Myocardial creatine kinase kinetics and isoform expression in hearts with severe LV hypertrophy

Left ventricular (LV) hypertrophy (LVH) results in a fetal shift in myocard ial creatine kinase (CK) expression. Because CK plays an important role in intracellular energy production, transport, and utilization, this study was performed to characterize changes in CK expression and CK flux in severe p ressure-overload LVH. Ascending aortic banding in 8-wk-old dogs resulted in LVH with a 92% increase in relative LV mass. In LVH hearts, CK-M isoform m RNA was decreased by 40% (P = 0.05) and protein was decreased by 50% (P<0.0 1), whereas mitochondrial CK protein was decreased by 22% (P<0.05). CK-B is oform mRNA was undetectable in normal hearts but was prominently expressed in LVH (P<0.01); CK-B protein was increased by more than 10-fold in LVH (P< 0.01). Despite these changes, total CK activity was normal in LVH. Myocardi al CK flux was examined using P-31 magnetic resonance spectroscopy magnetiz ation transfer. The CK forward rate constant was similar in normal and LVH hearts at baseline and did not change in either group during dobutamine tre atment. In hearts with LVH, the CK forward flux rate was reduced by similar to 60% (P<0.05) and decreased further during dobutamine. Thus, although pr essure-overload LVH caused alterations of expression of both CK mRNA and pr otein levels, LV performance and oxygen consumption in response to dobutami ne were normal. However, myocardial free ADP was increased in LVH hearts. T his finding suggests that the CK alterations result in a need for higher AD P levels to maintain ATP synthesis in the hypertrophied heart.