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The prevalence and medical expense associated with diabetes mellitus continue to increase. Using the diagnostic imaging techniques of coronary computed tomography angiography, cardiovascular magnetic resonance, and positron emission tomography, it may be possible to make earlier, non-invasive diagnoses of the type and extent of disease, thereby preventing or delaying some morbidity and mortality.

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.

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.

Background: Nonuniform 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 Results: The 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 201Tl 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., Conclusions: The 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.

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.

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 test's 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

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).

Heart disease is a major threat to women's health. However, noninvasive evaluation of women for the presence of significant heart disease is often problematic. Cardiovascular nuclear tests interrogate different consequences of physiologically significant coronary artery disease (CAD). Myocardial perfusion imaging supplies information about regional myocardial blood flow. Radionuclide angiocardiography provides information about ejection fraction and regional wall motion. Infarct and metabolic imaging yield information about myocardial viability. This article briefly discusses the concepts and radionuclides involved in cardiovascular nuclear testing and reviews published studies as they relate to assessment of coronary artery disease in women. Myocardial perfusion imaging is a reasonable test for detection of coronary artery disease in women, especially when attenuation artifacts from breast tissue are taken into account. Intravenous dipyridamole stress provides comparable overall accuracy in women and men although women reportedly have a higher incidence of side effects; gender-specific data have not been reported for adenosine. Sufficient gender-specific data are also not currently available for either 99mTc or positron-emitting perfusion tracers. Exercise radionuclide angiography can help determine the probability of significant left main or severe three vessel disease but provides only limited prognostic information in women with CAD. Thus in women, although choice of testing using nuclear techniques depends in part on local experience and expertise, myocardial perfusion imaging appears preferable to radionuclide angiocardiography for detection of significant CAD. To determine the most accurate methods to evaluate women for the presence of significant CAD, all current and future studies of diagnostic testing for CAD should analyze data separately for women and men.

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.

We used cine computed tomography (CT) to determine whether decreased mitral valve gradients and pulmonary artery pressures resulted in decreased right ventricular and atrial volumes after percutaneous mitral balloon commissurotomy (MBC). In patients treated for severe mitral stenosis, previous studies have shown that after the mitral valve gradient decreases, the left atrial volume is reduced and left ventricular stroke volume is increased. The effects of commissurotomy on right heart chamber sizes have been difficult to assess with angiography and echocardiography. Moreover, in follow-up studies performed after surgery, changes in cardiac chamber volumes occurring after the mitral valve gradient and pulmonary pressure are reduced are confounded by the effects of thoracotomy. Our group has previously demonstrated that cine CT can accurately measure both left and right cardiac chamber volumes. We studied 11 female patients before, immediately after, and at 1 year after MBC, and 9 female control subjects of comparable age. To assess cardiac chamber volumes, we used cine CT. To assess the effects of MBC, we used cardiac catheterization and Doppler echocardiography.(ABSTRACT TRUNCATED AT 250 WORDS)

Rationale and Objectives: Mitral balloon commissurotomy (MBC) can successfully increase the mitral valve area (MVA) in mitral stenosis, but the outcome is variable. In multicenter studies, qualitative echocardiographic scores obtained before MBC are only weakly predictive of the increase in MVA after MBC., Methods: To evaluate whether the change in MVA after MBC can be predicted by evaluating mitral valve morphology using cine computed tomography (CT), we studied 12 women with mitral stenosis and 11 female control subjects., Results: In the patients with mitral stenosis, MVA increased from 1.13 +/- 0.24 to 1.93 +/- 0.56 cm2 (P < .0001) after MBC. A standard echocardiographic score assessment of mitral valve morphology before MBC was not associated with the change in MVA after MBC in these patients (P > .20). However, the total mitral valve morphology score evaluated by cine computed tomography was strongly associated with the change in MVA after MBC (r = -.87; P < .0005). In addition, the individual morphologic characteristics of mitral valve mobility (P < .0025), leaflet thickness (P < .05), and subvalvular disease (P < .05) were significant predictors of the change in MVA after MBC., Conclusion: Cine computed tomography may be useful for predicting immediate increases in MVA in patients after MBC and may be helpful for preoperative assessment of these patients.

In patients who cannot perform treadmill exercise, both intravenous dipyridamole and arm exercise have been used with thallium-201 scintigraphy to detect significant coronary artery disease. However, no study has directly evaluated the results of intravenous dipyridamole and arm exercise thallium scintigraphy as compared with coronary angiography. It was the purpose of this study to compare intravenous dipyridamole and arm exercise thallium-201 single-photon emission computed tomographic (SPECT) scintigraphy for detection of significant coronary artery disease in patients who could not perform treadmill exercise. Data are presented for both intravenous dipyridamole and arm exercise thallium-201 SPECT scintigraphy in 18 men who could not perform treadmill exercise, and results are compared with those of coronary angiography. Ten of 11 (91%) patients with significant coronary artery disease were identified correctly, and the results of intravenous dipyridamole and arm exercise thallium scintigraphy were comparable. In patients without significant coronary artery disease, intravenous dipyridamole thallium images were interpreted correctly. However, initial arm exercise thallium images demonstrated a fixed inferior wall defect in two of seven patients without significant coronary artery disease. Images in one of these patients could not be retrieved from tape for further analysis. Review of the images in the other patient demonstrated relatively high background radioactivity, and when the images were displayed without background subtraction, the inferior wall was correctly interpreted as normal. We conclude that results of intravenous dipyridamole and arm exercise thallium-201 SPECT scintigraphy are comparable.

Rationale and Objectives: Determination of coronary artery patency may have therapeutic and prognostic significance particularly in the setting of acute myocardial infarction. Previous studies with cine computed tomography have demonstrated remarkable accuracy in the determination of coronary artery bypass graft patency. Recent improvements in resolution capability have afforded the potential for determination of native coronary artery patency. The accuracy of coronary artery patency determined by cine computed tomography is investigated in an animal model of coronary occlusion-reperfusion., Methods: Seven anesthetized dogs were studied during control, coronary occlusion, and reperfusion conditions. Cine computed tomography was performed using electrocardiogram-triggered serial scans after intravenous injection of contrast medium. Coronary patency was determined by dye appearance in the epicardial artery coincident with its appearance in the left ventricular cavity., Results: Patency was determined for the left anterior descending and left coronary arteries during three separate conditions in each dog, for a total of 42 patency determinations, and yielded the correct result in all cases., Conclusion: High-resolution cine computed tomography scanning can provide accurate determinations of coronary artery patency in an experimental model of occlusion-reperfusion.

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.

Coronary artery bypass graft patency can be assessed using the indirect techniques of evaluating patients' symptoms and exercise tolerance, changes in stress electrocardiogram, radioisotope regional perfusion, and myocardial wall contraction. The direct techniques assess graft patency directly by visualizing grafts using conventional computed tomography (CT), ultrafast CT, magnetic resonance imaging, digital subtraction angiography, and echocardiography. The advantages and disadvantages of each of these modalities are reviewed. At the present time, ultrafast CT and possibly magnetic resonance imaging and Doppler appear to be the only techniques besides angiography that can consistently evaluate bypass graft patency. Although they have the advantage of being minimally invasive, they cannot show graft stenosis or sequential graft patency. These techniques are best used in following patients after coronary bypass graft surgery and ruling out graft closure as the source of chest pain.

We routinely performed intravenous dipyridamole thallium imaging and resting radionuclide ventriculography on 190 patients being considered for elective vascular procedures. Patients with thallium redistribution underwent coronary arteriography. Patients in group 1 (n = 78) had clinical evidence of coronary artery disease, and patients in group 2 (n = 112) had no history or electrocardiographic evidence of coronary artery disease. The frequency of thallium redistribution was not significantly different in the two groups (45% in group 1 and 46% in group 2). Coronary arteriography identified severe three-vessel or left main disease in eight patients (10%) in group 1 and 16 patients (14%) in group 2. Selection of patients for dipyridamole thallium imaging prior to vascular reconstruction should be based on whether or not documentation of the extent of coronary artery disease would influence therapy rather than on clinical indicators of coronary disease.

To investigate the mechanism by which cardiac glucose utilization increases during hypoxia and increased work load, we studied the effect of 2 and 14 days of hypobaric hypoxia on the expression of two subtypes of the facilitative D-glucose transporter, the GLUT-4 or "insulin-regulatable" isoform and the GLUT-1 isoform thought to mediate basal transport. Rats lose weight when exposed to hypobaric hypoxia, so fasting controls were used in the 2-day studies and pair-fed controls in the 14-day experiments. Hypobaric hypoxia (PO2 69 mmHg) resulted in right ventricular (RV), but not left ventricular (LV), hypertrophy. RV and LV GLUT-1 mRNA levels increased 2- to 3-fold after 2 days and 1.5- to 2-fold after 14 days of hypobaric hypoxia compared with both fasted rats and normal controls. RV GLUT-1 protein increased approximately 3-fold and LV GLUT-1 protein increased 1.5-fold after 14 days of hypobaric hypoxia vs. both pair-fed and normal controls. RV GLUT-4 mRNA decreased to 26% and RV GLUT-4 protein decreased to 54% of normal control levels as a result of 2 days of hypobaric hypoxia. RV GLUT-4 mRNA decreased to 64% of normal control levels with no change in RV GLUT-4 protein as a result of 2 days of fasting. We conclude that hypobaric hypoxia increases cardiac GLUT-1 expression at the pretranslational level in both ventricles. The greater increase in GLUT-1 protein on the right suggests an additive effect of pressure overload. GLUT-4 expression is reduced early in the development of RV hypertrophy.

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.

Myocardial blood flow was evaluated in 31 subjects with not only visual but also, for the first time, circumferential profile analysis of rubidium 82 (82Rb) images acquired with positron emission tomography. Fifteen were control subjects and 16 subjects had significant coronary artery disease, defined as 50% or greater diameter stenosis in a major coronary artery or a first-order branch. Simultaneous 82Rb images at three myocardial levels were obtained before and after intravenous dipyridamole plus handgrip stress. In patients with significant coronary artery disease, visual analysis correctly identified significant disease in 26 (76%) of 34 arteries and its absence in 12 (86%) of 14 normal arteries. According to circumferential profile analysis, these numbers were 91% and 86%, respectively. Thus circumferential analysis of 82Rb images, obtained before and after intravenous dipyridamole plus handgrip stress, yielded improved sensitivity and comparable specificity compared with visual analysis.

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 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.

To investigate the effects of complete and incomplete revascularization on the response to exercise, 25 patients underwent symptom-limited exercise testing with continuous assessment of gas exchange a mean of 5 +/- 4 days prior to and 18 +/- 12 days following percutaneous transluminal coronary angioplasty. All antianginal medications were discontinued for testing. Revascularization was considered complete if all stenoses were reduced to less than 50% diameter (13 patients), and incomplete if one or more stenoses remained (12 patients). Consistent improvements in ST-segment depression were observed after angioplasty at matched submaximal exercise levels (mean range 0.5-0.8 mm; p less than 0.05), and were accompanied by a reduction in angina. Significant increases in heart rate and systolic blood pressure were observed at peak exercise following angioplasty in both groups. Gas exchange variables were significantly improved at maximal exercise, with a similar increase in oxygen uptake observed in both groups following angioplasty (mean increase 3.3-3.7 ml/kg/min; p less than 0.01). Thus, incomplete revascularization following coronary angioplasty resulted in hemodynamic, electrocardiographic, symptomatic, and gas exchange responses to exercise that were comparable to complete revascularization.

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 objective of this study was to demonstrate the causes, optimal definition, and predictive value of exercise-induced hypotension occurring during treadmill testing. This study included all patients referred for clinical reasons to the Long Beach Veterans Administration Medical Center treadmill laboratory and then followed for a 2-year period for cardiac events. The population consisted of 2,036 patients who underwent testing from April 4, 1984, to May 7, 1987, 131 of whom exhibited exercise-induced hypotension (6.4%). We found that exercise-induced hypotension is usually related to myocardial ischemia or myocardial infarction, is best defined as a drop in systolic blood pressure during exercise below the standing preexercise value, and indicates a significantly increased risk for cardiac events (3.2-fold, p less than 0.005). This increased risk was not found in those having no previous myocardial infarction or no signs or symptoms of ischemia during the exercise test, and the increased risk was also not found in those undergoing a treadmill test within 3 weeks after a myocardial infarction. Exercise-induced hypotension appeared to be reversed by revascularization procedures, but confirmation of a beneficial effect on survival requires a randomized trial. The clinical importance of this study is that we have demonstrated that a drop in systolic blood pressure below standing preexercise values during treadmill testing indicates an increased risk for cardiac events except in certain subsets of patients.

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.

The mechanism by which afterload reduction increases left ventricular stroke volume while decreasing left ventricular filling pressure has not previously been established. In 15 patients with severe congestive heart failure due to ischemic or idiopathic dilated cardiomyopathy, absolute ventricular volume, ejection fraction and total stroke volume from radionuclide ventriculography were compared with thermodilution stroke volume before and after intensive afterload reduction with vasodilators and diuretics titrated to hemodynamic goals. After 48 to 72 hours, pulmonary artery wedge pressure decreased from 32 +/- 8 to 16 +/- 4 mm Hg and systemic vascular resistance from 1,960 +/- 700 to 1,200 +/- 400 dynes s cm-5. End-diastolic volume decreased from 390 +/- 138 to 301 +/- 126 ml (p less than 0.01) and end-systolic volume from 316 +/- 127 to 241 +/- 111 (p less than 0.01). Ejection fraction did not change and total stroke volume decreased from 74 +/- 22 to 59 +/- 20 ml (p less than 0.01). Simultaneous forward stroke volume by thermodilution increased from 37 +/- 14 to 52 +/- 14 ml (p less than 0.01), and forward fraction increased from 0.55 +/- 0.40 to 0.96 +/- 0.42. Intensive reduction of ventricular filling pressure and systemic vascular resistance decreased total ventricular stroke volume by 20% but increased forward stroke volume by 40%. The major effect of intensive afterload reduction for severe congestive heart failure may be the reduction of ventricular volume and mitral regurgitation.

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)