ISOLATED MYOCYTE CONTRACTILE FUNCTION IS NORMAL IN POSTINFARCT REMODELED RAT-HEART WITH SYSTOLIC DYSFUNCTION

Background Postinfarction ventricular remodeling is associated with le ngthening and contractile dysfunction of the remote noninfarcted myoca rdium. Mechanisms underlying this phenomenon remain unclear. Methods a nd Results We studied serial changes in global left ventricular (LV) s tructure and function in infarcted (1, 2, 4, and 6 weeks after myocard ial 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 dev eloped 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 mu L, P<.01). This was accompanied by globa l 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 m m Hg, P<.001 for both), Myocytes isolated from these hearts showed sig nificant 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 functi on (LV developed pressure, r=-.81). However, LV myocytes from the same hearts showed normal contractile function and intracellular Ca2+ tran sients at baseline and during inotropic stimulation with increasing ex tracellular Ca2+ (1 to 6 mmol/L). The shortening-frequency relationshi p was also similar in myocytes from;sham and myocardial infarction rat s. Conclusions Postinfarct LV remodeling occurs predominantly by myocy te lengthening rather than by myocyte slippage. However, contractile f unction of the unloaded myocytes from the remote noninfarcted LV myoca rdium of the remodeled heart is normal. Therefore, myocyte contractile abnormalities may not contribute to global dysfunction of the remodel ed heart. Reduced myocyte mass and nonmyocyte factors like increased w all stress, altered LV geometry, and changes in the myocardial interst itium may be more important in the genesis of postinfarct LV dysfuncti on in this model.