Bionic Baroreceptor Corrects Postural Hypotension in Rats With Impaired Baroreceptor

Abstract

Background-Impairment of the arterial baroreflex causes orthostatic hypotension. Arterial baroreceptor sensitivity degrades with age. Thus, an impaired baroreceptor plays a pivotal role in orthostatic hypotension in most elderly patients. There is no effective treatment for orthostatic hypotension. The aims of this investigation were to develop a bionic baroreceptor (BBR) and to verify whether it corrects postural hypotension. Methods and Results-The BBR consists of a pressure sensor, a regulator, and a neurostimulator. In 35 Sprague-Dawley rats, we vascularly and neurally isolated the baroreceptor regions and attached electrodes to the aortic depressor nerve for stimulation. To mimic impaired baroreceptors, we maintained intracarotid sinus pressure at 60 mm Hg during activation of the BBR. Native baroreflex was reproduced by matching intracarotid sinus pressure to the instantaneous pulsatile aortic pressure. The encoding rule for translating intracarotid sinus pressure into stimulation of the aortic depressor nerve was identified by a white noise technique and applied to the regulator. The open-loop arterial pressure response to intracarotid sinus pressure (nϭ7) and upright tilt-induced changes in arterial pressure (nϭ7) were compared between native baroreceptor and BBR conditions. The intracarotid sinus pressure-arterial pressure relationships were comparable. Compared with the absence of baroreflex, the BBR corrected tilt-induced hypotension as effectively as under native baroreceptor conditions (native, Ϫ39Ϯ5

Heart Failure as a Disruption of Dynamic Circulatory Homeostasis Mediated by the Brain

“…Previously we determined that our bionic baroreflex system restores the pressure buffering function, and that the bionic baroreceptor would be an attractive therapy for orthostatic hypotension caused by baroreceptor impairment in rats. 26) In the present examination, our bionic baroreflex system was able to fully reverse the physiological volume intolerance in the FAIL animals (critical Vi: 23.1 ± 1.7 mL/kg, and systolic AP at critical Vi: 206 ± 7 mmHg). These results suggest that the bionic baroreflex system would be an attractive therapeutic tool for preventing flash pulmonary edema in HFpEF caused by baroreflex failure.…”

Orthostatic hypotension and mortality risk: a meta-analysis of cohort studies

“…Thus, intermittent ischaemia of important organs, such as heart, brain and kidney, may often occur during OH, and the related acute change in haemodynamic and organ perfusion status may lead to permanent damage of these organs. Third, baroreflex dysfunction is well recognised as one of the most important mechanisms of pathogenesis of OH, probably caused by baroreceptor impairment due to aging or atherosclerosis 31 32. However, impairment of the baroreflex as a marker of autonomic dysfunction has been related to an increased risk of mortality in patients with type 2 DM33 or chronic renal failure34 or after myocardial infarction35 36 perhaps through the induction of systematic inflammation 37.…”

Orthostatic Hypotension and the Risk of Congestive Heart Failure: A Meta-Analysis of Prospective Cohort Studies

“…Several suggested mechanisms may be helpful to understand the relationship between presence of OH and increased risk for future CHF, of which autonomic dysfunction is an interesting one. It has been well recognized that baroreflex dysfunction probably induced by impairment of baroreceptor due to aging or atherosclerosis, is one of the most important causes of OH [6], [24], [25]. Indeed, when subjects stand up from a supine position, blunted baroreceptor may fail to deactivate the baroreflex and the vagal output therefore can not be down-regulated, leading to OH [6], [24].…”