Task force IV: pharmacologic interventions. Emergency cardiac care.
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Biomedical subjects
Publications and source records attributed to R J Adolph.
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Myocardial uptake and washout of thallium-201 (201TI) were studied in an experimental dog model in which regional blood flow to the posterior wall was varied by transient 2-minute occlusion of the circumflex coronary artery to produce transient ischemia and reactive hyperemia. Thallium-201 myocardial activity in a region of interest was determined continuously after i.v. administration by a gamma camera and computer program. Activity in the posterior wall was compared with that in the anterior wall in the same dog and the posterior wall of control dogs. Thallium-201 uptake was directly related to blood flow. With reactive hyperemia, there was a rapid and absolute increase in uptake followed by rapid washout; with ischemia, there was slow and decreased uptake followed by a slow washout. The calculated myocardial activity during washout in both ischemic and hyperemic areas approached values in control dogs long after blood flow had returned to baseline levels. Significant differences in washout slopes were found between the three groups of dogs (-0.156%/min in control dogs, -0.244%/min after reactive hyperemia, and -0.076%/min after transient ischemia, with half-washout times of 5.3 hours, 3.4 hours and 11.0 hours, respectively). These data suggest that both the initial decrease in activity in the ischemic area and the initial excess in the hyperemic area are corrected by different washout rates of ischemic and hyperemic cells during redistribution.
After intravenous administration of Tc-99m DMPE the flow-dependent kinetics were studied in dogs during induced ischemia and during induced maximal reactive hyperemia. A control group was also studied. Mean time-activity curves obtained from the myocardial wall were compared within the same intervention group and also with other groups. During reactive hyperemia, there was a rapid and absolute increase in uptake followed by a rapid washout, whereas during ischemia there was a slow and decreased uptake followed by a slow washout. The magnitude of Tc-99m DMPE uptake during reactive hyperemia was slightly less than that of Tl-201, but the decreased uptake with ischemia was about equal for the two agents. Following maximal uptake in the myocardium the effective half-life of Tc-99m DMPE was one-third to one-fourth that of Tl-201. The similar kinetics of Tc-99m DMPE compared to Tl-201 suggests its usefulness in the evaluation of ischemic heart disease.
Newly synthesized Tc-99m dichlorobis(1,2-dimethylphosphino)ethane (DMPE) was investigated as a myocardial imaging agent with respect to its kinetics (dependent on both time and regional coronary blood flow), its percent organ uptake, and its imaging characteristics in the anesthetized dog. Most of these data are compared with those of Tl-201. Blood clearance of the two agents is essentially the same. Compared with Tl-201, Tc-99m DMPE shows faster overall kinetics, higher heart-to-lung ratio, equally good correlation with a wide range of regional blood flows, and higher liver uptake. At the time of peak myocardial uptake, the mean heart uptake of Tl-201 is 4.3%, compared with 2.9% for Tc-99m DMPE, yet only 0.9% uptake of Tc-99m DMPE is found in the lung as compared with 3.3% for Tl-201. These differences result in a heart-to-lung ratio of 2:1 for Tc-99m DMPE and 1:1 for Tl-201, based on the data obtained from the time-activity curve. The quantitative findings are supported by the superior quality of Tc-99m DMPE images of both normal and infarcted dog heart. The high hepatic uptake of Tc-99m DMPE is not a serious problem if images are obtained within 5-60 min after dose. These basic kinetic studies suggest that Tc-99m DMPE is a promising myocardial imaging agent.
It is generally appreciated in the cardiovascular literature that calcium emboli to a central retinal artery or its branches may be the presenting feature of otherwise uncomplicated calcific aortic stenosis. The ophthalmologic literature provides good evidence for this point. Over a 7-month period, four such cases have come to our attention. Other potential sources of emboli were excluded by standard noninvasive and invasive diagnostic techniques, and two patients underwent successful aortic valve replacement. Previous studies of calcific aortic stenosis have demonstrated postmortem histologic evidence of calcium emboli to various organs, for example, heart, kidney, or brain. Since these emboli are small, their occurrence is clinically silent. The retinal circulation is unique in that its occlusion by a calcium microembolus results in loss of vision, and this symptom may be a clue to the presence of calcific aortic stenosis.
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In nine subjects with chronic obstructive pulmonary disease (COPD) and pulsus paradoxus, M-mode echocardiograms showed inspiratory augmentation of right ventricular dimensions and inspiratory decrease of left ventricular diastolic dimensions. In five subjects in whom the echocardiographic transistor was in the subxiphoid position, mean right ventricular dimensions increased during inspiration from 1.4 +/- 0.20 to 2.96 +/- 0.38 cm (p < 0.01). With inspiration, mean left ventricular diastolic dimensions decreased from 4.8 +/- 0.61 to 3.7 +/- 0.63 cm (p < 0.01) in these five subjects. Two-dimensional echocardiograms, performed in three subjects, confirmed inspiratory augmentation of right ventricular cross-sectional area. Similar changes were produced in two normal volunteers by artificial obstruction to breathing. Left ventricular ejection time measurements demonstrated an inspiratory decline in left ventricular stroke volume. Inspiratory filling of the right ventricle is not hampered, but rather is exaggerated in patients with COPD and pulsus paradoxus, and left ventricular stroke volume is reduced during inspiration. Exaggerated variations in intrathoracic pressure alone did not explain pulsus paradoxus. Increased right ventricular filling and stroke volume during inspiration probably play a part.
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Three collimators--high-resolutions, converging, and pinhole--were evaluated for Tl-201 myocardial imaging. Line spread function, sensitivity measurements, and phantom and animal studies were used. Features common to all the collimators were: a) better resolution at a closer distance with higher count density, and b) higher infarct detection rate in the tangenital projection than in the en face view relative to the lesion. Furthermore, an infarct in the epicardial location was better visualized than one in the endocardial location. In terms of resolution and sensitivity, the high-resolution collimator was found to be satisfactory in most clinical imagings, but for visualization of an infarct, its size by weight must be over 10--12 g. The pinhole collimator could resolve an infarct as small as 7 g, and use of the pinhole yielded a diagnostic accuracy of over 90%, compared with 75-80% for the high-resolution collimator. Although the low sensitivity of the pinhole collimator precludes its routine clinical use, the selected view would increase diagnostic accuracy. The converging collimator performed poorly in terms of lesion detectability, and its routine clinical use is not encouraged. The conclusion drawn here is valid in the system we have studied, but the variety of converging collimators must be evaluated further for their specific purposes.
We studied 14 patients with cardiac tamponade and pulsus paradoxus; 11 were studied after relief of tamponade by pericardiocentesis. Right ventricle diastolic diameter increased during inspiration in each of 12 patients; left ventricle diastolic diameter decreased during inspiration in each of 13. Mitral valve DE amplitude decreased with inspiration in 13 of 14 patients. Mitral valve E-F slope could be measured in eight patients, and was rounded and not measurable in six. Six of the eight showed inspiratory decrease in mitral E-F slope. Similar changes were observed in two other patients with pulsus paradoxus who had chronic obstructive airway disease. Twenty patients with large pericardial effusions and no tamponade did not show these changes. These results suggest inspiratory augmentation of right ventricular filling and inspiratory diminution of left ventricular filling, not only in cardiac tamponade, but in obstructive airway disease associated with pulsus paradoxus.
Etidronate and pyrophosphate, labeled with Tc-95m and Tc-99m, were studied in experimentally infarcted mongrel dogs. A distribution study was conducted 2 hr after simultaneous administration of both agents in two groups of dogs. In one group, the injection was made 15 min after release of a 2-hr coronary arterial ligation. Another group was injected 48 hr after release of the ligation. The uptakes for each radiopharmaceutical and the ratio of uptakes for each sample were computed. The data show pyrophosphate to be a superior agent for the imaging of acute myocardial infarcts because of the higher uptake by infarcted myocardium and the greater contrast between infarcted myocardium and neighboring organs.
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The sizes of surgically induced acute myocardial infarctions were quantified in a study of 28 dogs. Four projections (right and left anterior oblique, anterior, and left lateral) were obtained with 129Cs myocardial scintigraphy. Control images, taken before surgery, were compared with images taken 24-72 hr after coronary artery ligation. From postmortem examination the size of the infarct was determined and expressed as a percentage of the total left ventricle. On a standard diagram four independent observers marked the infarcted areas in each projection, expressed the severity of involvement in each area, and determined overall infarction size as a percentage of the total left ventricle. A nonlinear least-squares method was also employed to derive the size of the infarct, using the results from each observer's diagram. There were positive correlations between each observer's percentage estimate and the autopsy results. The overall accuracy of the least-squares method was similar to that of the individual observers. In this study, Observer 3 proved that acute myocardial infarcts can be quantified accurately from multiple scintigraphic projections of the myocardium, but the other three observers had difficulty in estimating infarct size. This difficulty probably resulted from the lack of well-validated criteria to aid the observer in determining the area of infarction, the severity of involvement within that area, or the total size of a myocardial infarct. Improvement in these estimates will require the development of definitive criteria, the use of optical scanners or computer processing, and combinations of radionuclides.
Thallium-201, 129Cs, 43K, and 81Rb were evaluated as "static" myocardial-imaging agents. Optimal settings of the scintillation camera were determined for each agent. Accumulation for good-quality images can be started as early as 5 min after the dose with 43K, 10 min with 201T1, and 30 min with 129Cs. Imaging times were comparable for 43K, 129Cs, and 201T1 (using the 80-keV x-rays). High-energy photons from the 81Rb preparation, largely from 82mRb contaminant, made it impossible to obtain an interpretable image without the addition of more shielding. Absorbed radiation dose from 81Rb is lower than that from 43K, 129Cs, and 201T1. The highest background activity was observed with 81Rb, followed by 43K, 129Cs, and 201T1 in that order. Overall, 201T1 was best suited for imaging acute myocardial infarction with currently available equipment, and 129Cs was next best. However, because of instrument setting and commercially obtained preparations, 81Rb could not be properly compared with the other radionuclides in our study.
The effect of regional myocardial ischemia and hypoxia on myocardial scintigraphy was studied in patients and dogs after intravenous administration of cesium-129. Seven men with angiographically proved ischemic heart disease underwent exercise testing and 129Cs was given immediately when ischemia was manifested in the electrocardiogram. Defects were not evident in the scintigrams of any patient. Failure to visualize a defect might be related to delayed uptake of 129Cs by the myocardium (maximal uptake in 45 minutes). The ischemic state was dissipated before the disparity in uptake between normal and ischemic myocardium could be visualized. Cesium-129 is useful for identifying acute myocardial infarcts but should not be used to visualize transient exercise-induced regional ischemia. Six dogs were given 129Cs after induction of regional myocardial hypoxia by perfusion of the anterior descending coronary artery with venous blood. In each, scintigraphy revealed a defect that resolved after reperfusion with arterial blood. Two other dogs were given 129Cs before perfusion with hypoxemic blood; neither dog manifested a defect. Since perfusion was maintained by a pump these results suggest that the major cause of the scintigraphically observed defect was inadequate cellular uptake of 129Cs rather than excessive cellular loss. Since regional myocardial hypoxia produced a reversible defect, scintigraphic studies might overestimate the size of an acute myocardial infarct in man by including the ischemic zone surrounding the infarct.
The physical findings in hypertrophic cardiomyopathy with left ventricular outflow tract obstruction are well described. In the absence of outflow tract obstruction the findings are less distinctive. There have been several reported cases in which the cardiac findings have suggested the diagnosis of mitral stenosis, In this report we describe a patient whose auscultatory and roentgenographic findings more closely mimicked mitral stenosis. The patient had a loud first heart sound, mitral opening snap and an apical presystolic murmur; left atrial enlargement was present. Noninvasive studies, including phonocardiography, echocardiography and apex cardiography, strongly suggested the correct diagnosis of nonobstructive hypertrophic cardiomyopathy. The diagnosis and unusual auscultatory findings were confirmed by results of cardiac catheterization and intracardiac phonocardiography. The importance of recognizing this syndrome and the use of noninvasive methods to establish the diagnosis are stressed.
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