Pattern of neuronal activation in rats with CHF after myocardial infarction

To identify neuronal populations possibly contributing to the sympathetic h yperactivity in rats with congestive heart failure (CHF) after myocardial i nfarction (MI), immunohistochemical detection of Fra-like immunoreactivity (Fra-LI) was used as a marker of long-term neuronal activation. In adult Wi star rats, 2 and 4 wk after left coronary artery ligation, left ventricular (LV) peak systolic pressure and LV end-diastolic pressure were measured, i mmediately followed by transcardial perfusion and removal of the heart and brain. The brains were processed using an antibody that recognizes Fos, Fos B, Fra-1, and Fra-2 for the detection of Fra-LI and using an antibody that only recognizes Fos-like immunoreactivity (Fos-LI). At both 2 and 4 wk afte r large MI, LV peak systolic pressure was significantly decreased and LV en d-diastolic pressure increased. At 2 wk post-MI or sham surgery, Fra-LI was observed in several areas of either group but was significantly higher in the MI versus the sham group in the magnocellular division of the paraventr icular nucleus (PVN), supraoptic nucleus (SON), subfornical organ, and caud al part of the nucleus of the solitary tract. At 4 wk after large MI, Fra-L I was clearly detected in the parvocellular and magnocellular divisions of the PVN, SON, and locus ceruleus. Modest expression was noted in these nucl ei in rats with small MI, whereas Fra-like positive immunoreactive neurons were barely detectable in the sham group 4 wk postsurgery In these nuclei, the extent of expression of Fra-LI correlated significantly with the LV end -diastolic pressure. Fos-LI was only noted in the cerebral cortex. These re sults indicate clear activation of neurons as identified by Fra-LI in speci fic cardiovascular control centers in rats with CHF 2 and 4 wk post-MI.