Cost-effectiveness of cardiac positron emission tomography in the treatment of ischemic cardiomyopathy.
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Algorithms↗
Biomedical subjects
H R Schelbert
Publications and source records attributed to H R Schelbert.
Quantitative relation between myocardial viability and improvement in heart failure symptoms after revascularization in patients with ischemic cardiomyopathy.
BACKGROUND: Studies of patients with coronary artery disease and left ventricular dysfunction have shown that preoperative quantification of myocardial viability may be clinically useful to identify those patients who will benefit most from revascularization both functionally and prognostically. However, the relation between preoperative extent of viability and change in heart failure symptoms has not been documented carefully. We assessed the relation between the magnitude of improvement in heart failure symptoms after coronary artery bypass surgery (CABG) and the extent of myocardial viability as assessed by use of quantitative analysis of preoperative positron emission tomography (PET) images. METHODS AND RESULTS: We studied 36 patients with ischemic cardiomyopathy (mean left ventricular ejection fraction, 28 +/- 6%) undergoing CABG. Preoperative extent and severity of perfusion abnormalities and myocardial viability (flow-metabolism mismatch) were assessed by use of quantitative analysis of PET images with 13N ammonia and fluorine-18-deoxyglucose. Each patient's functional status was determined before and after CABG by use of a Specific Activity Scale. Mean perfusion defect size and severity were 63 +/- 13% and 33 +/- 12%, respectively. Total extent of a PET mismatch correlated linearly and significantly with percent improvement in functional status after CABG (r = .87, P < .0001). A blood flow-metabolism mismatch > or = 18% was associated with a sensitivity of 76% and a specificity of 78% for predicting a change in functional status after revascularization. Patients with large mismatches (> or = 18%) achieved a significantly higher functional status compared with those with minimal or no PET mismatch (< 5%) (5.7 +/- 0.8 versus 4.9 +/- 0.7 metabolic equivalents, P = .009). This resulted in an improvement of 107% in patients with large mismatches compared with only 34% in patients with minimal or no PET mismatch. CONCLUSIONS: In patients with ischemic cardiomyopathy, the magnitude of improvement in heart failure symptoms after CABG is related to the preoperative extent and magnitude of myocardial viability as assessed by use of PET imaging. Patients with large perfusion-metabolism mismatches exhibit the greatest clinical benefit after CABG.
Aged↗
Evidence for preserved cardiopulmonary baroreflex control of renal cortical blood flow in humans with advanced heart failure. A positron emission tomography study.
BACKGROUND: The effect of cardiopulmonary baroreflexes on the renal circulation in healthy humans and patients with heart failure is unknown because of the technical limitations of studying the renal circulation. Positron emission tomography (PET) imaging is a new method to measure renal cortical blood flow in humans that is precise, rapid, reproducible, and noninvasive. The purpose of this study was to compare the effect of acute cardiopulmonary baroreceptor unloading by phlebotomy on regional blood flow in healthy humans and humans with advanced heart failure. METHODS AND RESULTS: We compared renal cortical blood flow and forearm blood flow in 10 healthy volunteers and 8 patients with heart failure (left ventricular ejection fraction, 0.24 +/- 0.02) during cardiopulmonary baroreceptor unloading with phlebotomy (450 mL). The major findings of this study are: (1) At rest, renal cortical blood flow is markedly diminished in humans with heart failure compared with healthy humans (heart failure, 2.4 +/- 0.1 versus healthy, 4.3 +/- 0.2 mL.min-1.g-1, P < .001). (2) In healthy humans, during phlebotomy, forearm blood flow decreased substantially (basal, 3.3 +/- 0.4 versus phlebotomy, 2.6 +/- 0.3 mL.min-1.100 mL-1, P = .02) and renal cortical blood flow decreased slightly but significantly (basal, 4.3 +/- 0.2 versus phlebotomy, 4.0 +/- 0.3 mL.min-1.g-1, P = .01). (3) The small magnitude of reflex renal vasoconstriction is not explained by the inability of the renal circulation to vasoconstrict, since the cold pressor stimulus induced substantial decreases in renal cortical blood flow in healthy subjects (basal, 4.4 +/- 0.1 versus cold pressor, 3.7 +/- 0.1 mL.min-1.g-1, P = .003). (4) In humans with heart failure, during phlebotomy, forearm blood flow did not change (basal, 2.6 +/- 0.3 versus phlebotomy, 2.7 +/- 0.2 mL.min-1.100 mL-1, P = NS), but renal cortical blood flow decreased slightly but significantly (basal, 2.4 +/- 0.1 versus phlebotomy, 2.1 +/- 0.1 mL.min-1.g-1, P = .01). (5) The cold pressor stimulus induced substantial decreases in renal cortical blood flow in patients with heart failure (basal, 2.9 +/- 0.1 versus cold pressor, 2.3 +/- 0.1 mL.min-1.g-1, P = .008). Thus, in patients with heart failure, there is an abnormality in cardiopulmonary baroreflex control of the forearm circulation but not the renal circulation. CONCLUSIONS: This study demonstrates the power of PET imaging to study normal physiological and pathophysiological reflex control of the renal circulation in humans and describes the novel finding of selective dysfunction of cardiopulmonary baroreflex control of one vascular region but its preservation in another in patients with heart failure.
Adult↗
Effect of short-term cardiovascular conditioning and low-fat diet on myocardial blood flow and flow reserve.
BACKGROUND: Cardiovascular conditioning reduces resting myocardial oxygen demand by lowering systolic blood pressure and heart rate. Lower myocardial oxygen demand at rest would be expected to be associated with a decrease in resting myocardial blood flow and, consequently, an increase in myocardial flow reserve as the ratio of hyperemic to resting blood flow. However, the effect of controlled exercise together with a low-lipid diet on myocardial blood flow and flow reserve has not been examined in humans. METHODS AND RESULTS: Myocardial blood flow at rest and after dipyridamole-induced hyperemia (0.56 mg/kg i.v.) was quantified with [13N]ammonia and positron emission tomography in 13 volunteers before and upon completion of a 6-week program of cardiovascular conditioning and a low-fat diet. Exercise capacity and serum lipid profiles were also assessed at the start and finish of the program. Eight normal volunteers of similar age not participating in the conditioning program served as a control group. Cardiovascular conditioning lowered the resting rate-pressure product (8859 +/- 2128 versus 7450 +/- 1496, P < .001), serum cholesterol (217 +/- 36 versus 181 +/- 26 mg/dL), LDL cholesterol (140 +/- 32 versus 114 +/- 24 mg/dL), and triglycerides (145 +/- 53 versus 116 +/- 33 mg/dL, all P < .05). Exercise tolerance (metabolic equivalent of the task, METs) improved significantly from 10.0 +/- 3.0 to 14.4 +/- 3.6 (P < .01). Resting blood flow decreased (0.78 +/- 0.18 versus 0.69 +/- 0.14 mL.g-1.min-1, P < .05), whereas hyperemic blood flow increased (2.06 +/- 0.35 versus 2.25 +/- 0.40 mL.g-1.min-1, P < .05), resulting in an improved myocardial flow reserve (2.82 +/- 1.07 versus 3.39 +/- 0.91, P < .05). Overall, the myocardial flow reserve was significantly related to exercise performance (METs). In the control group, no changes in resting rate-pressure product, serum cholesterol levels, exercise performance, resting or hyperemic myocardial blood flow, or flow reserve were observed. CONCLUSIONS: Short-term cardiovascular conditioning together with a low-fat diet results in an improved myocardial flow reserve by lowering resting blood flow and increasing coronary vasodilatory capacity. These changes are associated with an improved exercise capacity and may offer a protective effect in patients with coronary artery disease.
Ammonia↗
Relation among stenosis severity, myocardial blood flow, and flow reserve in patients with coronary artery disease.
BACKGROUND: Coronary arteriography is considered the "gold standard" for evaluating the severity of a coronary stenosis. Because the resistance to blood flow through a stenotic lesion depends on a number of lesion characteristics, the physiological significance of coronary lesions of intermediate severity is often difficult to determine from angiography alone. This study of patients with coronary artery disease seeks to determine the relation between myocardial blood flow and flow reserve measured by positron emission tomography (PET) and the percent area stenosis on quantitative coronary arteriography. METHODS AND RESULTS: We studied 28 subjects: 18 patients with coronary artery disease (66 +/- 8 years) and 10 age-matched healthy volunteers (64 +/- 13 years) with dynamic N-13 ammonia PET imaging at rest and after dipyridamole (0.56 mg/kg). The percent cross-sectional area stenosis was quantified on the coronary arteriograms as described by Brown et al. In the 18 patients, a total of 41 non-infarct-related coronary vessels were analyzed. Myocardial blood flows in normal regions of patients with coronary artery disease were not different than those in healthy volunteers, both at rest and after dipyridamole. As a result, the myocardial flow reserve was also similar in both groups (2.4 +/- 0.4 versus 2.6 +/- 0.7, respectively; P = NS). Quantitative PET estimates of hyperemic blood flow (r = .81, P < .00001), flow reserve (r = .78, P < .00001), and an index of the "minimal coronary resistance" (r = .78, P < .00001) were inversely and nonlinearly correlated with the percent area stenosis on angiography. Of note, PET estimates of myocardial flow reserve successfully differentiated coronary lesions of intermediate severity (50% to 70% and 70% to 90%; 2.4 +/- 0.4 versus 1.8 +/- 0.5, respectively; P = .04). CONCLUSIONS: In patients with coronary artery disease, non-invasive measurements of myocardial blood flow and flow reserve by PET are inversely and nonlinearly related to stenosis severity as defined by quantitative angiography. Importantly, coronary lesions of intermediate severity have a differential flow reserve that decreases as stenosis increases that can be detected noninvasively by PET, thus allowing better definition of the functional importance of known coronary stenosis.
Aged↗
Different roads to the assessment of myocardial viability. Lessons from PET for SPECT.
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Humans↗
Guidelines for training in adult cardiovascular medicine. Core Cardiology Training Symposium (COCATS). Task Force 5: training in nuclear cardiology.
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Adult↗
Correction of spillover radioactivities for estimation of the blood time-activity curve from the imaged LV chamber in cardiac dynamic FDG PET studies.
In dynamic cardiac PET FDG studies for measurement of myocardial metabolic rate of glucose (MMRGlc), the plasma FDG time-activity curve (input function) is commonly obtained from the left ventricular (LV) region on the PET images. The input function is contaminated by spillover of radioactivity from the surrounding myocardium and this could cause significant error in the estimated MMRGlc. In this study, we determined the effect of myocardial to blood pool spillover on MMRGlc and developed a method to correct for this spillover of activity. The method is based on a reformulation of the FDG model equation in terms of the spillover contaminated input function that includes both the myocardium to blood pool and blood pool to myocardium spillover fractions as variable parameters (Fmb and Fbm). The reformulated model equation can be used to fit the global myocardial tissue activity curve to estimate Fmb and thus yields a spillover corrected input function. The MMRGlc estimate with the corrected input function was within 95% of the true value (compared to 85% using the uncorrected input function) in a set of computer simulation studies. Dynamic PET FDG data were obtained in eight human studies and blood samples were obtained during the study. As compared to the results with the uncorrected input function, the estimates of k4 by the new method were reduced by 69% into a range consistent with in vitro results. The method is effective in correcting Fmb spillover and leads to more accurate estimates of MMRGlc. The method also allows larger regions of interest (up to 150 mm2) to be drawn over the LV in dynamic PET images, thereby reducing the noise level in the input function.
Computer Simulation↗
Noninvasive assessment of myocardial perfusion and metabolism: feasibility of registering gated MR and PET images.
OBJECTIVE: Positron emission tomography (PET), the reference technique for in vivo noninvasive assessment of myocardial perfusion and metabolism, is hampered by limited resolution and low signal-to-noise ratio. Cardiac MR imaging, on the other hand, provides excellent soft-tissue contrast. This study examines the feasibility of combining the information of these two complementary techniques by the three-dimensional superimposition of regional myocardial blood flow or substrate metabolism as depicted in cardiac PET images on comparable MR images at the same cardiac phase and spatial location. SUBJECTS AND METHODS: Three-dimensional, gated PET and MR images of the heart were acquired at different phases of the cardiac cycle from six normal volunteers and from one patient with coronary artery disease that had been detected by coronary angiography. An interactive algorithm using morphologic operators was developed to contour the left ventricle on the MR and PET images. A three-dimensional surface-fitting technique was used to register the left ventricle surfaces. The accuracy of registration was estimated using 80 internal landmarks from six volunteer scans. RESULTS: These techniques yielded PET images resliced along the same spatial location and orientation as the MR images both in the transaxial and short-axis views. The average residual, a measure of the goodness of fit, was 26 (+/- 5.6) for the systolic and 13 (+/- 6.1) for the diastolic images compared with an increase of that index from 9.3 at the best fit to 13.2 when the images were deliberately misaligned by 2 mm in each of two directions. We verified that MR and PET images could be aligned with an accuracy of 1.95 mm (+/- 1.6), which was approximately equal to the larger of the two pixel sizes (i.e., 1.6 mm on PET images). CONCLUSION: MR and PET images of the heart at identical cardiac phases can be accurately superimposed. Both transaxial and short-axis views can be obtained, the latter being more useful for PET quantification. This technique offers the potential for characterizing regional interactions among contractile function, blood flow, and substrate metabolism, especially when these are altered regionally in cardiac diseases.
Algorithms↗
Effect of caffeine on myocardial blood flow at rest and during pharmacological vasodilation.
UNLABELLED: Stress testing with intravenous injection of dipyridamole is frequently used for noninvasive detection of coronary artery disease (CAD) with PET or SPECT. Dietary intake of caffeinated food, beverages or medication might alter both resting and dipyridamole-induced hyperemic blood flow, thereby compromising the diagnostic sensitivity of dipyridamole stress testing. METHODS: To quantify the effect on myocardial blood flow at rest and during intravenous injection of dipyridamole, 12 healthy volunteers (mean age 27 +/- 6 yr) with low risk for CAD were studied with dynamic PET and a tracer kinetic model for 13N-ammonia after 24 hr of caffeine abstinence and after caffeine intake. RESULTS: Caffeine tended to increase the rate pressure product from 6873 +/- 1494 to 7566 +/- 1102 (p = 0.051), whereas resting myocardial blood flow remained unchanged (0.61 +/- 0.13 versus 0.58 +/- 0.07 ml/g/min, p = ns). The heart rate response to dipyridamole was inversely related to serum caffeine levels. Hyperemic blood flow (2.01 +/- 0.46 versus 1.31 +/- 0.0.38 ml/g/min; p < 0.001) and flow reserve (3.4 +/- 0.8 versus 2.3 +/- 0.7; p < 0.001) were inversely related to the caffeine dose. Coronary vascular resistance at rest tended to increase (132 +/- 32 versus 147 +/- 25 mmHg/ml/g/min; p = 0.06), whereas minimal coronary vascular resistance was significantly higher after caffeine (41 +/- 9 to 69 +/- 25 mmHg/ml/g/min; p < 0.01). CONCLUSION: Caffeine intake alters the coronary vasomotor tone at rest, which might lower the threshold for ischemic events in patients with CAD. It reduces hyperemic blood flow and flow reserve and the dipyridamole-induced increase in heart rate in a dose-dependent fashion. These findings emphasize the importance of carefully screening patients for intake of caffeinated food, beverages or medication prior to dipyridamole stress testing.
Adult↗
Quantification of myocardial blood flow using dynamic nitrogen-13-ammonia PET studies and factor analysis of dynamic structures.
UNLABELLED: In this study, factor analysis of dynamic structures (FADS) was used to extract the "pure" blood-pool time-activity curves (TACs) and to generate parametric myocardial blood flow (MBF) images (pixel unit: ml/min/g). METHODS: Ten dynamic 13N-ammonia dog PET studies (three baseline, five hyperemia and two occlusion) were included. Three factors (TACs) and their corresponding factor images (the right ventricular and left ventricular blood pools and myocardial activities) were extracted from each study. The left ventricular factors matched well with the plasma TACs. The factor images of myocardium were then converted to a parametric images of MBF using a relationship derived from a two-compartment model. RESULTS: MBF estimates obtained from FADS correlated well with MBF estimates obtained with the two-compartment model (r = 0.98, slope = 0.84) and microsphere techniques (r = 0.96, slope = 0.94). FADS-generated MBF parametric images have better image quality and lower noise levels compared to those generated with Patlak graphical analysis. CONCLUSION: Regional MBF can be measured accurately and noninvasively with 13N-ammonia dynamic PET imaging and FADS. The method is simple, accurate and produces parametric images of MBF without requiring blood sampling and spillover correction.
Ammonia↗
Factor analysis for extraction of blood time-activity curves in dynamic FDG-PET studies.
UNLABELLED: Arterial sampling in dynamic PET studies can be eliminated by using left ventricular or aortic time-activity curves (TAC) obtained from user drawn regions of interest (ROIs) after appropriate spillover correction. In this study, we evaluated the feasibility of extracting the "pure" arterial TAC from dynamic PET images using factor analysis of dynamic structures (FADS). METHODS: Computer simulations were used to study the performance of the FADS algorithm with positivity constraints. Ten canine 13N-ammonia and two human FDG-PET dynamic studies were used to extract the blood TACs from FADS. Plasma samples and compartmental model fittings were used to validate the accuracy of the FADS-generated blood factors. RESULTS: We found that FADS with positivity constraints was sufficient to extract the blood factor from the composite dynamic images. The "pure" blood-pool TACs that matched well with the arterialized well counter measurements were generated from FADS in the canine and human studies. CONCLUSION: FADS has the potential to accurately extract "pure" blood TAC from dynamic PET images, allowing reliable quantitation of biological information from PET studies without blood sampling, ROI drawing or spillover correction.
Algorithms↗
Effects of modified pharmacologic stress approaches on hyperemic myocardial blood flow.
UNLABELLED: Pharmacologic stress testing with 0.56 mg/kg of intravenous dipyridamole is frequently used to noninvasively detect coronary artery disease (CAD). However, high-dose dipyridamole (0.80 mg/kg) or the combination of standard-dose dipyridamole (0.56 mg/kg) with the isometric handgrip maneuver might evoke a greater coronary hyperemic response. METHODS: To evaluate the effect of modified pharmacologic stress tests, myocardial blood flow as quantified in 11 male subjects (mean age: 27 +/- 7 yr) during standard-dose dipyridamole (0.56 mg/kg), high-dose dipyridamole (0.80 mg/kg) and standard-dose dipyridamole combined with the isometric handgrip exercise using dynamic PET and a two-compartment model for 13N-ammonia. RESULTS: Systolic blood pressure, heart rate and rate pressure product remained unchanged from standard to high-dose dipyridamole but increased with the addition of the isometric handgrip. Myocardial blood flow was unchanged from standard to high-dose dipyridamole but was lower with the addition of the isometric handgrip. CONCLUSION: The hyperemic response induced by standard-dose dipyridamole cannot be further enhanced by high-dose dipyridamole. The addition of the isometric handgrip exercise results in a modest, but significant decline in hyperemic blood flow possibly due to increased extravascular resistive forces or an increase in a mediated coronary vasoconstriction associated with exercise.
Adult↗
Parameter estimation of cardiac geometry by ECG-gated PET imaging: validation using magnetic resonance imaging and echocardiography.
UNLABELLED: The purpose of this study was to apply and validate a previously developed model-based image analysis technique which derives estimates of regional myocardial wall thickness and the left ventricular radius directly from gated cardiac PET images. METHODS: In 11 normal volunteers, gated myocardial 18F-deoxyglucose (FDG) images with 16 equal gates spanning the entire cardiac cycle were acquired for 20 min. To improve count statistics and thus image quality, 3 and 5 of 16 gates were summed to obtain systolic and diastolic images. Based on a five-parameter model, radial profiles from systolic and diastolic PET images were fit by nonlinear regression for myocardial wall thickness, left ventricular radius and tracer activities in the blood pool, the myocardial tissue and the extracardiac background. Echocardiography and gated magnetic resonance imaging (MRI) were performed in 11 and 7 volunteers, respectively. RESULTS: We observed a significant (p < 0.001) correlation between measurements obtained by gated PET imaging and the correlative imaging modalities for myocardial wall thickness and left ventricular radius. While good agreement was observed between measurements of average radial shortening, estimates of average wall thickening differed significantly. CONCLUSION: This model-based analysis offers accurate estimates of regional recovery coefficients directly from gated cardiac PET images and may also prove useful for the assessment of myocardial contractile function. These recovery coefficients are essential for the correction of partial volume effects when quantitative PET studies are performed.
Deoxyglucose↗
Cardiac PET: microcirculation and substrate transport in normal and diseased human myocardium.
The development and validation of quantitative assay techniques for the noninvasive study of human myocardium has opened up new avenues for the study of the normal and diseased human heart's physiology. Measurements of regional myocardial blood flow, which delineates nutrient rather than coronary blood flow, has enabled the exploration of the coronary microcirculatory physiology under normal and abnormal conditions. It permits the study of pharmacologic effects and of cardiovascular disease on the coronary resistance and capillary perfusion. If combined with metabolic assay techniques, the transcapillary exchange of substrates in oxygen can be quantified and changes imposed by physiologic interventions and substrate metabolism being measured. These study approaches further serve to characterize changes in response to reductions in coronary blood flow as well as altered states of potentially reversible contractile function. It is anticipated that further studies with PET will clarify at the microcirculatory level the changes associated with ischemia, post-ischemic stunning and myocardial hibernation. Further, it offers the possibility to measure potentially beneficial effects of therapeutic interventions or, alternatively, to provide a rationale for novel therapeutic approaches.
Coronary Circulation↗
Effect of exercise supplementation during adenosine infusion on hyperemic blood flow and flow reserve.
Physical stress might modulate myocardial blood flow in near-maximally dilated coronary arteries by increasing coronary perfusion pressure, myocardial contractility, and heart rate. The net effect of these changes on hyperemic blood flows has not yet been defined in humans. To quantify the effect of physical exercise on pharmacologically induced hyperemia, myocardial blood flow was measured in 11 healthy volunteers. Measurements were performed with positron emission tomographic imaging with nitrogen-13 ammonia at rest, during intravenous (i.v.) adenosine administration (140 micrograms.kg-1.min-1 over 6 minutes), and during i.v. adenosine administration plus supine bicycle exercise with a maximal workload of 125 W. Myocardial blood flow was quantified by using a previously validated graphic analysis. Heart rate, systolic blood pressure, rate-pressure product, and mean aortic blood pressures were significantly higher during combined physical and pharmacologic stress than during pharmacologic stress alone. However, myocardial blood flow decreased from 2.6 +/- 0.4 to 2.2 +/- 0.4 ml.min-1.gm-1 with the addition of physical stress (p < 0.05). This decline was associated with a significant increase in coronary vascular resistance (35 +/- 6 vs 52 +/- 13 mm Hg.ml-1.gm.min; p < 0.05). Accordingly, myocardial flow reserve declined, from 5.0 +/- 0.9 to 4.3 +/- 1.0, with exercise supplementation (p < 0.05). Exercise in addition to pharmacologic stress increases coronary vascular resistance and thus significantly decreases hyperemic myocardial blood flow and flow reserve. This decrease results most likely from an increase in extravascular restrictive forces caused by higher ventricular pressures and contractility during physical stress.
Adenosine↗
Responses of blood flow, oxygen consumption, and contractile function to inotropic stimulation in stunned canine myocardium.
To examine the effects of inotropic stimulation on regional myocardial blood flow (MBF), oxidative metabolism, and contractile function in stunned myocardium, nine closed-chest dogs were studied 2 hours postreperfusion after a 25 minute occlusion of the left anterior descending coronary artery (LAD). MBF was determined with microspheres, and regional myocardial oxygen consumption (MVO2) was estimated from the rate constant k1 of the rapid clearance phase of [1-11C] acetate time activity curves, recorded with dynamic positron emission tomography. Myocardium at risk was determined from [13N] ammonia images obtained during occlusion. Wall motion, assessed by two-dimensional echocardiography, was impaired in postischemic myocardium in all dogs 2 hours after reperfusion. Dobutamine infusion increased the rate pressure product by 70% +/- 31% and significantly improved contractile function in the postischemic region in all dogs. In remote myocardium, MVO2 increased from 5.7 +/- 1.2 to 8.6 +/- 1.6 mumol/gm/min, and blood flow from 0.87 +/- 0.16 to 1.52 +/- 0.42 ml/gm/min in response to dobutamine. In reperfused myocardium, MVO2 increased from 3.1 +/- 0.7 to 7.4 +/- 1.5 mumol/gm/min, and blood flow from 0.51 +/- 0.12 to 1.2 +/- 0.4 ml/gm/min. Oxygen extraction increased significantly in reperfused myocardium relative to remote myocardium consistent with a flow-limited response to dobutamine stimulation. The improvement in contractile function failed to correlate significantly with relative increases in MBF or MVO2, suggesting that mechanical function is not as tightly coupled as MBF and MVO2 in postischemic myocardium during inotropic stimulation.
Analysis of Variance↗
Validation of a model for [1-11C]acetate as a tracer of cardiac oxidative metabolism.
To develop a compartmental model for estimating myocardial oxygen consumption rate (MVO2) with [1-11C]acetate, the metabolic fate of radiolabeled acetate was determined in normoxic and ischemic conditions in isolated perfused rat hearts. Glutamate composed 63 +/- 1 and 44 +/- 7% of the total tissue radioactivity 2 min postinjection in normoxic and ischemic myocardium, respectively, and radiolabeled glutamate remained the largest fraction throughout 40 min of perfusion. Based on the biochemical pathway of the tracer and the temporal distribution of 14C-labeled metabolites, a six-compartment model was formulated. Studies using [1-11C]acetate and a pair of NaI detectors were then performed in the same perfused heart system to validate the model. Consistency between the model predictions and biochemical measurements of tissue and effluent metabolites supported the validity of the kinetic model in normoxic and ischemic conditions. Model-estimated MVO2 correlated well with experimentally measured MVO2 for normoxic, hypoxic, and ischemic conditions, with a slope of 0.97 (r = 0.95). In addition, the model-estimated rate constant, k42, which corresponded to the oxidative flux, correlated strongly with the myocardial clearance rate (k1 or kmono) determined from the tissue kinetics. These findings provide a mechanistic basis for the use of k1 or kmono as an index of MVO2 in both normoxic and ischemic myocardium studied with [1-11C]acetate and positron emission tomography.
Acetates↗