Impaired Cerebral Oxygenation, But Preserved Cerebrovascular Reactivity, In An Animal Model of Hepatic Encephalopathy

Abstract

Introduction: 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 [[1]Philips B.J. Armstrong I.R. Pollock A. Lee A. Cerebral blood flow and metabolism in patients with chronic liver disease undergoing orthotopic liver transplantation.Hepatology. 1998; 27: 369-376Crossref PubMed Scopus (43) Google Scholar]. Decreased lactate and reduced oxygen supply may lead to the CNS energy deficiency and have important neurological consequences, particularly in patients with advanced cirrhosis. Objectives: 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. Blood gas tensions and pH were monitored and maintained within the physiological ranges in both BDL (n = 10) and sham operated (n = 6) rats. Cerebral tissue PO2 was monitored by fluorescence method (Oxylite™, Oxford Optronics). 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: At the similar levels of blood PO2 (120 ± 4 vs. 113 ± 4 mmHg) and PCO2 (34 ± 1 vs. 35 ± 2 mmHg), BDL rats had a significantly lower brain PO2 (15.3 ± 2 mmHg; n = 10) compared to the shams (26 ± 2 mmHg; n = 6; P = 0.001). Systemic hypercapnia resulted in similar increases in cerebral PO2 in BDL and sham animals (ΔPO2 21 ± 2 vs. 24 ± 2 mmHg; P = 0.6). However, the peak increases in parenchymal PO2 was significantly smaller in BDL rats when compared to sham-operated animals; 36 ± 4 ± 2 vs. 50 ± 3 mmHg (P = 0.03). Additionally, under anesthesia, the mean systemic arterial blood pressure was found to be significantly lower in BDL animals (60 ± 3 vs. 84 ± 8 mmHg; P = 0.04). Conclusion: 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; low systemic arterial blood pressure could be a contributing factor considering the maximum increase in PO2 induced by hypercapnia was lower in BDL animals indicating decreased brain perfusion. The authors have none to declare.