ANAPLEROTIC EFFECTS OF PROPIONATE ON OXIDATIONS OF ACETATE AND LONG-CHAIN FATTY-ACIDS

Studies were performed to test the influence of propionate as a compet ing myocardial substrate on acetate and palmitate metabolism in reperf used pig hearts after an exposure of mild-to-moderate regional ischemi a. Experiments were conducted in intact, working pig hearts (n = 10) u sing an extracorporeal coronary perfusion technique. Half the animals received 2 mM propionate selectively into the anterior descending (LAD ) perfusate. Perfusion conditions in the LAD circulation were divided into three intervals: an aerobic, preischemic period (0-20 min); an is chemic period affected by a 60% reduction in LAD flow (20-60 min); and an aerobic, postischemic period (60-100 min). Steady-state infusions of [1-C-14]acetate and [9,10-H-3]palmitate were begun at 60 min perfus ion to monitor metabolism during reperfusion. Propionate had no effect on oxidation of acetate except for a slight delay in CO2 appearance. Propionate significantly suppressed oxidation of long-chain fatty acid s (-38 Delta%, P < 0.018), which was not explained by a selective scav enging of CoA units or carnitine by propionate, which might otherwise enhance fatty acid activation, transfer, or oxidation. Propionate by i ndirect estimates had no apparent effect on glucose metabolism. Propio nate-treated hearts, despite shifts in substrate preference, were not further compromised in energy metabolism as levels of creatine phospha te and adenine nucleotides were comparable to control hearts. Recovery of regional mechanical function was also comparable between groups bu t incompletely, with respect to preischemic performance, compatible wi th myocardial stunning. The data show in reperfused myocardium that pr opionate is capable of altering the preferred use of fatty acids, but that anaplerotic entry of carbon units during this reperfusion interva l was sufficient to prevent a selective imbalance of energy metabolism or deficit in mechanical recovery.