Spatial Heterogeneity in Fasting and Insulin-Stimulated ¹⁸ F-2-Deoxyglucose Uptake in Pigs With Hibernating Myocardium

Abstract

Background-Previous studies of hibernating myocardium in the fasting state have shown regionally increased 18 F-2-deoxyglucose (FDG) uptake with a marked transmural gradient. We hypothesized that this adaptation to chronic ischemia might be associated with altered maximal FDG uptake. Methods and Results-Pigs were instrumented with a 1.5-mm proximal left anterior descending artery (LAD) stenosis.Studies were conducted 106Ϯ4 days later on anesthetized animals with complete LAD occlusion and anteroapical dysfunction. In fasting animals (nϭ9), FDG uptake in dysfunctional LAD regions was 2-fold higher than in normally perfused myocardium (7.9Ϯ1.2 versus 4.0Ϯ0.5mol ⅐ min Ϫ1 ⅐ 100 g Ϫ1 , PϽ0.05), with a pronounced transmural gradient (endocardial/epicardial ratio 2.56Ϯ0.19 versus 1.25Ϯ0.03, PϽ0.05). Euglycemic, hyperinsulinemic clamp (insulin clamp, nϭ8) produced a 5-to 9-fold increase in FDG uptake, but there was no longer a regional difference in accumulation (LAD, 37.8Ϯ4.2 versus normal, 36.4Ϯ5.1 mol ⅐ min Ϫ1 ⅐ 100 g Ϫ1 , PϭNS) and the transmural distribution was uniform. FDG uptake in the fasting state varied inversely with coronary flow during vasodilation. In contrast, during insulin clamp there was no relation between FDG uptake and vasodilated flow, resulting in a reduced spatial heterogeneity in individual samples (relative dispersionϭSD/mean; fasting, 52Ϯ5% versus insulin, 24Ϯ2%, PϽ0.05). Conclusions-In the fasting state, FDG uptake in pigs with hibernating myocardium was heterogeneous and was increased in dysfunctional regions with a marked transmural gradient and high spatial heterogeneity. In contrast, FDG uptake was more homogeneously distributed during insulin clamp with (1) uptake in dysfunctional myocardium similar to remote normal regions, (2) uniform transmural distribution, and (3)

Comparison of thallium deposition with segmental perfusion in pigs with chronic hibernating myocardium

“…This model produces a large volume of viable dysfunctional myocardium, but overall left ventricular systolic function is preserved (13), thereby reducing the likelihood of remote region remodeling, which could affect remote region thallium retention. Furthermore, our methodology assured the direct quantification of thallium deposition (regional retention corrected for average arterial concentration), and viability in individual segments would be confirmed with simultaneous quantification of insulin-stimulated [ 18 F]-2 fluoro-2-deoxyglucose (FDG) deposition (10). Our results confirm the finding of enhanced thallium retention relative to resting flow and therefore support the clinical utility of late thallium imaging to identify myocardial viability.…”

“…To clarify thallium uptake in hibernating myocardium, the present study was performed in a very well-characterized chronic porcine model (10,11,13). This model produces a large volume of viable dysfunctional myocardium, but overall left ventricular systolic function is preserved (13), thereby reducing the likelihood of remote region remodeling, which could affect remote region thallium retention.…”

Normal and Pathological NCAT Image and Phantom Data Based on Physiologically Realistic Left Ventricle Finite-Element Models

“…Ex vivo studies have documented that the blood flow and metabolism requirements for the subendocardium can be markedly different than for the sub-epicardium [51][52][53][54][55][56]. The vulnerability to ischemia for the two regions is likewise dissimilar.…”

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

“…The total activity injected was ≈200 to 550 MBq for ammonia scans and 150 to 300 MBq for FDG scans (dose by weight; ≈15 kg at scan 1, and 40 kg at scan 2). To increase myocardial glucose uptake and image quality on the FDG scans, a euglycemic hyperinsulinemic clamp was used 21 ( Figure II in the online-only Data Supplement). The protocol is detailed in the online-only Data Supplement.…”