Anaplerotic effects of propionate on the oxidations of acetate and
long-chain fatty acids.
Liedtke, A. James, Timothy Hacker, Britta Renstrom, Stephen H. Nellis.
Cardiology Section, University of Wisconsin Hospital and Clinics,
600 Highland Avenue, H6/372, Madison, WI 53792-3248
APStracts 2:0520H, 1995.
Studies were performed to test the influence of propionate as a
competing myocardial substrate upon acetate and palmitate metabolism
in reperfused pig hearts following 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 2mM propionate selectively into the
anterior descending (LAD) perfusate. Perfusion conditions in the LAD
circulation were divided into three intervals: an aerobic, pre
-ischemia period (0-20 min), an ischemic period affected by a 60%
reduction in LAD flow (20-60 min), and an aerobic, post-ischemic
period (60-100 min). Steady state infusions of [1-14C] acetate and
[9,10-3H] 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 _%,
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 incomplete 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.
Received 8 September 1995; accepted in final form 9 November
1995.
APS Manuscript Number H845-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 8 December 95