FUNCTIONAL AND BIOENERGETIC CONSEQUENCES OF POSTINFARCTION LEFT-VENTRICULAR REMODELING IN A NEW PORCINE MODEL - MRI AND P-31-MRS STUDY

Background The underlying mechanisms by which left ventricular remodel ing (LVR) leads to congestive heart failure (CHF) are unclear. This st udy examined the functional and bioenergetic abnormalities associated with postinfarction ventricular remodeling in a new, large animal mode l. Methods and Results Remodeling was induced circumflex coronary arte ry ligation in young pigs. LV mass, volume, ejection fraction (EF)I th e ratio of scar surface area to LV surface area, and LV wall stresses were calculated from magnetic resonance imaging anatomic data and simu ltaneously measured LV pressure. Hemodynamics, transmural blood flow, and high-energy phosphates (spatially localized P-31-nuclear magnetic resonance) were measured under basal conditions, during hyperperfusion induced by pharmacological vasodilation with adenosine, and during py ruvate infusion (11 mg/kg per minute IV). Six of 18 animals with coron ary ligation developed clinical CHF while the remaining 12 animals had LV dilation (LVR) without CHF. The results were compared with 16 norm al animals. EF decreased from 55.9+/-5.6% in normals to 34.6+/-2.3% in the LVR group (P<.05) and 24.2+/-2.8% in the CHF group (P<.05 versus LVR). The infarct scar was larger in CHF hearts than in LVR hearts (P< .05). In normals, LV myocardial creatine phosphate (CP)/ATP ratios wer e 2.10+/-0.10, 2.06+/-0.16, and 1.92+/-0.12 in subepicardium (EPI), mi d myocardium (MID), and subendocardium (ENDO), respectively. In LVR he arts, the corresponding ratios were decreased to 1.99+/-0.13, 1.80+/-0 .14, and 1.57+/-0.15 (ENDO P<.05 versus normal). In CHF hearts, CP/ATP ratios were 1.41+/-0.14, 1.33+/-0.15, and 1.25+/-0.15; (P<.05 versus LVR in EPI and MID). The calculated myocardial free ADP levels were si gnificantly increased only in CHF hearts. Conclusions Bioenergetic abn ormalities in remodeled myocardium are related to the severity of LV d ysfunction, which, in turn, is dependent on the severity of the initia ting myocardial infarction.