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Baroreflex Dysfunction Underpins Mortality in a Rat model of Hepatic Encephalopathy
Author(s) -
Chan Samuel H.H.,
Tsai ChingYi
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.831.9
Subject(s) - baroreflex , medicine , medulla oblongata , nucleus ambiguus , anesthesia , heart rate , asystole , vasomotor , blood pressure , cardiology , central nervous system
Hepatic encephalopathy (HE) is a clinical emergency associated with 50‐90% mortality in patients without liver transplantation. Since baroreflex is responsible for maintaining blood pressure (BP) and heart rate (HR), we reasoned that dysfunction of this regulatory mechanism underlies the high mortality associated with HE. This hypothesis was tested using a thioacetamide (TAA)‐induced acute liver failure model of HE. TAA or saline was injected intraperitoneally at 24 h intervals in Sprague‐Dawley rats for 3 consecutive days. 24‐h BP and HR signals recorded by radiotelemetry in conjunction with on‐line and real‐time spectral analysis showed that HR was essentially maintained and cardiac vagal baroreflex was sustained until the abrupt occurrence of asystole that signifies cardiac death. On the other hand, drastic reduction in BP began to appear on Day 3, and at an accelerated rate on Day 4. More intriguingly, an index for baroreflex‐mediated sympathetic vasomotor tone began to decrease on Day 2, and reached zero on Day 4, signifying clinically the occurrence of brain death. Tractographic analysis based on magnetic resonance imaging/diffusion tensor imaging evaluation of the medulla oblongata further revealed that the functional connectivity between the nucleus tractus solitarii (NTS) and nucleus ambiguus was sustained until shortly before asystole took place. On the other hand, the connectivity between the NTS and rostral ventrolateral medulla underwent dramatic reduction beginning on Day 2, and was completely eliminated on Day 4. We conclude that dysfunction of baroreflex‐mediated sympathetic vasomotor tone underpins the high mortality associated with HE.