Anaplerotic effects of propionate on oxidations of acetate and long-chain fatty acids.

Studies were performed to test the influence of propionate as a competing myocardial substrate on acetate and palmitate metabolism in reperfused pig hearts after an exposure of mild-to-moderate regional ischemia. Experiments were conducted in intact, working pig hearts (n = 10) using 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 ischemic 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(-14)C) acetate and [9, 10(-3)H] palmitate were begun at 60 min perfusion 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 acids (-38 delta %, P < 0.018), which was not explained by a selective scavenging of CoA units or carnitine by propionate, which might otherwise enhance fatty acid activation, transfer, or oxidation. Propionate by indirect estimates had no apparent effect on glucose metabolism. Propionate-treated hearts, despite shifts in substrate preference, were not further compromised in energy metabolism as levels of creatine phosphate and adenine nucleotides were comparable to control hearts. Recovery of regional mechanical function was also comparable between groups but incompletely, with respect to preischemic performance, compatible with myocardial stunning. The data show in reperfused myocardium that propionate is capable of altering the preferred use of fatty acids, but that anaplerotic entry of carbon units during this reperfusion interval was sufficient to prevent a selective imbalance of energy metabolism or deficit in mechanical recovery.