Effect of global myocardial stunning on Ca2(+)-sensitive myofibrillar ATPase activity and creatine kinase kinetics.

Reperfusion of rabbit hearts after 15 min of global ischemia at 37 degrees C depressed developed pressure by 36% (myocardial stunning). Changes in myofilament function were investigated as causes of this depression. Kinetic analysis of the effects of stunning on myofibrillar catalyzed ATP hydrolysis showed that stunning lowered Michaelis constant (Km) slightly and left maximal enzyme reaction velocity unaltered in the stunned myofilaments. The myofilament end of the creatine kinase (CK) shuttle was also found to be unaffected in the stunned myofibrils. The Km ADP for myofibrillar CK from control and stunned hearts was 60.45 +/- 3.45 and 68.04 +/- 2.42 microM, respectively, and the CK activity at 100 microM ADP was 0.63 +/- 0.08 and 0.67 +/- 0.04 IU/mg myofibrillar protein from control and stunned hearts, a rate three times greater than the myofibrillar adenosinetriphosphatase (ATPase) rate and a rate sufficient to deliver ATP to the myofilaments. Myofilament Ca2+ sensitivity was assessed by measuring Ca2(+)-dependent myofibrillar Mg2(+)-ATPase activity at free [Ca2+] ranging from 10 nM to 32 microM and [Mg.ATP] of 0.8, 1.6, and 3.2 mM. The sensitivity of myofilaments to activation by Ca2+ was unaltered in the myofibrils isolated from stunned hearts. It is concluded from these analyses that the depression of pressure development observed in stunned hearts is not due to a defect in myofilament function.