Gordon Lahnborg

Human Granulocyte and Reticuloendothelial System Function During Intra lipid Infusion

In six patients, the phagocytic and catabolic functions of the RES (reticuloendothelial system), as measured by using 125I-microaggregated human serum albumin as a test substance, were not affected by Intralipid infusion. The nitroblue tetrazolium (NBT) reduction of granulocytes, the NBT reduction and the bacplasma, was significantly lower in eight patients during Intralipid infusion than before this treatment. When heat-killed E. coli were added for phagocytic stimulation in vitro, the same result was obtained only in the absence of plasma. The bactericidal capacity of granulocytes was significantly decreased in six patients during Intralipid infusion. When Intralipid was added in vitro to granulocytes, the NBT reduction, and the bactericidal capacity of these cells were decreased and the effect was mainly dose-dependent. Electron micrographs show that granulocytes phagocytize Intralipid. The loading of granulocytes with lipid particles may block the engulfment of bacteria and may be a reason for the decreased bactericidal capacity of these cells. An influence exerted by the lipid on the cell membrane is the most conceivable reason for the decreased NBT reduction.

EFFECT OF LOW-DOSE HEPARIN ON INCIDENCE OF POSTOPERATIVE PULMONARY EMBOLISM DETECTED BY PHOTOSCANNING

Abstract In a double-blind investigation thromboembolic prophylaxis with subcutaneous low-dose heparin was studied in 112 patients admitted for elective major surgery. Pulmonary embolism was diagnosed by photoscanning on the third or fourth day after operation, and plain chest X-rays were taken simultaneously. Deep vein thrombosis (D.V.T.) was detected by the 125 I-fibrinogen leg scanning technique. 58 patients were treated with heparin, each receiving 5000 units every 12 hours for 5 days, starting 2-5 hours before operation. In this group 11 patients (19%) had pulmonary embolism and/or D.V.T. Of the 54 patients in the control group 30 (56%) had pulmonary embolism and/or D.V.T. Thus low doses of heparin reduce the incidence of tromboembolism after major surgery.

Age-related differences in the serum prolactin response during standardized surgery

The aim with the present study was to assess possible age-related differences in the serum prolactin, cortisol and blood glucose responses to standardized surgical stress in humans. Relatively healthy men suffering from inguinal hernias were selected. The subjects were divided into a group of younger people (M=36.4 years, r=23-45, n=7) and one of older people (M=66.5 years, r=56-75, n=9). Surgery was carried out under general anesthesia. Blood was drawn before, during and following the operation. Blood pressure and pulse rate were also monitored. No differences were noticed in plasma prolactin, cortisol, and blood glucose during basal conditions. Even though plasma prolactin increased significantly in both groups during surgery, it was higher in the younger group (M=56.2 micrograms/1) as compared with 28.7 micrograms/l for the older group, p less than .01. Plasma prolactin during surgery, but not under basal conditions, correlated inversely with age. No differences between groups were found during surgery in blood glucose and serum cortisol. This study indicates a diminished stress response in older subjects, possibly due to age-related neuroendocrine changes.

Age-related differences in the pituitary prolactin response to thyrotropin-releasing hormone

We have previously reported that human subjects undergoing surgery for inguinal hernias exhibit an age-related attenuation in the plasma prolactin response, with no differences during resting conditions. We suggested that these differences were due to age-related neuroendocrine changes, but that peripheral factors may play a role as well. In the present study, we have assessed the pituitary response to 500 micrograms of thyrotropin-releasing hormone (TRH) in the very same subjects previously studied during surgery. Blood samples were drawn immediately prior to, as well as 10, 20, 40 and 60 minutes following the intravenous administration of TRH. There was a clear-cut age-related attenuation in the pituitary prolactin response with no difference in the thyrotropin (TSH) response. Maximum prolactin response in the young subjects was 31.7 micrograms/l and 19.2 micrograms/l in old subjects (F(4) = 3.5, p less than .01, two-way ANOVA). These results indicate that the age-related differences in the prolactin response to stress are mainly due to pituitary changes. However, prolactin-secreting cells are under the control of the hypothalamus. Therefore, the possibility must be considered that aging or other concurrent factors could be exerting their influence via the hypothalamus and not necessarily directly at the pituitary level.

Influence of Cardiopulmonary Bypass on Some Host Defence Functions in Man

Four different functions of the immune defence were studied in six men undergoing open-heart surgery with cardiopulmonary bypass (CPB). Pre-operatively, a few hours after and three days after surgery the following tests were performed: (I) in vivo phagocytic and metabolic functions of the reticuloendothelial system (RES), (II) haemolytic activity of blood monocytes, (III) nitroblue tetrazolium (NBT) reduction by granulocytes, and (IV) bactericidal capacity of granulocytes. Compared to the pre-operative values, the RES functions were unchanged postoperatively, whereas there was a significant increase in the haemolytic activity of monocytes and in the NBT reduction of granulocytes. The capacity of the granulocytes to kill bacteria was normal a few hours after surgery, but significantly increased on day 3. No infectious complications occurred and all patients recovered uneventfully. These results suggest that, at the present time, open-heart surgery under CPB is accompanied by an increased activity of granulocytes and monocytes in the early postoperative period.

Reticuloendothelial function in human renal allograft recipients.

The phagocytic and metabolic functions of the reticuloendothelial system (RES) were determined, by measuring the plasma clearance rate of 125I-labelled microaggregated human serum albumin and the increase in plasma metabolites of this test substance, in patients with chronic renal failure and in renal transplant recipients at different times after transplantation. All transplant recipients received triple immunosuppressive therapy consisting of azathioprine, corticosteroids, and antilymphocyte globulin. The intravascular clearance of microaggregated albumin was significantly depressed in patients when tested at 1 to 12 days (P < 0.001), 1 to 4 months (P < 0.02), and 6 to 9 months (P < 0.001) after transplantation compared to pretransplantation. The 1− to 3-year transplant survivors had a normal RES phagocytosis. Furthermore, the metabolic RES function in all groups of transplant recipients except the group of patients tested at 1 to 4 months after transplantation was significantly impaired compared to pretransplantation. Administration of antilymphocyte globulin and extremely high daily doses of steroids were probably responsible for the significant depression in the RES functions recorded immediately post-transplantation. The further development of the phagocytic ability of the RES was shown to be correlated to the cumulative dose of steroids given over the last 12 months. The azathioprine regime seemed to have no influence on the RES functions. The RES is a major host defence mechanism against bacterial and viral infections (1–4) and tumour growth (5–7). Macrophage phagocytosis and metabolism are also important in the induction of an immune response to foreign antigens (8–10) and in the rejection of allografts (11, 12). Depression of the RES function induced by various agents (methyl palmitate, trypan blue, silica, carrageenan, or antimacrophage serum) was shown to prolong the survival of organ as well as tumour grafts (13–17). On the other hand, glucan-induced stimulation of the RES was associated with enhanced rejection of both tumour and bone marrow transplants (14, 17). Immunosuppressive agents such as azathioprine, corticosteroids, and antilymphocyte serum, used in transplantation surgery to suppress the immune response, have been reported to impair RES phagocytosis (18–21). Several investigations have been made in animals and some in man on the capacity of the RES to clear various colloids and lipid emulsions from the circulation (22–25). In recent years, moreover, methods have been developed for the determination of not only the phagocytic but also the metabolic function of the RES (26–28). Those used most frequently utilize a rapidly metabolizable RES test substance of microaggregated human serum albumin labelled with radioactive iodine, a substance which can safely be used in man (26, 28). The purpose of the present study was to determine both the phagocytic and the metabolic functions of the RES in patients undergoing renal transplantation during immunosuppressive therapy. As RES test substance, microaggregated human serum albumin labelled with 125I was used.

The effect of major surgery, low doses of heparin and thromboembolism on plasma antithrombin. Comparison of immediate thrombin inhibiting capacity and the antithrombin III content

Abstract Antithrombin in plasma was studied by two different methods in a group of patients undergoing major surgery and taking part in a double-blind investigation on low-dose heparin treatment. The AT III results (Mancini method) were only slightly affected by thromboembolism which is in agreement with earlier findings. The immediate thrombin inhibiting capacity using a chromogenic tripeptide as substrate was, however, found to increase in connection with thromboembolism. The fact that the low doses of heparin given to the patients have no effect on any of the antithrombin methods used and that clinical effect was achieved, suggests that the prophylactic effect may depend on inhibition of earlier stages in the development of thrombosis.

EFFECT OF LOW-DOSE HEPARIN PROPHYLAXIS ON ARTERIAL OXYGEN TENSION AFTER HIGH LAPAROTOMY

The effect of low doses of heparin (5000 units of sodium heparin every 12 hours for 5 days) on arterial oxygenation was studied in 24 patients in the postoperative period after upper abdominal surgery. Another 24 patients served as a control group. The arterial oxygen tension was the same in both groups preoperatively and was equally significantly reduced during the 1st postoperative day. During the 2nd day, oxygen tension rose in the heparin-treated group to values which no longer differed significantly from the peroperative level. In the control group the significant reduction persisted until the 4th postoperative day. The arterial carbon-dioxide tension did not differ between the groups, neither did it vary significantly between days. There were no clinical signs of large pulmonary embolism during the postoperative period, chest X-ray was normal in all patients examined and a photoscan was normal in 23 of 24 subjects studied. Low-dose heparin treatment may apparently shorten the period of postoperative hypoxaemia, probably by counteracting both large pulmonary emboli and microthromboembolism.

Phagocytic and catabolic function of the reticuloendothelial system in dogs subjected to defibrinogenation.

Abstract There is evidence that the reticuloendothelial system (RES) serves as an important protective mechanism in disseminated intravascular coagulation. The influence of defibrinogenation on the RES is studied in this investigation. For this purpose dogs were defibrinogenated with Defibrase R — a thrombin-like enzyme from the venom of Bothrops atrox. The phagocytic and catabolic functions of the RES were tested by the use of a test substance of heat-aggregated human serum albumin labelled with 125 I. Defibrase R was given in three groups of dogs at the time when the RES function was tested, 1 hour and 2 hours before the test. A significant delay of both the phagocytic and the catabolic activity was seen with increasing time between defibrinogenation and the RES-test, indicating a block of the RES with fibrin/fibrinogen degradation products. The reasons for this are discussed.