Echocardiographic definition of the left ventricular centroid. I. Analysis of methods for centroid calculation from a single tomogram.

Quantitation of myocardial contraction requires a frame of reference. Most investigators have sought a single reference frame per image, centered in some manner with respect to the mass of myocardium. Because there is no anatomic marker for the center of the heart, many different approaches have been pursued to identify a centroid of the left ventricle. The issue of whether the reference should be fixed throughout the cardiac cycle or float from image to image has been addressed in previous studies, but the more fundamental question of how a centroid can best be defined has not been answered. This study examines this basic issue by analysis of variance from observer to observer, cycle to cycle, animal to animal and method to method. Both endocardial and epicardial borders were digitized twice by each of two observers at 1/30 s intervals spanning the cardiac cycle for each of three cardiac cycles in six normal dogs. The left ventricular centroid was calculated by six methods: center of endocardial coordinates, center of epicardial coordinates, center of mid-myocardial (average) coordinates, center of endocardial area, center of epicardial area and center of mid-myocardial (average) area. The path of each centroid was correlated between observers and correlation coefficients were transformed for analysis of variance. This analysis indicates a best approach to centroid definition through distinct minimization of the variance: the best of the six methods proved to be center of endocardial area.

Echocardiographic definition of the left ventricular centroid. II. Determination of the optimal centroid during systole in normal and infarcted hearts.

Although two-dimensional echocardiography is widely used in both clinical and experimental evaluations of regional cardiac wall motion, there is no established clinical method for quantitative analysis of the wall motion, not even for the normal radial motion observed in short-axis images. Measurement of radial wall motion requires determination of a centroid from which the radii emanate. Depending on its definition, the centroid is variously affected throughout systole by cardiac translation, regional wall motion and any shift of the subject position or transducer. A floating centroid is defined relative to the ventricular walls frame by frame, whereas a fixed centroid never moves with respect to the transducer. Evaluation of the best approach to definition of a centroid was previously presented (part I, this issue). The next question is how to use the centroid. This study examines which of four centroid applications provides the best reference for quantifying regional wall motion during systole. Method 1 is a floating centroid (defined separately for every image frame), method 2 uses the end-diastolic centroid as a fixed reference for all image frames, method 3 uses the end-systolic centroid as a fixed reference and method 4 uses the average as a fixed reference. Wall motion was measured with respect to each of these centroids by determining radial wall motion from end-diastole to end-systole and correlating radial motion throughout the cardiac cycle with that in normal control hearts.(ABSTRACT TRUNCATED AT 250 WORDS)

The natural history of regional wall motion in the acutely infarcted canine ventricle.

Two-dimensional echocardiography was employed to define the natural history of regional wall motion abnormalities in a canine model of acute experimental myocardial infarction. Serial short-axis two-dimensional echocardiograms were recorded in 11 closed chest dogs before coronary occlusion and 10, 30, 60, 180 and 360 minutes after permanent coronary ligation. Radiolabeled microsphere-derived blood flows were obtained in each study period and the histochemical (triphenyltetrazolium chloride) extent of infarction was determined at 6 hours. Previously published methods were used to quantitate field by field (every 16.7 ms) excursion of 36 evenly spaced endocardial targets. The circumferential extent of abnormal wall motion was followed sequentially using previously published definitions of abnormality: 1) systolic fractional radial change of less than 20%; 2) dyskinesia (systolic bulging) at the point in time (echocardiographic field) in which there is maximal dyskinesia; and 3) correlation with composite normal ray motion falling outside the 95% confidence limits defined in the control period. On the basis of the triphenyltetrazolium chloride staining pattern, the ventricle was divided into five zones: central infarct zone, zone with greater than 25% transmural infarction, total infarct zone, border zones and normal zone. Mean systolic fractional radial change was calculated for each zone and used as an index of the magnitude of abnormal wall motion. Regardless of the definition of abnormality employed, the circumferential extent of abnormal wall motion manifested at 10 minutes after occlusion did not significantly change, even up to 6 hours later. Similarly, 10 minutes after coronary occlusion the three infarct zones and border zones demonstrated significantly reduced systolic fractional radial change. This remained stable over the remainder of the 6 hour study period. It is concluded that once established at 10 minutes after coronary occlusion, the circumferential extent and magnitude of abnormal wall motion do not significantly change in the immediate postinfarct (6 hour) period.

Assessment of regional myocardial perfusion with thallium imaging during transient left anterior descending coronary arterial occlusion during angioplasty.

To define the jeopardized territory perfused through a single coronary arterial stenosis, thallium-201, 2 mCi, was injected into the pulmonary artery at the onset of the last of a series of percutaneous transluminal coronary angioplasty (PTCA) balloon inflations in 10 patients with single-vessel left anterior descending coronary artery disease. Imaging was begun immediately after PTCA. Arterial thallium activity peaked 30 seconds after injection and decreased to 34 +/- 6% (mean +/- standard error of the mean) of peak activity at the time of balloon deflation. Regional thallium activity during exercise vs PTCA was scored qualitatively and quantitatively. A computer quantification program was used that permitted automatic realignment and normalization of the 2 initial thallium images. Only mean quantitative posterior activity was lower (93 +/- 1% vs 86 +/- 2%, p less than 0.05) on exercise scans compared with PTCA scans. The other 5 segments showed no difference in mean scores. There were no qualitative differences in initial thallium distribution, nor were there qualitative or quantitative differences in the number of abnormal segments or severity of reduction in activity in the segment with the lowest activity. In conclusion, regional thallium myocardial distribution with a single severe stenoses with injection during peak exercise is similar to that after complete coronary occlusion.

Importance of temporal heterogeneity in assessing the contraction abnormalities associated with acute myocardial ischemia.

A number of recent two-dimensional echocardiographic studies have attempted to relate quantitative changes in short-axis left ventricular radial wall motion to underlying myocardial ischemia/infarction. The significance of temporal variation in the contraction sequence within these ischemic regions in the overall evaluation of segmental left ventricular dysfunction, however, remains undefined. To assess this, we examined the motion of 192 individual radii that intersected known ischemic segments at 16.7 msec intervals from end-diastole to end-systole. The studies were performed in 13 dogs 1 hr after acute coronary ligation (six of the left anterior descending and seven of the circumflex coronary artery). Zones of infarction were confirmed by triphenyltetrazolium chloride staining at the termination of the experiment and by a corresponding decrease of more than 75% in myocardial perfusion at the 1 hr sampling period. Dyskinesis (defined for each radius as negative or outward excursion relative to the end-diastolic reference on two consecutive fields) was noted along 168 of 192 radii (88%) at some point in the contraction sequence. The maximal outward or dyskinetic motion occurred most commonly in the fourth decile of the normalized contraction sequence. In 147 of the 168 dyskinetic radii (88%) the maximal outward motion occurred during the first half of systole while in only two radii in one animal was the maximal outward motion noted at end-systole. The total number of radii showing dyskinetic motion at any given point in the contraction sequence likewise varied with time. Although again the greatest number of radii showed abnormal motion during the fourth decile of the normalized contraction sequence, only 66 of 168 or 39% remained dyskinetic to end-systole. No relationship was observed between the point of maximal dyskinesis (time-weighted average of all dyskinetic radii for a given animal) and (1) the total number of radii showing dyskinesis, (2) the total number of radii within the infarct zone, or (3) the infarct area expressed as a percent of the slice area. The major factor determining persistence of dyskinesis to end-systole for any radius was the maximal outward motion of the endocardial segment at the point of maximal dyskinesis. Therefore, simple measurement of endocardial excursion from end-diastole to end-systole may fail to detect important wall motion abnormalities and, in some cases, may miss dyskinetic segments completely.

The effects of intravenous and oral cimetidine in primary hyperparathyroidism.

In vitro studies suggest that cimetidine affects parathyroid hormone secretion. It has been reported that cimetidine (Ci) reduces serum immunoreactive parathyroid hormone (iPTH) in hyperparathyroid subjects (HPTH) and chronic renal failure patients. Studies were performed to determine the effects of intravenous and 8 days of oral Ci on serum iPTH, total calcium (TCAL), ionized calcium (ICAL), phosphorus (PHO), and magnesium (MAG), as well as on the urinary excretion of calcium, PHO, and cAMP. Ci, 300 mg, was injected intravenously into 11 HPTH and 9 of these received normal saline as a control. Eight normal subjects (N) were similarly studied. Results analyzed by analysis of variance indicated that although IV Ci and placebo both caused a significant change with time in iPTH, in HPTH and N, the fall was greater with Ci (P less than 0.005). Intravenous Ci decreased iPTH in HPTH approximately 36% (P less than 0.001) and N approximately 25% (P less than 0.025). In HPTH and N, ICAL was affected by neither IV cimetidine nor placebo. IV Ci decreased TCAL and MAG in a similar fashion when compared to placebo, though change in each variable was statistically insignificant. In 6 HPTH an 8 day period of oral Ci, 300 mg every 8 hours, produced no consistent changes in the measured serum variables. In summary, though the acute effect of IV Ci was to reduce iPTH, it appears to have no independent effect on ICAL or TCAL. Oral Ci during an 8 day period of administration had no consistent effect on mineral metabolism. We conclude that the therapeutic efficacy of oral Ci in HPTH has yet to be demonstrated.

Evaluation of bone mass and growth in young diabetics.

To determine the relationships among bone mass, bone growth and serum glucose control in young, insulin-dependent diabetics, we performed photon absorptiometry and radiogrammetry on a clinically well-characterized group of 78 diabetics (mean age 15.2 yr, mean duration of diabetes 6.7 yr). Total and ionized calcium (TCa, ICa), magnesium (Mg), immunoreactive parathyroid hormone (iPTH) and phosphorus (P) were measured in fasting serum. Bone age was calculated from hand x-rays; and bone measurements, heights, and weights were standardized against normal groups of corresponding age, sex, and race. Mean deviation of bone mass measurement score was 1.24 SD below the normal mean (p less than .001); mean cortical area score was .22 SD and percent cortical area .25 SD below the normal means (both p less than .05). Radical width and metacarpal width for the diabetics were not less than normal. Mean percentiles for height and weight were 52.3 and 57.1 respectively, the latter significantly elevated (p less than .02). Bone mass and cortical area were inversely related to duration of disease (r = -.228, p less than .05; r = -.216, p less than .05). They were not correlated with serum parameters of mineral metabolism or of glucose control. Bone age was not significantly different from chronological age in those who had not achieved maturity (14.4 versus 14.5 yr). Mean age of menarche was 12.9 yr. When compared to normals the diabetic sample had diminished serum ICa (p less than .001), and Mg (p less than .001), though P and iPTH were not significantly different. We have demonstrated: (1) bone mass in this sample of juvenile diabetics is depressed, without evidence of impaired overall growth or delayed maturation, (2) this reduced bone mass probably results from a failure to gain the normal component of endosteal bone expected at this age, (3) this abnormality in bone growth progresses with disease but does not appear to vary with serum glucose control, and (4) in this population of diabetics there is a minimal but significant reduction in serum total and ionized calcium and serum magnesium without compensatory elevation of parathyroid hormone. The relationship of this metabolic abnormality of impaired bone growth in unknown.

A prospective study of change in bone mass with age in postmenopausal women.

For the first time a model for age-related bone loss has been developed from prospective data utilizing a new weighted least squares method. Two hundred and sixty-eight Caucasian women ranging in age from 50 to 95 were studied. A quadratic function best fit the data, and correcting for body weight and bone width reduced variance. The derived equation is: bone mass = (0.6032) (bone width) (cm) + (0.003059) (body weight) (kg) - (0.0163) (age - 50) + (0.0002249) (age - 50)2. Analysis of cross-sectional data on 583 Caucasian women of similar age showed a quadratic function with very similar coefficients. This quadratic function predicts an increase in bone mass after age 86, therefore 42 women over age 70 who had been followed for at least 2.5 yr were identified to test for this effect. of these, 13 had significantly positive regression coefficients of bone mass on age, and rate of change in bone width was positive in 40 of 42 individuals, of which 5 were significant. Since photon absorptiometry measures net changes on all bone envelopes, the most likely explanation for the observed changes is an early exponential loss of endosteal bone which ultimately slows or perhaps stops. There is a positive balance on the periosteal envelope which only becomes apparent in later years when the endosteal loss stops. These new statistical methods allow the development of models utilizing data collected at irregular intervals. The methods used are applicable to other biological data collected prospectively.

Injury of the cell's respiratory system by heat and by formaldehyde. Thermokinetics and early molecular events.

This is a study of the manner in which the respiratory system of the cell is injured either by elevated temperature or by exposure to diluted formaldehyde. Molecular mechanisms were identified by thermokinetic measurements. The rates at which respiratory failure developed in mouse liver slices in an injurious environment were measured at various temperatures. The data were fitted to the Arrhenius equation, and the effective activation energies of the injury processes were calculated. These data show that (1) the thermokinetics of injury to the cell's respiratory system, whether by thermal or chemical means, follows the Arrhenius law. (2) Thermal injury of the cell's respiratory system has a high activation energy, indicating that the critical, rate-determining event is a protein denaturation. Other mechanisms such as imbalance of metabolic reaction rates and thermal liquefaction of membrane lipids can be ruled out. (3) Repression of cell respiration by diluted formaldehyde has an activation energy compatible with a chemical reaction but low enough to exclude protein denaturation as a mechanism.