increased workload can be thought of as a measure of metabolic reserve. Our data suggest metabolic reserve for free fatty acid oxidation is impaired in myocardium supplied by a significantly stenosed coronary artery and that this impairment can be detected by analysis of myocardial 11C-palmitate clearance.

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.

To validate the determination of the arterial input function by noninvasive dynamic PET imaging, measurements of blood-pool activity in canine LV by PET were compared to beta probe measurements of arterial blood withdrawn directly from the LV. PET scans were done during intravenous bolus injections of [13N]ammonia or 82Rb, while the activity of blood withdrawn continuously from a catheter inserted in the LV was measured with a beta probe. PET determinations of LV blood-pool activity were compared with dispersion-corrected beta probe time-activity curves. In 15 experiments involving four dogs under a wide range of physiologic conditions, LV time-activity curves obtained with PET matched well in shape with those obtained with the beta probe. Linear regression yielded slopes within 10% of unity (95% confidence interval) and high correlation (r greater than 0.968, p less than 0.001). We conclude that noninvasive measurement of the arterial input function by dynamic PET imaging is valid.

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)