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Biomedical subjects

Robert J Gropler

Publications and source records attributed to Robert J Gropler.

At least 19 recordsLinked to original sources
PubMed2006

Increased myocardial fatty acid metabolism in patients with type 1 diabetes mellitus.

OBJECTIVES: The purpose of this study was to determine if myocardial fatty acid utilization (MFAU) and myocardial fatty acid oxidation (MFAO) are increased in diabetic patients. BACKGROUND: Experimental models of diabetes mellitus demonstrate that MFAU and MFAO are increased, and that this dependence on myocardial fatty acid metabolism may be detrimental to cardiac function. Whether similar metabolic changes occur in humans with diabetes mellitus is unclear. METHODS: Eleven healthy non-diabetic control patients (5 women, ages 25 +/- 5 years) and 11 otherwise healthy patients with type 1 diabetes mellitus (T1DM) (8 women, ages 36 +/- 10 years, HbA1c 8.4 +/- 1.9%) underwent positron emission tomography for the determination of myocardial blood flow (MBF); myocardial oxygen consumption (MVO2); myocardial glucose utilization (MGU); and MFAU, MFAO, and %MFAO. RESULTS: Plasma lactate, insulin, and MBF levels were similar between the two groups. However, plasma glucose (5.71 +/- 0.98 mumol/ml vs. 5.28 +/- 0.65 mumol/ml, p = 0.04), free fatty acid levels (0.60 +/- 0.24 mumol/ml vs. 0.19 +/- 0.07 mumol/ml, p < 0.0001), and MVO2 (6.64 +/- 2.21 vs. 4.51 +/- 1.39 mumol/g/min, p = 0.007) levels were higher in the T1DM subjects. Furthermore, compared with control patients, T1DM subjects exhibited higher MFAU (213 +/- 135 nmol/g/min vs. 57 +/- 28 nmol/g/min, p = 0.0004), MFAO (206 +/- 131 nmol/g/min s. 50 +/- 26 nmol/g/min, p = 0.0002), and %MFAO (94 +/- 6% vs. 81 +/- 19%, respectively, p = 0.04). In contrast, MGU was lower in T1DM subjects than in controls (207 +/- 108 nmol/g/min vs. 403 +/- 191 nmol/g/min, p = 0.0008). CONCLUSIONS: Humans with diabetes mellitus exhibit increased MFAU and MFAO and reduced MGU consistent with observations obtained in experimental models of diabetes.

Adult↗
PubMed2006

Alterations in left ventricular structure and function in type-1 diabetics: a focus on left atrial contribution to function.

This study was designed to determine the effects of type 1 diabetes mellitus (T1DM) on left ventricular (LV) and particularly left atrial (LA) structure and function. We evaluated 88 non-obese subjects: 44 with T1DM, 44 age- and gender-matched normal controls (age 39 +/- 11 years). LV and LA structure and function were quantified using two-dimensional echocardiography, pulse-wave Doppler, and tissue Doppler imaging, including early and late diastolic myocardial velocities (Em global and Am global, respectively). The T1DM subjects averaged higher heart rate, relative wall thickness, and ejection fraction, and lower indexed end-systolic volume than normal controls (P < .001, P < .05, P = .01, and P < .05, respectively). T1DM was related to A wave velocity, Am global, A wave integral, LA ejection fraction, and LA systolic ejection fraction (P < .01, P < .05, P < .0005, P < .001, and P < .0005, respectively). In multivariate analyses, T1DM was an independent predictor of the A wave integral, LA ejection fraction, and LA systolic ejection fraction (P < .01, P < .01, and P < .005, respectively). Thus, despite increased relative wall thickness, LV systolic function is increased and early diastolic filling is normal in T1DM subjects; however, they possess changes in LA transport function suggesting increased reliance on LA contribution to LV filling.

Adolescent↗
PubMed2006

Assessment of myocardial blood flow using 15O-water and 1-11C-acetate in rats with small-animal PET.

UNLABELLED: This feasibility study was undertaken to determine whether myocardial blood flow (MBF, mL/g/min) could be quantified noninvasively in small rodents using microPET and 15O-water or 1-11C-acetate. METHODS: MBF was measured in 18 healthy rats using PET and 15O-water (MBF-W) under different interventions and compared with direct measurements obtained with microspheres (MBF-M). Subsequently, MBF was estimated in 24 rats at rest using 1-11C-acetate (MBF-Ace) and compared with measurements obtained with 15O-water. Using factor analysis, images were processed to obtain 1 blood and 1 myocardial time-activity curve per tracer per study. MBF-W was calculated using a well-validated 1-compartment kinetic model. MBF-Ace was estimated using a simple 1-compartment model to estimate net tracer uptake, K1 (K1 (mL/g/min) = MBF.E; E = first-pass myocardial extraction of 1-11C-acetate) and washout (k2 (min(-1))) along with F(BM) (spillover correction) after fixing F(MM) (partial-volume correction) to values obtained from 15O-water modeling. K1 values were converted to MBF values using a first-pass myocardial extraction/flow relationship measured in rats (E = 1.0-0.74.exp(-1.13/MBF)). RESULTS: In the first study, MBF-W correlated well with MBF-M (y = 0.74x + 0.96; n = 18, r = 0.91, P < 0.0001). However, the slope was different than unity, P < 0.05). Refitting of the data after forcing the intercept to be zero resulted in a nonbias correlation between MBF-W and MBF-M (y = 0.95x + 0.0; n = 18, r = 0.86, P < 0.0001) demonstrating that the underestimation of the slope could be attributed to the overestimation of MBF-W for 2 MBF-M values lower than 1.50 mL/g/min. In the second study, MBF-Ace values correlated well with MBF-W with no underestimation of MBF (y = 0.91x + 0.35; n = 24, r = 0.87, P < 0.0001). CONCLUSION: MBF can be quantified by PET using (15)O-water or 1-11C-acetate in healthy rats. Future studies are needed to determine the accuracy of the methods in low-flow states and to develop an approach for a partial-volume correction when 1-11C-acetate is used.

Acetates↗
PubMed2006

Assessment of myocardial metabolism in diabetic rats using small-animal PET: a feasibility study.

UNLABELLED: This feasibility study was undertaken to determine whether kinetic modeling in conjunction with small-animal PET could noninvasively quantify alterations in myocardial perfusion and substrate metabolism in rats. METHODS: All small-animal PET was performed on either of 2 tomographs. Myocardial blood flow and substrate metabolism were measured in 10 male Zucker diabetic fatty rats (ZDF, fa/fa) and 10 lean littermates (Lean, Fa/+) using (15)O-water, 1-(11)C-glucose, 1-(11)C-acetate, and 1-(11)C-palmitate. Animals were 12.0 +/- 1.4-wk old. RESULTS: Consistent with a type 2 diabetic phenotype, the ZDF animals showed higher plasma hemoglobin A(1c), insulin, glucose, and free fatty acid (FFA) levels than their lean controls. Myocardial glucose uptake (mL/g/min) was not significantly different between the 2 groups. However, higher glucose plasma levels in the ZDF rats resulted in higher myocardial glucose utilization (nmol/g/min) (Lean, 629 +/- 785, vs. ZDF, 1,737 +/- 1,406; P = 0.06). Similarly, myocardial FFA uptake (mL/g/min) was not significantly different between the 2 groups, (Lean, 0.51 +/- 28, vs. ZDF, 0.72 +/- 0.19; P = not significant) However, due to higher FFA plasma levels, utilization and oxidation (nmol/g/min) were significantly higher in the ZDF group (Lean, 519 +/- 462, vs. ZDF, 1,623 +/- 712, P < .001; and Lean, 453 +/- 478, vs. ZDF, 1,636 +/- 730, P < .01). CONCLUSION: Noninvasive measurements of myocardial substrate metabolism in ZDF rats using small-animal PET are consistent with the expected early metabolic abnormalities that occur in this well-characterized model of type 2 diabetes mellitus. Thus, small-animal PET demonstrates significant promise in providing a means to link the myocardial metabolic abnormalities that occur in rat of disease with the human condition.

Acetic Acid↗
PubMed2005

The effects of plasma insulin and glucose on myocardial blood flow in patients with type 1 diabetes mellitus.

OBJECTIVES: The objective of this study was to determine the impact of insulin and glucose on myocardial vasodilator function in patients with type 1 diabetes mellitus (T1DM). BACKGROUND: The relative importance of plasma insulin and glucose levels on the abnormal vasodilator function observed in T1DM is unknown. METHODS: Twenty T1DM patients underwent positron emission tomography studies to measure myocardial blood flow (MBF) (in ml/g/min) at rest (MBFr) and during adenosine (MBFa), both under baseline metabolic conditions and then during either hyperinsulinemic-euglycemic clamp (HE) (n = 10; 40 +/- 9 years, 8 female subjects, hemoglobin A1c [HbA1c] 7.8 +/- 1.1%) or hyperinsulinemic-hyperglycemic clamp (HH) (n = 10; 44 +/- 12 years, 8 female subjects, hemoglobin A1c 7.7 +/- 0.6%). RESULTS: Both groups showed similar MBFr and MBFa under baseline metabolic conditions (p = NS). Compared with baseline conditions, MBFr increased in the HH group (p < 0.005), whereas it did not change in the HE group. Compared with baseline conditions, MBFa decreased in the HH group (p < 0.05) but did not change in the HE group. Myocardial perfusion reserve (MPR) (MBFa/MBFr) was similar between the HE and HH groups at baseline (p = NS). During clamp, MPR tended to decrease in the HH group (p < 0.1) but did not change in the HE group (p = NS) when compared with baseline conditions. However, during the clamp MPR was significantly lower in the HH group when compared with the HE group (p < 0.0001). CONCLUSIONS: In the short term, hyperglycemia has a deleterious effect on myocardial vasodilator function, which outweighs the beneficial effect of hyperinsulinemia.

Adult↗
PubMed2005

Accurate myocardial T1 measurements: toward quantification of myocardial blood flow with arterial spin labeling.

In this study, we investigated a method for accurately measuring myocardial T(1) for the quantification of myocardial blood flow (MBF) with arterial spin labeling (ASL). A single-shot gradient-echo (GE)-based ASL sequence with an adiabatic hyperbolic secant inversion recovery pulse was modified to acquire a pair of myocardial T(1)'s within a breath-hold. A multivariable regression algorithm that accounted for the magnetization saturation effects was developed to calculate T(1). The MBF was then determined with a well-developed model. The accuracy of our T(1) calculation was first evaluated in a phantom, and then in six dogs for the MBF calculation, with (N = 4) and without (N = 2) coronary artery stenosis. In the phantom study, the accuracy of T(1) measured with a slice-selective inversion prepared pulse was within 2.5% of error. In healthy dogs, the MBF increased 2-5 times during vasodilation. In contrast, regional differences of MBF were well visualized in the stenotic dogs during vasodilation (perfusion reserve of 2.75 +/- 0.83 in normal myocardium, and 1.46 +/- 0.75 in the stenotic area). A correlation analysis revealed a close agreement in MBF between the ASL and microsphere (MS) in both healthy and stenotic dogs. In summary, the modified ASL technique and T(1) regression algorithm proposed here provide an accurate measurement of myocardial T(1) and demonstrate potential for reliably assessing MBF at steady state.

Algorithms↗
PubMed2005

Techniques necessary for multiple tracer quantitative small-animal imaging studies.

INTRODUCTION: An increasing number and variety of studies on rodent models are being conducted using small-animal positron emission tomography scanners. We aimed to determine if animal handling techniques could be developed to perform routine animal imaging in a timely and efficient manner and with minimal effect on animal physiology. These techniques need to be reproducible in the same animal while maintaining hemodynamic and physiological stability. METHODS: The necessary techniques include (a) the use of inhalant anesthesia, (b) arterial and venous cannulation for multiple tracer administrations and blood sampling, (c) development of small-volume analytic columns and techniques and (d) measurement of the physiological environment during the imaging session. RESULTS: We provide an example of a cardiac imaging study using four radiotracers (15O-water, 1-[11C]-acetate, 1-[11C]-palmitate and 1-[11C]-glucose) injected into normal rats. Plasma substrates, CO2 production and total metabolites were measured. The animals remained anesthetized over the entire imaging session, and their physiological state was maintained. CONCLUSION: The intrastudy stability of the physiological measurements and substrate levels and interstudy reproducibility of the measurements are reported.

Animals↗
PubMed2005

Single-session magnetic resonance coronary angiography and myocardial perfusion imaging using the new blood pool compound B-22956 (gadocoletic acid): initial experience in a porcine model of coronary artery disease.

OBJECTIVE: The objective of this study was to evaluate a new blood pool contrast agent, B-22956, for detecting myocardial perfusion abnormality and coronary artery stenosis by magnetic resonance imaging (MRI) in 1 setting. MATERIALS AND METHODS: Coronary artery atherosclerotic stenoses were created in 6 miniswine. Myocardial first-pass perfusion imaging was performed with a bolus injection of 0.015 mmol/kg B-22956 during pharmacologic stress followed by postcontrast coronary artery imaging after another injection of B-22956/1. The total doses for the 6 pigs were 0.1 mmol/kg (n=3) and 0.15 mmol/kg (n=3). Perfusion upslope maps were analyzed and MR coronary artery images were reviewed by 2 readers. RESULTS: For all 6 pigs, the normalized upslopes of the perfusion curves were 0.83+/-0.12, 0.74+/-0.15, and 0.52+/-0.05 (P<0.01 vs. normal) with normal or mild (<50% area stenosis), moderate (<50% and <75%), and severe stenosis (>75%), respectively. Mean signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) in right coronary artery images improved 90% and 200%, respectively, with a total dose of 0.1 mmol/kg of B-22956. Excellent agreements (kappa=0.82) were achieved for evaluating the grade of stenosis between MR postcontrast coronary artery images and histopathology by 2 reviewers. CONCLUSION: The MR blood pool contrast agent B-22956 demonstrated the ability for detecting myocardial perfusion abnormalities and coronary artery stenosis in 1 setting.

Animals↗
PubMed2004

Effect of obesity and insulin resistance on myocardial substrate metabolism and efficiency in young women.

BACKGROUND: Obesity is a risk factor for impaired cardiac performance, particularly in women. Animal studies suggest that alterations in myocardial fatty acid metabolism and efficiency in obesity can cause decreased cardiac performance. In the present study, we tested the hypothesis that myocardial fatty acid metabolism and efficiency are abnormal in obese women. METHODS AND RESULTS: We studied 31 young women (body mass index [BMI] 19 to 52 kg/m2); 19 were obese (BMI >30 kg/m2). Myocardial oxygen consumption (MVO2) and fatty acid uptake (MFAUp), utilization (MFAU), and oxidation (MFAO) were quantified by positron emission tomography. Cardiac work was measured by echocardiography, and efficiency was calculated as work/MVO2. BMI correlated with MVO2 (r=0.58, P=0.0006), MFAUp (r=0.42, P<0.05), and efficiency (r=-0.40, P<0.05). Insulin resistance, quantified by the glucose area under the curve (AUC) during an oral glucose tolerance test, correlated with MFAUp (r=0.55, P<0.005), MFAU (r=0.62, P<0.001), and MFAO (r=0.58, P<0.005). A multivariate, stepwise regression analysis showed that BMI was the only independent predictor of MVO2 and efficiency (P=0.0005 and P<0.05, respectively). Glucose AUC was the only independent predictor of MFAUp, MFAU, and MFAO (P<0.05, <0.005, and <0.005, respectively). CONCLUSIONS: In young women, obesity is a significant predictor of increased MVO2 and decreased efficiency, and insulin resistance is a robust predictor of MFAUp, MFAU, and MFAO. This increase in fatty acid metabolism and decrease in efficiency is concordant with observations made in experimental models of obesity. These metabolic changes may play a role in the pathogenesis of decreased cardiac performance in obese women.

Adult↗
PubMed2004

Alterations in left ventricular structure and function in young healthy obese women: assessment by echocardiography and tissue Doppler imaging.

OBJECTIVES: This study was designed to determine the effects of obesity on left ventricular (LV) structure and function in young obese women. BACKGROUND: Severe prolonged obesity in older adults results in increased plasma volume, eccentric LV hypertrophy, and systolic and diastolic dysfunction. Obese women are at increased risk for the development of heart failure. However, the effects of the obesity on cardiac structure and function in young, otherwise-healthy women are controversial. METHODS: Fifty-one women were evaluated: 20 were obese (body mass index [BMI] > or =30 kg/m(2)) and 31 were non-obese (BMI <30 kg/m(2)). Left ventricular structure and systolic and diastolic function were assessed by two-dimensional echocardiography and tissue Doppler imaging, including the load-independent systolic myocardial velocity (Sm global) and early diastolic myocardial velocity (Em global), respectively. The effects of BMI on LV structure and function were assessed using multivariate regression analyses. RESULTS: Obese women had higher end-diastolic septal and posterior wall thickness, LV mass, and relative wall thickness than non-obese women; BMI values showed significant correlations with these variables (r = 0.58, p < 0.0001; r = 0.50, p < 0.0002; r = 0.52, p < 0.0001, and r = 0.40, p < 0.005, respectively). The Sm global and Em global were lower in obese women, suggesting systolic and diastolic function are decreased; both were negatively correlated with BMI (r = -0.43, p <. 002 and r = -0.61, p < 0.0001, respectively). Multivariate analysis showed BMI was the only independent predictor of relative wall thickness, Sm global, and Em global. CONCLUSIONS: Obesity in young otherwise-healthy women is associated with concentric LV remodeling and decreased systolic and diastolic function. These early abnormalities in LV structure and function may have important implications for explaining the myocardial dysfunction that is associated with increased cardiovascular morbidity and mortality caused by obesity.

Adult↗
PubMed2004

Relationship of apparent myocardial T2 and oxygenation: towards quantification of myocardial oxygen extraction fraction.

PURPOSE: To explore the relationship of myocardial T(2) and oxygenation for the quantification of myocardial oxygen extraction fraction (OEF). MATERIALS AND METHODS: A proposed myocardial T(2)-OEF relationship was evaluated by computer simulation and in nine normal dogs in vivo. The relationship was based on a simplified two-compartment T(2) model. In the dogs, dipyridamole was infused intravenously to increase blood flow and change in myocardial oxygen content. The accuracy of the measurement in myocardial OEF in vivo by magnetic resonance imaging (MRI) was determined by arterial and coronary sinus blood sampling. RESULTS: Global myocardial T(2) increased 16.1% from rest to the peak of dipyridamole-induced vasodilation (44.6 +/- 2.1 msec vs. 51.4 +/- 2.1 msec, P < 0.001). Corresponding OEF measured by arterial and venous (AV) sampling decreased from 0.64 +/- 0.15 at rest to 0.18 +/- 0.08 during the dipyridamole vasodilation, whereas OEF calculated by MRI at the peak effect of dipyridamole was 20 +/- 4%. Global myocardial OEF measured dynamically by MRI showed a strong correlation with OEF measured by blood sampling (correlation coefficient (CC) = 0.83) during pharmacologic vasodilation. CONCLUSION: When combined with vasodilator stress, assessment of OEF may provide a putative measure of myocardial flow reserve, allowing consecutive monitoring of myocardial dose-responses to a variety of interventions and offering a new tool for the detection of coronary artery disease.

Animals↗
PubMed2004

Dynamic estimation of the myocardial oxygen extraction ratio during dipyridamole stress by MRI: a preliminary study in canines.

The myocardial oxygen extraction fraction (OEF) reflects the balance between myocardial oxygen supply and demand. The feasibility of quantifying myocardial OEF was demonstrated with MRI during pharmacologic vasodilation in dogs. Dipyridamole was infused intravenously to increase blood flow and change in myocardial oxygen content. Arterial and coronary sinus blood sampling was performed during dipyridamole-induced vasodilation to measure the myocardial blood oxygen content. Myocardial T(2) was measured dynamically during the vasodilation, and quantified with a simplified diffusion model as a function of myocardial OEF and blood volume. The results showed a strong correlation (R(2) = 0.89) between myocardial OEF values measured by MRI and those measured by blood sampling. Regional differences in the OEF were demonstrated by direct infusion of dipyridamole into coronary arteries in dogs. Combined with vasodilator stress, dynamic assessments of the OEF may provide a putative measurement of myocardial flow reserve and allow consecutive monitoring of myocardial dose and response.

Animals↗
PubMed2004

Recent advances in cardiac positron emission tomography in the clinical management of the cardiac patient.

Despite being primarily a research tool, positron emission tomography (PET) has seen slow but steady growth in the clinical management of the cardiac patient. The two major clinical applications of cardiac PET are regional myocardial perfusion imaging to determine the presence and severity of coronary artery disease and metabolic imaging to differentiate viable from nonviable myocardium in patients with ischemic left ventricular dysfunction. Indeed, PET with either nitrogen 13 ammonia or rubidium 82 may offer advantages over current single photon emission computed tomography approaches to assess myocardial perfusion. PET with fluorine 18 fluorodeoxyglucose is considered the current gold standard for identifying viable myocardium. Finally, the use of PET to quantify myocardial perfusion, metabolism, and innervation has led to key insights into the role of altered microvascular function, substrate metabolism, and neuronal function in a variety of cardiac disease processes.

Coronary Artery Disease↗
PubMed2004

Noninvasive, quantitative assessment of left ventricular function in ischemic cardiomyopathy.

BACKGROUND: Coronary artery disease characteristically impacts left ventricular (LV) function on a regional basis, although ultimately global function may be affected as well. Echocardiography is commonly clinically used for the assessment of regional function; however, it is only semiquantitative and in its current iteration is only two-dimensional in nature. Magnetic resonance imaging (MRI) with tissue tagging offers the possibility for noninvasive, three-dimensional (3D) assessment of transmural and segmental left ventricular strain and, thereby, function. Accordingly, we have explored methodologies to accurately and quantitatively characterize regional systolic function in three dimensions in patients with ischemic heart disease using MRI. MATERIALS AND METHODS: MRI radiofrequency tissue tagging was performed at rest and during dobutamine administration (10 mg/kg/min) on 10 normal volunteers (age: 26 +/- 6) and 8 patients with severe ischemic cardiomyopathy (age: 60 +/- 5, EF 26 +/- 11%). Three-dimensional global and regional systolic strain calculations were made based on 3D myocardial point displacements and compared with conventional measures. RESULTS: Global left ventricular strains were significantly decreased in ischemic patients at rest (0.14 +/- 0.04 versus 0.25 +/- 0.02, P < 0.001) and with dobutamine (0.14 +/- 0.03 versus 0.29 +/- 0.03, P < 0.001). In the regional analysis (216 LV wall segments) this methodology accurately differentiated normal from abnormally contracting regions. CONCLUSIONS: Noninvasive dobutamine MRI tissue tagging with calculation of 3D regional strains has significant promise as a clinical tool which is capable of the identification, quantification, and display of regionally varying ventricular function.

Aged↗
PubMed2004

Impact of reversible trapping of tracer and the presence of blood metabolites on measurements of myocardial glucose utilization performed by PET and 18F-fluorodeoxyglucose using the Patlak method.

In this study we demonstrated that significant egress of FDG from myocardium occurs within the first hour after tracer injection leading to nonlinear Patlak plots. There are also significant amounts of acidic FDG metabolites present in the blood. However, the impact of these metabolites on the estimates of myocardial glucose utilization (MGU) is negligible. Although further studies will be required to elucidate the reason for the egress of tracer from myocardium, not accounting for it will result in erroneous estimates of MGU.

Algorithms↗