Chronic catecholamine depletion switches myocardium from carbohydrate to lipid utilisation.
OBJECTIVE
Chronic cardiac transplantation denervation (i.e., global sympathetic denervation with myocardial catecholamine depletion, plus parasympathetic denervation) is known to inhibit myocardial oxidation of glucose. It is not known whether this is due to increased utilization of lactate, lipid or ketone bodies. The purpose of the present study was to test the hypothesis that the extraction and contribution of blood-borne fatty acids (FA) to overall oxidative energy conversion is increased.


METHODS
In anaesthetised dogs (control n = 6, cardiac denervated n = 6), we investigated fatty acid (FA) utilization. The studies were made at least four weeks after surgical cardiac denervation. Measurements were made of total FAs and with a radio-labelled tracer (U-14C palmitate).


RESULTS
The contribution of FA utilisation to overall substrate oxidation rose from 31% (control) to 48% (cardiac denervated). The increase in the ratio (%) of CO2 production from palmitate oxidation to total CO2 production increased from 4.0 +/- 1.8 (control) to 10.6 +/- 5.8 (denervated, p = 0.04). The time from uptake of FA to release of CO2 product was unaltered.


CONCLUSIONS
We conclude that the contribution of FA oxidation to overall energy conversion is increased in chronically denervated hearts, which is postulated to result from a decline in the active form of pyruvate dehydrogenase. This would appear to be a result of chronic catecholamine depletion.
Drake-Holland
A J
AJ
Cardiothoracic Surgery, National Heart and Lung Institute, Imperial College School of Medicine, University of London, UK. a.drake-holland@ic.ac.uk
Van der Vusse
G J
GJ
Roemen
T H
TH
Hynd
J W
JW
Mansaray
M
M
Wright
Z M
ZM
Noble
M I
MI
D000704:Analysis of Variance; D000818:Animals; D050260:Carbohydrate Metabolism; D003714:Denervation; D004285:Dogs; D004734:Energy Metabolism; D005230:Fatty Acids, Nonesterified / Q000097:blood / Q000378:metabolism*; D005260:Female; D006321:Heart / Q000294:innervation; D016027:Heart Transplantation; D006439:Hemodynamics; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism*
D005230:Fatty Acids, Nonesterified; D011768:Pyruvate Dehydrogenase Complex