Metabolic alterations in the chronically denervated dog heart.
OBJECTIVE
Previous studies have shown that chronic cardiac denervation impairs myocardial glucose oxidation. To investigate this further we tested whether the tissue content of glucose transporters, activity of glycolytic enzymes or metabolic capacity of pyruvate dehydrogenase were altered. Moreover, we investigated whether the decline in glucose utilization was associated with an upregulation of proteins and enzymes involved in fatty acid handling. Chronic cardiac denervation results also in decreased left ventricular efficiency. We explored whether alterations in mitochondrial properties could be held responsible for this phenomenon.


METHODS
Twelve adult dogs were included in the study. In 6 of them chronic cardiac denervation was accomplished by surgical ablation of the extrinsic nerve fibers. The other 6 dogs were sham-operated. Biopsies were obtained from the left ventricle after 4-5 weeks of denervation. The content or enzymatic activity of proteins involved in fatty acid and glucose handling was assessed. Features of glutamate oxidation were measured in freshly isolated mitochondria.


RESULTS
The content or activity of a set of fatty acid handling proteins did not change during chronic cardiac denervation. In contrast GLUT1 content significantly increased in the chronically denervated left ventricle, while the active form of pyruvate dehydrogenase declined (p < 0.05). Glutamate oxidation characteristics in freshly isolated mitochondria were not affected by chronic denervation.


CONCLUSIONS
The impairment of glucose oxidation in the chronically denervated myocardium is most likely caused by a decline of pyruvate dehydrogenase in its active form. It is unlikely that the decrease in work efficiency is caused by alterations in mitochondrial properties.
van der Vusse
G J
GJ
Department of Physiology, Maastricht University, Netherlands. vandervusse@fys.unimaas.nl
Dubelaar
M L
ML
Coumans
W A
WA
Seymour
A M
AM
Clarke
S B
SB
Bonen
A
A
Drake-Holland
A J
AJ
Noble
M I
MI
D000818:Animals; D002333:Carnitine Acyltransferases / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004285:Dogs; D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids / Q000097:blood / Q000378:metabolism*; D005260:Female; D005947:Glucose / Q000378:metabolism*; D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D018698:Glutamic Acid / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D006321:Heart / Q000294:innervation; D050356:Lipid Metabolism; D008055:Lipids / Q000097:blood; D008297:Male; D008929:Mitochondria, Heart / Q000378:metabolism; D009004:Monosaccharide Transport Proteins / Q000378:metabolism; D009124:Muscle Proteins; D018996:Myelin P2 Protein / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D009363:Neoplasm Proteins; D010084:Oxidation-Reduction; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism; D013562:Sympathectomy
D002352:Carrier Proteins; D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids; D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D008055:Lipids; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D018996:Myelin P2 Protein; D009363:Neoplasm Proteins; D011768:Pyruvate Dehydrogenase Complex; D018698:Glutamic Acid; D006003:Glycogen; D002333:Carnitine Acyltransferases; D005947:Glucose