VOLUME EXPANSION FAILS TO NORMALLY ACTIVATE NEURAL PATHWAYS IN THE BRAIN OF CONSCIOUS RABBITS WITH HEART-FAILURE

Immunohistochemical detection of the protein, Fos, was used to identif y neurons in the brain activated following a volume load in conscious rabbits with doxorubicin-induced congestive cardiomyopathy. The plasma expander, Haemaccel, was infused intravenously into rabbits for 60 mi n and significantly increased right atrial pressure, blood pressure an d heart rate. The rabbits were perfusion fixed 90 min after the start of the infusion and the distribution of Fos-positive cell nuclei was e xamined. Compared to control rabbits with heart failure, there was a s mall significant increase in the number of Fos-positive cell nuclei in the organum vasculosum of the lamina terminalis following volume expa nsion. In other regions of the brain that were studied in detail, ther e were no significant increases in Fos production. These included the parvocellular paraventricular nucleus (PVN) of the hypothalamus, the m idbrain periaqueductal gray, the nucleus tractus solitarius (NTS), are a postrema and the ventrolateral medulla (VLM). In the supraoptic nucl eus and the magnocellular PVN, no Fos-positive cell nuclei were presen t as expected. The median preoptic nucleus, the bed nucleus of the str iae terminalis and the diagonal band of Broca contained some Fos but t here was no marked difference between volume expanded and control anim als. In the anterior cortical and medial subnuclei of the amygdala the re was a high concentration of Fos but there was no consistent differe nce between the two groups. The present findings in heart failure rabb its suggest that most brain regions are not activated sufficiently by the stimulus to elicit Fos expression. The results are in accord with findings showing that sympathetic reflexes initiated by volume expansi on are attenuated in heart failure. (C) 1998 Elsevier Science B.V. All rights reserved.