Morten M. Brinkløv

Natural killer cell activity during cortisol and adrenaline infusion in healthy volunteers.

Abstract. The effects of cortisol and adrenaline on natural killer (NK) cell activity and the distribution of circulating lymphocyte subpopulations were studied in twenty volunteers, using a continuous intravenous infusion pattern to simulate some of the hormonal changes induced by major surgery. The participants were allocated to receive either cortisol for 5 h, adrenaline for 1 h, cortisol for 5 h with simultaneous adrenaline during the last hour, or placebo for 5 h. Cortisol induced leucocytosis, neutrophilia, and lymphopenia with marked reduction in the number of T‐lymphocyte subsets (OKT3+, OKT4+, and OKT8+ cells). No changes were induced in the activity or number of NK (Leu 11+) cells. Adrenaline produced an instantaneous increase in NK‐cell activity accompanied by a selective increase in circulating NK cells. Significant leucocytosis, lymphocytosis and neutrophilia occurred. All measurements returned to preinfusion levels within 15 min after completing infusion. The effects of simultaneous infusion of cortisol and adrenaline were equal to the additive response to the hormones administered separately, except for the leucocytosis, which clearly exceeded this. In the placebo group all measurements remained unchanged. The results confirm the role of adrenaline as a potent stimulator/inducer of NK‐cell activity. Adrenaline may be responsible for the increase in NK‐cell activity during anaesthesia and major surgery.

Natural Killer Cell Activity and Lymphocyte Function During and After Coronary Artery Bypass Grafting in Relation to the Endocrine Stress Response

The effects of elective coronary artery bypass grafting (CABG) and the associated endocrine stress response on natural killer (NK) cell activity in peripheral blood, the distribution of lymphocyte sub-populations, and the phytohemagglutinin (PHA)-induced lymphocyte transformation were studied in 20 patients anesthetized with cither etomidate-high dose fentanyl (75–125 μg · kg-1) or midazo-lam-low dose fentanyl (<20 μ · kg-1). The endocrine response to surgery was measured as changes in scrum cortisol, plasma epinephrine, and norepinephrine. Compared with control values, a significant increase of NK cell activity was found in both groups prior to induction of anesthesia, followed by a decrease after induction until initiation of cardiopulmonary bypass (CPB) and a gradual increase to levels exceeding controls during CPB. Postoperatively, NK cell activity and the lymphocyte transformation to PHA stimulation were significantly depressed for at least 1–3 days. These changes were accompanied by severe lymphopenia affecting the T-lymphocytes (T3, T4, and T8) and the NK cells (Leu 11). Apart from a delayed cortisol increase in the etomidate group, the endocrine response showed a similar pattern in the two groups. Compared with control values, a significant decrease in the serum cortisol until CPB could be demonstrated, followed by a significant increase persisting for at least 6 days postoperatively. The plasma catecholamines showed a steep rise and, consequently, a significant increase during CPB, followed by a gradual return to control values in the postoperative period. The results indicate that, in patients undergoing CABG, immune surveillance is impaired prior to CPB and during the early postoperative period. The mechanisms underlying the fluctuations in NK cell activity and lymphocyte function arc complex, but the results suggest that the endocrine stress response may be of major importance.

Acid—Base Interactions with Noradrenaline-induced Contractile Response of the Rabbit Isolated Aorta

The effect of acidosis and alkalosis on vascular smooth muscle contractions evoked by noradrenaline was studied. Helical strips of rabbit aorta were mounted for isometric tension recording. Acidosis (pH 7.24–6.51) was obtained by either increasing the Pco2 (hypercapnic) and/or lowering the HCO3-concentration (hypobicarbonatic). Acidosis shifted the noradrenaline concentration-response curve to the right in a competitive manner. The maximal developed tension was unchanged at pH 7.24–6.90 and decreased by 30% at pH 6.51. Alkalosis (pH 7.61–8.04) did not alter nor-adrenaline-evoked contractions. The results suggest that hydrogen ions during acidosis (pH < 7.40) but not during alkalosis (pH > 7.40) exert α-adrenoceptor blocking properties.

Urinary Loss of Oxypurines in Hypoxic Premature Neonates

The daily urinary excretion of the oxypurines hypoxanthine, xanthine and uric acid during each of the first 3 days of life was determined in premature infants without hypoxia (PI) and in hypoxic premature infants (HPI) with the respiratory distress syndrome. The loss of uric aic was statistically significantly greater in the HPI during days 1, 2, and 3 of life, and so was the loss of xanthine on days 1, and 2, but not on day 3. As to the loss of hypoxanthine, no difference could be shown. In both groups of infants the excretion of hypoxanthine and xanthine together made up about 2% of the total oxypurine loss for each day, the loss of xanthine being the greater of the two. The results did not seem to bear relation to differences between the two groups concerning urinary output, birth weight, gestational age, method of delivery, or administration of exogenic purines. So it appears that the increased loss of oxypurines in HPI is caused by the impact of hypoxia, probably owing to be compromised cellular respiration with a subsequent general displacement of the purine metabolism in the catabolic direction.

Catabolism of haemoglobin-haptoglobin complexes in haemolytic uraemia-like syndromes of different etiologies

The catabolism of haemoglobin-haptoglobin complexes was studied in four patients with increased vascular haemolysis as part of acute or subacute haemolytic uraemic syndromes. The apparent volumic substance elimination rates for haemoglobin (Fe) bound to haptoglobin in plasma were 1.1 mumol/h/l and 2.9 mumol/h/l in two patients suffering from sublimate and hydrochloric acid poisoning, respectively. This is estimated to correspond to a normal catabolism, when the increased haptoglobin synthesis is taken into account. In the other two patients suffering from serum-sickness there was reduced clearance and thereby an accumulation of haemoglobin-haptoglobin complexes in plasma during penicillin administration. When the offending drug was withdrawn the plasma concentration of haemoglobin bound to haptoglobin remained high for about three days and then fell rapidly (approximately with 3.8 mumol/l/h and 1.9 mumol/l/h). Thus, also in these patients the clearance capacity could be normalized after discontinuation of the drug.

Natural Killer Cell Activity during Epinephrine and Cortisol Infusion in Healthy Volunteers

Using a continuous intravenous infusion pattern to simulate some of the hormonal changes induced by major surgery the effect of epinephrine and cortisol on natural killer (NK) cell activity and circulating lymphocyte subpopulations were investigated.

Natural Killer Cell Activity and Lymphocyte Function During and after Open-Heart Surgery in Relation to the Endocrine Stress Response

The effect of elective open-heart surgery on natural killer (NK) cell activity was studied in 20 patients allocated to two different anaesthetic techniques. To clarify the mechanisms behind changes in NK cell activity the distribution of lymphocyte subpopulations and lymphocyte blastogenesis to PHA were determined. The endocrine response to surgery was measured as serum cortisol and plasma catecholamines.

The Venturi principle for scavenging anaesthetic gases

I . DUNDEE, J.W. & WYANT, G.M. (1974) Intravenous Anaesthesia, 1st edn. Churchill Livingstone. Edinburgh. 2. ADAMS, R.C. (1944) Intravenous Anaesthesia, 1st edn, p. 454. Paul B. Hoeber, Inc. New York & London. 3. DUNDEE, J.W. (1956) Thiopentone and other Thiobarbiturates, 1st edn, p. 6. E & S Livingstone Ltd, Edinburgh & London. 4. LUNDY, J.S. & TOVELL, R.M. (1934) Some of the newer Local and General Anaesthetic Agents; Methods of their administration. North West Medicine, 33, 308. 5 . PRATT, T.W., TATUM, A.L., HATHAWAY, H.R. & WATERS, RM. (1936) Sodium ethyl (1 methyl butyl) thiobarbiturate; preliminary experimental and clinical study. American Journal of Surgery, 31, 464. A reply from D r Rajaratnam and Scoft