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Positron Emission Tomography was used to measure global and regional cardiac β-adrenergic function in 19 normal subjects and 9 congestive heart failure patients. [ 11 C]-meta-hydroxyephedrine was used to image norepinephrine transporter function as an indicator of pre-synaptic function and [ 11 C]-CGP12177 was used to measure cell surface β-receptor density as an indicator of post-synaptic function. Pre-synaptic, but not post-synaptic, function was significantly different between normals and CHF patients. Pre-synaptic function was well matched to post-synaptic function in the normal hearts but significantly different and poorly matched in the CHF patients studied. This imaging technique can help us understand regional sympathetic function in cardiac disease.

In this Institutional Review Board-approved investigation, an 82-year-old male underwent carotid endarterectomy for a >80% asymptomatic carotid stenosis. Six weeks prior, the subject had undergone carotid endarterectomy of the contralateral carotid artery for a symptomatic >70% stenosis. Approximately 1 hour before surgery, the patient was injected with 7.9 mCi [18]Fluorodeoxyglucose (FDG). After resection of the plaque using a surgical technique that maintained its integrity, the specimen was imaged using micro-positron emission tomography (PET) (Siemens Inveon) and magnetic resonance imaging (3T Philips Achieva). Subsequently, the specimen was fixed in formalin, sectioned at 1 mm intervals, and stained with hematoxylin and eosin. Immunocytochemistry was performed using antibodies to detect macrophages (HAM-56, Dako, 1:100), leukocytes (CD-45, Dako, 1:200), and smooth muscle cell actin (anti–σ-actin Sigma, 1:100). The …

Both gamma imaging and positron emission tomography (PET) imaging of cell surface receptors have become possible through the development of agonists and antagonists with high specific radioactivity and high specificity for the receptors. An understanding of the physiology of the cardiac receptor system is essential to comprehending receptor imaging. The complexity of the physiologic information developed over the past decade has been compounded by the concomitant discovery of additional receptor subtypes. The following is a review of a select group of cardiac receptors and their regulation-namely, adrenergic, muscarinic-cholinergic, adenosine, and angiotensin I and II receptors. The role of imaging regional receptor localization and function in providing new insights into cardiac pathology and therapeutic avenues is explored.

An appropriate oxygen tension is a basic condition for normal cardiac function. Most of the energy needs of the myocyte are met by oxidative processes, and oxygen deficiency results in the metabolic and functional abnormalities associated with ischemic heart disease. Despite the central importance of tissue pO2 in normal and pathophysiological cardiac function, little is known about intracellular pO2 in the human heart. There is also uncertainty about what level of pO2 constitutes tissue hypoxia. Contractile abnormalities occur when coronary sinus pO2 is reduced to 10–15 mmHg, but in vitro normal mitochondrial function is supported at much lower pO2 [1].

Eosinophilic gastroenteritis (EG) is a rare inflammatory disease of unknown etiology, characterized by focal or diffuse eosinophilic infiltration of the gastrointestinal tract. Although little over 250 cases of EG have been reported in the literature, EG is probably more common than reports in the literature would indicate. A retrospective review of 25 patients with EG along with a review of the literature was done to identify clinical, laboratory, radiographic, and therapeutic features. An allergic disorder was present in 14 (56%) and a peripheral eosinophilia was present in 24 (96%) of our patients. The most common radiographic manifestations of the stomach and small bowel included stenosis and fold thickening, respectively. Thirteen patients had esophageal involvement, with the esophageal stricture being the most common abnormality found in these patients. Steroids produced a good therapeutic result in most patients; the remaining patients responded to cromolyn and/or surgery.

Adam M. Alessio received his PhD in Electrical Engineering from the University of Notre Dame in 2003. During his graduate studies he developed tomographic reconstruction methods for correlated data and helped construct a high-resolution PET system. He is currently a Research Assistant Professor in Radiology at the University of Washington. His research interests focus on improved data processing and reconstruction algorithms for PET/CT systems with an emphasis on quantitative imaging. Erik Butterworth recieved the BA degree in Mathematics from the University of Chicago in 1977. Between 1977 and 1987 he worked as a computer programmer/analyst for several small commercial software firms. Since 1988, he has worked as a software engineer on various research projects at the University of Washington. Between 1988 and 1993 he developed a real-time data aquisition for the analysis of estuarine sediment transport in the department of Geophysics. Between 1988 and 2002 he developed I4, a system for the display and analysis of cardic PET images in the department of Cardiology. Since 1993 he has worked on physiological simulation systems (XSIM from 1993 to 1999, JSim since 1999) at the National Simulation Resource Facility in Cirulatory Mass Transport and Exchange, in the Department of Bioengineering. His research interests include simulation systems and medical imaging. James H. Caldwell, MD, University of Missouri-Columbia 1970, is Professor of Medicine (Cardiology) and Radiology and Adjunct Professor of Bioengineering at the University of Washington School of Medicine and Acting Head, Division of Cardiology and Director of Nuclear Cardiology for the University of Washington Hospitals, Seattle WA, USA. James B. Bassingthwaighte, MD, Toronto 1955, PhD Mayo Grad Sch Med 1964, was Professor of Physiology and of Medicine at Mayo Clinic until 1975 when he moved to the University of Washington to chair Bioengineering. He is Professor of Bioengineering and Radiology. In 1979, he established a National Simulation Resource Facility in Circulatory Mass Transport and Exchange and in 1997, he initiated the Human Physiome Projects. He is a member of the US National Academy of Engineering. His research is on quantitative integration of cellular and cardiovascular systems.Positron emission tomography (PET) is a nuclear medicine imaging modality based on the administration of a positron-emitting radiotracer, the imaging of the distribution and kinetics of the tracer, and the interpretation of the physiological events and their meaning with respect to health and disease. PET imaging was introduced in the 1970s and numerous advances in radiotracers and detection systems have enabled this modality to address a wide variety of clinical tasks, such as the detection of cancer, staging of Alzheimer's disease, and assessment of coronary artery disease (CAD). This review provides a description of the logic and the logistics of the processes required for PET imaging and a discussion of its use in guiding the treatment of CAD. Finally, we outline prospects and limitations of nanoparticles as agents for PET imaging.

Data were acquired on the uptake of metabolic substrates and on well-retained ions in small regions of the myocardium, 1 to 2 min after injection into the left atrium, and compared with estimates of local myocardial blood flows in each of the 250 to 500 regions, per heart. The data showed approximately linear relationships between the deposition of these solutes and the local flows. Models for blood-tissue exchange kinetics based on an assumption of the constancy of permeability-surface area products for capillary and cellular uptake in all regions being the same were not compatible with the data. Using axially distributed multiregional models appropriate to the solutes, the data could be fitted only when the permeability-surface area products were proportional to the local flow in each region. Within myocardial pieces of 0.1 to 0.2 G, the range of flows was about six-fold; if within the pieces having the lowest flows the regional metabolism was at the average rate for the whole heart, tissue viability could not be supported by flows available. These regions must therefore have less than average metabolic requirements. Likewise high flow regions would be extravagantly perfused if their metabolic rates were at the average rate. We conclude that although the link between transport capacities and flow is well established, that between local metabolism and flows is not proven, but it is highly likely that local flows transport capacities and metabolic requirements are well matched.

The Western Washington Intracoronary Streptokinase In Myocardial Infarction Trial enrolled 250 patients with acute myocardial infarction. After the coronary angiographic diagnosis of thrombosis, patients were randomly assigned to receive either conventional therapy with heparin or intracoronary streptokinase followed by heparin. Of the 232 patients who survived at least 60 days, 207 (89%) underwent radionuclide ventriculographic determination of global and regional ejection fraction at a single institution at 62 +/- 35 days after infarction. In the first 100 patients, infarct size was also determined by quantitative single-photon emission tomographic imaging with thallium-201 (201Tl) and expressed as a percentage of the left ventricle with a perfusion defect. Overall, global ejection fraction did not differ between patients treated with streptokinase (45.9 +/- 13.9%; n = 115) and control patients (46.1 +/- 14.4%; n = 92, p = NS). Similarly, the regional posterolateral, inferior, and anteroseptal ejection fraction did not differ between the two groups. Infarct size as measured by 201Tl tomography was 19.4 +/- 12.8% (n = 52) of the left ventricle for the streptokinase group and 19.6 +/- 11.8% (n = 48; p = NS) for the control group. When patients were compared within groups by electrocardiographic location of infarction, time to treatment, or the presence or absence of vessel opening, there were no significant differences between streptokinase and control patients. Statistical inclusion of the 18 patients who died early and were unavailable for study also failed to modify the results, except for a possible reduction in inferior infarct size as measured by 201Tl tomography.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of gastric inhibitory polypeptide on lower esophageal sphincter pressure was studied in cats to determine whether the effect was similar to that of its structurally related hormones, secretin, glucagon, and vasoactive intestinal peptide. Five healthy cats without endoscopic evidence of esophagitis were manometrically evaluated for 75 min using triple lumen open-tipped constantly perfused catheters. Exogenous gastric inhibitory polypeptide, 0.2 μg per kg per min, alone significantly decreased ( P P

Twenty-four depressed patients with heart disease were treated for four weeks in a double-blind trial of imipramine, doxepin, or placebo to assess the effects of tricyclic antidepressants on ventricular function and rhythm. The tricyclic antidepressants had no effect on left ventricular ejection fraction at rest or during maximal exercise, as measured by radionuclide ventriculograms obtained before and after treatment. Premature ventricular contractions were reduced by imipramine but were not consistently changed by doxepin or placebo. Treatment with imipramine and doxepin, but not placebo, was associated with significant improvement (P less than 0.001) in standard ratings of depression. Our findings underscore the need for a reappraisal of the cardiovascular risks of tricyclic antidepressants and suggest that in the absence of severe impairment of myocardial performance, depressed patients with preexisting heart disease can be effectively treated with these agents without an adverse effect on ventricular rhythm or hemodynamic function.

Intraduodenal amino acids are known to stimulate the release of gastric inhibitory polypeptide and cholecystokinin. In order to separate and quantitate gastric inhibitory polypeptide secretion selectively, 12 normal subjects received an intraduodenal perfusion of a mixed amino acid solution (158 mM) containing either methionine, phenylalanine, tryptophan, and valine (perfusate 1), or an amino acid solution containing arginine, histidine, isoleucine, leucine, lysine, and threonine (perfusate 2). Serum concentrations of gastric inhibitory polypeptide and insulin were significantly greater in the group receiving perfusate 2 ( P

Serial hemodynamic and plasma catecholamine responses were compared among 10 healthy men (27 +/- 3 years) (+/- 1 standard deviation) during symptom-limited handgrip (33% maximal voluntary contraction for 4.4 +/- 1.8 minutes), cold pressor testing (6 minutes) and symptom-limited supine bicycle exercise (22 +/- 5 minutes). Plasma catecholamine concentrations were measured by radioenzymatic assays: ejection fraction and changes in cardiac volumes were assessed by equilibrium radionuclide angiography. During maximal supine exercise, plasma norepinephrine and epinephrine concentrations increased three to six times more than during either symptom-limited handgrip or cold pressor testing. Additionally, increases in heart rate, systolic blood pressure, rate-pressure product, stroke volume, ejection fraction and cardiac output were significantly greater during bicycle exercise than during the other two tests. A decrease in ejection fraction of 0.05 units or more was common in young normal subjects during the first 2 minutes of cold pressor testing (6 of 10 subjects) or at symptom-limited handgrip (3 of 10), but never occurred during maximal supine bicycle exercise. The magnitude of hemodynamic changes with maximal supine bicycle exercise was greater, more consistent and associated with much higher sympathetic nervous system activation, making this a potentially more useful diagnostic stress than either handgrip exercise or cold pressor testing.

Intestinal mucosal biopsy immunoglobulin content in a patient with eosinophilia, allergic gastroenteropathy (atopy, food sensitivities, protein-losing enteropathy, iron deficiency anemia, and growth retardation), and hyperimmunoglobulinemia E (68,000 units) was compared with that of a control group and a group with eosinophilic gastroenteritis who had no atopic features. The patient had no evidence of cellular or humoral immunodeficiency but was severely hypersensitive to multiple inhalant and dietary allergens. In contrast to the findings in patients with nonallergic eosinophilic gastroenteritis, whose intestinal immunoglobulin content was similar to that of controls, tissue immunoglobulin IgE and IgG was markedly increased in the allergic patient. These results support an intestinal reaginic mechanism in the etiology of the allergic form of eosinophilic gastroenteritis.

To determine the relation between regional myocardial perfusion and regional wall motion in humans, tomographic thallium-201 imaging and two-dimensional echocardiography at rest were performed on the same day in 83 patients 4 to 12 weeks after myocardial infarction. Myocardial perfusion and wall motion were assessed independently in five left ventricular regions (total 415 regions). Regional myocardial perfusion was quantitated as a percent of the region infarcted (range 0 to 100%) using a previously validated method. Wall motion was graded on a four point scale as 1 = normal (n = 266 regions), 2 = hypokinesia (n = 64), 3 = akinesia (n = 70), 4 = dyskinesia (n = 13) or not evaluable (n = 2).Regional wall motion correlated directly with the severity of the perfusion deficit (r = 0.68, p < 0.0001). Among normally contracting regions, the mean perfusion defect score was only 2 ± 4. Increasingly severe wall motion abnormalities were associated with larger perfusion defect scores (hypokinesia = 6 ± 5, akinesia = 11 ± 7 and dyskinesia = 18 ± 5, all p < 0.01 versus normal). Among regions with normal wall motion, only 3% had a perfusion defect score ≥ 10. Conversely, among 68 regions with a large (≥ 10) perfusion defect, only 13% had normal motion whereas 87% had abnormal wall motion. The relation between perfusion and wall motion noted for the entire cohort was also present in subgroups of patients with anterior or inferior infarction.In patients with prior myocardial infarction, the severity of the tomographic thallium perfusion defect correlates directly with echocardiographically defined wall motion abnormalities, both globally and regionally. Hypokinetic regions have an intermediate reduction in perfusion compared with normally contracting or akinetic-dyskinetic regions. The combination of techniques described in this report may prove useful in the noninvasive evaluation of therapy designed to improve both regional perfusion and function.

We examined the effect of 150 ml of caffeinated instant coffee at two pHs, 4.5 and 7.0, on lower esophageal sphincter pressure in 20 normal volunteers and 16 patients with reflux esophagitis. When ingested alone coffee at pH 4.5 and 7.0 caused a decrease in basal sphincter pressure in normal volunteers from 19.4 +/- 1.5 to 13.7 +/- 1.0 mmHg (P ? 0.01) and from 18.7 +/- 1.5 to 16.0 +/- 0.8 mmHg (P < 0.05) respectively. When coffee at pH 4.5 was drunk with a mixed nutrient test meal, the resting sphincter pressure in normal subjects fell after 30-60 min with the nadir, 11.2 +/- 1.0 mmHg, being recorded at 60 min (P < 0.01). Coffee at pH 7.0 with the test meal resulted in a fall in pressure to 14.3 +/- 1.5 mmHg (P < 0.02) at 60 min. In patients with reflux esophagitis, coffee at pH 4.5 lowered lower esophageal sphincter pressure from 9.1 +/- 1.0 to 5.5 +/- 0.6 mmHg (P < 0.005); coffee at pH 7.0 decreased lower esophageal sphincter pressure from 8.5 +/- 1.1 to 6.9 +/- 0.7 mmHg (P < 0.05). In these patients, mean basal pressure, 9.2 +/- 0.8 mmHg, decreased to 5.2 +/- 0.7 mmHg (P < 0.001) 45 min after drinking coffee at pH 4.5 with the test meal. Coffee at the neutral pH caused a fall in pressure from 8.8 +/- 1.1 to 6.5 +/- 0.7 mmHg at 60 min after the test meal. Thus, coffee at either pH 4.5 or 7.0 caused a decrease in fasting and postcibal lower esophageal sphincter pressure in normal volunteers and patients with reflux esophagitis. The magnitude and the duration of the effect were greater after coffee at the lower pH. These data support the clinical belief that coffee may cause or aggravate heartburn by decreasing lower esophageal sphincter pressure.

One hundred fifty-four survivors of out-of-hospital ventricular fibrillation (VF) with coronary artery disease underwent radionuclide ventriculography an average of 4.2 months after VF. All patients were studied at rest, and 91 of these patients were also studied during supine bicycle exercise. Clinical histories and 24-hour ambulatory electrocardiograms were also assessed, and patients were followed for an average of 3.1 years after ventriculography. The mean left ventricular (LV) ejection fraction (EF) at rest was 40 ± 16%; in 34% of patients, it was 30% or less; in 37%, 31 to 50%; and in 29%, more than 50%. Regional LV wall motion was normal in 18%. The most severe segmental abnormality was hypokinesia in 22%, akinesia in 45% and dyskinesia in 14%. Wall motion abnormalities were usually located at the apex. During exercise, only 3% of patients (3 of 91) had a normal increase in EF of more than 5%, and the mean EF decreased from 42 to 38%. New exercise-induced wall motion abnormalities occurred in 30%. During the follow-up period, 54 patients died (35%): 48 from cardiac causes and 42 from unexpected and sudden causes. Predictors of death included EF at rest, presence of akinesia or dyskinesia on the ventriculogram at rest, the number of abnormal LV segments, history of congestive heart failure, history of acute myocardial infarction, absence of acute myocardial infarction at the time of VF and the presence of ventricular arrhythmia. In a stepwise regression analysis, EF at rest, arrhythmia frequency, history of congestive heart failure and absence of acute infarction at the time of VF were selected as independently predictive for death, with EF selected first. When all clinical variables were forced into the model, only EF added significant predictive information; other radionuclide measurements as well as ambulatory electrocardiographic arrhythmia frequencies were of no or borderline significance. In conclusion, the radionuclide LVEF at rest is the best predictor of death in patients resuscitated from out-of-hospital VF. The diversity of rest and exercise levels of LV function suggest multifactorial pathophysiologic mechanisms in this syndrome.

To determine the site of endogenous release of gastric inhibitory polypeptide (GIP), glucose perfusions (556 mmoles per liter) of duodenum, proximal jejunum, midjejunum, and ileum were performed in human volunteers using an occluding balloon perfusion technique. Preperfusion GIP concentrations were below assay sensitivity (125 pg per ml) in all subjects. After glucose perfusion, maximal serum GIP concentrations for the four groups were: duodenum, 1383 ± 152 pg per ml; proximal jejunum, 904 ± 87 pg per ml; midjejunum, 545 ± 91 pg per ml, and ileum 305 ± 38 pg per ml. Integrated GIP secretion was significantly greater with duodenal perfusion (111 ± 21 ng-min ml-1) d proximal jejunal perfusion (69 ± 5 ng-min ml-1), as compared to either midjejunal (47 ± 7 ng-min ml-1) or ileal (25 ± 6 ng-min ml-1) perfusions. Peak serum insulin concentrations and integrated insulin secretion were also significantly greater with perfusion of the duodenum or proximal jejunum. Serum glucose concentrations, integrated serum glucose, and glucose absorption were similar for the four areas perfused. The results of this study indicate that the proximal small intestine is the primary site of endogenous GIP release in man, but that smaller quantities are also released by the distal small bowel.

Candida albicans is the most common fungal infection which can occur in patients receiving total parenteral nutrition therapy. While rare, Candida endophthalmitis also can occur and must be considered as a potential risk of this treatment. Early detection and management of this disorder can alter the visual outcome for these patients. Systemic administration of amphotericin B and fluocytosine is the most common form of treatment for Candida endophthalmitis. In cases not responsive to systemic administration of antifungal agents, surgical management through pars plana vitrectomy can potentially eradicate the infection and preserve vision. We present a case of bilateral Candida endophthalmitis treated with amphotericin B and fluocytosine, and also with pars plana vitrectomy with the intracameral injection of amphotericin B into the anterior vitreous cavity. Systemic and intracameral use of antifungal drug therapy combined with vitrectomy restored useful vision to the patient.

The effect of furosemide on secretin-stimulated pancreatic secretion was examined in 12 normal subjects using a perfusion method to quantitate pancreatic output. During continuous secretin infusion (0.9 U per kg per hr), secretory volume rose to a steady state level of 32.5 ± 10.2 ml per min. When a bolus injection of furosemide (20 mg) was given during continuous secretin infusion, mean secretory volume increased further to a maximum value of 110 ± 14.7 ml per min. Similarly, the outputs of bicarbonate, sodium, and chloride increased significantly after furosemide, compared to values obtained with secretin infusion alone. Total bilirubin output fell after furosemide, suggesting that the effect of furosemide on secretory volume and electrolyte output was not due to a stimulatory effect on bile flow. Furosemide also had no effect on duodenal water transport. These observations demonstrate that furosemide stimulates pancreatic secretion of water and electrolytes, possibly via inhibition of pancreatic ductal absorption of sodium.

Transaxial tomograhic imaging with thallium-201 was compared with standard, planar imaging in 38 patients with remote myocardial infarction and in 15 normal patients. Tomographic images were reconstructed from 64 views collected by a gamma camera that rotated about the anterior circumference of the patient's chest. A series of consecutive transverse-section images which encompassed the cardiac volume were reconstructed at a 6 mm plane spacing by filtered back-projection. No correction was made for attenuation losses. The set of transverse-section images was reformatted by 3-dimensional interpolation to obtain tomograms along the long and short axes of the myocardium. Tomographic and planar images were interpreted qualitatively. Overall, tomography detected 33 of 38 (87%) prior infarctions whereas planar imaging detected 24 of 38 (63 %) (p = 0.01). Improvement of the tomographic imaging method occurred only in the combined subset of transmural inferior and subendocardial infarctions, and not in transmural anterior infarctions. Peak increases in creatinine phosphokinase were smaller in patients detected only by tomography compared with those detected by both the planar and the tomographic approach (3.1 × normal versus 10.4 × normal, p = 0.04). Five patients (13%) with prior infarction were not detected by either approach. For 6 of the 9 patients detected by tomography alone, realignment of the image data along the short and long axes of the heart was essential for making the diagnosis. Fourteen of 15 patients without infarction were normal on both planar and tomographic imaging. A single normal patient had a defect detected by both techniques, yielding a specificity of 93% for each. We conclude that transaxial tomography significantly improves the detection of thallium-201 myocardial perfusion defects in patients with prior myocardial infarction.

This study examined right ventricular function during exercise in patients with chronic obstructive pulmonary disease to answer the following questions: Is there a significant correlation between oxygen consumption at maximal exercise and exercise right ventricular ejection fraction? Does the right ventricular ejection fraction response to exercise correlate with exercise changes in pulmonary artery pressure, total pulmonary resistance or pulmonary vascular resistance? Which combinations of cardiac, ventilatory and blood gas variables are the best predictors of oxygen consumption at maximal exercise? Twenty-six patients with stable chronic obstructive pulmonary disease performed symptom-limited supine bicycle exercise with simultaneous hemodynamic and radionuclide ventriculographic measurements. The oxygen consumption at maximal exercise correlated with the exercise right ventricular ejection fraction (n = 21, r = 0.66; p less than 0.005), exercise stroke volume (r = 0.68; p less than 0.001), exercise cardiac output (r = 0.77; p less than 0.00005) and exercise ventilation (r = 0.85; p less than 0.00001). The change in right ventricular ejection fraction from rest to exercise correlated inversely with the change from rest to exercise in total pulmonary resistance (r = -0.51; p less than 0.05) but not with the change in mean pulmonary pressure (r = -0.37) or in pulmonary vascular resistance (r = 0.09). Multivariate analysis showed that the variables giving the highest combined correlation with oxygen consumption were ventilation and right ventricular ejection fraction (r = 0.95, adjusted r2 = 0.88). These results suggest that exercise oxygen consumption of patients with chronic obstructive pulmonary disease is related to right ventricular systolic function, exercise right ventricular dysfunction is related, in part, to abnormal exercise total pulmonary resistance, and exercise limitation in chronic obstructive pulmonary disease occurs as a result of the dynamic interaction between disordered right heart function and ventilation.

A new method for measuring left ventricular (LV) volume based on gated single-photon emission computed tomography (SPECT) is described. Preliminary phantom studies showed an excellent correlation between SPECT and observed volumes (r = 0.99, standard error of the estimate [SEE] = 4.9 ml). SPECT was performed 24 hours after biplane contrast LV angiography in 36 patients. Transaxial blood pool tomograms were reconstructed by filtered back projection and reoriented to views orthogonal to the cardiac axes. Volume was calculated from serial short-axis tomograms by determining the base, apex and lateral borders of the LV blood pool, ascertaining the number of pixels in this volume and multiplying by the known volume of a pixel. Gated SPECT volumes were compared with contrast angiographic volumes. At end-systole, r = 0.96 and SEE = 12 ml; at end-diastole, r = 0.81 and SEE = 27 ml. For ejection fraction, r = 0.85 and SEE = 0.06. To test interobserver variation in processing, count data from 5 patients were processed twice (r = 0.98, SEE = 8.3 ml). There is an excellent correlation between SPECT and contrast angiographic volumes at end-systole; at end-diastole the relation is good. SPECT requires no arbitrary background correction, allows systematic isolation of the left ventricle from other overlapping cardiac chambers and requires no geometric assumptions for volume determination. It has promise as a direct method for measuring LV volume in a minimally invasive manner.

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)

Previous studies of digitalis glycoside metabolism and excretion have indicated that these compounds undergo a significant enterohepatic cycle in some species. It has been suggested that the existence of such a cycle in man contributes to the prolonged action of certain cardiac glycosides. Previous studies have demonstrated that cholestyramine binds digitoxin and digoxin in vitro and accelerates the metabolic disposition of digitoxin in rats and guinea pigs, presumably by interrupting the enterohepatic circulation. In order to assess the role of the enterohepatic circulation in the metabolism of digitalis glycosides in humans, maintenance doses of cholestyramine were administered to 7 of 15 normal human subjects beginning 8 hr after digitalization with 1.2 mg of digitoxin-3H. All subjects had frequent measurements of serum radioactivity, left ventricular ejection time (LVET), and electromechanical systole (QS2), the latter recorded as the interval from onset of Q wave to first major component of second heart sound. Measurement of the LVET and QS2 intervals affords a sensitive index of the cardiac response to digitalis. In addition, chloroform extraction of serum was performed to separate unchanged digitoxin and active metabolites from cardioinactive metabolites of digitoxin. Cholestyramine treatment resulted in reduction in half-life to total serum radioactivity from 11.5 to 6.6 days, and in chloroform-extractable radioactivity from 6.0 to 4.5 days, as compared to controls. In addition, cholestyramine treatment was accompanied by more rapid return to base line values of digitoxin-induced changes in the LVET and QS2 intervals. A significant positive correlation was found between QS2 values and chloroform-extractable radioactivity, the latter reflecting unchanged digitoxin-H3 (r=0.64; P=

The clinical characteristics and long-term survival of 284 patients from the Coronary Artery Surgery Study (CASS) registry data base who had moderate to severe congestive heart failure symptoms and a left ventricular ejection fraction ≥0.45 were studied. A control group consisting of registry patients with an ejection fraction ≥0.45 who did not have heart failure was used for comparison. Patients who had heart failure were older and more likely to be female and to have a higher incidence of hypertension, diabetes and chronic lung disease than registry patients who did not have heart failure. As a group, patients with heart failure had more severe angina and were more likely to have had a prior myocardial infarction than were registry patients without heart failure.At 6 year follow-up, 82% of patients in the heart failure group survived compared with 91% of patients in the control group (p < 0.0001). Multivariate analysis using the Cox proportional hazards model identified the following independent predictors of mortality: regional ventricular systolic dysfunction, number of diseased coronary arteries, advanced age, hypertension, lung disease, diabetes, increased left ventricular end-diastolic pressure and heart failure symptoms. Among patients with heart failure, the 6-year survival rate of those who had three-vessel coronary artery disease was 68% compared with 92% for the group without coronary artery disease. However, the 6-year survival rate for patients with heart failure who underwent surgical revascularization of diseased coronary arteries was not significantly improved compared with that of patients treated medically.It appears from these data that the presence of moderate to severe heart failure symptoms in patients with an ejection fraction ≥0.45 is a clinical marker for a distinct patient group characterized by increased age, more severe clinical coronary artery disease, hypertension and an increased incidence of additional medical illnesses that have independent value in predicting long-term survival. As a result of the high incidence of concurrent illnesses, this patient group has a significantly reduced 6-year survival rate compared with a CASS registry patient group that did not have heart failure, and the additional presence of coronary artery disease dramatically reduces their survival. However, surgical treatment of coronary artery disease is not associated with improved survival over a 6-year follow-up period in this CASS registry subgroup.

To determine whether intracoronary streptokinase improves late regional wall motion or reduces left ventricular aneurysm or thrombus formation in patients with acute myocardial infarction, two-dimensional echocardiography was performed at 8 +/- 3 weeks after infarction in 83 patients randomized to streptokinase (n = 45) or standard therapy (n = 38) in the Western Washington Intracoronary Streptokinase Trial. Among the patients treated with streptokinase, the average time to treatment was 4.7 +/- 2.5 hours after the onset of chest pain, and 67% had successful reperfusion. Regional wall motion was assessed in nine left ventricular segments on a scale of 1 to 4 (normal, hypokinetic, akinetic and dyskinetic). Left ventricular thrombus formation was interpreted as positive, equivocal or negative. All patients received anticoagulant therapy in the hospital and 52 received such therapy after hospital discharge. The mean (+/- SD) global (1.5 +/- 0.4 in both groups) and regional wall motion scores in the streptokinase-treated and control groups were not significantly different. The prevalence of aneurysm was 16% in both groups. Left ventricular thrombus was identified in only five patients (positive identification in four, and equivocal in one), all in the streptokinase-treated group (p = NS). There were also no differences between streptokinase and control treatment in any of the echocardiographic variables in subgroups of patients with anterior infarction, inferior infarction, no prior infarction or reperfusion with streptokinase. It is concluded that intracoronary streptokinase given relatively late in the course of acute myocardial infarction does not result in improved global or regional wall motion or a reduction in left ventricular thrombus or aneurysm formation in survivors studied 2 months after myocardial infarction.

ObjectivesThe study was done to determine whether the effects of parasympathetic withdrawal on heart rate, blood pressure (BP), and systolic and diastolic function are altered with normal aging.BackgroundCardiac responses to beta-adrenergic sympathetic stimulation decline with aging as does the heart rate response to parasympathetic withdrawal, but the extent to which other responses to parasympathetic withdrawal decrease is less clear.MethodsHeart rate, BP, systolic function, and diastolic filling responses to parasympathetic withdrawal induced by atropine (0.02 mg/kg) were compared in 50 healthy subjects, 28 older (ages 65 to 80 years, mean 70 years; 18 females all on estrogen) and 22 young (age 18 to 32 years, mean 26 years; 12 females) subjects, using radionuclide angiography.ResultsParasympathetic withdrawal in the older group caused less of an increase in heart rate (+33 vs. +48 beats/min), cardiac index (+0.6 vs. +1.5 l/m2), systolic blood pressure (−1 vs. +7 mm Hg), and early diastolic filling rate (+1.7 vs. +2.4 end-diastolic volumes/s) (all p ≤ 0.01). At similar declines in the diastolic filling period, end-diastolic volume index (EDVI) fell substantially more in the older group (−11.6 vs. −2.4 ml/m2, p < 0.001). The only gender difference was in diastolic filling rate, which was similar in the young males and females, but significantly less in older males than in older females.ConclusionsThe responses to parasympathetic withdrawal as well as sympathetic stimulation decline with aging, and both contribute to the reduced cardiovascular responses to stress with advancing age.

Although caffeine is known to stimulate small intestinal water secretion in man, no available studies have examined the effect of coffee on small intestinal fluid transport. We have studied the effect of both coffee and caffeine on jejunal sodium and water transport by the triple lumen intestinal perfusion technique. Both caffeine and coffee solutions had equivalent caffeine concentrations, approximating the caffeine concentration in one cup of coffee. Control and coffee perfusion resulted in net absorption of 0.9 ± 0.2 and 1.1 ± 0.3 ml per min per 30 cm, respectively, whereas caffeine perfusion resulted in net water secretion of 2.4 ± 0.4 ml per min per 30 cm ( P P

We studied a young man with persistent elevation of transaminases and indirect bilirubin following acute viral hepatitis. Liver biopsy showed chronic persistent hepatitis, and clinical evaluation was otherwise negative for significant liver disease. The indirect-reacting serum bilirubin rose after both caloric restriction and intravenous nicotinic acid, responses believed by some to be characteristic of Gilbert's syndrome. Fasting and postprandial serum bile acid conjugates were not elevated. These results suggest that "Gilbert's-like" aberrations in bilirubin metabolism may be part of the spectrum of chronic persistent hepatitis.

Secretion of tritium-labeled digoxin was studied in rats using noneverted gut sacs, in ligated and perfused intestinal preparations in bile duct ligated rats, and by measuring 4 day fecal excretion of total radioactivity in bile duct ligated rats. Serosal to mucosal transfer was proportional to substrate concentration in vitro. In ligated intestinal loops radioactivity was concentrated in the lumen relative to serum. In perfused intestinal preparations the fraction of dose increased with time and was similar over a 100-fold range of doses. Bile duct ligated rats excreted 13.4 +/- 5.8 (S.D.) % of parenterally administered label in 4 day stool collections. Bile duct ligated rats treated with p.o. activated charcoal excreted significantly more radioactivity (33.4 +/- 7.9%). The results suggest that net nonbiliary intestinal secretion of digoxin and metabolites can be augmented by intraluminal binding. A role for this phenomenon in accounting for some effects of diseases and drug interactions is suggested.

Changes in left ventricular (LV) volumes and ejection fraction between rest and maximal supine exercise were evaluated in 11 patients who had had four epicardial markers placed during coronary artery surgery. After calibrating marker distances with respect to volume (r = 0.92--0.99) over one cardiac cycle for each patient, regression equations were used to compute LV volume from marker measurements for beats before and during exercise. The response of the left ventricle to exercise and the extent of revascularization could not be predicted from resting LV volume or ejection fraction. Ten patients had normal resting end-diastolic volumes and eight had normal resting ejection fractions. With exercise, three had a rise in end-diastolic volume and four had a fall in ejection fraction. Graft patency was greater in the group with an unchanged or increased ejection fraction (86 vs 50%, P less than 0.05). Epicardial clip motion can be used to determine LV volumes and ejection fraction during supine maximal exercise in man. The revascularized ventricle with normal or nearly normal performance in studies done at rest responds by decreasing end-diastolic and end-systolic volume and by increasing the ejection fraction. Increases in volumes or decreases in ejection fraction reflect old myocardial damage from infarction, fibrosis or ischemia from incomplete revascularization.

Nine normal, healthy young males performed graded, maximal supine bicycle exercise with monitoring of hemodynamic and gated blood pool parameters. Right ventricular ejection fraction (RVEF) was greater than 0.45 in all acquisitions at rest (mean +/- SD = 0.53 +/- 0.05) and increased greater than 0.05 in all subjects with maximal exercise (mean +/- SD = 0.69 +/- 0.06 at stage 4). There was a very close correspondence between RV and LV stroke counts from the radionuclide angiograms at rest and all exercise levels in all patients. Cardiac output changes by radionuclide data from the RV correlated closely with those obtained by the Fick technique. Multivariate analysis of RVEF vs pulmonary artery pressure, total pulmonary resistance, and heart rate showed that RVEF was inversely related to total pulmonary resistance in these patients (n = 43 acquisitions, r = 0.61, RVEF = 0.75 -- 0.001 TPR in dynes-sec/cm5 Sy.x = 0.07) and positively related to heart rate (n = 43, 4 = 0.78, RVEF = 0.34 + 0.0025 x HR Sy.x = 0.05). RVEF was not significantly related to the other hemodynamic parameters. These results suggest that in normal subjects RV systolic function is afterload-dependent and that total pulmonary resistance may be a suitable afterload index. The results emphasize that heart rate must be considered when comparing RVEF changes.

SUMMARY Fifty–two patients with suspected coronary artery disease underwent coronary angiography, thallium-201 myocardial imaging, and ECG–gated blood pool ventriculography at rest and at maximal exercise. In 11 patients without coronary artery disease, all thallium images were normal. The resting ejection fraction (EF) was normal in all 11 patients and increased during exercise in six, was unchanged in three, and decreased in two. Of the 41 patients with coronary artery disease, the thallium image was normal at rest and at exercise in six (15%), whereas the exercise EF was abnormal in these six. A new (18 patients) or enlarged (11 patients) defect appeared on the thallium image in 29 of 41 patients (71%) with coronary disease. Six of 41 patients (15%) had an abnormal rest thallium image that was unchanged with exercise. An abnormal rest and/or exercise image defect identified 35 of 41 patients (85%) with coronary artery disease. The resting EF was normal in 26 of the 41 patients (63%) and in 24 patients demonstrated an abnormal response to exercise. Fifteen patients (37%) had an abnormal resting EF, and 14 of these 15 demonstrated persistent abnormalities. Thus, an abnormal exercise EF response identified 38 of 41 (93%) patients with coronary disease. The specificity of the thallium image was 100% and for the exercise EF determination, 54% (p < 0.02). We conclude that an abnormal exercise EF response and the rest–exercise thallium image have similar sensitivities for detecting coronary disease; however, an abnormal exercise ejection fraction was significantly more sensitive than was a new thallium abnormality alone (93% vs 71%). Combined, the two studies detected all patients with coronary disease.

A young man with pectus excavatum and Gilbert's syndrome was found to have an abnormal hepatic photoscan, repeatedly interpreted as showing a mass lesion in the left lobe. Although his habitus suggested that it was a normal anatomic variant, numerous diagnostic procedures did not convincingly exclude disease of the liver. Peritoneoscopy confirmed that the left lobe was thin but otherwise normal. We review the causes of false positive liver scans.

We have measured the biliary excretion of 3H-digoxin in normal subjects by intestinal perfusion methods which impose minimal interruption of the enterohepatic circulation. In contrast to data obtained in patients with liver disease and postoperative patients with biliary fistulas, our data show that about 30% of an intravenous dose of 3H-digoxin reaches the digestive tract in 24 hr. Most of the excreted radioactivity is chloroform-soluble and presumably reabsorbably and most of this fraction is probably biologically active drug. The results suggest that (1) consideration of hepatobiliary function may be relevant in observations regarding digoxin pharmacokinetics and that this route may be exploited in trials of therapy designed to shorten the duration of digoxin intoxication.

A 51-year-old man was admitted to University Hospital in August 1986 with a three-day history of intractable nausea and vomiting, moderate epigastric pain, and blood-streaked emesis on the day of admission. He had become progressively weak, lightheaded, and faint when standing, and was unable to retain medication or liquids at home. His prior history was relevant for emergency ulcer surgery nineteen years previously, believed to be for perforation. Details of the operation were not known to the patient and records were not immediately available. Since then, he had experienced episodic pain, nausea and vomiting for a few days every year or so. These symptoms were usually relieved by fasting and antacids. He had sought little formal medical care but periodically received a prescription for Cimetidine from a public clinic and used it for indigestion, pain, or emesis. Past history was otherwise not remarkable. Family history included peptic ulcer disease in the father; no details were known to the patient. The patient worked part-time parking cars, was married, and smoked two packs of cigarettes daily. He denied past or present alcohol or drug abuse, or use of any other medication.

Visual analysis of the severity of coronary stenosis is limited by observer variability. However, more complex techniques of proved accuracy are tedious and costly. Therefore, a new digital electronic caliper (DEC) was evaluated as a potentially more accurate, rapid and less costly alternative for measuring stenosis severity. Stenosis minimum diameter (Dmin) and percent diameter reduction (% S) were measured from the screen of the cine projector using a DEC. These measurements were compared with visual estimates (VIS) by 4 experienced angiographers and with measurements made by a computer-assisted method (QCA) of proved accuracy. In routine cineangiograms from 7 patients, 10 lesions were significant (greater than 50% S) and 8 were mild (less than 50% S). Variability, the standard deviation of multiple estimates of Dmin and % S, averaged 0.09 mm and 3.1% for QCA; 0.18 mm and 5.9% for DEC; and 0.26 mm and 7.4% for VIS. Compared with QCA, the visual determination of % S significantly underestimates (-5%; p less than 0.02) mild and overestimates (+11%; p less than 0.002) significant stenosis. VIS underestimates Dmin in significant lesions by 20% (p less than 0.04). In contrast, the mean error for DEC measurement of Dmin and % S was not significantly different from 0 in either lesion group. For the entire group of lesions, and particularly in significant lesions, the mean error for measurement of these 2 indexes of disease was significantly less with DEC than with VIS. Thus, variability and error with DEC are acceptably low for clinical use.(ABSTRACT TRUNCATED AT 250 WORDS)

Medical treatment of the Zollinger-Ellison syndrome has been generally accepted because of the proven efficacy of the histamine (H2)-receptor antagonists in achieving symptomatic relief, and because of early reports indicating that few, if any, gastrinomas were resectable for cure. Gastrin radioimmunoassay (RIA) has made earlier and more certain diagnosis possible, and therefore reevaluation of the surgical management of gastrinomas is necessary. Experience with 60 gastrinoma patients is reported. Comparison between the pregastrin RIA years (before 1970) and post-gastrin RIA years was made to determine whether there was evidence to support the continuation of medical treatment without attempts to resect the gastrinoma. Twenty-five cases were diagnosed in the pre-RIA years. Age at diagnosis ranged from 17 to 68 years (median, 45 years). All patients were operated on. Metastases were found in 56 percent. No tumor was identified in 8 percent. Tumor was resected for "cure" (normal fasting gastrin levels for two years postoperatively) in one patient. Seventeen patients have died, and tumor was the cause of death in 70 percent. The five-year survival rate was 44 percent; the 10-year survival rate was 40 percent. Thirty-five cases were diagnosed after 1970. Age at diagnosis ranged from 39 to 61 years (median, 46 years). Thirty patients were operated on. Metastases were identified in 23 percent and no tumor was found in 17 percent. Tumor was resected for "cure" in 30 percent of patients. Seven patients have died and tumor caused death in 42 percent. The five-year survival rate was 82 percent; the 10-year rate was 64 percent. Advances in diagnosis and surgical technique since 1970 have made early operative treatment applicable in patients with gastrinoma. Because death in most cases is caused by progression of the tumor, an aggressive surgical approach to resect the tumor is advised soon after the diagnosis of Zollinger-Ellison syndrome is established.

Three cases of esophageal intramural pseudodiverticulosis (EIP) are described and the literature reviewed. We conclude that EIP is an inflammatory disease of unknown etiology characterized by dilatation of the esophageal submucosal glandular elements. The classic radiographic picture which is that of collar-button-shaped outpouchings projecting in a perpendicular fashion from the luminal surface is mainly related to dilatation in the glandular ductal system. It is usually diagnosed in the sixth and seventh decades, but all ages may be affected. Dysphagia is a very common but not universal symptom of the disease process. Approximately one third of these patients have diabetes mellitus. Strictures of the esophagus are frequently seen, and varying degrees of esophagitis may be manifest endoscopically. Esophageal motility disturbances are common and may be severe. Candida infestation with and without tissue invasion has been seen in a number of patients and should be searched for in all cases of EIP.

The biliary excretion of 3H-digoxin in rats prepared for bile sampling with minimal interruption of the enterohepatic circulation was compared with that in rats with complete interruption after intraduodenal or intravenous administration. Following dosage by either route, significantly more radioactivity was recovered from animals with nearly intact enterohepatic circulation. The method described allows direct measurement of this cycle in unanesthetized animals without the consequences of bile depletion.