Myocardial creatine kinase kinetics in hearts with postinfarction left ventricular remodeling

Yo Murakami, Jianyi J Zhang, Marcel H.J. Eijgelshoven, Wei Chen, Wenda C. Carlyle, Yi Zhang, Guangrong Gong, Robert J Bache

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Abstract

This study examined whether alterations in myocardial creatine kinase (CK) kinetics and high-energy phosphate (HEP) levels occur in postinfarction left ventricular remodeling (LVR). Myocardial HEP and CK kinetics were examined in 19 pigs 6 wk after myocardial infarction was produced by left circumflex coronary artery ligation, and the results were compared with those from 9 normal pigs. Blood flow (microspheres), oxygen consumption (MV̇O2), HEP levels [31P magnetic resonance spectroscopy (MRS)], and CK kinetics (31P MRS) were measured in myocardium remote from the infarct under basal conditions and during dobutamine infusion (20 μg · kg-1 · min-1 iv). Six of the pigs with LVR had overt congestive heart failure (CHF) at the time of study. Under basal conditions, creatine phosphate (CrP)-to-ATP ratios were lower in all transmural layers of hearts with CHF and in the subendocardium of LVR hearts than in normal hearts (P < 0.05). Myocardial ATP (biopsy) was significantly decreased in hearts with CHF. The CK forward rate constant was lower (P < 0.05) in the CHF group (0.21 ± 0.03 s-1) than in LVR (0.38 ± 0.04 s-1) or normal groups (0.41 ± 0.03 s-1); CK forward flux rates in CHF, LVR, and normal groups were 6.4 ± 2.3, 14.3 ± 2.1, and 20.3 ± 2.4 μmol · g-1 · s-1, respectively (P < 0.05, CHF vs. LVR and LVR vs. normal). Dobutamine caused doubling of the rate-pressure product in the LVR and normal groups, whereas CHF hearts failed to respond to dobutamine. CK flux rates did not change during dobutamine in any group. The ratios of CK flux to ATP synthesis (from MV̇O2) under baseline conditions were 10.9 ± 1.2, 8.03 ± 0.9, and 3.86 ± 0.5 for normal, LVR, and CHF hearts, respectively (each P < 0.05); during dobutamine, this ratio decreased to 3.73 ± 0.5, 2.58 ± 0.4, and 2.78 ± 0.5, respectively (P = not significant among groups). These data demonstrate that CK flux rates are decreased in hearts with postinfarction LVR, but this change does not limit the response to dobutamine. In hearts with end-stage CHF, the changes in HEP and CK flux are more marked. These changes could contribute to the decreased responsiveness of these hearts to dobutamine.

Original languageEnglish (US)
Pages (from-to)H892-H900
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume276
Issue number3 45-3
StatePublished - Mar 1 1999

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Keywords

  • 31-phosphorus nuclear magnetic resonance spectroscopy
  • Coronary occlusion
  • Heart failure
  • High-energy phosphates

Cite this

Murakami, Y., Zhang, J. J., Eijgelshoven, M. H. J., Chen, W., Carlyle, W. C., Zhang, Y., Gong, G., & Bache, R. J. (1999). Myocardial creatine kinase kinetics in hearts with postinfarction left ventricular remodeling. American Journal of Physiology - Heart and Circulatory Physiology, 276(3 45-3), H892-H900.