1. Although hepatic function is well known to deteriorate following
bacterial infection, the underlying mechanisms remain poorly understood. We have previously reported that
nitric oxide (NO) radical leads to a decrease in the
ketone body ratio (
KBR) and in
ATP content due to the inhibition of mitochondrial electron transport in primary cultured rat hepatocytes. 2. To evaluate the effects of NO radical on the liver in patients with postoperative
sepsis, we analysed both the stable end-product of
nitric oxide radical (NOx) as well as the arterial
KBR (AKBR), which reflects liver tissue
NAD+/
NADH. 3. Twenty patients who had undergone general abdominal surgery and who developed postoperative
sepsis were divided into two groups: (i) surviving; and (ii) non-surviving. Blood samples were collected before the development of postoperative
sepsis and every 3 days until the patient either died or was discharged from hospital. 4. Plasma NOx levels in seven patients who subsequently died became progressively higher than those in the 13 surviving patients over the
clinical course of postoperative
sepsis. 5. In the non-surviving group, the AKBR was significantly lower than in surviving patients, indicating impaired hepatic function. In contrast, plasma NOx levels in non-surviving patients were significantly higher than in surviving patients. 6. Decreases in AKBR to levels below 0.7 in non-surviving patients followed high NOx levels. Moreover, plasma NOx levels were closely correlated with the AKBR, indicating that NO radical is associated with
mitochondrial dysfunction in the liver. 7. It is likely that the overproduction of NO radical plays an important role in causing fatal metabolic disorders in patients with postoperative
sepsis.