Metabolism of radioiodinated fatty acid analogs in ischemic and hypoxic canine myocardium

Myocardial metabolism of 17-[I-123]-iodoheptadecanoic acid (IHDA), 15-(p-[I -131]-iodophenyl)pentadecanoic acid (pIPPA) and 15-(p-[I-125]-iodophenyl)-3 ,3-dimethylpentadecanoic acid (DMIPP) was assessed during ischemia and hypo xia; The simultaneous investigation allowed us to evaluate differences in m etabolic handling of these three fatty acids. Methods: In 17 open-chest dog s, the left ascending coronary artery was, cannulated and extracorporeal by pass (ECB) perfused. In 3 dogs, ECB flow was kept normal, and these control experiments showed that kinetics of the radioiodinated fatty acids were no t 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 intraven eous 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. Resul ts: In ischemic (Is) but not in hypoxic (Hy) myocardium, peak total activit y of IHDA, pIPPA and DMIPP decreased significantly versus normal (N) myocar dium (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 vers us 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 w ere prolonged for IHDA and pIPPA but were shortened for DMIPP in ischemic a nd 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, pi PPA 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 hig hest for pIPPA and lowest for DMIPP. Incorporation into triacylglycerols in creased significantly for IHDA, pIPPA and DMIPP in both ischemic and hypoxi c myocardium. In normal myocardium, DMIPP was already mainly incorporated i nto triacylglycerols. Activity of IHDA and pIPPA in acylcarnitine increased significantly in ischemic and hypoxic myocardium. Conclusion: Kinetics of the radioiodinated fatty acid analogs in myocardium are altered during oxyg en deprivation in a similar fashion as documented in literature for natural fatty acids. However, the changes were different between IHDA, pIPPA and D MIPP, suggesting different metabolic handling and thus reflecting different aspects of myocardial fatty acid metabolism.