(Circulation. 1996;94:1089-1100.)
© 1996 American Heart Association, Inc.
Articles |
Functional and Bioenergetic Consequences of Postinfarction Left Ventricular Remodeling in a New Porcine Model
MRI and 31P-MRS Study
the Departments of Biochemistry, Medicine, and Radiology and the Center for Magnetic Resonance Research, University of Minnesota, and the Department of Veterans Affairs Medical Center, Minneapolis, Minn.
Correspondence to Jianyi Zhang, MD, PhD, Box 508, University of Minnesota Health Science Center, 420 Delaware St SE, Minneapolis, MN 55455. E-mail zhang047@maroon.tc.umn.edu.
Background The underlying mechanisms by which left ventricular remodeling (LVR) leads to congestive heart failure (CHF) are unclear. This study examined the functional and bioenergetic abnormalities associated with postinfarction ventricular remodeling in a new, large animal model.
Methods and Results Remodeling was induced by circumflex coronary artery ligation in young pigs. LV mass, volume, ejection fraction (EF), the ratio of scar surface area to LV surface area, and LV wall stresses were calculated from magnetic resonance imaging anatomic data and simultaneously measured LV pressure. Hemodynamics, transmural blood flow, and high-energy phosphates (spatially localized 31P–nuclear magnetic resonance) were measured under basal conditions, during hyperperfusion induced by pharmacological vasodilation with adenosine, and during pyruvate infusion (11 mg/kg per minute IV). Six of 18 animals with coronary ligation developed clinical CHF while the remaining 12 animals had LV dilation (LVR) without CHF. The results were compared with 16 normal 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 were 2.10±0.10, 2.06±0.16, and 1.92±0.12 in subepicardium (EPI), mid myocardium (MID), and subendocardium (ENDO), respectively. In LVR hearts, 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 significantly increased only in CHF hearts.
Conclusions Bioenergetic abnormalities in remodeled myocardium are related to the severity of LV dysfunction, which, in turn, is dependent on the severity of the initiating myocardial infarction.
Key Words: ventricles • remodeling • heart failure • phosphates • spectroscopy
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|
|
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|
|
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|
|
|
|
|
|
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|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
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|
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