17-iodoheptadecanoic-acid and 15-(4-iodophenyl)-3-3-dimethylpentadecanoic-acid

Myocardial metabolism of 17-[123I]-iodoheptadecanoic acid (IHDA), 15-(p-[131I]-iodophenyl)pentadecanoic acid (pIPPA) and 15-(p-[125I]-iodophenyl)-3,3-dimethylpentadecanoic acid (DMIPP) was assessed during ischemia and hypoxia. The simultaneous investigation allowed us to evaluate differences in metabolic handling of these three fatty acids.. In 17 open-chest dogs, the left ascending coronary artery was cannulated and extracorporeal bypass (ECB) perfused. In 3 dogs, ECB flow was kept normal, and these control experiments showed that kinetics of the radioiodinated fatty acids were not affected by the ECB technique itself. In 9 dogs, ECB flow was reduced to one third (ischemia), and in 5 dogs, the ECB area was perfused with venous blood and was kept at control values (hypoxia). After simultaneous intravenous injection of IHDA, pIPPA and DMIPP, seven paired biopsy specimens from the native and ECB-perfused myocardium were taken over an assay period of 35 min. Total activity and the distribution in the aqueous phase and lipid fractions were determined, and time-activity curves were constructed.. In ischemic (Is) but not in hypoxic (Hy) myocardium, peak total activity of IHDA, pIPPA and DMIPP decreased significantly versus normal (N) myocardium (IHDA: N = 700 +/- 267 versus Is = 335 +/- 158 dpm/mg/mCi; pIPPA: N = 988 +/- 318 versus Is = 438 +/- 180 dpm/mg/mCi; DMIPP: N = 352 +/- 146 versus Is = 179 +/- 82 dpm/mg/mCi; all P values < 0.001). The relative decrease was similar for IHDA, pIPPA or DMIPP. Half-time values of total activity were prolonged for IHDA and pIPPA but were shortened for DMIPP in ischemic and hypoxic myocardium (IHDA: N = 22, Is = 44 and Hy = 50 min; pIPPA: N = 24, Is = 95 and Hy = 169 min; DMIPP: N = 528, Is = 409 and Hy = 115 min). The aqueous phase activity for IHDA, pIPPA and DMIPP decreased significantly versus normal myocardium in both ischemic (IHDA: N = 71% +/- 9% versus Is = 36% +/- 9%, P < 0.001; pIPPA: N = 62% +/- 10% versus Is = 25% +/- 8%, P < 0.001; DMIPP: N = 26% +/- 11% versus Is = 18% +/- 3%, P < 0.05) and hypoxic (IHDA: N = 76% +/- 8% versus Hy = 62% +/- 8%, P < 0.05; pIPPA: N = 66% +/- 8% versus Hy = 46% +/- 10%, P < 0.05; DMIPP: N = 32% +/- 6% versus Hy = 24% +/- 4%, P < 0.05) myocardium. The relative decrease was significantly highest for pIPPA and lowest for DMIPP. Incorporation into triacylglycerols increased significantly for IHDA, pIPPA and DMIPP in both ischemic and hypoxic myocardium. In normal myocardium, DMIPP was already mainly incorporated into triacylglycerols. Activity of IHDA and pIPPA in acylcarnitine increased significantly in ischemic and hypoxic myocardium.. Kinetics of the radioiodinated fatty acid analogs in myocardium are altered during oxygen deprivation in a similar fashion as documented in literature for natural fatty acids. However, the changes were different between IHDA, pIPPA and DMIPP, suggesting different metabolic handling and thus reflecting different aspects of myocardial fatty acid metabolism.

Topics: Animals; Cell Hypoxia; Dogs; Extracorporeal Circulation; Fatty Acids; Heart; Iodine Radioisotopes; Iodobenzenes; Myocardial Ischemia; Myocardium; Radionuclide Imaging

The kinetics of 17-[123I]iodoheptadecanoic acid (IHDA), 15-(p-[125I]iodophenyl)pentadecanoic acid (pIPPA) and 15-(p-[131I]iodophenyl)-3,3-dimethylpentadecanoic acid (DMIPPA) were investigated in normal canine myocardium. After simultaneous intravenous injection, myocardial biopsy specimens and samples of arterial blood were taken over 80 min. IHDA showed the highest myocardial uptake (995 +/- 248 dpm/mg.mCi versus pIPPA: 785 +/- 197 dpm/mg.mCi, ns) and the largest size of oxidation (74% +/- 4% versus pIPPA: 65% +/- 5%, p < 0.05). Myocardial activity of IHDA decreased with a half-time value of 11.2 min (pIPPA: 13.2 min). Phospholipids were the main lipid fraction into which IHDA was incorporated, whereas pIPPA was predominantly incorporated into triacylglycerols. DMIPPA myocardial activity remained constant during the assay period and instead of being oxidized, DMIPPA was mainly incorporated into triacylglycerols (55% +/- 12%). The myocardium-to-blood ratios of DMIPPA were greater than 10:1. The ratios at peak for IHDA and pIPPA were 4.1:1 and 3.9:1, respectively (both p < 0.0001 versus DMIPPA). In conclusion, differences have been found in the myocardial uptake, oxidation and lipid distribution of IHDA, pIPPA and DMIPPA. DMIPPA is a promising tracer for fatty acid uptake studies with single-photon emission computerized tomography because of its prolonged retention and high myocardium-to-blood ratios.

Topics: Animals; Dogs; Fatty Acids; Heart; Iodine Radioisotopes; Iodobenzenes; Myocardium; Tomography, Emission-Computed, Single-Photon

The aim of this study was to assess the phospholipid distribution of radioiodinated 17-iodoheptadecanoic acid (IHDA), 15-(p-iodophenyl)pentadecanoic acid (p-IPPA) and 15-(p-iodophenyl)-3,3-dimethylpentadecanoic acid (DMIPPA) under normoxic conditions and to compare these data with the fatty acid composition of the phospholipid classes. After simultaneous i.v. injection of the radioiodinated fatty acids (I-123-IHDA; I-131-p-IPPA; I-125-DMIPPA) in open-chest dogs seven myocardial biopsies were taken over 40 min (n = 26). After lipid extraction of the biopsies the organic phase was analyzed for both neutral and polar lipids by two different TLC systems. The following polar lipid fractions were analyzed: lysophosphatidylcholine (LPC), sphingomyelin (SPH), phosphatidylcholine (PC; lecithin), phosphatidylinositol (PI), phosphatidylserine (PS), phosphatidylethanolamine (PE), diphosphatidylglycerol (DPG; cardiolipin) and neutral lipids. Fractions were counted in a gamma well counter and corrected for cross-over and recovery. Results of the polar phospholipids analysis showed that IHDA has the highest incorporation into the phospholipids. The IHDA was mainly incorporated into PI (45.6%) followed by PC (30.9%), PE (14.0%) and PS (5.6%). The p-IPPA was predominantly incorporated incorporated into PC (37.2%), followed by PS (20.1%) and PE (13.7%). In contrast to IHDA, incorporation of p-IPPA into PI was small (6.4%). The DMIPPA analogue was incorporated into phospholipids to only a very small degree, compared to IHDA and p-IPPA.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Dogs; Fatty Acids; Hemodynamics; Iodobenzenes; Male; Membrane Lipids; Myocardium; Oxygen; Phospholipids