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 (MO₂), 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 · kg¹ · min¹ 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 s¹) than in LVR (0.38 ± 0.04 s¹) or normal groups (0.41 ± 0.03 s¹); 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 · g¹ · s¹, 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 MO₂) 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.

heart failure; high-energy phosphates; 31-phosphorus nuclear magnetic resonance spectroscopy; coronary occlusion

This article has been cited by other articles:

				Q. Xiong, Q. Li, A. Mansoor, M. N. Jameel, F. Du, W. Chen, and J. Zhang Novel strategy for measuring creatine kinase reaction rate in the in vivo heart Am J Physiol Heart Circ Physiol, September 1, 2009; 297(3): H1010 - H1019. [Abstract] [Full Text] [PDF]

				J. Feygin, A. Mansoor, P. Eckman, C. Swingen, and J. Zhang Functional and bioenergetic modulations in the infarct border zone following autologous mesenchymal stem cell transplantation Am J Physiol Heart Circ Physiol, September 1, 2007; 293(3): H1772 - H1780. [Abstract] [Full Text] [PDF]

				A. V. Naumova, V. P. Chacko, R. Ouwerkerk, L. Stull, E. Marban, and R. G. Weiss Xanthine oxidase inhibitors improve energetics and function after infarction in failing mouse hearts Am J Physiol Heart Circ Physiol, February 1, 2006; 290(2): H837 - H843. [Abstract] [Full Text] [PDF]

				G. Gong, J. Liu, P. Liang, T. Guo, Q. Hu, K. Ochiai, M. Hou, Y. Ye, X. Wu, A. Mansoor, et al. Oxidative capacity in failing hearts Am J Physiol Heart Circ Physiol, July 11, 2003; 285(2): H541 - H548. [Abstract] [Full Text] [PDF]

				Y. Ye, C. Wang, J. Zhang, Y. K. Cho, G. Gong, Y. Murakami, and R. J. Bache Myocardial creatine kinase kinetics and isoform expression in hearts with severe LV hypertrophy Am J Physiol Heart Circ Physiol, July 1, 2001; 281(1): H376 - H386. [Abstract] [Full Text] [PDF]

				Y. Ye, G. Gong, K. Ochiai, J. Liu, and J. Zhang High-Energy Phosphate Metabolism and Creatine Kinase in Failing Hearts : A New Porcine Model Circulation, March 20, 2001; 103(11): 1570 - 1576. [Abstract] [Full Text] [PDF]

				M. Wyss and R. Kaddurah-Daouk Creatine and Creatinine Metabolism Physiol Rev, July 1, 2000; 80(3): 1107 - 1213. [Abstract] [Full Text] [PDF]