In heart failure, lesion of the area postrema reduces cardiac sympathoexcitation and improves cardiac function

Abstract

Heart Failure (HF) is associated with increased cardiac sympathetic nerve activity (CSNA), but the mechanisms causing this are unclear. The area postrema (AP), a brainstem circumventricular organ, plays an important role in controlling SNA. We hypothesized that lesioning the AP would reduce CSNA and attenuate the decline in cardiac function. In sheep with pacing-induced HF, lesion of the AP or sham lesion (n = 6/group) was performed when ejection fraction (EF) had fallen to ~50%. In conscious sheep, blood pressure, heart rate and CSNA were recorded when EF had decreased to b40%. Compared with heathy sheep, sheep with HF had a large increase in CSNA (34 ± 4 vs. 89 ± 3 bursts/100 heartbeats, respectively), which was significantly reduced in HF sheep with lesion of the AP (45 ± 10 bursts/100 heartbeats, P b 0.01). In rats, AP lesion or sham lesion (n= 18/group) was performed before HF was induced by myocardial infarction. Eight weeks later, left ventricular end-diastolic pressure in anaesthetised ratswas significantly lower in theAP lesiongroup compared with the sham lesion group (9± 2 vs 16 ± 2mmHg, respectively, P b 0.05) and ejection fraction was higher. These findings suggest that the AP plays a critical role in setting the high level of CSNA in HF and indicate that lesion of the AP reduces the decline in cardiac function postmyocardial infarction, possibly due to the reduction in CSNA.