123I-phenylpentadecanoic acid as a tracer of cardiac free fatty acid metabolism. Experimental and clinical results

Abstract

Metabolism of 15(p-123I-phenyl-) pentadecanoic acid (I-PPA) was investigated in Langendorff perfused rat hearts, fasted Wistar rats, pentobarbital-anaesthetized dogs and, in clinical studies, in patients with coronary artery disease. In murine experiments metabolism of I-PPA was compared quantitatively with 1-14 C-palmitic acid in double tracer studies. In these experiments I-PPA is taken up and metabolized very similarly to palmitic acid. Metabolic intervention studies showed identical directional changes of the rate of cardiac I-PPA and palmitic acid-oxidation during isoproterenol stimulated or lactate-suppressed cardiac lipolysis. Total heart uptake and turnover, as well as kinetics of labelled cardiac lipids, were found to be highly significantly related, when 14C-palmitic acid- and I-PPA-metabolism were analysed in vivo in an identical metabolic environment. In canine experiments initial uptake of I-PPA in the heart muscle is related to regional myocardial blood flow under control conditions and in ischaemia. Pacing induced hyperaemia is associated with an only moderate increase of I-PPA uptake, resulting in a threshold value at flow rates of about 150-200 ml min-1 (100 g-1) In clinical studies, myocardial infarcts can be accurately detected, localized and potentially quantitated. In significant coronary artery disease (greater than 75% diameter reduction), detection rates of 50-75% are found in studies performed at rest. Regional abnormalities of cardiac kinetics of I-PPA were found in about 60% of segments dependent on highly stenosed vessels (greater than 75% diameter reduction).(ABSTRACT TRUNCATED AT 250 WORDS)