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UBC Theses and Dissertations

The use of a radioiodinated fatty acid analogue in the study of myocardial ischemia and infarction Hudon, Marck P.J.

Abstract

The purpose of this study was to utilize 15-p-¹²³I-phenylpenta-decanoic acid (¹²³IPPA) and 15-p-12 3I-β-methyl iodophenylpentadecanoic acid (B¹²³IPPA) in the assessment of myocardial metabolism and perfusion following ischemia and infarction. Canine models of global ischemia, regional ischemia and infarction were used. Time-activity curve analysis was performed on the first two models using 15-p-¹²³I-iodophenylpentadecanoic acid to determine changes in metabolic status of the myocardium. Reported are the half-life values ± SD. B¹²³IPPA, ²⁰¹Tl and a histochemical method (tetrazolium staining) were used in the latter model to assess perfusion defects, including ischemic risk zone. Significant differences in the elimination rate (mins) of ¹²³IPPA metabolic by-products for the early and late phases of the time-activity curves of the global ischemia model in the lateral wall (early and late phase) and apical wall (late phase) were observed with Iso-osmolar (Tyers) solution. There were no significant differences for either the Iso-osmolar + superoxide dismutase (SOD) or Iso-osmolar + allopurinol. Also there was no significant difference in t½ values between the three areas of the left ventricle (apex, septal wall and lateral wall) within the control group. Results with the regional ischemia model indicate an increase in early phase t½ values representing ¹²³IPPA washout, between control and 14 days post-operative animals in both the lateral wall (22±10 to 60±107 min -p>0.05) and the apical wall (23±10 to 37±33 min - p>0.05) and a decrease in ¹²³IPPA washout in the septal wall (22±14 to 14±7 min - p>0.05). An increase in t½ between control and 14 days was seen in the late phase post-operatively in the lateral wall (34±12 to 71±50 min - p>0.05), the apex (44±8 to 115±104 min - p>0.05) and the septal wall (34±2 to 626±1325 min -p>0.05). The results of the myocardial infarction model indicated a greater degree of correlation between the size of perfusion defects estimated by a histochemical method (TTZ staining) vs. B¹²³IPPA (r = 0.65, p<0.005), than vs. ²⁰¹Tl (r = 0.49, p<0.005). The following conclusions can be made on the basis of the results obtained. The utilization of iodinated free fatty acids within each area of the left ventricle (lateral wall, apical wall and septal wall) demonstrate similar rates of ¹²³IPPA washout. The effect of reversible global ischemia on myocardial washout of 15-¹²³IPPA may be modified by the addition of SOD or allopurinol to the control iso-osmolar cardioplegic solution. The imaging agent ¹²³IPPA may be a useful indicator of metabolic status of the myocardium, revealing changes in washout rates during the period of developing regional ischemia. Lastly, the utilization of B¹²³IPPA does not appear to be effective in determining the size of perfusion defects, or in identifying the ischemic risk zone because of border demarcation problems.

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