Creatine kinase kinetics studied by phosphorus-31 nuclear magnetic resonance in a canine model of chronic hypertension-induced cardiac hypertrophy

Abstract

To determine whether cardiac hypertrophy secondary to chronic renovascular hypertension is associated with altered in vivo myocardial metabolism, phosphorus-31 nuclear magnetic resonance saturation transfer techniques were used to study creatine kinase (CK) kinetics in six chronically hypertensive dogs with moderate cardiac hypertrophy and eight control dogs. The forward rate constant of CK and the flux of phosphocreatine to adenosine triphosphate were determined in both groups of dogs before and during norepinephrine administration (1 μg/kg per min), used to increase heart rate × systolic blood pressure (rate-pressure product), cardiac output and oxygen consumption.Baseline and norepinephrine-induced changes in rate-pressure product, cardiac output and oxygen consumption were similar in both groups of dogs, as were baseline forward rate constant and flux of phosphocreatine to adenosine triphosphate. However, the norepinephrine-induced changes in forward rate constant and flux were significantly less in hypertensive than in control dogs (p < 0.05) even though changes in hemodynamic and functional variables were similar in both groups.These data demonstrate that moderate myocardial hypertrophy is associated with altered CK kinetics, which do not appear to affect the heart's ability for global mechanical recruitment at this stage in the hypertensive process. It is possible that the changes in myocardial enzyme kinetics may contribute to diastolic dysfunction previously reported in this model and may be a precursor for ultimate development of heart failure if hypertension is maintained for prolonged periods.The data also suggest that the heart of moderately hypertensive animals may work less per gram muscle and that it may have greater metabolic efficiency because it can maintain lower adenosine diphosphate levels (as indicated by lower forward rate constant of CK) than those of control hearts. However, it appears that either the CK system has a large safety factor such that the lower forward rate constant and flux found in hypertensive dogs is sufficient to support normal global mechanical function or that the phosphocreatine shuttle is not a critical factor in maintaining mechanical function in the moderately hypertrophied heart.