External detection and visualization of myocardial ischemia with 11C-substrates in vitro and in vivo

To characterize externally detectable changes in myocardial metabolism of free fatty acids (FFA) and glucose associated with ischemia, isovolumically beating rabbit hearts were perfused under conditions of selected flows with cyclotron-produced, short-lived (t1/2 - 20.4 minutes), 11C-labeled isotopes of glucose and FFA. Tension-time index decreased 83% and lactate production increased from 0.5 +/- 1.9 (SE) to 5.3 +/- 2.1 mumol/min per g of dry weight reflecting myocardial ischemia after flow was reduced from 20 to 5 ml/min. After 30 minutes of low flow the myocardial accumulation of 11C-octanoate, expressed as the extraction fraction, declined from 56 +/- 15% to 30 +/- 3%, reflecting metabolic suppression of FFA extraction during low flow. Effects attributable exclusively to prolonged residence time were excluded. Similar results were obtained with 11C-palmitate. The myocardial avidity for 11C-palmitate was demonstrable by rectilinear whole body scanning in dogs given 5 mCi of the agent intravenously. Diminished 11C-palmitate uptake in zones of myocardium rendered ischemic for 20 minutes prior to reflow in intact dogs was delineated by electrocardiographically gated positron-emission transaxial computer reconstruction tomography. Thus, diminished 11C-FFA extraction, externally detectable, accompanies decreased perfusion in isolated perfused hearts, and decreased 11C-FFA uptake reflecting myocardial ischemia in vivo can be evaluated noninvasively by positron-emission transaxial tomography.