Effects of in vivo heart irradiation on myocardial energy metabolism in rats.
To investigate the effect of in vivo heart irradiation on myocardial energy metabolism, we measured myocardial adenosine nucleotide concentrations and mitochondrial oxygen consumption in left ventricular tissue of rats 0-16 months after local heart irradiation (20 Gy). At 24 h and 2 months no difference in myocardial adenosine nucleotide concentration was apparent between irradiated and control hearts. The total myocardial adenosine nucleotide concentrations in irradiated hearts compared to those of nonirradiated controls tended to be lower from 4 months onward. The rate of oxidative energy production (state 3 respiration) in irradiated hearts was significantly reduced compared with that of age-matched controls from 2 months onward. Moreover, as a result of aging, a time-dependent decrease in the rate of oxidative energy production was observed in both irradiated and control hearts (P < 0.001). The respiratory control index (RCI = oxygen consumption in state 3/oxygen consumption in state 4) in irradiated hearts was not different from the RCI measured in age-matched control animals. During the period of study the RCI diminished significantly with age in both groups (P < 0.005). The number of oxygen atoms used per molecule of ADP phosphorylated (P/O ratio) was not influenced by the irradiation. The P/O ratio for the NAD(+)-linked substrates remained unchanged at a value of about 3 during the period studied. At 6 months after irradiation activities of myocardial enzymes such as lactate dehydrogenase, creatine kinase, citrate synthase, and cytochrome c oxidase were reduced. The reduction in myocardial energy production and the changes in energy supplies provide a mechanism to explain impaired contractility after local heart irradiation.
Franken
N A
NA
Department of Clinical Oncology, University Hospital, Leiden, The Netherlands.
Hollaar
L
L
Bosker
F J
FJ
van Ravels
F J
FJ
van der Laarse
A
A
Wondergem
J
J
D000227:Adenine Nucleotides / Q000032:analysis; D000818:Animals; D004734:Energy Metabolism / Q000528:radiation effects*; D005260:Female; D006321:Heart / Q000528:radiation effects*; D008929:Mitochondria, Heart / Q000378:metabolism / Q000528:radiation effects; D009206:Myocardium / Q000378:metabolism*; D010101:Oxygen Consumption / Q000528:radiation effects; D051381:Rats; D017207:Rats, Sprague-Dawley
D000227:Adenine Nucleotides