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Title: A STUDY OF CHANGES IN DEFORMATION AND METABOLISM IN LEFT VENTRICLE AS A FUNCTION OF HYPERTROPHY IN SPONTANEOUS HYPERTENSIVE RATS USING MICROPET TECHNOLOGY

Abstract

Problem: In the case of hypertrophy caused by pressure overload (hypertension) there is an increase in cardiac mass and modification cardiac metabolism. Aim: This study was designed to study the changes in glucose metabolism, ejection fraction, and deformation in the left ventricle with the progression of hypertrophy in spontaneous hypertensive rats (SHR). Methods: Dynamic PET data were acquired using the microPET II at UC Davis. Two rats were imaged at 10-week intervals for 18 months. Each time a dose of approximately 1- 1.5 mCi of F-18-FDG was injected into a normotensive Wistar Kyoto (WKY) rat and the same dose was injected into a SHR rat. Each rat was imaged using a gated dynamic acquisition for 80 minutes acquiring list mode data with cardiac gating of approximately 600-900 million total counts. For the analysis of glucose of metabolism, the list mode data were histogrammed into a dynamic sequence (42 frames over 80 mins). For each time frame, projection data of 1203 140x210 sinograms of 0.582 mm bins were formed by summing the last three gates before and one after the R-wave trigger to correspond to the diastolic phase of the cardiac cycle. Dynamic sequences of 128x128x83 matrices of 0.4x0.4x0.582 mm3 voxelsmore » in x, y, and z were reconstructed using an iterative MAP reconstruction which used a prior that penalized the high frequency components of the reconstruction using appropriate weighting between 26 nearest neighboring voxels. Time activity curves were generated from the dynamic reconstructed sequence for the blood and left ventricular tissue regions of interest which were fit to a 2-compartment model to obtain a least squares fit for the kinetic parameters. For the analysis of deformation, the list mode data were histogrammed into 8 gates of the cardiac cycle, each gate was the total sum of the later 60 mins of the 80 min acquisition. Images of 128x128x83 matrices for each gate were reconstructed using the same iterative MAP reconstruction used to reconstruct the dynamic sequence. The in-plane image dimensions were doubled to 256x256x83 in order to increase the resolution for the Warping analyses. These image data sets were then cropped to 128x128x83. The end-systolic image data sets were designated as the template images and the end-diastole image data sets were designated as the target images, thus providing an analysis of the diastolic relaxation and filling phases of the cardiac cycle. The template images were manually segmented to create surface definitions representing the epi- and endocardial surfaces. Finite element models of the left ventricles were created using the segmented surfaces and defining a transversely isotropic material with fiber angles varying from the epicardial surface to the endocardial surface. A Warping analyses was performed to obtain the LV strain tensor and fiber stretch distributions. Results: In one study, the average first principal Green-Lagrange strain, fiber stretch, ejection fraction, and metabolic rate of F-18-FDG was 0.22, 1.08, 80%, 0.1 for the WKY rat and 0.16, 1.06, 50%, 0.25 for the SHR rat, respectively. These same rats studied a year later presented with a metabolic rate of F-18-FDG of 0.11 and 0.25 for the WKY and SHR, respectively. A follow-up study the average strain (n=10) and ejection fraction (n=18) was 0.21, 72.7% for WKY and 0.17, 69.8% for the SHR, respectively. Conclusion: In the case of pressure overload there is an increased reliance on carbohydrate oxidation in an attempt to maintain contractile function.« less

Authors:
; ; ; ; ; ;
Publication Date:
Research Org.:
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Sponsoring Org.:
Life Sciences Division
OSTI Identifier:
1363639
Report Number(s):
LBNL-1006557
Journal ID: ISSN 1071-3581; ir:1006557
Resource Type:
Conference
Resource Relation:
Journal Volume: 12; Journal Issue: 2; Conference: Internation Conference on Nuclear Cardiology, Lisbon, Portugal, 05/08/2005
Country of Publication:
United States
Language:
English

Citation Formats

Gullberg, Grant, T, Huesman, Ronald, H, Reutter, Bryan, W, Sitek, Arkadiusz, Veress, Alexander, I, Weiss, Jeffrey, A, and Yang, Yongfeng. A STUDY OF CHANGES IN DEFORMATION AND METABOLISM IN LEFT VENTRICLE AS A FUNCTION OF HYPERTROPHY IN SPONTANEOUS HYPERTENSIVE RATS USING MICROPET TECHNOLOGY. United States: N. p., 2017. Web. doi:10.1016/j.nuclcard.2004.12.232.
Gullberg, Grant, T, Huesman, Ronald, H, Reutter, Bryan, W, Sitek, Arkadiusz, Veress, Alexander, I, Weiss, Jeffrey, A, & Yang, Yongfeng. A STUDY OF CHANGES IN DEFORMATION AND METABOLISM IN LEFT VENTRICLE AS A FUNCTION OF HYPERTROPHY IN SPONTANEOUS HYPERTENSIVE RATS USING MICROPET TECHNOLOGY. United States. doi:10.1016/j.nuclcard.2004.12.232.
Gullberg, Grant, T, Huesman, Ronald, H, Reutter, Bryan, W, Sitek, Arkadiusz, Veress, Alexander, I, Weiss, Jeffrey, A, and Yang, Yongfeng. Tue . "A STUDY OF CHANGES IN DEFORMATION AND METABOLISM IN LEFT VENTRICLE AS A FUNCTION OF HYPERTROPHY IN SPONTANEOUS HYPERTENSIVE RATS USING MICROPET TECHNOLOGY". United States. doi:10.1016/j.nuclcard.2004.12.232. https://www.osti.gov/servlets/purl/1363639.
@article{osti_1363639,
title = {A STUDY OF CHANGES IN DEFORMATION AND METABOLISM IN LEFT VENTRICLE AS A FUNCTION OF HYPERTROPHY IN SPONTANEOUS HYPERTENSIVE RATS USING MICROPET TECHNOLOGY},
author = {Gullberg, Grant, T and Huesman, Ronald, H and Reutter, Bryan, W and Sitek, Arkadiusz and Veress, Alexander, I and Weiss, Jeffrey, A and Yang, Yongfeng},
abstractNote = {Problem: In the case of hypertrophy caused by pressure overload (hypertension) there is an increase in cardiac mass and modification cardiac metabolism. Aim: This study was designed to study the changes in glucose metabolism, ejection fraction, and deformation in the left ventricle with the progression of hypertrophy in spontaneous hypertensive rats (SHR). Methods: Dynamic PET data were acquired using the microPET II at UC Davis. Two rats were imaged at 10-week intervals for 18 months. Each time a dose of approximately 1- 1.5 mCi of F-18-FDG was injected into a normotensive Wistar Kyoto (WKY) rat and the same dose was injected into a SHR rat. Each rat was imaged using a gated dynamic acquisition for 80 minutes acquiring list mode data with cardiac gating of approximately 600-900 million total counts. For the analysis of glucose of metabolism, the list mode data were histogrammed into a dynamic sequence (42 frames over 80 mins). For each time frame, projection data of 1203 140x210 sinograms of 0.582 mm bins were formed by summing the last three gates before and one after the R-wave trigger to correspond to the diastolic phase of the cardiac cycle. Dynamic sequences of 128x128x83 matrices of 0.4x0.4x0.582 mm3 voxels in x, y, and z were reconstructed using an iterative MAP reconstruction which used a prior that penalized the high frequency components of the reconstruction using appropriate weighting between 26 nearest neighboring voxels. Time activity curves were generated from the dynamic reconstructed sequence for the blood and left ventricular tissue regions of interest which were fit to a 2-compartment model to obtain a least squares fit for the kinetic parameters. For the analysis of deformation, the list mode data were histogrammed into 8 gates of the cardiac cycle, each gate was the total sum of the later 60 mins of the 80 min acquisition. Images of 128x128x83 matrices for each gate were reconstructed using the same iterative MAP reconstruction used to reconstruct the dynamic sequence. The in-plane image dimensions were doubled to 256x256x83 in order to increase the resolution for the Warping analyses. These image data sets were then cropped to 128x128x83. The end-systolic image data sets were designated as the template images and the end-diastole image data sets were designated as the target images, thus providing an analysis of the diastolic relaxation and filling phases of the cardiac cycle. The template images were manually segmented to create surface definitions representing the epi- and endocardial surfaces. Finite element models of the left ventricles were created using the segmented surfaces and defining a transversely isotropic material with fiber angles varying from the epicardial surface to the endocardial surface. A Warping analyses was performed to obtain the LV strain tensor and fiber stretch distributions. Results: In one study, the average first principal Green-Lagrange strain, fiber stretch, ejection fraction, and metabolic rate of F-18-FDG was 0.22, 1.08, 80%, 0.1 for the WKY rat and 0.16, 1.06, 50%, 0.25 for the SHR rat, respectively. These same rats studied a year later presented with a metabolic rate of F-18-FDG of 0.11 and 0.25 for the WKY and SHR, respectively. A follow-up study the average strain (n=10) and ejection fraction (n=18) was 0.21, 72.7% for WKY and 0.17, 69.8% for the SHR, respectively. Conclusion: In the case of pressure overload there is an increased reliance on carbohydrate oxidation in an attempt to maintain contractile function.},
doi = {10.1016/j.nuclcard.2004.12.232},
journal = {},
number = 2,
volume = 12,
place = {United States},
year = {Tue Jun 13 00:00:00 EDT 2017},
month = {Tue Jun 13 00:00:00 EDT 2017}
}

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  • The objective of this research was to assess applicability of a technique known as hyperelastic warping for the measurement of local strains in the left ventricle (LV) directly from microPET image data sets. The technique uses differences in image intensities between template (reference) and target (loaded) image data sets to generate a body force that deforms a finite element (FE) representation of the template so that it registers with the target images. For validation, the template image was defined as the end-systolic microPET image data set from a Wistar Kyoto (WKY) rat. The target image was created by mapping themore » template image using the deformation results obtained from a FE model of diastolic filling. Regression analysis revealed highly significant correlations between the simulated forward FE solution and image derived warping predictions for fiber stretch (R2 = 0.96), circumferential strain (R2 = 0.96), radial strain (R2 = 0.93), and longitudinal strain (R2 = 0.76) (p<0.001for all cases). The technology was applied to microPET image data of two spontaneously hypertensive rats (SHR) and a WKY control. Regional analysis revealed that, the lateral freewall in the SHR subjects showed the greatest deformation compared with the other wall segments. This work indicates that warping can accurately predict the strain distributions during diastole from the analysis of microPET data sets.« less
  • Using longitudinal micro positron emission tomography (microPET)/computed tomography (CT) studies, we quantified changes in myocardial metabolism and perfusion in spontaneously hypertensive rats (SHRs), a model of left ventricular hypertrophy (LVH). Fatty acid and glucose metabolism were quantified in the hearts of SHRs and Wistar-Kyoto (WKY) normotensive rats using long-chain fatty acid analog 18F-fluoro-6-thia heptadecanoic acid ( 18F-FTHA) and glucose analog 18F-fluorodeoxyglucose ( 18F-FDG) under normal or fasting conditions. We also used 18F-fluorodihydrorotenol ( 18F-FDHROL) to investigate perfusion in their hearts without fasting. Rats were imaged at 4 or 5 times over their life cycle. Compartment modeling was used to estimatemore » the rate constants for the radiotracers. Blood samples were obtained and analyzed for glucose and free fatty acid concentrations. SHRs demonstrated no significant difference in 18F-FDHROL wash-in rate constant (P = .1) and distribution volume (P = .1), significantly higher 18F-FDG myocardial influx rate constant (P = 4×10 –8), and significantly lower 18F-FTHA myocardial influx rate constant (P = .007) than WKYs during the 2009-2010 study without fasting. SHRs demonstrated a significantly higher 18F-FDHROL wash-in rate constant (P = 5×10 –6) and distribution volume (P = 3×10 –8), significantly higher 18F-FDG myocardial influx rate constant (P = 3×10 –8), and a higher trend of 18F-FTHA myocardial influx rate constant (not significant, P = .1) than WKYs during the 2011–2012 study with fasting. Changes in glucose plasma concentrations were generally negatively correlated with corresponding radiotracer influx rate constant changes. The study indicates a switch from preferred fatty acid metabolism to increased glucose metabolism with hypertrophy. Increased perfusion during the 2011-2012 study may be indicative of increased aerobic metabolism in the SHR model of LVH.« less
  • Spontaneously hypertensive rats were given an angiotensin-converting enzyme (ACE) inhibitor (benazepril or quinapril) or hydralazine and were left for up to 6 hr. To examine whether administration of antihypertensive agents affects expression of immediate early genes in left ventricular myocardium, groups of rats were sacrificed at 1, 3, and 6 hr after dosing; total RNA was extracted from left ventricular tissue and analyzed by blot hybridization technique using labeled probes for c-myc, c-fos, and GAPDH mRNA. All three antihypertensive agents reduced pressure similarly, and treatment with the two ACE inhibitors increased c-fos and c-myc mRNA expression in left ventriculum. Bymore » contrast, hydralazine did not increase steady-state mRNA expression of either proto-oncogene. Thus, in parallel with the pressure fall, acute administration of the ACE inhibitors induced expression of c-fos and c-myc mRNAs in the left ventricle. Since the equidepressor dose of hyralazine did not affect expression of these proto-oncogenes, this effect of ACE inhibitors is independent of their hemodynamic action. 27 refs., 1 fig., 2 tabs.« less
  • Studies investigated whether changes in omega- and (omega-1)-hydroxylation (OH) of lauric acid (LA) occurred in renal microsomes prepared from SHR compared to Wistar-Kyoto (WK) control rats. Systolic blood pressure in age-matched adult SHR and WKR were 189 +/- 3 and 123 +/- 4 mm Hg(anti X +/- SE) respectively (p < 0.001). No significant differences between SHR and WKR were seen in body weight, kidney weight or renal microsomal protein content. Renal microsomes, prepared from whole kidneys, were incubated with 10 mM NADPH and (/sup 14/C)LA at concentrations between 5-50 ..mu..M. The 11- and 12-OH metabolites of LA were separatedmore » by HPLC using a reverse phase column with a methanol:water:acetic acid (62:37.8:0.2) mobile phase. Apparent (app) V/sub max/ values for 12-OH in WKR and SHR were 0.87 +/- 0.19 vs 1.48 +/- .11 nmoles/mg protein/min (p < 0.05), respectively, while values for 11-OH were 0.51 +/- 0.12 vs 0.60 +/- .07, respectively. No significant differences were found in app K/sub m/ values for either 11- or 12-OH between the two strains. SDS-polyacrylamide gel electrophoresis of renal microsomes showed the increased prominence of a 52,000 dalton protein in SHR preparations. Thus data suggest that selective alterations in renal cytochrome P-450 monooxygenase reactions may be associated with the endogenous biochemical processes underlying hypertension.« less