The effects of cyanide and iodoacetate intoxication and ischaemia on enzyme release from the perfused rat heart.
Isolated rat hearts perfused in the presence of iodoacetate show inhibition of glycolysis and release enzymes into the perfusate. Hearts perfused with cyanide, a mitochondrial inhibitor, show acceleration of glycolysis and no enzyme release. The adenine nucleotide content of the iodoacetate, but not the cyanide-perfused hearts was reduced. These results indicate that the membranes were permeable in the former treatment group. The adenylate energy charge and the ATP content of both the cyanide and iodoacetate treatment groups were similar but, as the extent of enzyme release was quite different, it appears that the energy state of the cell was not the prime factor controlling membrane integrity. Isolated perfused hearts were rendered ischaemic by placing a one-way ball valve in the aortic outflow tract. ATP concentration declined, as did ADP after an initial rise of short duration. AMP concentrations rose as the time of ischaemia increased. At the time at which enzyme release was first determined, the intracellular total adenine nucleotide content began to decline, suggesting that the membrane had become permeable to both small and large molecules. Glycolysis was stimulated by the hypoxia induced in the preparation and then this increase became inhibited. The point at which this inhibition was observed was also the point at which membrane permeability was evident. Taken together, the data from these experiments suggest that the energy derived from the activity of the glycolytic pathway may be important to the heart for maintenance of membrane function, particularly in ischaemia.
D000227:Adenine Nucleotides / Q000378:metabolism; D000818:Animals; D002463:Cell Membrane Permeability / Q000187:drug effects; D003327:Coronary Disease / Q000378:metabolism; D003486:Cyanides / Q000633:toxicity*; D004734:Energy Metabolism / Q000187:drug effects; D006019:Glycolysis / Q000187:drug effects; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D007461:Iodoacetates / Q000633:toxicity*; D019807:Iodoacetic Acid; D007770:L-Lactate Dehydrogenase / Q000378:metabolism*; D008297:Male; D009206:Myocardium / Q000378:metabolism; D010477:Perfusion; D051381:Rats
D000227:Adenine Nucleotides; D003486:Cyanides; D007461:Iodoacetates; D007770:L-Lactate Dehydrogenase; D019807:Iodoacetic Acid