125I-BMIPP and 18F-FDG uptake in a transgenic mouse model of stunned myocardium

Abstract

Reported metabolic patterns in myocardial stunning are not uniform. We investigated relative myocardial perfusion, glucose and fatty acid uptake using a technetium-99 hexakis-2-methoxyisobutyl-isonitrile (MIBI), fluorine-18 2-fluoro-2-deoxyglucose (FDG) and iodine-125 15-(p-iodo-phenyl)-3(R,S)-methylpentadecanoic acid (BMIPP) mixture, in a recently developed transgenic (TR) mouse model which mimics stunned myocardium. Twenty-seven mice - 14 TR and 13 age-matched wild type controls (C) - were divided into four groups: TR-fed, TR-fasted, C-fed and C-fasted. Animals were sacrificed 2 h after injection, tissue samples counted and percent-injected dose/gram tissue (% id/g) calculated for each radioisotope. Tissues were also Folch extracted and 125I incorporation into the various lipid pools (TG, triglycerides; DG, diglycerides; FFA, free fatty acids; PL, phospholipids) was determined by thin-layer chromatography (TLC). The pooled data for each of the four groups (TR-fed vs C-fed and TR-fed vs C-fasted) showed no differences in myocardial blood flow (% MIBI id/g), glucose uptake (% FDG id/g) or fatty acid uptake (% BMIPP id/g). Only minor differences were observed in the incorporation of 125I-BMIPP into the myocardial TG, DG, FFA and PL lipid pools. However, significantly decreased myocardial FDG uptake was observed in a subset of fasted mice - four out of ten TR-fasted mice (3.4% vs 20.5% id/g) and three out of nine C-fasted mice (5.5% vs 30.6% id/g). The transgenic mouse model of stunned myocardium shows normal myocardial perfusion and overall intact myocardial glucose and myocardial fatty acid uptake as determined with clinically applicable radiolabelled analogues. These data are in line with the hypothesis that the contractile inefficiency in stunned myocardium is not linked to metabolic alterations but is associated with an insufficient chemical to mechanical energy coupling.

High-Density Lipoprotein Stimulates Myocardial Perfusion In Vivo

“…We used this value as a surrogate marker of myocardial perfusion, although it is not an absolute measure of perfusion but rather reflects the net uptake of the tracer in the myocardium ("MIBI flow"). It is critically dependent on accurate measurements of the injected activity and the heart weight, 8 and we meticulously controlled for both.…”

“…8 Five minutes after intravenous tracer injection, mice were euthanized by cervical dislocation, and the whole heart was taken out, rinsed, dabbed dry, and weighed. The radioactivity of the whole heart was measured by a gamma counter system (Wallac 1480 Wizard), calibrated with 5% of the injected dose (100 kBq).…”

“…We used this value as a surrogate marker of myocardial perfusion, although it is not an absolute measure of perfusion but rather reflects the net uptake of the tracer in the myocardium ("MIBI flow"). It is critically dependent on accurate measurements of the injected activity and the heart weight, 8 and we meticulously controlled for both.Basal myocardial 99mTc-MIBI uptake in the murine heart in vivo was 14.47Ϯ0.39% ID/g. Intravenous administration of HDL (2 mg/kg body wt) enhanced myocardial 99m Tc-MIBI uptake by 18% (17.01Ϯ0.54% ID/g; Pϭ0.036) ( Figure 1A).…”

“…Myocardial perfusion was finally estimated by the MIBI flow, calculated as percentage of injected dose (ID) of 99m Tc-MIBI measured in the whole heart divided by the heart weight (% ID/g). 8,9 To study the effect of S1P and HDL on myocardial perfusion, MIBI flow was measured in untreated animals (baseline) and 15 minutes after intravenous injection of S1P (Sigma; 38 g/kg body wt in 50 L 1% BSA/PBS), HDL (2 mg/kg body wt in 50 L 0.9% saline), or vehicle, respectively. HDL (dϭ1.125 to 1.210 g/mL) was isolated from human plasma as described.…”

Myocardial blood flow mapping in mice using high‐resolution spin labeling magnetic resonance imaging: Influence of ketamine/xylazine and isoflurane anesthesia

“…Measurements in well-controlled anesthetic conditions have only been reported using microspheres (4 -6) requiring the sacrifice of the animal for the measurement. Recent advances using microSPECT have shown only relative perfusion measurements with rather low spatial resolutions (7,8). A semi-quantitative approach using microPET has provided in vivo measurements of myocardial blood flow changes under drug influence (9).…”