P: 18 Impaired Cerebral Oxygenation, but Preserved Cerebrovascular reactivity, in an Animal Model of Hepatic Encephalopathy

Abstract

BACKGROUND: We have recently obtained evidence of energy deficiency, in the form of impaired lactate release, in the brains of cirrhotic animals with hepatic encephalopathy (HE). Previous reports of cerebral hypoperfusion in patients with HE indicated that cerebral oxygen supply could also be compromised (Dam et al., 2013). Decreased lactate and reduced oxygen supply may lead to CNS energy deficiency and have important neurological consequences, particularly in patients with advanced cirrhosis. In this study we assessed cerebral tissue oxygen tension and CO2 cerebrovascular reactivity in an animal model of HE. METHODS: HE was induced by bile duct ligation (BDL) and after 4 weeks rats were anesthetized with α-chloralose (100 mg·kg−1), instrumented for arterial blood pressure recording and artificially ventilated. 7 BDL and 6 sham-operated animals were treated daily for one week with an ammonia lowering treatment, ornithine phenylacetate (OP) in order to investigate the role of ammonia on brain oxygenation. Blood gas tensions and pH were maintained within physiological ranges in all animal groups. Cerebral tissue PO2 was monitored by fluorescence method (Oxylite™). After a small craniotomy, optical sensors were placed in the somatosensory cortex and sealed. PO2 at baseline and in response to systemic hypercapnia (10% CO2, 5 min) was recorded. RESULTS: BDL resulted in high plasma ammonia concentrations which was lowered with OP treatment. At similar levels of blood PO2 and PCO2, BDL rats had a significantly lower brain PO2 (15.3 ± 2 mm Hg; n = 10) compared to sham controls (26 ± 2 mm Hg; n = 6; P = 0.001). BDL rats treated with OP showed a significant improvement in cerebral PO2 (22 ± 1 mm Hg, n = 6, P = 1), increasing the oxygen tension to levels similar to that recorded in OP treated sham rats (27 ± 2 mm Hg, n = 7), when blood PO2 and PCO2 were constant. Systemic hypercapnia resulted in similar increases in cerebral PO2 in BDL and sham-operated animals (ΔPO2 21 ± 2 vs. 24 ± 2 mm Hg; P = 0.6). Additionally, under anaesthesia, the mean systemic arterial blood pressure was found to be significantly lower in BDL animals (60 ± 3 vs. 84 ± 8 mm Hg; P = 0.04). Cerebral oxygenation did not recover when the blood pressure was normalised via infusion of phenylephrine, but it significantly improved with infusion of acetazolamide which increases cerebral blood flow. CONCLUSIONS: In the BDL model of HE, cerebral tissue oxygen tension is compromised but cerebrovascular reactivity to CO2 appears to be preserved. The cause of the low basal PO2 remains unknown however; high ammonia concentrations and hypoperfusion could be contributing factors.