DEVELOPMENT AND PREVENTION OF SKELETAL-MUSCLE STRUCTURAL ALTERATIONS AFTER EXPERIMENTAL MYOCARDIAL-INFARCTION

The present study was designed to assess whether structural alteration s develop within skeletal muscle 1 yr after myocardial infarction (IM) and failure and, if so, whether these structural alterations can be p revented by angiotensin-converting enzyme (ACE) inhibition. Infarcted rats were randomized and treated for 1 yr with either placebo (MI-IF, n = 9), a low dose of lisinopril (MI-LH, 0.5 mg.kg(-1)day(-1), n = 12) , or a high dose of lisinopril (MI-LH, 5 mg . kg(-1) day(-1), n = 9). Sham-operated animals served as controls (SH, n = 14). One year after MI, in situ fixation of rat hindlimb was performed to investigate inte rstitial collagen volume fraction (CVF), capillary density, and media thickness of resistance vessels (80-200 mu m) of musculus quadriceps f emoris muscle. Infarct size was similar in all infarct groups and aver aged 26 +/- 4%. Right ventricular weight was increased in MI-IF compar ed with SH, MI-LL, and MI-LH. Both left ventricular (LV) CVF and skele tal muscle CVF were increased in MI-IP. LV CVF and skeletal muscle CVF were closely related to each other (n = 44, r = 0.5377, P < 0.002). I n infarcted rats, high-dose ACE inhibition significantly reduced skele tal muscle and LV CVF. Skeletal muscle capillary density and capillary -to-muscle fiber ratio were significantly decreased in infarcted rats but were restored by low- and high-dose ACE inhibition. Media thicknes s of intramuscular resistance vessels was increased in the MI-IP group and significantly reduced by high-dose ACE inhibition. In summary, st ructural interstitial and vascular alterations develop within the skel etal muscle in chronic heart failure after MI and may contribute to im paired exercise-induced vasodilatation and skeletal muscle hypoperfusi on. High-dose ACE inhibition completely prevented these structural alt erations.