Myocardial creatine kinase kinetics in hearts with postinfarction left ventricular remodeling

This study examined whether alterations in myocardial creatine kinase (CK) kinetics and high-energy phosphate (HEP) levels occur in postinfarction lef t ventricular remodeling (LVR). Myocardial HEP and CK kinetics were examine d in 19 pigs 6 wk after myocardial infarction was produced by left circumfl ex coronary artery ligation, and the results were compared with those from 9 normal pigs. Blood flow (microspheres), oxygen consumption ((M(V)over dot O(2)), HEP levels [P-31 magnetic resonance spectroscopy (MRS)], and CK kine tics (P-31 MRS) were measured in myocardium remote from the infarct under b asal conditions and during dobutamine infusion (20 mu g.kg(-1).min(-1) iv). Six of the pigs with LVR had overt congestive heart failure (CHF) at the t ime of study. Under basal conditions, creatine phosphate (CrP)-to-ATP ratio s were lower in all transmural layers of hearts with CHF and in the subendo cardium of LVR hearts than in normal hearts (P < 0.05). Myocardial ATP (bio psy) was significantly decreased in hearts with CHF. The CK forward rate co nstant 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 forwar d flux rates in CHF, LVR, and normal groups were 6.4 +/- 2.3, 14.3 +/- 2.1, and 20.3 +/- 2.4 mu mol.g(-1).s(-1), respectively (P < 0.05, CHF vs. LVR a nd LVR vs. normal). Dobutamine caused doubling of the rate-pressure product in the LVR and normal groups, whereas CHF hearts failed to respond to dobu tamine. CK flux rates did not change during dobutamine in any group. The ra tios of CK flux to ATP synthesis (from M(V)over dotO(2)) under baseline con ditions were 10.9 +/- 1.2, 8.03 +/- 0.9, and 3.86 +/- 0.5 for normal, LVR, and CHF hearts, respectively teach 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 rate s are decreased in hearts with postinfarction LVR, but this change does not limit the response to dobutamine. In hearts with end-stage CHF, the change s in HEP and CK flux are more marked. These changes could contribute to the decreased responsiveness of these hearts to dobutamine.