Cardiac performance and creatine kinase flux during inhibition of ATP synthesis in the perfused rat heart.
To study the relation among mitochondrial energy supply, cardiac performance, and energy transfer through creatine kinase (CK), two acute models of inhibition of ATP synthesis were compared in the isovolumic acetate-perfused rat heart. Similar impairments of mechanical performance (rate-pressure product, RPP) were achieved by various stepwise decreases in O(2) supply (PO(2) down to 20% of control) or by infusing CN (0.15-0.25 mM). The forward CK flux measured by saturation-transfer (31)P NMR spectroscopy was 6.1 +/- 0. 4 mM/s in control hearts. Only after severe hypoxia (PO(2) < 40% of control) did CK flux drop (to 1.9 +/- 0.2 mM/s at PO(2) = 25% of control) together with impaired systolic activity and a rise in end-diastolic pressure. In contrast, in mild hypoxia CK flux remained constant and similar to control (5.3 +/- 0.5 mM/s, not significant) despite a twofold reduction in systolic activity. Similarly in all CN groups, constant CK flux was maintained for a threefold reduction in RPP, showing the absence of a relation between cardiac performance and global NMR-measured CK flux during mild ATP synthesis inhibition.
Unité 446, Institut National de la Santé et de la Recherche Médicale, Cardiologie Cellulaire et Moléculaire, Université Paris-Sud, 92296 Chatenay Malabry, France.
P
P
Mateo
V
V
Stepanov
B
B
Gillet
J C
JC
Beloeil
J A
JA
Hoerter
D000255:Adenosine Triphosphate / Q000096:biosynthesis*; D000818:Animals; D003402:Creatine Kinase / Q000378:metabolism*; D006321:Heart / Q000502:physiology*; D000860:Hypoxia / Q000378:metabolism; D007700:Kinetics; D008297:Male; D009206:Myocardium / Q000201:enzymology*; D010100:Oxygen / Q000378:metabolism; D006180:Proton-Translocating ATPases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D000255:Adenosine Triphosphate; D003402:Creatine Kinase; D006180:Proton-Translocating ATPases; D010100:Oxygen