AJP - Heart and Circulatory Physiology, Vol 251, Issue 3 547-H553, Copyright © 1986 by American Physiological Society
Effects of 2-tetradecylglycidic acid on myocardial function in swine hearts
W. P. Miller, A. J. Liedtke and S. H. Nellis
Fatty acids in excess impair myocardial function in intact hearts both
during aerobic and ischemic blood flow. The purpose of these studies was to
determine whether decreases in acylcarnitine, effected by
2-tetradecylglycidic acid (TDGA), would result in the preservation of
myocardial function in intact hearts during fatty acid excess. Two groups
of intact working swine hearts in which serum fatty acids were augmented
three- to fourfold were perfused extracorporeally with whole blood and
compared over 90 min. Labeled [U-14C]palmitate was administered selectively
into the left anterior descending coronary circulation to follow fatty acid
oxidation, and regional myocardial function was assessed with ultrasonic
crystals. Coronary flow in this bed was decreased by 50% over the final 30
min of perfusion. Treated swine (n = 10) were compared with a
placebo-treated control group (n = 9). At similar levels of aerobic flow,
TDGA effected a marked decrease in 14CO2 production during 60 min of
aerobic perfusion, but levels were similar during the final 30 min of
ischemia. Tissue levels of acylcarnitine were significantly reduced and
acetyl-CoA levels significantly increased in TDGA-treated hearts both in
aerobic and ischemic myocardium. This inhibition of fatty acid metabolism
during aerobic flow was associated with an increase in regional myocardial
shortening in the treated group. This occurred at similar levels of O2
consumption, evidencing enhanced carbohydrate substrate utilization. During
the first 30 min of ischemia 14CO2 production and mechanical function were
compromised similarly, whereas lactate production was 70% less (P less than
0.025) in the treated group.(ABSTRACT TRUNCATED AT 250 WORDS)
