Relative rates of oxidation of glucose and free fatty acids by ischaemic and non-ischaemic myocardium after coronary artery ligation in the dog.

Abstract

Abstract. 1. Small regional ischaemic lesions, involving about 7 % of the volume of the whole heart, were produced in the greyhound dog by ligation of a branch of the anterior descending coronary artery. Arteriovenous differences across ischaemic tissue were studied by cannulation of a local vein visibly draining the ischaemic area, whereas arteriovenous differences across the non‐ischaemic tissue were obtained by coronary sinus samples. This system permitted study of those ischaemic cells draining into the local vein and perfused by residual collateral circulation. Flow factors were common to all metabolites measured in local venous blood, thereby allowing detection of changes in substrate metabolism relative to each other. As the contribution of local venous blood to coronary sinus blood was negligible, it was possible to use coronary sinus values as non‐ischaemic control data for each local venous sample.—2. The contributions of glucose, free fatty acids (FFA) and other substrates (lactate, pyruvate, ketones, triglycerides) to the residual oxidative metabolism of the ischaemic, infarcting dog myocardium were indirectly assessed by calculations of the oxygen extraction ratio (OER), and directly by the rate of 14CO2 formation from 14C‐labelled glucose or palmitic acid.—3. Within two hours of arterial ligation, the arteriovenous difference of glucose across the ischaemic tissue was increased relative to that of IT A. Whether calculated from OER or from 14CO2 data, there was an increase in the oxidation rate of glucose relative to that of FFA. In absolute terms the oxygen uptake of ischaemic tissue fell almost as much as the flow rate, and the glucose uptake probably fell too. Nevertheless, glucose competed more favourably than did FFA for the residual oxidative metabolism of the ischaemic tissue.—4. In coronary sinus blood, draining predominantly non‐ischaemic tissue, formation of 14CO2 accounted for about half the uptake of 14C‐glucose and formation of 14C‐lactate was very low. In local venous blood draining predominantly ischaemic tissue, 14CO2 formation accounted for about 30–40% and 14C‐lactate for about 10% of the arteriovenous difference of 14C‐glucose. The chemical oxygen extraction ratio of glucose and FFA could account for 90–100% of the residual oxygen uptake of the ischaemic myocardium 60–100 min. post‐ligation, with glucose accounting for nearly twice as much oxygen as FFA. Thus an unexpected finding was that a major part of the glucose extracted by the ischaemic myocardium was oxidized, possibly because local venous blood drained the less severely ischaemic areas.—5. The major fate of labelled FFA extracted by the non‐ischaemic myocardium also appeared to be oxidation. After arterial ligation, rates of FFA oxidation fell as assessed by both OER calculation and by rates of 14CO2 formation. More 14C‐label was recovered in the “mitochondrial” and less in the “microsomal” lipid fractions of the ischaemic tissue.—6. Lactate uptake by the normal myocardium was changed to lactate discharge by the ischaemic myocardium. Initially, tissue glycogen was the major source of the lactate formed, but 60–120 min. after arterial ligation there was less discharge of lactate and circulating 14C‐gIucose became a major source of venous lactate.—7. It was concluded that not only was anaerobic metabolism of glucose accelerated by coronary artery ligation, but the aerobic metabolism of glucose increased relative to that of FFA.