Myocardial glucose utilization and the optimization of F-18-FDG PET imaging in patients with NIDDM, CAD and LV dysfunction

Vitale, George; Ruddy, Terrence D.; deKemp, Rob; Golanowski, L.; Aung, May; Aubrey, B

doi:10.1016/s0735-1097(98)80646-3

Cited by 27 publications

(32 citation statements)

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“…A 12-lead ECG was used to monitor the heart. After a low-dose 137 Cs transmission 17 or x-ray computed tomography 18 scan for attenuation correction, each animal underwent rest and dipyridamole stress (0.56 mg/kg) imaging with 13 N-NH 3 (20 minutes) 19 and rest imaging with 18 F-FDG (60 minutes) 20 to obtain regional estimates of MBF (mL·min…”

Section: Imaging Sequencementioning

confidence: 99%

Preclinical Evaluation of Biopolymer-Delivered Circulating Angiogenic Cells in a Swine Model of Hibernating Myocardium

Giordano

Thorn

Renaud

et al. 2013

Circ: Cardiovascular Imaging

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M yocardial hibernation is a common clinical condition affecting patients with advanced coronary artery disease, 1 for whom cell-based therapies are targeted. In hibernation, repetitive episodes of ischemia and reperfusion lead to metabolic and functional changes in cardiomyocytes, ultimately impairing left ventricular (LV) function. Current therapies such as coronary artery bypass grafting or percutaneous coronary intervention are well established but not suitable for all patients; in previous clinical research from our group, more than one third of patients referred for revascularization did not undergo intervention because of unsuitable vessel anatomy, comorbidities, or other reasons.1 These patients are at high risk of cardiac events, and novel approaches such as cell-based vasculogenic therapy could provide them with an alternative form of therapy. Clinical Perspective on p 991Circulating angiogenic cells (CACs) constitute a heterogeneous population of peripheral blood-derived fibronectincultured cells. Although what defines their phenotype is still debated, 2 they were shown to uptake acetylated low-density lipoprotein, bind Ulex europaeus agglutinin-1 lectin, and express the pan-leukocyte marker CD45. They can also stain positive for monocyte/macrophage (CD14, CD11b/Mac-1, and CD11c) and endothelial (vascular endothelial growth factor receptor 2, von Willebrand factor, vascular endothelialcadherin, and CD31) markers. [3][4][5] Transplanted cells likely contribute to neovascularization through a paracrine mechanism by secreting and recruiting cardioprotective or proangiogenic growth factors. 6,7 The revascularization potential of Background-Vasculogenic cell-based therapy combined with tissue engineering is a promising revascularization approach targeted at patients with advanced coronary artery disease, many of whom exhibit myocardial hibernation. However, to date, no experimental data have been available in this context; we therefore examined the biopolymer-supported delivery of circulating angiogenic cells using a clinically relevant swine model of hibernating myocardium. Methods and Results-Twenty-five swine underwent placement of an ameroid constrictor on the left circumflex artery.After 2 weeks, animals underwent echocardiography, rest and stress ammonia-positron emission tomography perfusion, and fluorodeoxyglucose positron emission tomography viability scans. The following week, swine were randomized to receive intramyocardial injections of PBS control (n=10), circulating angiogenic cells (n=8), or circulating angiogenic cells+collagen-based matrix (n=7). The imaging protocol was repeated after 7 weeks. Baseline positron emission tomography myocardial blood flow and myocardial flow reserve were reduced in the left circumflex artery territory (both P<0.001), and hibernation (mismatch) was observed. At follow-up, stress myocardial blood flow had increased (P≤0.01) and hibernation decreased (P<0.01) in the cells+matrix group only. Microsphere-measured myocardial blood flow validated the perfusion resu...

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Section: Imaging Sequencementioning

confidence: 99%

Preclinical Evaluation of Biopolymer-Delivered Circulating Angiogenic Cells in a Swine Model of Hibernating Myocardium

Giordano

Thorn

Renaud

et al. 2013

Circ: Cardiovascular Imaging

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“…To determine the myocardial activity over time, a custom program (FlowQuant) developed in our institution was used to automatically reoriented the images along the long axis of the heart and sample the LV myocardium into dynamic polar maps with 460 sectors, assuming a recovery coefficient value of 1.0. 15 A cylindrical region was defined automatically within the LV and atrial cavities to determine the arterial blood-pool activity over time.…”

Section: Pet Image Processingmentioning

confidence: 99%

In Vivo Assessment of Myocardial Glucose Uptake by Positron Emission Tomography in Adults With the PRKAG2 Cardiac Syndrome

Renaud

deKemp

et al. 2009

Circ: Cardiovascular Imaging

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Background-The PRKAG2 cardiac syndrome is an inherited metabolic disease of the heart characterized by excessive myocardial glycogen deposition. The biochemical alterations associated with this condition remain controversial and have not previously been studied in affected humans. Methods and Results-Positron emission tomography (PET) imaging was used to quantitatively assess myocardial glucose uptake (MGU) in 6 adult subjects with the PRKAG2 cardiac syndrome and 6 healthy, matched control subjects using the glucose analogue 18 F-Fluoro-2-deoxyglucose (FDG). Studies were performed under a euglycemic hyperinsulinemic clamp to ensure stable blood glucose levels. Rubidium-82 perfusion scans were performed to ensure that myocardial differences in myocardial glucose uptake were not the result of significant myocardial scar. In adult patients with phenotypic expression of disease, the median myocardial glucose uptake of the left ventricle was 0.18 mol/min/g (interquartile range, 0.14, 0.24), compared with 0.40 mol/min/g (interquartile range, 0.30 to 0.45) in the control group (Pϭ0.01). The median blood glucose during FDG-PET imaging was 4.72 mmol/L (interquartile range, 4.32 to 4.97) in the PRKAG2 group and 4.38 mmol/L (interquartile range, 3.90, 4.79) in the control group (PϭNS). The significant decrease observed in myocardial glucose uptake in affected patients occurred in the absence of significant myocardial scar. Conclusions-The PRKAG2 cardiac syndrome is associated with a reduction of glucose uptake in adult patients affected with this genetic condition. In this pilot study,

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“…Previous evidence [29][30][31] has shown that nicotinic acid enhances myocardial GU by reducing plasma NEFA availability. In our study, the myocardial glucose clearance (Ki, ml min −1 ml −1…”

Section: Discussionmentioning

confidence: 99%

Independent effects of circulating glucose, insulin and NEFA on cardiac triacylglycerol accumulation and myocardial insulin resistance in a swine model

et al. 2014

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Aims/hypothesis Cardiac steatosis and myocardial insulin resistance elevate the risk of cardiac complications in obesity and diabetes. We aimed to disentangle the effects of circulating glucose, insulin and NEFA on myocardial triacylglycerol (TG) content and myocardial glucose uptake. Methods Twenty-two pigs were stratified according to four protocols: low NEFA+low insulin (nicotinic acid), high NEFA+low insulin (fasting) and high insulin+low NEFA± high glucose (hyperinsulinaemia-hyperglycaemia or hyperinsulinaemia-euglycaemia). Positron emission tomography, [U-13 C]palmitate enrichment techniques and tissue biopsies were used to assess myocardial metabolism. Heart rate and rate-pressure product (RPP) were monitored. Results Myocardial glucose extraction was increased by NEFA suppression and was similar in the hyperinsulinaemiahypergylcaemia, hyperinsulinaemia-euglycaemia and nicotinic acid groups. Hyperglycaemia enhanced myocardial glucose uptake due to a mass action. Myocardial TG content was greatest in the fasting group, whereas hyperinsulinaemia had a mild effect. Heart rate and RPP increased in hyperinsulinaemia-euglycaemia, in which cardiac glycogen content was reduced. Heart rate correlated with myocardial TG and glycogen content. Conclusions/interpretation Elevated NEFA levels represent a powerful, self-sufficient promoter of cardiac TG accumulation and are a downregulator of myocardial glucose uptake, indicating that the focus of treatment should be to 'normalise' adipose tissue function to lower the risk of cardiac TG accumulation and myocardial insulin resistance. The observation that hyperinsulinaemia and nicotinic acid led to myocardial fuel deprivation provides a potential explanation for the cardiovascular outcomes reported in recent intensive glucoselowering and NEFA-lowering clinical trials.

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Myocardial glucose utilization and the optimization of F-18-FDG PET imaging in patients with NIDDM, CAD and LV dysfunction

Cited by 27 publications

References 0 publications

Preclinical Evaluation of Biopolymer-Delivered Circulating Angiogenic Cells in a Swine Model of Hibernating Myocardium

Preclinical Evaluation of Biopolymer-Delivered Circulating Angiogenic Cells in a Swine Model of Hibernating Myocardium

In Vivo Assessment of Myocardial Glucose Uptake by Positron Emission Tomography in Adults With the PRKAG2 Cardiac Syndrome

Independent effects of circulating glucose, insulin and NEFA on cardiac triacylglycerol accumulation and myocardial insulin resistance in a swine model

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