The hypertrophied myocardium accumulates the MB-creatine kinase isozyme

Abstract

Myocardial hypertrophy was produced in the dog by volume overload, secondary to hypertension, and pressure overload to left or right ventricles and in the rat by pressure overload to the left or right ventricles, by elevating thyroxine-levels and secondary to spontaneous hypertension in order to test whether there are changes in the creatine kinase system in hypertrophied heart. Although there was little or no change in total creatine kinase activity, there were changes in the distribution of the creatine kinase isozymes. In the dog, a 4-10-fold increase in the tissue content of MB-creatine kinase was observed for heart chambers with a 40-90% increase in the ratio of ventricular weight to body weight. In the rat, MB-creatine kinase also accumulated in hypertrophied ventricles. For the spontaneously hypertensive rat, the correlation between increased fetal creatine kinase isozymes and increased ratio of ventricular weight to body weight was excellent (r approximately 0.92). During the transition from compensated hypertrophy to failure in the spontaneously hypertensive rat, there is a 50% decrease in mitochondrial creatine kinase activity. P-31 NMR magnetization transfer experiments suggest that flux through the creatine kinase reaction is 3-fold lower than normal in these failing hearts. These results show that there are changes in the distribution of the creatine kinase isozymes in hypertrophied heart and suggest that one of these changes characterizes compensated hypertrophy (increased fetal-type creatine kinase isozymes) while another characterizes the transition to failure (decreased mitochondrial creatine kinase).

Development and Evaluation of a New Canine Myocardial Infarction Model Using a Closed-Chest Injection of Thrombogenic Material

“…In the present study, serum CK-MB, m-GOT and HBD transiently increased 1 day after coronary artery occlusion. The changes in the serum enzyme levels with time after coronary artery occlusion were in agreement with previously reported clinical data in patients with AMI, [15][16][17][18] which would seem to confirm infarction. Indeed, extensive transmural anteroinferior myocardial infarction was observed.…”

Acute toxicity of doxorubicin on isolated perfused heart: response of kinases regulating energy supply

“…Basically, such an isoenzyme shift is known to occur in the heart under chronic pathological conditions, as, e.g., in hypertrophy, characterized by a compromised cellular energy state (15,20,45,52). First, higher levels of BCK protein led to an increase in the enzymatic activity of BBCK and MBCK, which may efficiently compensate for an inhibition of other CK isoenzymes, mainly MMCK.…”

Bioenergetic abnormalities associated with severe left ventricular hypertrophy.

“…In rat models of LVH, the greatest abnormalities of intracellular enzyme composition and bioenergetics were also associated with the more severe later stages of LVH (36).…”

“…These considerations suggest that the causes of the abnormalities in HEP levels in severely hypertrophied myocardium are complex and likely reflect alterations of many cellular characteris- enzyme activity in hypertrophied myocardium. Ingwall et al (36,37) found an increased percentage of the fetal-type isoenzyme ofCK, but decreased mitochondrial CK activity in moderately hypertrophied myocardium. Saturation transfer 31P-NMR studies in the setting of myocardial hypertrophy have suggested that CK forward flux is reduced (as compared with normal) during inotropic stimulation (38).…”