Detrimental actions of endogenous fatty acids and their derivatives. A study of ischaemic mitochondrial injury.
Functional and structural alterations of myocardial mitochondria were investigated after four conditions of myocardial ischaemia in guinea pig heart: (1) 45 min complete ischaemia, (2) 60 min low-flow anoxic perfusion (0.3 ml/g wet weight per minute) with a modified Tyrode solution, (3) as (2) with 0.4 mM palmitic acid added to the perfusate, and (4) as (2) with 0.4 mM oleic acid added. Under conditions (1) and (2) the loss of tissue ATP (20-30% of aerobic control) and the degree of mitochondrial injury were similar. But when fatty acids were present during low-flow anoxia, ATP loss and mitochondrial injury were more severe. Oleic acid caused greater injury than palmitic acid. The extent of mitochondrial injury corresponded to variations in mitochondrial long-chain acyl CoA content. Compared to aerobic control values, acyl CoA was increased 1.5 fold under condition (1), not significantly altered under condition (2), increased 3.2 fold under condition (3) and increased 4.3 fold under condition (4). In low-flow anoxia fatty acids enhanced the depression of oxidative phosphorylation, the loss of cytochromes, the inhibition of adenine nucleotide translocase and the reduction of mitochondrial Ca2+ sequestration. Fatty acid induced injury differed in quality from that of conditions (1) and (2): complex II dependent respiration was markedly affected, cytochrome b was lost extensively, and cytochrome oxidase activity was distinctly reduced. The results indicate that fatty acids, when administered to ischaemic myocardium, interfere with mitochondrial membranes at several sites, probably by their CoA esters. The more lipophilic oleyl moiety has a greater effect than the palmityl moiety.
Piper
H M
HM
Zentrum Physiologie, Universität Düsseldorf, F.R.G.
Das
A
A
D000214:Acyl Coenzyme A / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002331:Carnitine / Q000378:metabolism; D003327:Coronary Disease / Q000378:metabolism*; D003580:Cytochromes / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008929:Mitochondria, Heart / Q000378:metabolism*; D000226:Mitochondrial ADP, ATP Translocases / Q000378:metabolism; D010085:Oxidative Phosphorylation; D010477:Perfusion
D000214:Acyl Coenzyme A; D003580:Cytochromes; D005227:Fatty Acids; D000255:Adenosine Triphosphate; D000226:Mitochondrial ADP, ATP Translocases; D003576:Electron Transport Complex IV; D002331:Carnitine