Effect of endurance exercise training on heart rate variability at rest in healthy young and older men.

Heart rate variability (HRV) (SD of the RR interval), an index of parasympathetic tone, was measured at rest and during exercise in 13 healthy older men (age 60 to 82 years) and 11 healthy young men (age 24 to 32 years) before and after 6 months of aerobic exercise training. Before exercise training, the older subjects had a 47% lower HRV at rest compared with the young subjects (31 +/- 5 ms vs 58 +/- 4 ms, p = 0.0002). During peak exercise, the older subjects had less parasympathetic withdrawal than the young subjects (-45% vs -84%, p = 0.0001). Six months of intensive aerobic exercise training increased maximum oxygen consumption by 21% in the older group and 17% in the young group (analysis of variance: overall training effect, p = 0.0001; training effect in young vs old, p = NS). Training decreased the heart rate at rest in both the older (-9 beats/min) and the young groups (-5 beats/min, before vs after, p = 0.0001). Exercise training increased HRV at rest (p = 0.009) by 68% in the older subjects (31 +/- 5 ms to 52 +/- 8 ms) and by 17% in the young subjects (58 +/- 4 ms to 68 +/- 6 ms). Exercise training increases parasympathetic tone at rest in both the healthy older and young men, which may contribute to the reduction in mortality associated with regular exercise.

Quantitative gated blood pool tomographic assessment of regional ejection fraction: definition of normal limits.

OBJECTIVE: Our aim was to select a method of analysis for gated blood pool tomography that reduced variability in a group of normal subjects, allowed comparison with normal limit files and displayed results in the bull's-eye format. BACKGROUND: Abnormalities in left ventricular function may not be accurately detected by measures of global function because hyperkinesia in normal regions may compensate for abnormal regional function. Gated blood pool tomography acquires three-dimensional data and offers advantages over other noninvasive modalities for quantitative assessment of global and regional function. METHODS: Alternative methods for selecting the ventricular axis, calculating regional ejection fraction and choosing the number of ventricular divisions were studied in 15 normal volunteers to select the combination of parameters that produced the lowest variability in quantitative regional ejection fraction. Methods for quantitative comparison of regional ejection fraction with normal limit files and for display in the bull's-eye format were also examined. RESULTS: A fixed axis (the geometric center of the ventricle defined for end-diastole and used for end-systole) gave ejection fractions that were significantly higher in the lateral wall versus in the septum, 82 +/- 8 (mean +/- 1 SD) versus 39 +/- 17 (p less than 0.001) at the midcavity and 66 +/- 11 versus 21 +/- 20 (p less than 0.001) at the base. A floating axis system (axis defined individually for end-diastole and end-systole and realigned at the center) gave more uniform regional ejection fraction: 63 +/- 6 versus 64 +/- 8 (p = NS) at the midcavity and 44 +/- 16 versus 45 +/- 15 (p = NS) at the base. The coefficient of variability for regional ejection fraction was consistently lower using a floating axis. Calculating regional ejection fraction by dividing the regional stroke volume by the end-diastolic volume of the region gave a lower coefficient of variability and a more easily understood value than dividing the regional stroke volume by the total end-diastolic volume of the ventricle. Although the variability was lower using five versus nine ventricular divisions, nine regions offer greater spatial resolution. Comparison of regional ejection fraction with normal data identified regions greater than 2.5 SD below the mean as abnormal. We described the two-dimensional bull's-eye format as a method for displaying the regional three-dimensional data and illustrated abnormalities in patients with prior myocardial infarction. CONCLUSIONS: Gated blood pool tomography performed using a floating axis system, regional stroke volume calculation of ejection fraction and nine regions uses all the three-dimensional blood pool data to calculate regional ejection fraction, allow quantitative comparison with normal limit files, display the functional data in the two-dimensional bull's-eye format and demonstrate abnormalities in patients with myocardial infarction.

Four radionuclide methods for left ventricular volume determination: comparison of a manual and an automated technique.

This study compared the accuracy and reproducibility of three previously described and one new radionuclide method of measuring left ventricular volumes in 19 subjects using contrast ventriculographic volumes (n = 38, mean volume = 126.6 ml) as the gold standard. The four methods were compared using both manual and automated ROIs. For manual ROIs, the Links (189.7 ml, r = 0.85), Starling (183.2 ml, r = 0.77) and the new count ratio method (141.4 ml, r = 0.90) overestimated contrast volumes, while the Massardo method (122.5 ml, r = 0.91) provided accurate volumes. For the automated ROIs, we performed an interpolative background subtraction and used a 50% threshold of the highest count pixel to define the ventricular regions. The automated Massardo method severely underestimated the contrast volume (59.5 ml, r = 0.90), while the other automated methods yielded accurate volumes: Links (122.4 ml, r = 0.89), Starling (118.1 ml, r = 0.81) and the new count ratio method (125.0 ml, r = 0.90). The interobserver reproducibility of the automated methods was excellent (mean difference = 1%-4%) compared to the manual methods (2%-8%). Because no additional images, blood counting, attenuation, or decay correction were necessary, the manual Massardo method and the automated count ratio method are the simplest to perform. We conclude that automated determination of left ventricular volumes using the new count ratio method is rapid, accurate, reproducible and could readily be incorporated into routine clinical use.

Rarity of preclinical alcoholic cardiomyopathy in chronic alcoholics less than 40 years of age.

Preclinical alcoholic cardiomyopathy, myocardial damage in the absence of overt congestive heart failure in chronic alcoholics, is well characterized at necropsy, but attempts to identify such a clinical entity before death have produced conflicting results. Studying subjects only at rest, the inclusion of older alcoholics and limitations of noninvasive techniques may explain some of the disagreement. To determine if preclinical alcoholic cardiomyopathy could be identified independent of the aforementioned limitations, 25 asymptomatic chronic alcoholics aged less than 40 years (mean 34), each of whom had consumed a minimum of 1 pint of whiskey or one 6-pack of beer greater than or equal to 5 days per week for greater than or equal to 5 years, underwent radionuclide ventriculography for measurements of systolic and diastolic function at rest, peak supine exercise and during recovery, and echocardiography for assessment of chamber size, wall thickness and left ventricular mass. Red blood cell levels of selenium and thiamine were measured to determine whether abnormalities were present in these 2 potential mediators of alcoholic cardiomyopathy. For comparison, an age-matched group of healthy control subjects was also studied. For alcoholics and control subjects at rest, mean ejection fraction (67 +/- 7% vs 71 +/- 6%) and diastolic peak filling rate (3.4 +/- 0.6 vs 3.3 +/- 0.6 end-diastolic volumes per second [EDV/s]) were similar.(ABSTRACT TRUNCATED AT 250 WORDS)

The influence of collimators on SPECT center of rotation measurements: artifact generation and acceptance testing.

Misalignment between the electronic and mechanical axes of rotation will result in artifact generation and image degradation during single photon emission computed tomography (SPECT) reconstruction. Acceptance and quality control testing procedures have not emphasized the variability in center of rotation (COR) measurements caused by collimators and the need to verify uniformity across the full collimator field of view (FOV). Variation from the mean COR across the FOV was tested in four different collimators using multiple point source acquisitions. The mean COR was different for each collimator and two of the four had a greater than 0.5 pixel difference from the mean COR on some area of the FOV. This variation makes these collimators unacceptable for SPECT acquisition. Thus, initial acceptance testing of SPECT collimators should verify a uniform COR across the full FOV and collimators with a variability from the mean COR greater than 0.5 pixels should be rejected.

Evaluation of myocardial perfusion and function by single photon emission computed tomography.

Although planar radionuclide techniques provide accurate, noninvasive measurements of myocardial perfusion and function that are of proven clinical value in the evaluation of the cardiac patient, they are limited by poor object contrast and superimposition of surrounding structures. Due to incomplete angular sampling and significant longitudinal distortion, limited angle tomography did not solve these problems. Single photon emission computed tomography (SPECT) can acquire scintillation information over very small angles of rotation and, thus, improve both object contrast and delineation of overlying or adjacent structures without distortion. The early SPECT systems were cumbersome, dependent on individual user developed software, and had extremely long acquisition and processing time. Improved camera design, new software algorithms, and the use of array processors have simplified and standardized quality control, decreased processing time, and minimized the number of user interventions. New image display formats and quantitative methods of analysis have made interpretation less cumbersome, more reliable and highly reproducible. Cardiac SPECT has been used with thallium-201 and gated blood pool imaging in both research and clinical applications and shown an improvement over planar methods of acquisition.

Quantitation of size of relative myocardial perfusion defect by single-photon emission computed tomography.

The purpose of this study was to validate a semiautomatic method for quantitating the size of relative myocardial perfusion defects from single-photon emission computed tomographic (SPECT) images. We compared the size of the image defect in vivo, expressed as percent of involved left ventricle, as determined by this method with the anatomic size of the defect in vitro in 19 dogs. To test the method under optimal conditions, we first labeled the left ventricular myocardium in nine dogs by left atrial injection of 99mTc-labeled macroaggregated albumin particles after acute occlusion of one coronary artery. The "defect volume" was defined as the volume of the left ventricular myocardium for which counts fell 2 or more SDs below the distribution of counts in the myocardium supplied by a normal coronary artery in a series of animals. The relative in vivo defect volume by SPECT occupied 26.46 +/- 12.7% of the left ventricular volume (mean +/- SD), compared with a relative defect size in vitro of 33.3 +/- 13.7% (p = NS) of left ventricular volume as determined by well counting of myocardial samples. There was a close correlation between the two measurements (r = .92). However, myocardial relative defect volumes involving less than 5% of myocardium were not identified by SPECT. The defect volume weighted for the relative reduction in flow within the defect zone or the relative "reduced perfusion volume" was also determined. The correlation between the estimates by SPECT and those made in vitro for relative reduced perfusion volume was also high (r = .94).(ABSTRACT TRUNCATED AT 250 WORDS)

Regional distribution of myocardial blood flow measured by single-photon emission tomography: comparison with in vitro counting.

An emission computed tomography system (SPECT), which uses a single large-field-of-view gamma camera, was evaluated for its ability to measure the relative distribution of myocardial blood flow and to assess the effect of attenuation, scatter, and cardiac motion on the tomographic images. Normalized regional myocardial counts from the SPECT images of the living dogs correlated closely with those from the anatomic slices and the samples counted at necropsy except for an over-estimate of tracer in the perfusion defect (SPECT) 57.7 compared to tissue count 32.1; p less than 0.05. The differences were less for the other imaging conditions. Heart and thorax motion, attenuation, and scatter contributed less than 25% to the over-estimate of defect counts. We conclude that the SPECT system accurately reflects regional distribution of myocardial blood flow except for overestimation of flow in regions of perfusion defects. Small perfusion defects might therefore be missed, but no artifactual defects are created.

Positron imaging feasibility studies. I: Characteristics of [3H]thymidine uptake in rodent and canine neoplasms: concise communication.

Uptake [3H] thymidine was studied in BALB/c mice with EMT-6 sarcoma, in Buffalo rats with Morris 7777 hepatoma, and in nine dogs with spontaneous neoplasms: four lymphomas, two osteosarcomas, two soft-tissue sarcomas, and a thyroid carcinoma. High tumor-to-tissue ratios were observed for all tumor types assayed, and absolute uptakes, when computed as percent dose per gram tumor normalized for body weight, were similar for transplanted and spontaneous tumors. In the rodent tumors, radiothymidine was retained for at least 3 hr in the tumor without appreciable loss. In canine neoplasms, although the highest uptakes were observed in cellular tumors with many mitotic figures, tumor uptake showed significant variability that did not correlate with any obvious histologic change, and thus may reflect true biologic differences in metabolism among tumors at different sites in the same animal. These studies provide additional experimental evidence that the ratios of neoplastic to normal tissue and the kinetics of thymidine uptake by tumors are suitable for positron emission tomography of neoplasms in small and large animals, including both transplanted and spontaneous tumors.

Positron imaging feasibility studies. II: Characteristics of 2-deoxyglucose uptake in rodent and canine neoplasms: concise communication.

Uptake of [3H]2-deoxyglucose was studied in BALB/c mice with EMT-6 sarcoma, in Buffalo rats with Morris 7777 hepatoma, and in eight dogs with spontaneous neoplasms: five osteosarcomas and three diffuse lymphomas. High tumor-to-tissue ratios were observed for all tumor types studied. In rodents, peak levels of uptake occurred between 30 min and 1 hr, with a slow loss from the tumor of about 10% per hour thereafter. In dogs there was considerable variability in uptake, both between individuals and at different tumor sites within an individual. Necrotic tumor did not take up the radiotracer. Absolute uptakes, when normalized for body weight, were similar for spontaneous and transplanted neoplasms. These studies provide additional support for the concept that positron emission tomography can be used to obtain functional images of important metabolic processes of tumors, including glycolysis.

Seven-pinhole emission tomography with thallium-201 in patients with prior myocardial infarction.

Thirty-six patients with prior myocardial infarction, and 14 patients without, had myocardial imaging at rest using both seven-pinhole emission tomography and planar imaging with thallium-201. The sensitivity and specificity of the two approaches for the detection of prior myocardial infarction were compared. Qualitatively, planar imaging yielded sensitivities of 69% (25 of 36) and 80% (29 of 36) with Polaroid and video display formats, respectively. A semiquantitative analysis gave a sensitivity of 75% (27 of 36). Specificities for these three planar approaches were, respectively, 100% (14 of 14), 93% (13 of 14), and 71% (10 of 14) for the Polaroid, video, and semiquantitative analyses. Seven-pinhole tomography had a sensitivity of 83% (30 of 36) by qualitative or visual inspection and 86% (31 of 36) by semiquantitative analysis. Specificities by these two techniques were 71% (10 of 14) and 57% (8 of 14). There were no statistically significant differences in either sensitivity or specificity between the planar and tomographic approaches. Repeat seven-pinhole images were identical in 95% (46 of 48) of patients, showing that reproducibility was satisfactory. We conclude that the seven-pinhole tomographic approach has no advantage over standard planar imaging in the detection of prior myocardial infarction.

In vivo simulation of thallium-201 myocardial scintigraphy by seven-pinhole emission tomography.

Seven-pinhole emission tomography has been studied under conditions that simulate clinical myocardial imaging with thallium-201, and is compared with planar imaging with a heart phantom. The seven-pinhole technique produces reconstructed images that offer a tomographic presentation of the object but do not quantitatively represent true cross sections of the object's activity distribution. Tomography produces significantly greater image contrast than planar imaging, even when maximal background subtraction is used to enhance the planar images. Two quantitative limitations of seven-pinhole tomography are noted for a simulated 24-g, 1.5-cm-thick complete transmural infarct: (a) the defect's activity concentration is not accurately reconstructed, and (b) it propagates longitudinally into some reconstructed planes that do not contain it. The imaging limitations of seven-pinhole tomography under the conditions studied are shown to be consistent on several camera/computer/software configurations.

Common pathway for tumor cell uptake of gallium-67 and iron-59 via a transferrin receptor.

We studied the tumor uptake of [67Ga]citrate, [59Fe]citrate, and 125I-labeled transferrin (TF) by the in vitro growth form of EMT-6, a sarcoma-like mammary tumor of BALB/c mice. In analyzing the binding experiments, we developed a new mathematical model based on a formulation originally used to express the interaction of hormones with specific tissue receptors. The uptake of both carrier-free 67Ga and 59Fe by tumor cells was mediated by kinetically identical TF receptors. We also studied teric acid extracts of the stroma of EMT-6 tumors grown both in vivo and in vitro. Chromatography of these extracts on Sephacryl S-200 SF demonstrated that the cellular stroma contained specific TF-binding macromolecules. On the basis of these findings, we proposed the "transferrin receptor hypothesis" for the mechanism of 67Ga uptake by tumors. According to this view, a tumor-associated TF receptor is the functional unit responsible for the affinity of gallium for certain neoplasms. This receptor was also active in the uptake of iron by tumors.