title: [Metabolic and functional consequences of complete inhibition of creatine kinase by iodoacetamide in the perfused heart].
abstract: Treatment of perfused rat hearts with 0.5 mM iodoacetamide (IAAm) for 15 min at different workloads resulting in a nearly complete inhibition of creatine kinase (CK, 99%) was followed by a rapid decline of the phosphocreatine (PCr) level (30%) and a 2-fold increase of the P(i) level which then stabilized. Conversely, the ATP content started to drop monotonously at the beginning of the IAAm washout and reached 30% 90 min after the IAAm removal under medium load. Under low workload the ATP decay occurred at later periods. Neither the ADP-stimulated mitochondrial respiration in skinned fibers, nor the Ca(2+)-stimulated ATPase activity of myofibrils was affected by IAAm treatment. The sensitivity of the resting tension of skinned fibers to Ca2+ tended to a slight increase. The cardiac work index (PRP-pressure-rate product) decreased by 25%, while the end diastolic pressure (EDP) rose by 15 mm Hg when IAAm acted under medium load. In contrast, under low work these parameters were practically stable. The hearts poisoned with IAAm performed a two times lower maximal work and had reduced (by 35%) oxygen consumption rates. The efficiency of energy utilization for mechanical work decreased by 40%. The changes in PRP and EDP correlated with the cytosolic [ATP]/[ADP] ratio in such a way that the decrease in the latter was associated with a decrease in PRP and the elevation of EDP. These data suggest that the creatine kinase system is necessary for the effective translation of a high [ATP]/[ADP] ratio from the intermembrane space of mitochondria to the cytoplasm, myofibrils and ionic pumps. This provides a high level of mechanical work and good relaxation of the left ventricle and protects cytosolic adenine nucleotides from the breakdown.
authors.forename: O V
authors.initials: OV
authors.lastname: Korchazhkina
authors.forename: V L
authors.initials: VL
authors.lastname: Lakomkin
authors.forename: V I
authors.initials: VI
authors.lastname: Veksler
authors.forename: A Ia
authors.initials: AIa
authors.lastname: Shteĭnshneĭder
authors.forename: G V
authors.initials: GV
authors.lastname: Elizarova
authors.forename: V A
authors.initials: VA
authors.lastname: Saks
authors.forename: V I
authors.initials: VI
authors.lastname: Kapel'ko
authors.forename: V V
authors.initials: VV
authors.lastname: Kupriianov
mesh_terms: D000227:Adenine Nucleotides / Q000378:metabolism; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D003402:Creatine Kinase / Q000037:antagonists & inhibitors*; D004734:Energy Metabolism; D007460:Iodoacetamide / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008929:Mitochondria, Heart / Q000378:metabolism; D009206:Myocardium / Q000201:enzymology*; D010100:Oxygen / Q000378:metabolism; D010477:Perfusion; D010725:Phosphocreatine / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D000227:Adenine Nucleotides; D010725:Phosphocreatine; D003402:Creatine Kinase; D000251:Adenosine Triphosphatases; D010100:Oxygen; D007460:Iodoacetamide