Comparisons of the effects of anesthesia and stress on release of tumor necrosis factor-alpha, leptin, and nitric oxide in adult male rats

Bacterial lipopolysaccharide ((LPS) stimulates massive release of tumor nec rosis factor-alpha (TNF-alpha) together with nitric oxide (NO) and a lessor release of leptin, We hypothesized that other types of stress such as that of surgery might also release these cytokines and NO. Adult male rats were anesthetized with [ketamine/acepromazine/xylazine anesthesia (90 + 2 + 6 m g/ml, respectively) and an external jugular catheter was inserted for remov al of blood samples (0.6 ml) at various times postoperatively Plasma TNF-al pha was almost undetectable in decapitated rats and was near zero immediate ly following the placement of the jugular catheter (time zero [t0]). As the rats awakened from anesthesia, there was a rise in TNF-alpha at 30 min tha t peaked at 2 hr with a 400-fold increase and then precipitously declined 4 0-fold to a level still greater than zero at 3 hr, At 6 hr on the following morning, TNF-alpha values were near zero, hut following connection of tubi ng and withdrawal of the initial blood sample, there was a 100-fold increas e 1 hr later, followed by a decline over the next 3 hr, In contrast, plasma [NO3/NO2] from decapitated rats was 117 muM. Values at t0 were decreased a nd plummeted 4-fold within 30 min, then rose slightly in the ensuing 3 hr, At 6 hr on the next day [NO3/NO2] values were lower than at t0 and declined gradually during the next 4 hr, Leptin gradually declined from pre-operati ve concentrations, reaching a minimum at 3 hr and its concentration was una ffected by the bleeding stress of the second day. We conclude that release of TNF-alpha, [NO3/NO2], and leptin are neurally controlled since plasma le vels of all three declined as a result of anesthesia. TNF-alpha secretion w as remarkably stress responsive, whereas NO release appeared to he suppress ed by the combined operative and bleeding stress, and leptin was stress unr esponsive.