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(Circulation. 1997;96:3974-3984.)
© 1997 American Heart Association, Inc.
Articles |
Isolated Myocyte Contractile Function Is Normal in Postinfarct Remodeled Rat Heart With Systolic Dysfunction
From the Department of Cardiology, University of Minnesota School of Medicine, VA Medical Center (Minneapolis).
Correspondence to Inder S. Anand, MD, DPhil (Oxon), FRCP, Professor of Medicine, Department of Cardiology, VA Medical Center 111C, Minneapolis, MN 55417. E-mail anand001{at}maroon.tc.umn.edu
Background Postinfarction ventricular remodeling is associated with lengthening and contractile dysfunction of the remote noninfarcted myocardium. Mechanisms underlying this phenomenon remain unclear.
Methods and Results We studied serial changes in global left ventricular (LV) structure and function in infarcted (1, 2, 4, and 6 weeks after myocardial infarction) and sham-operated rat hearts and correlated them with structural and functional changes in myocytes isolated from the remote LV myocardium in the same hearts. Rats with myocardial infarction developed significant remodeling. The heart weight–to–body weight ratios were increased. LV volumes at filling pressure of 10 mm Hg were higher (305±28 versus 215±12 µL, P<.01). This was accompanied by global LV dysfunction (in vivo LV end-diastolic pressure, 4±1 versus 23±1.6 mm Hg; Langendorff LV developed pressure, 105±4 versus 62±9 mm Hg, P<.001 for both). Myocytes isolated from these hearts showed significant structural remodeling (LV myocytes, 24% longer and 15% wider; right ventricular myocytes, 38% longer and 31% wider, all P<.05). LV myocyte length correlated with changes in LV volume (r=.79) and function (LV developed pressure, r=-.81). However, LV myocytes from the same hearts showed normal contractile function and intracellular Ca2+ transients at baseline and during inotropic stimulation with increasing extracellular Ca2+ (1 to 6 mmol/L). The shortening-frequency relationship was also similar in myocytes from sham and myocardial infarction rats.
Conclusions Postinfarct LV remodeling occurs predominantly by myocyte lengthening rather than by myocyte slippage. However, contractile function of the unloaded myocytes from the remote noninfarcted LV myocardium of the remodeled heart is normal. Therefore, myocyte contractile abnormalities may not contribute to global dysfunction of the remodeled heart. Reduced myocyte mass and nonmyocyte factors like increased wall stress, altered LV geometry, and changes in the myocardial interstitium may be more important in the genesis of postinfarct LV dysfunction in this model.
Key Words: myocardial infarction • remodeling heart failure • contractility • myocytes
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