Nitric oxide production and hepatic dysfunction in patients with postoperative sepsis

1. Although hepatic function is well known to deteriorate following bacteri al infection, the underlying mechanisms remain poorly understood. We have p reviously reported that nitric oxide (NO) radical leads to a decrease in th e ketone body ratio (KBR) and in ATP content due to the inhibition of mitoc hondrial electron transport in primary cultured rat hepatocytes. 2. To evaluate the effects of NO radical on the liver in patients with post operative sepsis, we analysed both the stable end-product of nitric oxide r adical (NOx) as well as the arterial KBR (AKBR), which reflects liver tissu e NAD(+)/NADH. 3. Twenty patients who had undergone general abdominal surgery and who deve loped 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 progres sively higher than those in the 13 surviving patients over the clinical cou rse of postoperative sepsis, 5. In the non-surviving group, the AKBR was significantly lower than in sur viving patients, indicating impaired hepatic function. In contrast, plasma NOx levels in non-surviving patients were significantly higher than in surv iving 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 dysfu nction in the liver. 7. It is likely that the overproduction of NO radical plays an important ro le in causing fatal metabolic disorders in patients with postoperative seps is.