High-resolution cardiac PET in rabbits: imaging and quantitation of myocardial blood flow

A high-resolution PET system for small animals was tested for its applicability to the investigation of regional myocardial blood flow (MBF) in rabbits. METHODS: Nineteen measurements were performed in 10 closed-chest anesthetized rabbits at baseline and during infusions of adenosine (0.2 mg/kg/min) and propranolol (0.20-1.20 mg slow infusion) to obtain a wide range of MBF. Myocardial blood flow was assessed both by dynamic 13N-ammonia PET and by colored microspheres. Blood was withdrawn directly from the femoral artery, and arterial 13N activity was measured by coincidence type gamma detection system for the input function. Nitrogen-13 myocardial uptake was calculated by dividing the myocardial 13N activity by the integral value of the input function. RESULTS: Three or four contiguous cross-sectional myocardial images were obtained after 13N-ammonia injection. The left ventricular wall and cardiac cavity were clearly visualized. Moreover, initial passage of the tracer through the heart was obtained with serial 10-sec PET images. Nitrogen-13 myocardial uptake correlated well with flow measured with microspheres (r = 0.88). CONCLUSION: Our cardiac PET system can be used for in vivo imaging and quantitation of MBF in small animals and may play an important role in the future study of animal models of cardiovascular diseases.     

Oramucosal delivery of LHRH: pharmacokinetic studies of controlled and enhanced transmucosal permeation

A method base on the two-compartment model was developed to measure quantitative cerebral blood flow (CBF) and partition coefficient (lambda) of IMP from dynamic SPECT and single arterial blood sampling. In this method, the linear differential equation of two-compartment model, Yokoi proposed, was employed and quantitative CBF and lambda values were measured with the standard input function calibrated by single arterial sampling. The input function was derived from the standard input function scaled by a factor determined by the single arterial blood sample. This new technique was applied to 5 normal volunteers (Ages ranged from 25 to 29 yr., average 26 yr.). The optimal time to calibrate the standard input function in the individual study and optimal the period of the upper limit time to which input function is integrated from IMP administration for analysis of the equation were determined to minimize the difference between integration of the calibrated standard input function and of the individual input function. Minimization of the difference yields an optimal calibration time (4 to 10 min after IMP administration) and the period of the upper limit time (8 to 60 min after acquisition start). Comparison of CBF and lambda values obtained by the graphical method using the calibrated standard data and individual input function were performed. It should be noted that CBF values were in good agreement between the two methods, respectively (r = 0.92, P<0.01; r = 0.72, p = 0.01). This method is easy to estimate CBF and lambda by only single arterial blood sampling and IMP dynamic SPECT, and useful for routine studies.     

Imaging of myocardial perfusion and metabolism with positron emission tomography

Positron emission tomography (PET) has been providing new information in the diagnosis and the pathophysiological assessment of heart diseases. The PET tracers commonly used in Japan are 13N-ammonia, 18F-fluorodeoxyglucose (FDG) for imaging of myocardial perfusion and metabolism, respectively. Measurement of regional myocardial blood flow by 13N-ammonia dynamic PET scan and a compartment model analysis is applied to the functional estimation of coronary stenotic lesions and the detection of perfusion abnormalities in hypertrophic heart diseases, familial hyperchlesterolemia and other diseases with possible microvascular lesions. 18F-FDG is commonly used to differentiate ischemic but viable tissue from myocardial scar in coronary artery disease and also used to detect cardiac tumor and the cardiac involvement in sarcoidosis. In addition to these two tracers, 11C-acetate is now expected to provide the clinical analysis of pathophysiology of heart failure by estimating the efficiency of energy conversion of the heart into external work.     

A novel class of mosquitocidal delta-endotoxin, Cry19B, encoded by a Bacillus thuringiensis serovar higo gene

Construction of computational blood flow models from magnetic resonance (MR) scans of real arteries is a powerful tool for studying arterial hemodynamics. In this report we experimentally determine a lower bound for errors associated with such an approach, and present techniques for minimizing such errors. A known, simple three-dimensional geometry (cylindrical tube) was imaged using a commercial MR scanner, and the resulting images were used to construct finite element flow models. Computed wall-shear stresses were compared to known values and peak errors of 40-60% were found. These errors can be attributed to limited spatial resolution, image segmentation and model construction. A simple smoothing technique markedly reduced these peak errors. We conclude that smoothing is required in the construction of arterial models from in vivo MR images. If used appropriately, such images can be used to construct acceptably accurate computational models of realistic arterial geometries.     

HSPF Simulation of Runoff and Sediment Loads in the Upper Changjiang River Basin, China

To evaluate the performance of a computer model simulating runoff and sediment load in the upper region of the Changjiang (Yangtze River) basin over a relatively short time interval, including examining the applicability of the input precipitation data generated from global circulation models and satellite data, we used a spatially distributed model, HSPF with the International Satellite Land Surface Climatology Project (ISLSCP) precipitation data for 1987 and 1988 as input data. The Nash–Sutcliffe coefficient (R2) for 5-day average streamflow was 0.94 in the calibration period and 0.95 in the verification period for the whole upper region. Moreover, the model simulated the 5-day average streamflow well in each main tributary, as shown by R2 values of 0.46–0.96, except that it underestimated the peak flow rates during the flood season over 2 years by up to 71% in Tuojiang and 61% in Jialingjiang. The model simulated the 5-day concentrations of suspended solids (SS) fairly well in the headwaters and upper regions of the Jinshajiang, Yalongjiang, and Minjiang watersheds, as shown by R2 values of 0.31–0.65. In the other regions, however, the model underestimated the SS load by up to 72%, and rarely simulated the fluctuation of SS concentration in each river channel during the flood season. These errors led to the underestimation of sediment runoff volume from the whole upper region during the flood season, as shown by the ratio of the simulated sediment load to the observed data at Yichang: 0.69 in the calibration period and 0.68 in the verification period. The ISLSCP precipitation tended to be more frequent and less intense than the measured precipitation. This was probably the main reason why the HSPF did not perform well in all regions at all times.     

Missed targets are more frequent than false alarms: a model for error rates in visual search

In many visual search tasks, reaction times (RTs) for target detection are measured as a function of display size. The corresponding error rates are usually low but increase with increasing display size. Missed-target errors are more common than false alarms. In recent models of visual search, the error rates were attributed to a premature search termination and error rates increasing with display size were interpreted as indicating a speed-accuracy trade-off and an underestimation of search times per item (obtained from RT slopes). A model is described in which errors occur as a result of imperfect rather than incomplete search (i.e., it is assumed that there are task-specific probabilities of categorizing a target or a distractor incorrectly). Signal-detection theory is used to show that the observed error rate properties can be attributed to an optimized decision strategy. "Corrections" of RT data are thus questionable.     

Effect of hematocrit variations on coronary hemodynamics and oxygen utilization

Twenty-five closed-chest pentobarbitalized dogs were used for studying coronary flow dynamics and myocardial oxygen utilization following variations of hematocrit (Hct) by isovolumetric exchange of blood with plasma or packed red cells. Coronary blood flow (133Xe washout) and cardiac output varied inversely with Hct. Coronary systemic, and pulmonary flow resistances varied in the same direction with Hct. Blood viscosity played a significant role in determining the flow resistances in these three regions. Analysis of vascular hindrance (vascular resistance/blood viscosity) suggested that coronary vasodilation occurred following Hct changes beyond the range of 20-60%. In systemic and pulmonary circulations, however, there was vasoconstriction following hemodilution. The range of optimum Hct for maximum O2 transport (blood flow X arterial O2 content) was much wider in coronary (20-60% Hct) than in systemic circulation (40-60% Hct). The O2 consumptions in total body and in myocardium were essentially constant over a wide range of Hct (20-60%). The maintenance of total body O2 consumption over the Hct range of 20-40% was attributable to an increase in A-V O2 extraction. The O2 extraction ratio in the coronary circulation was constant over the entire range of Hct studied, suggesting that the myocardial O2 consumption was primarily determined by the coronary O2 transport.     

A graphical analysis method to estimate blood-to-tissue transfer constants for tracers with labeled metabolites

The Patlak graphical analysis technique is a popular tool for estimating blood-to-tissue transfer constants from multiple-time uptake data. Our objective was to extend this technique to tracers with labeled metabolites, the presence of which can cause errors in the standard Patlak analysis. METHODS: Based on previously described formulations, we generalized the graphical technique for use under specific conditions. To test the extended graphical approach, we applied the method to both simulated and patient data using a preliminary compartmental model for the PET tumor proliferation marker, 2-[11C]-thymidine. RESULTS: When given conditions are met, a linear relationship exists between the normalized tissue activity (tissue activity/blood activity) and a new set of graphical analysis basis functions, including a new definition of normalized time, which takes the presence of labeled metabolites into account. Graphical estimations of the tumor thymidine incorporation rate for simulated data were accurate and showed close agreement to the results of detailed compartmental analysis. In patient studies, the graphical and compartmental estimates showed good agreement but a somewhat poorer correlation than in the simulations. CONCLUSION: The extended graphical analysis approach provides an efficient method for estimating blood-tissue transfer constants for tracers with labeled metabolites.     

Rat liver transport and biotransformation of a cytostatic complex of bis-cholylglycinate and platinum (II)

Dobutamine is used as an alternative to exercise in conjunction with 99mTc-sestamibi SPECT perfusion imaging for detection of coronary artery disease. However, the use of quantitative dobutamine 99mTc-sestamibi SPECT imaging for enhanced detection of coronary stenosis has not been established. The goal of this study is to examine the effects of dobutamine stress on regional myocardial blood flow and relative myocardial 99mTc-sestamibi activity in the presence of a single-vessel stenosis. METHODS: In six open-chest dogs with left circumflex artery stenosis, radiolabeled microspheres were injected during baseline, severe stenosis and peak dobutamine stress (10 microg/kg/min). Technetium-99m-sestamibi was injected intravenously at peak dobutamine. Hearts were excised 20 min after 99mTc-sestamibi injection for SPECT imaging and post-mortem gamma-well counting. RESULTS: Dobutamine significantly increased heart rate, rate-pressure product and the first derivative of left ventricular pressure. Ischemic zone (left circumflex) myocardial blood flows (in ml/min/g) were: baseline, 0.92 +/- 0.15; stenosis, 0.65 +/- 0.16; and dobutamine, 1.19 +/- 0.38. Nonischemic zone myocardial blood flows were: baseline, 0.99 +/- 0.18; stenosis, 1.01 +/- 0.12; and dobutamine, 1.94 +/- 0.32 (p < 0.01 versus stenosis). Ischemic flows, expressed as percentages of nonischemic flows, were: baseline, 94% +/- 2%; stenosis, 63% +/- 11% (p < 0.05 versus baseline) and dobutamine, 60% +/- 12% (p was not significant versus stenosis). Technetium-99m-sestamibi activity in the ischemic zone (75% +/- 6% nonischemic) underestimated the relative flow deficit produced during dobutamine stress (p = 0.056). Myocardial 99mTc-sestamibi activity correlated with flow when flow was less than 1.0 ml/min/g. At higher flow ranges (1.0 ml/min/g-3.5 ml/min/g), 99mTc-sestamibi did not track flow. CONCLUSION: In a canine model of flow-limiting, single-vessel stenosis, dobutamine (10 microg/kg/min) did not augment flow heterogeneity. In addition, relative myocardial 99mTc-sestamibi activity underestimated microsphere flow at higher flows induced by dobutamine, leading to underestimation of ischemia. These findings suggest that dobutamine stress 99mTc-sestamibi scintigraphy may underestimate the relative flow deficit.     

Characteristics of patients at risk for perioperative myocardial infarction after infrainguinal bypass surgery: an exploratory study

Two numerical brain phantoms were generated in order to investigate errors which might be included in the quantitative measurement of regional CBF with use of single photon emission computed tomography (SPECT). The first phantom simulated the normal brain, and effects of the limited spatial resolution of the SPECT scanner were evaluated for 4 tracer kinetic models of the conventional microsphere model, the intra-carotid bolus injection technique of 133Xe, 133Xe Kanno-Lassen method, and the IMP-autoradiography (IMP-ARG) method. The second phantom simulated the diseased brain with middle-carotid artery (MCA) occlusion, and effects of the limited first-pass extraction fraction were investigated for the microsphere model with various permeability-surface area products. The limited spatial resolution caused systematic underestimation of the radioactivity concentration in the gray matter regions, and systematic overestimation in the low CBF regions. These errors in the original radioactivity distribution were found to cause further systematic errors in the calculated regional CBF images. It was also found that these errors were highly dependent on the tracer kinetic model employed, e.g., regional CBF values were overestimated in the clearance and the Kanno-Lassen methods compared with the conventional microsphere method, whereas values were underestimated in the IMP-ARG method. It was also shown in this study that the limited first-pass extraction fraction caused significant underestimation in the calculated rCBF values. In addition, regional contrast can be reduced when using a tracer with small PS product.(ABSTRACT TRUNCATED AT 250 WORDS)     

Clinical expression of myotonic dystrophy: the predictive role of DNA diagnosis

The two-compartment open model is currently used to assess glomerular filtration rate (GFR) with multiple blood samples. Numerous limited sampling models have been developed to reduce the number of blood samples. In the present study, the three-compartment closed model was used to assess GFR after a single intravenous injection. The three-compartment closed model includes blood, peripheral and urine compartments, thus the samples in urine can be used to estimate parts of pharmacokinetic parameters, thus to reduce the number of blood samples. Theoretically, the three-compartment closed model can assess GFR with one blood sample at any sampling time and three urine samples at any three sampling times.     

Body fat estimation in late pregnancy and early postpartum: comparison of two-, three-, and four-component models

Accurate methods for determining body fat mass during reproduction are necessary to evaluate energy balance. However, determination of fat mass is complicated during pregnancy by the accretion of water, which invalidates assumptions underlying standard two-compartment models. The extent to which the variability in body water during pregnancy invalidates use of pregnancy-corrected two-compartment models for determination of fat mass in individual women is unknown. Moreover, it is unclear whether body water returns to nonpregnant values by 2 wk postpartum, which is frequently used as the baseline in studies of postpartum women. The present study uses a four-component model as a criterion for evaluating two- and three-component models. Fifty-six healthy, normotensive women between the ages of 19 and 35 y were studied at 36 +/- 1 wk gestation and 15 +/- 2 d postpartum. Total body water (TBW), total body potassium (TBK), body density, and bone mineral content were measured by deuterium dilution, whole-body potassium counting, hydrodensitometry, and dual-energy X-ray absorptiometry (postpartum only), respectively. At 2 wk postpartum, hydration and density of fat-free mass (FFM) had not returned to nonpregnant values, and differed between lactating and nonlactating women (P < 0.05). Accordingly, standard TBW and body density estimates of fat mass differed from four-component estimates at both time points (P < 0.005). Moreover, our data indicate that even when pregnancy-specific values for hydration or density of FFM are used in TBW and body density models, individual fat mass estimates may differ by > 3 kg from the four-component value. Fat mass by TBK may differ by > 10 kg from fat mass by the four-component model during pregnancy, and by 6 kg postpartum. Use of standard two-compartment models to estimate fat mass results in significant error both during pregnancy and at 2 wk postpartum. Pregnancy-corrected two-compartment models produce reliable mean fat mass estimates during pregnancy, but individual fat mass estimates may vary widely from four-component values.     

Uptake of seven myocardial tracers during increased myocardial blood flow by dobutamine infusion

RATIONALE AND OBJECTIVES: Direct comparison of myocardial perfusion tracers has been made difficult by variability in experimental models, and by a virtual absence of data comparing tracer uptake to myocardial blood flow under conditions of increased myocardial oxygen consumption, similar to what occurs with dynamic exercise. METHODS: Tracer uptake versus myocardial blood flow was evaluated for thallium-201 (201TI) and six technetium-99m (99mTc) myocardial-imaging agents in 24 open-chest canines with an occluded left-anterior descending coronary artery during dobutamine infusion. Data were fitted to the exponential model y = ax(1 - exp[-PSc/x]), where y is the tissue tracer/g normalized to normal (activity at 1 mL/minute/g) and x is the blood flow measured by the radioactive microsphere method. RESULTS: With dobutamine, myocardial tracer uptake was linear across a wide range of ischemic and hyperemic flows for each tracer. Based on the permeability surface area product, 201TI and 99mTc Q3 provided the best tracer estimate of myocardial blood flow (5.30+/-0.86 mL/minute/g, r = 0.91; 5.46+/-0.58 mL/minute/g, r = 0.94, respectively). Correlation coefficient (r) values for other tracers studied were 99mTc Q4 (r =0.93), 99mTc Q12 (r = 0.93), 99mTc sestamibi (r = 0.90), 99mTc tetrofosmin (r = 0.96), and 99mTc-N-Noet (r = 0.82). CONCLUSIONS: Of the 99mTc tracers examined under conditions of dobutamine-altered myocardial contractility, the myocardial uptake properties of 99mTc Q3 were most similar to those of 201TI.     

Regional blood flow, capillary permeability, and compartmental volumes: measurement with dynamic CT--initial experience

Sequential computed tomographic scanning was performed in patients with neck tumors after contrast material administration. For data analysis, a pharmacokinetic two-compartment model was employed that takes into account both capillary blood supply and bidirectional diffusion of the contrast agent across the capillary wall. This approach offers the possibility to quantitatively characterize tissue microcirculation with regional blood flow, capillary permeability, and relative compartmental volumes.     

Blink reflex recovery cycle in patients with blepharospasm unilaterally treated with botulinum toxin

To study the role of arterial blood dynamics in the thrombogenesis of thrombin-induced experimental retinal vein obstruction, the retinal blood flow velocity was evaluated using scanning laser ophthalmoscopic fluorescein videoangiography in an experimental rabbit retinal vein obstruction model. Retinal vein obstruction was made by transadventitial direct instillation of thrombin to the retinal vessels from the vitreous side. The blood flow velocity in the retinal artery and vein was estimated by measuring the passing velocity of the flow head of the dye bolus and venous filling time, respectively. 23 animals were treated with thrombin and compared with 18 controls not treated. In the control group retinal artery blood flow velocity and retinal venous fluorescein filling time was 5.3 +/- 1.1 mm/sec (mean +/- standard deviation) and 6.2 +/- 1.2 sec, respectively. In the treated group the values were 5.7 +/- 1.3 mm/sec and 5.8 +/- 1.0 sec before the thrombin administration, and 3.0 +/- 0.9 mm/sec at 24 hours after its administration, and 5.7 +/- 2.0 sec and 4.0 +/- 1.5 mm/sec and 4.5 +/- 1.4 sec at 48 hours after the administration. These results indicate that a decrease in retinal artery blood flow velocity is strongly involved in the thrombogenesis in thrombin-induced experimental retinal vein obstruction.     

Comparison of technetium-99m-ECD to Xenon-133 SPECT in normal controls and in patients with mild to moderate regional cerebral blood flow abnormalities

Technetium-99m-1,1-ethyl cysteinate dimer (ECD) has been proposed as a "chemical microsphere" for SPECT measurement of regional cerebral blood flow (rCBF). However, its distribution has not yet been compared in humans to an established rCBF measure. Therefore, we compared the uptake and distribution of ECD with rCBF measured by 133Xe SPECT in subjects with mild to moderate flow abnormalities and in normal volunteers. Blood and urine chemistries and vital signs were unchanged from pre-ECD values up to seven days postinjection. Profile plots demonstrated pattern agreement between rCBF ratios (133Xe) and ECD count density ratios. A significant correlation of rCBF ratios to ECD count density ratios was observed (r = 0.77), with a slope of 0.64 and intercept of 0.36. To explore whether or not the relationship between rCBF and ECD was dependent on absolute flow, ECD region of interest data were expressed in units of ml/min/100 g by equating global CBF (133Xe) and ECD global count density. A closer correlation (r = 0.88) was found for these data than for the count ratio data. The slope was closer to one (m = 0.83) and the intercept was closer to zero (b = 8.2). Also, a significant correlation was observed between ECD-derived rCBF and 133Xe rCBF in the lesion area (r = 0.92) for patients with well-demarcated rCBF lesions. The slope (0.80) suggested a slight underestimation of lesion flow by ECD. Finally, ECD clearance from cortical gray matter ROIs derived from high-resolution scans from 1 to 4 hr postinjection was slow (2.4%/hr). In summary, ECD is a safe and effective marker of regional cerebral perfusion. The distribution of ECD is linearly related to rCBF measured by 133Xe SPECT, although our data suggest a mild underestimation of flow at the high end of the normal range.     

Calibration and Verification of a 2D Hydrodynamic Model for Simulating Flow around Emergent Bendway Weir Structures

The predictive capability of a two-dimensional (2D)-hydrodynamic model, the finite-element surface water modeling system (FESWMS), to describe adequately the flow characteristics around emergent bendway weir structures was evaluated. To examine FESWMS predictive capability, a sensitivity analysis was performed to identify the flow conditions and locations within the modeled reach, where FESWMS inputs for Manning’s n and eddy viscosity must be spatially distributed for to better represent the river bed flow roughness characteristics and regions where the flow is highly turbulent in nature. The sensitivity analysis showed that high flow conditions masked the impact of Manning’s n and eddy viscosity on the model outputs. Therefore, the model was calibrated under low flow conditions when the structures were emergent and had the largest impact on the flow pattern and model inputs. Detailed field measurements were performed under low flow conditions at the Raccoon River, Iowa for model calibration and verification. The model predictions were examined for both spatially averaged and distributed Manning’s n and eddy viscosity model input values within the study reach for an array of emergent structures. Spatially averaged model inputs for Manning’s n and eddy viscosity provided satisfactory flow depth predictions but poor velocity predictions. Estimated errors in the predicted values were less than 10% for flow depth and about 60% for flow velocity. Distributed Manning’s n and eddy viscosity model inputs, on the contrary, provided both satisfactory flow depth and velocity predictions. Further, distributed inputs were able to mimic closely the recirculation flow pattern in the wake region behind the bendway weir structures. Estimated errors in the predicted values were less than 10 and 25% for flow depth and velocity, respectively. Overall, in the case of distributed model inputs, FESWMS provided satisfactory results and allowed a closed depiction of the flow patterns around the emergent bendway weirs. These findings suggest that 2D models with spatially distributed values for Manning’s n and eddy viscosity can adequately replicate the velocity vector field around emergent structures and can be valuable tools to river managers, except in cases when detailed three-dimensional flow patterns are needed. The study was limited to the examined low flow conditions, and more field data, especially under high flow conditions, are necessary to generalize the findings of this study regarding the model prediction capabilities.     

Noradrenaline modulates the electrical activity of white adipocytes by a cAMP-dependent mechanism

The two-compartment open model is currently used to assess the glomerular filtration rate (GFR) after a single intravenous injection or a constant rate intravenous infusion. This model needs multiple blood samples from a patient, thus numerous limited sampling models have been so far developed to reduce the number of blood samples. In the present study, the three-, four- and n-compartment closed models have been developed to assess GFR after and during a constant rate intravenous infusion, which include the renal and all possible non-renal elimination pathways. Although more non-renal elimination compartments were included in the modelling, the results show it only leads to the increase in the similar analytical solutions for these compartments and the analytical solution for the blood compartment is the same as that in the two-compartment open model. Theoretically, the developed models can be used to assess GFR with a single blood sample at any sampling time with several urine samples.     

Modeling blood flow heterogeneity

It has been known for some time that regional blood flows within an organ are not uniform. Useful measures of heterogeneity of regional blood flows are the standard deviation and coefficient of variation or relative dispersion of the probability density function (PDF) of regional flows obtained from the regional concentrations of tracers that are deposited in proportion to blood flow. When a mathematical model is used to analyze dilution curves after tracer solute administration, for many solutes it is important to account for flow heterogeneity and the wide range of transit times through multiple pathways in parallel. Failure to do so leads to bias in the estimates of volumes of distribution and membrane conductances. Since in practice the number of paths used should be relatively small, the analysis is sensitive to the choice of the individual elements used to approximate the distribution of flows or transit times. Presented here is a method for modeling heterogeneous flow through an organ using a scheme that covers both the high flow and long transit time extremes of the flow distribution. With this method, numerical experiments are performed to determine the errors made in estimating parameters when flow heterogeneity is ignored, in both the absence and presence of noise. The magnitude of the errors in the estimates depends upon the system parameters, the amount of flow heterogeneity present, and whether the shape of the input function is known. In some cases, some parameters may be estimated to within 10% when heterogeneity is ignored (homogeneous model), but errors of 15-20% may result, even when the level of heterogeneity is modest. In repeated trials in the presence of 5% noise, the mean of the estimates was always closer to the true value with the heterogeneous model than when heterogeneity was ignored, but the distributions of the estimates from the homogeneous and heterogeneous models overlapped for some parameters when outflow dilution curves were analyzed. The separation between the distributions was further reduced when tissue content curves were analyzed. It is concluded that multipath models accounting for flow heterogeneity are a vehicle for assessing the effects of flow heterogeneity under the conditions applicable to specific laboratory protocols, that efforts should be made to assess the actual level of flow heterogeneity in the organ being studied, and that the errors in parameter estimates are generally smaller when the input function is known rather than estimated by deconvolution.     

Coronary vasodilatory capacity is impaired in patients with dilated cardiomyopathy

Increases in wall stress because of left ventricular enlargement and/or alterations in coronary vasomotor tone might affect myocardial blood flow and vasodilatory capacity in patients with dilated cardiomyopathy. To test this hypothesis myocardial blood flow was measured at rest and during intravenous administration of dipyridamole (0.56 mg/kg) using dynamic nitrogen 13-ammonia positron emission tomography (two-compartment model) in 10 patients with dilated cardiomyopathy (mean left ventricular ejection fraction 28 +/- 8% 1 woman, 9 men; 47 +/- 13 years of age). Ten age and gender matched healthy volunteers served as controls. Coronary artery disease was ruled out by coronary angiography and left ventricular hypertrophy by two dimensional-echocardiography. Baseline heart rate (70 +/- 13 v 64 +/- 12 bpm), systolic blood pressure (111 +/- 20 v 114 +/- 12 mm Hg) and rate pressure product (7,686 +/- 1264 v 7,306 +/- 1,645) were similar in patients and controls. During dipyridamole administration, the rate pressure product increased similarly in both groups. Myocardial blood flow at rest did not differ between groups of patients and volunteers (0.69 +/ -0.27 v 0.67 +/- 0.17 mL/g/min) but correlated with the rate pressure product only in controls (myocardial blood flow, 0.18 + 0.000068214; rate pressure product, .67; P < .05). Hyperemic myocardial blood flow was lower in patients (1.57 +/- 0.39 v 1.92 +/- 0.31 mL/g/min, p < .05, whereas myocardial flow reserve did not differ between groups of patients and controls (2.57 +/- 1.15 v 3.02 +/- 0.94). Coronary vasodilatory capacity is reduced in patients with severe nonischemic cardiomyopathy. Increases in extravascular compressive forces or increased serum catecholamine levels, which in turn induce coronary vasoconstriction, might account for this finding.