Spatial and temporal characteristics of the transmural distribution of collateral flow and energy metabolism during regional myocardial ischemia in the dog

Abstract

To characterize the temporal and spatial characteristics of transmural gradients of flow, ATP and CP, dogs (n = 17) were subjected to coronary artery ligation for either 30 minutes or 24 hours. Different radioactive microspheres were given at the onset and end of the ischemic period. Simultaneous multiple transmural biopsies (up to 20 per heart) were obtained (in situ freezing) from central ischemic and surrounding normal tissue after either 30 minutes or 24 hours of elapsed ischemia. After lyophilization each biopsy was divided into up to 6 transmural sub-fragments, each of which was analysed for flow, ATP and CP. At the onset of ischemia flow declined to less than 15% throughout the ischemic zone and there was a slight transmural gradient of flow from epi- to endocardium (12.4 +/- 1.6, 13.5 +/- 2.0, 11.0 +/- 1.8, 10.3 +/- 1.7, 8.5 +/- 1.9 and 8.3 +/- 3.1% of non-ischemic tissue). After 30 minutes of ischemia, collateral flow to the epicardial tissue had increased substantially but endocardial flow remained unchanged, the epi- to endo- gradient was 20.8 +/- 2.5, 18.9 +/- 2.4, 13.7 +/- 2.1, 10.8 +/- 1.5, 8.5 +/- 1.2, 7.6 +/- 1.7. After 24 hours there were further increases in the epi- and mid- myocardial regions but the endocardial flow remained severely depressed, the epi- to endo- gradient was 23.9 +/- 3.2, 24.5 +/- 3.0, 23.6 +/- 4.8, 16.4 +/- 3.3, 9.8 +/- 2.9, 5.8 +/- 2.9%. ATP and CP were severely depressed after 30 minutes of ischemia and reflected flow closely with sharp linear epi- to endo- gradients (17.5 to 10.9 muMol/g dry wt for ATP and 7.4 to 3.1 muMol/g dry wt for CP). After 24 hours, the decline in ATP had been slowed and there was a striking recovery of CP in the epi- and mid- myocardial regions which had experienced increasing collateral flow. CP in the endocardium remained severely depressed. Progressive supplementation of collateral flow early and throughout a 24 hour period of regional myocardial ischemia and the selective delivery of this flow to subepi- and mid- myocardial tissue accounts in part for the natural salvage of this tissue and the deterioration of the endocardium to necrosis. Gradients of flow and metabolism further influence these events and account for the "wave front" of cell death.