The kinetics of β-methyl-substituted labelled fatty acids in ischaemic myocardium: an analysis in man and with a blood-perfused isolated heart model

Abstract

beta-Methyl-substituted free fatty acids (FFAs) have been developed for myocardial single-photon emission tomography (SPET) imaging, but little is known about their kinetics in ischaemic conditions. The aim of this study was to determine the changes in the myocardial kinetics of a beta-methyl-branched FFA, [123I]16-iodo-3-methyl-hexadecanoic acid (MIHA), under ischaemic conditions. The kinetics of MIHA were analysed: (a) using a blood-perfused isolated heart model subjected to moderate ischaemia (50% flow reduction) and (b) in patients who had an exercise thallium-201 SPET defect corresponding to either necrotic (n = 13) or chronically ischaemic and viable (n = 15) myocardium, and who underwent two consecutive SPET studies after MIHA injection. In animals, the myocardial early retention fraction of MIHA, but not its clearance rate, was dependent on coronary flow, the early retention fraction being higher in ischaemic than in normoxic conditions (0.24 +/- 0.10 vs 0.14 +/- 0.04, P = 0.004). In the patient SPET studies, the uptake of MIHA calculated in ischaemic and viable areas (G1: 74% +/- 9% of maximal left ventricular value) was different from that calculated in necrotic (G2: 59% +/- 7%, P < 0.001) or normal (G3: 88 +/- 6%, P < 0.001) areas. By contrast, MIHA-clearance calculated between the two consecutive SPET studies was not different in G1, G2 and G3. Unlike in the case of other FFAs, the myocardial clearance of MIHA is not decreased by ischaemia. However, the early retention of MIHA is increased in the case of a moderate reduction in coronary flow, a property which might help in the detection of viability in chronically ischaemic myocardium.

Changes in First-Pass Interstitial Kinetics of DTPA in Myocardium Submitted to Low-Flow Ischemia

“…8,10,14,15 Final perfusate contained 30% of bovine red blood cells, 5 g/l Ϫ1 bovine serum albumin (A-6003; Sigma Chemica Co., St. Louis, MO), and the following electrolytes and substrates: NaCl (127 mM), MgSO 4 (0.9 mM), CaCl 2 (2.5 mM), NaHCO 3 (25 mM), KH 2 PO 4 (1.17 mM), glucose (11 mM), and lactate (0.9 mM). Bovine red blood cells were supplied by a regional slaughterhouse (Socopa SA, Mirecourt); before use, they were washed twice with a 0.9% NaCl solution.…”