Hypothermia in barbiturate-anesthetized rats suppresses natural killer cell activity and compromises resistance to tumor metastasis - A role for adrenergic mechanisms

Background: Clinical studies have implicated surgery in promoting infection s and compromising immune functions, including natural killer cell activity . Animal studies indicate that surgery-induced suppression of natural kille r cell activity also promotes tumor metastasis. Hypothermia, a common surgi cal complication, has been suggested to underlie some of the deleterious co nsequences of surgery. This study evaluated the effect of hypothermia on th e activity and number of blood natural killer cells and on host susceptibil ity to metastasis. The involvement of adrenergic mechanisms was also consid ered. Methods: Fischer-344 rats remained awake in their cages (control group) or were anesthetized with 70 mg/kg thiopental and maintained for 2.5 h at core body temperatures of 30-32 degrees C (hypothermia group) or 38 degrees C ( normothermia group). Thereafter, at several time points, blood was drawn so natural killer cell activity could be assessed, or rats were injected with syngeneic MADB106 tumor cells that metastasize only to the lungs. Lungs we re removed 9 h later for assessment of lung tumor retention, or 4 weeks lat er for counting of metastases. Results: Normothermic anesthesia reduced natural killer cell activity (lyti c units at 30% specific killing, mean rt SEM) to 39 +/- 6.2% of control lev els and hypothermia further reduced it to 15 +/- 6.6%, These changes were n ot accompanied by alterations in the numbers of circulating natural killer cells. Hypothermia increased tumor retention to 250% of control levels, and the number of metastases increased from 1.1 +/- 0.4 to 4.7 +/- 1.2. Normot hermia had no significant effects on this index. Nadolol (0.4 mg/kg) a beta -adrenergic antagonist, significantly attenuated the effect of hypothermia on tumor retention. Conclusions: Hypothermia under thiopental anesthesia suppresses natural kil ler cell activity and compromises host resistance to metastatic formation, possibly via adrenergic mechanisms. Such suppression may place patients wit h metastasizing tumors or dormant viral infections at greater risk for comp lications after intraoperative hypothermia.