Biomedical subjects

M E Phelps

Publications and source records attributed to M E Phelps.

At least 109 records · Page 6Linked to original sources

PubMed1996

Derivation of input function from FDG-PET studies in small hearts.

UNLABELLED: The extraction of pure arterial time-activity curves (TACs) from dynamic PET images of a small animal heart using factor analysis of dynamic structures (FADS) was found to be unsuccessful due to the small size of the cardiac chamber that causes extensive mixture of TACs of different structures. METHODS: In this study, we used digital phantoms of the left ventricle (LV cavity size: 1-2 cm) and small monkey (LV cavity size: approximately 2 cm) dynamic FDG PET studies to evaluate FADS for extracting the pure blood-pool TACs by adding a single blood sample (taken at a late scan time) constraint. RESULTS: In the digital phantom studies, spillover fractions in the extracted blood-pool TACs using FADS without a blood sample constraint (FADS(-)) and with a blood sample constraint (FADS(+)) were 3%-91% and < 3%, respectively. In the monkey studies (n = 4), FADS(+) extracted blood-pool TACs matched well with the arterialized well counter measurements (% differences of curve integration; FADS(-) < 82%; FADS(+) < 9%). The microparameters (K1*, k2*, k3*, k4*) and macroparameters (Knlr), obtained from the FADS(+) blood-pool TACs, were similar to those obtained from plasma samples in a three-compartment model fitting (% differences of Knlr:phantom studies < 5%; monkey studies < 9%). CONCLUSION: The FADS technique with a single-blood sample has the potential to extract the pure blood-pool TACs directly from dynamic PET images of a small animal without multiple blood sampling, region of interest definition or spillover correction.

Animals↗

PubMed1996

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.

Adult↗

PubMed1995

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↗

PubMed1995

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↗

PubMed1995

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↗

PubMed1995

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↗

PubMed1995

The assessment of the non-equilibrium effect in the 'Patlak analysis' of Fdopa PET studies.

'Patlak analysis' is a common approach used in Fdopa PET studies to calculate the uptake constant (Ki) of the tracer. It is assumed in the Patlak analysis that the reversible compartment of tissue radioactivity used is in effective equilibrium with the tracer in plasma. Therefore, using the data prior to equilibrium is in conflict with the assumption, and its effect on the estimate thus needs to be examined. In this study, we used simulations to investigate the errors due to the violation of the equilibrium assumption. Two factors affecting the estimate of Ki were examined--the eigenvalue of the model response function and the shape of the input function. The Ki estimate obtained from the Patlak analysis was found to be markedly biased because the system is not in equilibrium during the first 2 h post Fdopa injection. The magnitude of the bias was found to be dependent on the time interval used in the analysis (10% difference when comparing results from intervals 30-120 min and 60-120 min) and on the eigenvalue of the response function (10% change in Ki when the eigenvalue was changed by 20% around the nominal value). The estimates are also affected by the intersubject variations in the plasma time-activity curves. Therefore, Patlak analysis users should interpret their results with caution, particularly when examining small intersubject differences and small changes due to physiological or pharmacological interventions.

Blood-Brain Barrier↗

PubMed1995

Positron-emission tomography in tardive dyskinesia.

Cerebral glucose metabolic rates were determined in normal control subjects (n = 26) and schizophrenic patients with tardive dyskinesia (n = 14). Globus pallidus and primary motor cortex (precentral gyrus) metabolic values divided by those of the cerebral hemispheres were significantly increased in the patient group. A similar metabolic pattern has not been reported for schizophrenic patients without tardive dyskinesia, and the abnormalities were demonstrated despite the normal appearance of the basal ganglia on X-ray CT. The findings differed markedly from the reduced metabolic rates of the basal ganglia previously identified in other choreiform disorders, including Huntington's and Wilson's diseases. The findings suggest that tardive dyskinesia is characterized by increased pallidal synaptic activity resulting from either altered striatopallidal input or increased pallidal interneuron firing.

Adult↗

PubMed1995

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↗

PubMed1995

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↗

PubMed1995

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↗

PubMed1995

Quantitative PET imaging of bone marrow glucose metabolic response to hematopoietic cytokines.

UNLABELLED: To evaluate the effects of hematopoietic cytokines on bone marrow glucose metabolism noninvasively, we studied serial quantitative FDG-PET images in 18 patients with metastatic melanoma and normal bone marrow who were undergoing granulocyte-macrophage colony-stimulating factor (GMCSF) or macrophage colony-stimulating factor (MCSF) administration as an adjunct to chemotherapy. METHODS: All patients received 14 days of cytokine therapy in three groups: four patients were treated with GMCSF (5 micrograms/kg/d SQ), eight patients were treated with GMCSF (5 micrograms/kg/d SQ) and monoclonal antibody (MAbR24) and six patients were treated with MCSF (80 micrograms/kg/d IVCI) and MAbR24. Dynamic FDG-PET imaging was performed over the lower thoracic or upper lumbar spine at four time points in each patient. RESULTS: Baseline glucose metabolic rates in the bone marrow of these three groups of patients were similar (5.2 +/- 0.7, 4.4 +/- 0.8 and 4.8 +/- 1.2 micrograms/min/g as mean value and standard deviations, respectively). In both GMCSF and GMCSF + R24 groups, rapid increases in bone marrow glucose metabolic rates were observed during therapy. After GMCSF was stopped, bone marrow glucose metabolic rates rapidly decreased in both groups. The glucose metabolic response in these two groups was not significantly different by pooled t-statistics (p = 0.105). In the MCSF+R24 group, the increase of glucose metabolic rate on Days 3 and 10 was 35% and 31% above baseline on the average, but was not significant. CONCLUSION: The results support the use of parametric FDG-PET imaging for noninvasive quantitation of bone marrow glucose metabolic changes to hematopoietic cytokines in vivo.

Bone Marrow↗

PubMed1995

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↗

PubMed1994

Use of positron emission tomography with fluorodeoxyglucose in patients with extracranial head and neck cancers.

BACKGROUND: The purpose of this study was to evaluate the utility of positron emission tomography- (PET) 2-[18F]-fluoro-2-deoxy-D-glucose (FDG) imaging in extracranial head and neck cancers. METHODS: Sixty patients with biopsy-proven cancers were studied using PET-FDG. Thirty-four patients were studied before therapy (staging), of which 15 patients received primary radiotherapy and serial PET-FDG imaging (monitoring). Seven patients with advanced disease had laser excision (monitoring), and 19 patients were evaluated for recurrent disease (recurrence). RESULTS: Four patients had unknown primary lesions. PET-FDG imaging located the primary tumor in two of four patients, and magnetic resonance imaging (MRI) in none of four. In the remaining patients (staging), PET-FDG imaging detected the primary tumor in 29 of 30 patients, and MRI in 23 of 30. In the staging group, PET-FDG imaging identified the presence or absence of lymph node involvement in 32 of 34 patients, and MRI in 31 of 34. PET-FDG imaging was helpful in evaluating tumor response to radiation therapy or laser excision. Ten patients evaluated for recurrent disease had biopsy-confirmed recurrences, and 7 had no recurrence. PET-FDG imaging results were positive for primary tumor recurrence in 9 of 10 patients, and MRI results were positive in 6 of 10. MRI results were negative for lymph node disease in one of these patients with recurrent primary tumor where PET-FDG imaging and biopsy demonstrated nodal involvement. PET-FDG results were negative for recurrent disease in seven of seven patients, and MRI results were negative for recurrent disease in in four of seven. CONCLUSION: In this series, the authors found that PET-FDG is a useful diagnostic modality for evaluating the patient with an unknown primary, monitoring response to therapy, and in detecting recurrent tumors.

Adult↗

PubMed1994

Hippocampal neuronal loss and regional hypometabolism in temporal lobe epilepsy.

The pathophysiology of widespread interictal hypometabolism in temporal lobe epilepsy is unknown but might reflect neuronal loss and diaschisis. We found no significant correlation between any cortical region's metabolism on preoperative [18F]fluorodeoxyglucose positron emission tomography and neuronal density of resected hippocampi in 40 patients. We conclude that hippocampal neuronal loss and diaschisis cannot account for the regional interictal hypometabolism of temporal lobe epilepsy.

Epilepsy, Temporal Lobe↗

PubMed1994

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↗

PubMed1994

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↗

PubMed1994

Localization of motor areas adjacent to arteriovenous malformations. A positron emission tomographic study.

Motor cortex activity was localized with positron emission tomography (PET) in 4 patients with large arteriovenous malformations adjacent to or undercutting the left primary motor cortex. Relative cerebral blood flow responses were measured during execution of a visually guided motor tracking task performed with the right index finger, hand, great toe, tongue, or eyes alone (control) and mapped onto each patient's corresponding magnetic resonance imaging (MRI) scan. The relative cerebral blood flow responses in the contralateral precentral gyrus, adjacent to each arteriovenous malformation, demonstrated a normal somatotopic distribution, similar to that in a control population. In the 3 patients with preserved motor function, responses were also present in the ipsilateral primary motor cortex, bilateral supplementary motor area, and ipsilateral anterior cerebellum, similar in location to those of a control population. In the fourth patient with a hemiparesis, responses were attenuated in the primary motor cortex, increased in the supplementary motor area, and absent in the cerebellum. The results demonstrate that PET cerebral blood flow mapping can localize motor cortex despite the presence of significant blood flow abnormalities in adjacent arteriovenous malformations. The method, particularly when combined with MRI, may be used in the planning of surgical, radiation, or embolization therapy.

Adult↗