BIOENERGETIC CONSEQUENCES OF LEFT-VENTRICULAR REMODELING

Background Left ventricular (LV) remodeling is associated with LV dysfunction and decrease of coronary flow reserve. The underlying mechanisms responsible for these alterations are unclear. Changes in myocardial high-energy phosphate levels may be associated with these alterations. Methods and Results Twelve dogs with LV remodeling secondary to discrete necrosis produced by transmyocardial DC shock were compared with 8 normal dogs. LV mass and end-diastolic volume were measured by magnetic resonance imaging 7 days before and 12.9+/-1.3 months after DC shock. Transmurally localized P-31 nuclear magnetic resonance spectra from five layers across the LV wall were obtained simultaneously with transmural blood flow measurements (microspheres) under basal conditions and during pacing at 200 and 240 beats per minute. LV mass and end-diastolic volume were significantly increased after DC shock (33% and 26%, respectively, each P<.01). Under basal conditions, the subendocardial creatine phosphate (CP)/ATP ratio was significantly lower in remodeled LV compared with the control group (1.71+/-0.09 versus 2.04+/-0.09, P<.05). The subendocardial CP/ATP ratio was inversely correlated with both the increase in LV mass and LV end-diastolic volume (r=-.77 and r=-.70, P<.01 and P<.05, respectively). In remodeled myocardium, pacing induced a significant increase in LV end-diastolic pressure (from 8+/-1 to 20+/-3 mm Hg, P<.05), which was accompanied by a significant decrease of subendocardial/subepicardial (Endo/Epi) blood flow ratio (from 1.01+/-0.10 to 0.63+/-0.11, P<.05) and a significant decrease in subendocardial CP/ATP ratio (from 1.78+/-0.07 to 1.61+/-0.10, P<.05) and increase of Delta P-i/ATP ratio (from 0 to 0.24+/-0.05, P<.01). The decrease in subendocardial CP/ATP ratio was correlated with the decrease in Endo/Epi blood flow ratio (r=.79, P<.05). Conclusions These results demonstrate that alterations in myocardial high-energy phosphate levels are correlated with the extent of LV remodeling. In remodeled hearts, pacing-induced tachycardia produces further changes of myocardial high-energy phosphate levels in the subendocardium that appear to be related to ventricular dysfunction and redistribution of blood flow away from the subendocardium.