METHODS: 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.
RESULTS: 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.
CONCLUSION: 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.