Immune perturbations in patients along the perioperative period: alterations in cell surface markers and leukocyte subtypes before and after surgery.

BACKGROUND: Surgery renders patients susceptible to life-threatening complications, including infections, multiple organ failure, and presumably cancer metastases. Surgery-induced immune perturbations were suggested to contribute to such deleterious effects, but also to facilitate post-injury healing. Preoperative psychological and physiological stress responses may contribute to these immune perturbations, and could thus jeopardize patients even before surgery. The current study assessed the effects of various operations on an array of immune indices during the perioperative period. To qualify immune changes before surgery, patients' immune status was also compared to that of healthy controls. METHODS: A total of 81 subjects (operated patients and healthy controls) provided up to five daily blood samples during the perioperative period, for assessment of leukocyte subtypes (granulocytes, monocytes, Tc, Th, NK, NKT, CD4+CD25+, CD8(bright)CD4(dim), and B cells) and their surface markers (HLA-DR and LFA-1). RESULTS: Even before surgery patients displayed immune perturbations, including reduced lymphocyte HLA-DR expression and increased monocyte LFA-1 expression. Following surgery, we recorded a reduction in lymphocyte numbers that was subtype specific, increased granulocyte numbers, and reduced expression of HLA-DR by lymphocytes and monocytes. Finally, no significant associations were found between alteration in leukocyte numbers and cell surface markers (although these indices showed high correlations with other variables), implying differential mediating mechanisms. CONCLUSION: Several immune alterations are manifested prior to surgery, and contribute to the marked postoperative changes, which are commonly interpreted as immune suppression. We discuss the possible adaptive and maladaptive nature of these perturbations in the context of natural injury, stress, and surgery.

The effect of perioperative intravenous lidocaine on postoperative pain and immune function.

BACKGROUND: Surgery-associated tissue injury leads to nociception and inflammatory reaction, accompanied by increased production of proinflammatory cytokines. These cytokines can induce peripheral and central sensitization, leading to pain augmentation. Recently, a frequently used local anesthetic, lidocaine, was introduced as a part of a perioperative pain management technique. In addition to its analgesic effects, lidocaine has an antiinflammatory property, decreasing the upregulation of proinflammatory cytokines. We focused on the effects of preincisional and intraoperative IV lidocaine on pain intensity and immune reactivity in the postoperative period. METHODS: Sixty-five female patients (ASA physical status I-II) scheduled for transabdominal hysterectomy were recruited to this randomized, placebo-controlled study. Thirty-two patients in the treatment group received IV lidocaine starting 20 min before surgery, whereas the control group (33 patients) received a matched saline infusion. Both groups received patient-controlled epidural analgesia during the postoperative period. Blood samples were collected before, 24, 48, and 72 h after surgery to measure ex vivo cytokine production of interleukin (IL)-1 receptor antagonist (IL-1ra) and IL-6, as well lymphocyte mitogenic response to phytohemagglutinin-M. A 10-cm visual analog scale was used to assess pain intensity at rest and after coughing. RESULTS: Patients in the lidocaine + patient-controlled epidural analgesia group experienced less severe postoperative pain in the first 4 and 8 h after surgery (visual analog scale 4/3.7 at rest and 5.3/5 during coughing versus 4.5/4.2 and 6.1/5.3, respectively, in the placebo group). There was significantly less ex vivo production of IL-1ra and IL-6, whereas the lymphocyte proliferation response to phytohemagglutinin-M was better maintained than in the control group. CONCLUSION: The present findings indicate that preoperative and intraoperative IV lidocaine improves immediate postoperative pain management and reduces surgery-induced immune alterations.

Blood transfusion promotes cancer progression: a critical role for aged erythrocytes.

BACKGROUND: In cancer patients, allogeneic blood transfusion is associated with poorer prognosis, but the independent effect of the transfusion is controversial. Moreover, mediating mechanisms underlying the alleged cancer-promoting effects of blood transfusion are unknown, including the involvement of donors' leukocytes, erythrocytes, and soluble factors. METHOD: Two syngeneic tumor models were used in Fischer 344 rats, the MADB106 mammary adenocarcinoma and the CRNK-16 leukemia. Outcomes included host ability to clear circulating cancer cells, and host survival rates. The independent impact of blood transfusion was assessed, and potential deleterious characteristics of the transfusion were studied, including blood storage duration; the role of erythrocytes, leukocyte, and soluble factors; and the kinetics of the effects. RESULTS: Blood transfusion was found to be an independent and significant risk factor for cancer progression in both models, causing up to a fourfold increase in lung tumor retention and doubling mortality rates. Blood storage time was the critical determinant of these deleterious effects, regardless of whether the transfused blood was allogeneic or autogenic. Surprisingly, aged erythrocytes (9 days and older), rather than leukocytes or soluble factors, mediated the effects, which occurred in both operated and nonoperated animals. The effects of erythrocytes transfusion in the MADB106 model emerged immediately and dissipated within 24 h. CONCLUSIONS: In rats, transfusion of fresh blood is less harmful than transfusion of stored blood in the context of progressing malignancies. Further studies should address mediating mechanisms through which erythrocytes' storage duration can impact the rate of complications while treating malignant diseases and potentially other pathologies.

Comparison of two patient-controlled analgesia techniques on neuropsychological functioning in the immediate postoperative period.

Pain may contribute to cognitive decline, which is a common complication in the early postoperative period. We compared the effects of two common pain management techniques, intravenous patient-controlled analgesia (PCA-IV) and patient-controlled epidural analgesia (PCEA), on cognitive functioning in the immediate postoperative period. Patients hospitalized for elective surgery were randomly assigned to one of the treatment groups (30 patients per group). A battery of objective, standardized neuropsychological tests was administered preoperatively and 24 hours after surgery. Pain intensity was also evaluated. Nonoperated volunteers served as controls. Patients of the PCA-IV group exhibited significantly higher pain scores than did patients of the PCEA group. PCA-IV patients exhibited significant deterioration in the postoperative period in all the neuropsychological measures, while the PCEA patients exhibited significant deterioration only in one cognitive index, compared to controls.

Relationship between fentanyl dosage and immune function in the postoperative period.

BACKGROUND: Anesthesia and surgery are associated with impairment of the immune system expressed as an excessive proinflammatory immune response and suppression of cell mediated immunity. Opioids, an integral part of anesthetic technique, possess an inhibitory effect on both humoral and cellular immune responses. It was the aim of the present study to examine the effect of various doses of fentanyl on cytokine production during the perioperative period. INTERVENTION: The effect of large (LDFA, 70-100 microg/kg), intermediate (IDFA, 23-30 microg/kg) and small (SDFA, 2-4 microg/kg) doses of fentanyl on the immune function in the postoperative period was investigated. PARTICIPANTS: Sixty patients, randomly assigned to one of the three groups according to the dose of fentanyl were included in the study. METHODS: The ex vivo secretion of IL-1beta, IL-2, IL-6, and IL-10 and NK cell cytotoxicity (NKCC) of peripheral blood mononuclear cells (PBMC) was tested before, and at 24, 48, and 72 hours following surgery. RESULTS: The pattern of postoperative secretion of the proinflammatory cytokines IL-1beta and IL-6 and that of the anti-inflammatory cytokine IL-10 differed significantly between patients receiving SDFA and those receiving IDFA and LDFA, but was similar between the last two groups. A similar suppression of NKCC and IL-2 secretion was observed in the three groups. CONCLUSIONS: The diminished proinflammatory cytokine response observed in patients treated by LDFA and IDFA suggests that although more stable immune function can be achieved by those methods in comparison with SDFA, it is recommendable to apply IDFA to avoid the side effects that might be observed using LDFA method.

Interleukin-1 signaling is required for induction and maintenance of postoperative incisional pain: genetic and pharmacological studies in mice.

Postoperative incisional pain is characterized by persistent acute pain in the area of the cut, and is associated with release of proinflammatory cytokines, including interleukin-1 (IL-1), which play important hyperalgesic and allodynic roles in various inflammatory conditions. In the present study, we tested the role of IL-1 signaling in postoperative incisional pain using three mouse strains impaired in IL-1 signaling due to deletion of the IL-1 type I receptor on a mixed genetic background (IL-1rKO) or congenic background (IL-1rKOCog), or due to transgenic over-expression of IL-1 receptor antagonist (IL-1raTG). We used the relevant wild-type (WT) mice both as controls for the mutant strains, and for assessing the effects of pharmacological blockade of IL-1-signaling. Mechanosensitivity was assessed using the von-Frey filament test before, and up to 4 days following plantar incision, an animal model of postoperative pain. WT mice developed significant allodynia in the incised, compared with the intact, hind-paw beginning 3h after the incision and lasting up to 48h postoperatively. In contrast, IL-1rKO, IL-1rKOCog, and IL-1raTG mice, as well as WT mice chronically treated with IL-1ra, did not display increased mechanical pain sensitivity in either hind-paw. To test the hypothesis that IL-1-signaling is also involved in the maintenance of postoperative pain, WT mice were acutely treated with IL-1ra 24h following the incision, when allodynia was already evident. This treatment reversed the allodynic response throughout the observation period. Together, these findings suggest that IL-1 plays a critical role in the development and maintenance of postoperative incisional pain.

Cytokines and cholinergic signals co-modulate surgical stress-induced changes in mood and memory.

Inflammatory cytokines and the cholinergic system have been implicated in the effects of stressors on mood and memory; however, the underlying mechanisms involved and the potential interrelationships between these pathways remain unclear. To address these questions, we administered neuropsychological tests to 33 generally healthy surgery patients who donated blood samples several days prior to undergoing moderate surgery (baseline), on the morning of the surgery (i.e., a psychological stressor), and one day after surgery. Eighteen control subjects were similarly tested. Serum levels of inflammatory cytokines, acetylcholinesterase (AChE) activity, and the stressor-inducible AChE-R variant were measured. An elevation in anxiety levels, an increase in depressed mood, and a decline in declarative memory were observed on the morning of the surgery, prior to any medical intervention, and were exacerbated one day after surgery. The surgical stressor-induced elevated IL-1 beta levels, which contributed to the increased depressed mood and to the post-surgery increase in AChE-R expression. The latter increase, which was also predicted by pre-surgery AChE-R and post-surgery mood disturbances, was associated with exacerbated memory impairments induced by surgery. In addition, elevated levels of AChE-R on the morning of the surgery predicted the post-surgery elevation in IL-6 levels, which was associated with amelioration of the memory impairments induced by surgery. Taken together, these findings suggest that exposure to a surgical stressor induces a reciprocal up-regulation of AChE-R and pro-inflammatory cytokines, which are involved in regulating the surgery-induced mood and memory disturbances.

The existence of gender difference in IL-1Ra gene polymorphism.

Interleukin-1beta (IL-1beta) and its endogenous antagonist IL-1 receptor antagonist (IL-1ra) play an important role in various inflammatory responses. The production of IL-1 and IL-1ra is regulated by genotypic and nongenotypic factors and is different between men and women. The aim of this study was to examine the existence of gender difference in the genetic polymorphism of these two cytokines. The genotypes of IL-1beta-511 biallelic polymorphism and that of IL-1Ra (IL-1RN) penta-allelic polymorphism were determined in 319 healthy Jewish subjects, 156 female and 163 male, using PCR amplification. The results showed that there was a gender difference in IL-1Ra gene polymorphism expressed by a higher incidence of IL1RN*1/IL1RN*1 homozygotes and a lower occurrence of IL1RN*1/IL1RN*2 heterozygotes in men compared with women. Furthermore, allele IL1RN*1 was more frequent in men, whereas allele IL1RN*2 was more prevalent in women. There was no difference in IL-1beta gene polymorphism between the two genders. It is conceivable that the gender difference in IL-1Ra gene polymorphism found in the current study may affect IL-1 and IL-1ra levels. This diversity might be one of the causes for the sex differences in immune response observed in various conditions, such as autoimmune diseases, pain perception, and premature delivery.

Comparison of postoperative pain management techniques on endocrine response to surgery: a randomised controlled trial.

The present study compared three postoperative pain management techniques in patients undergoing lower abdominal surgery: intermittent opiate regimen (IOR), patient-controlled analgesia (PCA), and patient-controlled epidural analgesia (PCEA), on cortisol and prolactin levels during the first 48 h postoperatively. Ninety-two patients scheduled for a lower abdominal surgery, were randomly assigned to one of three study groups: IOR (N=31), PCA (N=31), and PCEA (N=30). Patients of the IOR group received postoperatively 50-75 mg of pethidine IM on demand. Patients of the PCA group received a loading dose of morphine (3-4 mg), followed by 1mg bolus of morphine IV per demand. Patients of the PCEA group received 3 ml of 0.1% bupivacaine plus 2 microg/ml of fentanyl per demand, with continuous background infusion of 6ml/h. Venous blood samples were collected preoperatively, and 24 and 48 h after surgery, and were later assayed for serum cortisol and prolactin levels. Patients of the PCEA group exhibited diminished postoperative elevation of serum cortisol levels at 24 and 48 h (24.4, 18.6 microg/dl, respectively) compared with both IOR (31.9, 21.9) and PCA (28.5, 22.3) groups. Similarly, patients of the PCEA group exhibited diminished postoperative elevation of serum prolactin level (20.7, 15.7 ng/mL) compared with PCA (24.9, 17.1) group. The present results indicate that the PCEA technique offers an advantageous treatment associated with reduced postoperative pain, and attenuated neuroendocrine response.

The involvement of glucocorticoids and interleukin-1 in the regulation of brain prostaglandin production in response to surgical stress.

BACKGROUND: This study examined the role of glucocorticoids (GC) and interleukin-1 (IL-1) in regulating the production of brain prostaglandin E(2) (PGE(2)) in response to surgical stress. METHODS: Surgical stress was induced in rats by laparotomy or exploration of the carotid. PGE(2) ex vivo production was measured in the frontal cortex or central amygdala of adrenalectomized rats, or of rats treated with either the GC type II receptor blocker (RU38486) or synthetic GC (dexamethasone). IL-1 involvement in mediating PGE(2) response to surgical stress was examined in IL-1 receptor type I deficient (IL-1rKO) mice. RESULTS: Surgical stress elevated serum corticosterone and increased PGE(2) production by the frontal cortex and the central amygdala. A more pronounced PGE(2) response was found in adrenalectomized rats and in rats treated with RU38486, whereas administration of dexamethasone inhibited stress-induced PGE(2) production. IL-1rKO mice exhibited lower PGE(2) production in the frontal cortex under basal condition and failed to increase PGE(2) production in response to surgical stress. CONCLUSIONS: Surgical stress-induced production of brain PGE(2) is specifically regulated by GC via the mediation of type II corticosteroid receptors. Normal IL-1 signaling is required for the production of brain PGE(2) under basal conditions and in response to surgical stress.

Blood rheology in PCA and PCEA after total knee arthroplasty.

The rheological events in 2 groups of patients undergoing total knee arthroplasty were compared--15 patients were given general anesthesia and controlled their postoperative pain applying intravenous patient-controlled analgesia; 17 individuals received combined spinal-epidural anesthesia and controlled their postoperative pain by patient-controlled epidural analgesia (PCEA). Twenty-four and 48 hours after surgery, the patient-controlled analgesia group showed a significant increase in whole-blood viscosity at the 3 shear rates (P < .01), as well as in relative viscosity at both periods (P < .001 and .01, respectively). Similar findings were observed for red blood cell aggregation (P < .001) and fibrinogen level (P < .001). These values were less expressed in the PCEA group, particularly 48 hours after surgery (P < .01), and the patients showed lower scores on the visual analog pain scale. The better results observed in the PCEA group favor the application of epidural anesthesia and PCEA analgesia in patients undergoing total knee arthroplasty.

Postoperative pain management and proinflammatory cytokines: animal and human studies.

The postoperative period is associated with neuroendocrine, metabolic, and immune alterations, which are the combined result of tissue damage, anesthesia, postoperative pain, and psychological stress. Limited evidence indicates that pain management in the postoperative period can affect the outcome of the surgery, reducing cardiac, pulmonary, and metabolic complications. Recent evidence indicates that pain and immune factors, especially proinflammatory cytokines, mutually interact and influence each other. A series of animal studies demonstrates that effective preemptive analgesia improved postoperative recovery, and this effect was enhanced by coadministration of IL-1ra together with the preemptive analgesics. Furthermore, preemptive analgesia attenuated surgery-induced PGE(2) production in the amygdala and the activation of the HPA axis. IL-1 signaling is required for the production of amygdala PGE(2) in response to surgical stress, and may thus affect the physiological and psychological aspects of surgical stress. These reports suggest that short-term effective analgesia can have long-lasting beneficial effects on surgery recovery. They further suggest that IL-1 blockade should be considered in the clinical management of pain associated with peripheral or nerve injury. Another series of human studies describes an interaction between the effectiveness of postoperative pain relief and surgery-associated immune alterations: In three separate studies, the more effective pain management technique was associated with diminished surgery-induced immune alterations, especially diminished elevation of IL-1. Reduced elevation of postoperative IL-1 and effective pain relief may both contribute to an attenuated illness response and a better surgery outcome.

Tramadol does not impair the phagocytic capacity of human peripheral blood cells.

PURPOSE: The inhibitory effect of opioids on phagocytic cell capacity is well established. However, the effect of synthetic analgesics on this aspect of cell function is controversial. It was the aim of the study to compare the in vitro effect of tramadol with that of morphine on the engulfing ability of peripheral blood phagocytic cells from healthy volunteers. METHODS: Peripheral blood polymorphonuclear cells and monocytes from healthy volunteers were incubated with 5, 10 and 20 microg.mL(-1) tramadol, or with 20, 40 and 80 etag.mL(-1) morphine. To each tube, 0.05 mL of 5% suspension of latex beads 0.8 microm in diameter was added. After incubation for 60 min the percentage of cells engulfing latex particles and the phagocytic index (number of particles phagocytized by each individual cell) were detected. RESULTS: Tramadol affected neither the percentage of cells phagocyting latex particles, nor the phagocytic index of both polymorphonuclear cells and monocytes. On the other hand, incubation with 20, 40 and 80 etag.mL(-1) morphine caused 11%, 14% and 24% decrease in phagocytosis (P < 0.01 - P < 0.001). The percentage of monocytes phagocyting latex particles was lower by 16%, 19% and 12% at the three doses tested (P < 0.01 - P < 0.001). The three doses of morphine caused a dose dependent decrease in the monocyte phagocyting index by 20%, 29% and 35.5% respectively (P < 0.05). The polymorphonuclear phagocyting index was not significantly lower following incubation with the drug (P = 0.053). CONCLUSION: The lack of noxious effect of tramadol on the engulfing capacity of phagocytic cells suggests additional benefit to the relatively safe profile of the drug.

The effects of perioperative pain management techniques on food consumption and body weight after laparotomy in rats.

UNLABELLED: We examined the effects of two perioperative pain management techniques on recovery after laparotomy, as assessed by body weight (BW) and food consumption (FC). All rats received a preoperative intrathecal mixture of morphine plus bupivacaine combined with one of two treatments: (a) injection of slow-release morphine at the end of the surgery or (b) an antiinflammatory drug, interleukin-1 receptor antagonist (IL-1ra), combined with the preoperative mixture. Laparotomy significantly decreased FC and BW. Both analgesic treatments resulted in a faster recovery of FC and BW. This beneficial effect was more pronounced in the group receiving preoperative analgesics combined with IL-1ra. IMPLICATIONS: Effective perioperative pain management can improve postoperative recovery. We studied the effects of two preoperative pain management techniques on recovery after laparotomy in rats. Both analgesic treatments resulted in a faster recovery, especially preoperative analgesics combined with interleukin-1 receptor antagonist.

Effect of a BIOcocktail on the immune response at the early postoperative period in mice.

Since human subjects and laboratory animals may develop impaired immune response during surgery and the postoperative period, efforts have been made to preserve normal immune functions following surgery by the administration of nutritional supplements and probiotics. The present study was designed to examine the effect of a new nutritional supplement, BIOcocktail, on immune parameters in mice exposed to surgery. Forty mice were assigned to 4 groups containing 10 animals each. Two control groups (with and without subsequent sham laparotomy) were given tap water for 45 min every day for 2 weeks. The remaining 2 groups, with and without laparotomy, received BIOcocktail given orally for the same period of time. The proliferative response of splenic cells (splenocytes) stimulated with phytohemagglutinin (PHA), concanavalin A (Con A) and lipopolysaccharide (LPS) was determined by [3H]thymidine uptake. Cytokine levels were measured in splenocyte supernatants and sera using enzyme-linked immunosorbent assay (ELISA) kits. Natural killer cell activity of splenocytes was evaluated by 51Cr-release assay. Laparotomy, without BIOcocktail administration, was followed by a decreased proliferative response of splenocytes to PHA, Con A, and LPS and an increase in interleukin (IL)-6 serum level. In addition, a decreased secretion of IL-1beta, IL-12 and tumor necrosis factor (TNF)-alpha by the splenocytes was observed. Mice treated with BIOcocktail before laparotomy maintained a preoperative level of splenocyte proliferative response and serum concentrations of IL-12. It is concluded that BIOcocktail administered to mice for 2 weeks before operation resulted in the preservation of T- and B-cell proliferative response to mitogens and in the prevention of postoperative decrease in IL-12 serum level.

General anesthesia for surgery influences melatonin and cortisol levels.

The purpose of this study was to investigate the effect of general anesthesia and surgery on melatonin production, and to assess the relationship between melatonin secretion and cortisol levels. Twenty (9 males and 11 females) consecutive otherwise healthy patients aged 27 to 52 years were included in this study. The patients underwent laparoscopic cholecystectomy or laparoscopic hernioplasty. All patients had general anesthesia with the same anesthetic drugs. Serum cortisol levels were measured at several time periods. Urine collections for melatonin were performed from 18:00 to 7:00 the day prior to surgery, on the operation day, and on the first postoperative day. Baseline melatonin metabolites were measured the night prior to surgery, and the level was found to be 1979 +/- 1.76 ng. The value decreased to 1802 +/- 1.82 ng (NS) on the night of surgery, and it became a significantly higher, reaching 2981 +/- 1.55 ng the night after surgery (p = .003). The baseline daytime cortisol level was significantly lower than the baseline night cortisol level (6.87 +/- 1.51 microg/dl, 14.89 +/- 1.66 micrograms/dl, respectively, p < 0.0001). Surgery induced a significant increase in both day and night cortisol levels. Daytime cortisol levels increased from 6.89 +/- 1.51 microg/dl to 16.90 +/- 1.27microg/dl (p < 0.0001), whereas right levels increased from 14.89 +/- 1.66 microg/dl to 29.20 +/- 1.24 microg/ dl (p <0.0001). The morning after surgery, cortisol levels decreased to 10.16 +/- 1.40 microg/dl, lower than the value obtained on the day of surgery (p < 0.0001). As was true of melatonin, cortisol levels did not reach the pre operative level (p < 0.005). The finding of the current study is that melatonin and cortisol levels show an inverse correlation after surgery.

Effects of surgical stress on brain prostaglandin E2 production and on the pituitary-adrenal axis: attenuation by preemptive analgesia and by central amygdala lesion.

Surgical stress is the combined result of tissue injury, anesthesia, and postoperative pain. It is characterized by elevated levels of adrenocorticotropin (ACTH), corticosterone (CS), and elevated levels of prostaglandin E2 (PGE2) in the periphery and in the spinal cord. The present study examined the effects of perioperative pain management in rats undergoing laparotomy on serum levels of ACTH, CS, and on the production of PGE2 in several brain regions, including the amygdala. The amygdala is known to modulate the pituitary-adrenal axis response to stress. We, therefore, also examined the effects of bilateral lesions in the central amygdala (CeA) on laparotomy-induced activation of the pituitary-adrenal axis in rats. In the first experiment, rats either underwent laparotomy or were not operated upon. Half the rats received preemptive analgesia extended postoperatively, the other received saline. ACTH, CS serum levels, and ex vivo brain production of PGE2 were determined. In the second experiment, rats underwent bilateral lesions of the CeA. Ten days later, rats underwent laparotomy, and ACTH and CS serum levels were determined. Laparotomy significantly increased amygdala PGE2 production, and CS and ACTH serum levels. This elevation was markedly attenuated by perioperative analgesia. Bilateral CeA lesions also attenuated the pituitary-adrenal response to surgical stress. The present findings suggest that the amygdala plays a regulatory role in mediating the neuroendocrine response to surgical stress. Effective perioperative analgesia attenuated the surgery-induced activation of pituitary-adrenal axis and PGE2 elevation. The diminished elevation of PGE2 may suggest a mechanism by which pain relief mitigates pituitary-adrenal axis activation.

Rheological events following laparoscopic and conventional laparotomy.

Laparoscopic surgery has become a widely used procedure with many advantages compared to conventional laparotomy. Although rare, this technique is not entirely absent from clinical hazards and particularly thromboembolic events. This complication is due to activation of the coagulation cascade, as well as factors that may cause alterations in blood rheology. Apart from high hematocrit, presence of abnormal proteins and elevated fibrinogen level, the type of anesthesia, temperature, and increased intra-abdominal pressure following CO(2) insufflation may affect blood viscosity. Therefore, the objective of the study was to compare rheological events in 17 patients undergoing laparoscopic surgery to those in 15 patients who underwent laparotomy. Both groups of patients did not show any complications during the early and late post-operative period. The values of whole blood viscosity in patients undergoing laparoscopy did not differ from those in patients treated by laparotomy. A slight, although significant decrease in plasma viscosity and red blood cell aggregation was observed in patients who underwent laparotomy. The results suggest that the benefits of laparoscopic surgery in the present series were not affected by alterations in blood and plasma viscosity, as well as in red blood cell aggregation.

The relationship between partial splenectomy and peripheral leukocyte count.

BACKGROUND: Partial splenectomy is accepted as a treatment modality for hypersplenism permitting preservation of the spleen functions. Since a prominent leukocytosis is a marked event after total splenectomy, it was the aim of the present study to compare the peripheral white blood cell counts (PWBC) and immune response in mice following partial and total splenectomy. MATERIALS AND METHODS: Four groups of animals were included in the study: mice in which 70% of the spleen was removed, animals that underwent total splenectomy, mice with sham operation, and a group of mice that served as controls. The proliferative response of peripheral blood mononuclear cells, peritoneal cells, and splenocytes was examined using concavalin (Con) A. RESULTS: In distinction from marked leukocytosis observed in mice after total splenectomy, in partially splenectomized mice the PWBC counts did not show any significant increase during a follow-up period of up to 2 months after surgery. The mitogen response of the mononuclear cells to Con A in partially splenectomized mice was similar to that of controls, while in animals after total splenectomy, it was increased in cells from the peripheral blood and decreased in those from the peritoneum. CONCLUSIONS: The results indicate that removal of as much as about 70% of the spleen in mice is sufficient to maintain a normal PWBC count, suggesting a regulatory role of the spleen remnant on the PWBC production. The normal mitogen response of the cells to Con A indicates that the spleen rudiment preserves at least a part of the immune activity of the intact spleen.

Effects of fentanyl on natural killer cell activity and on resistance to tumor metastasis in rats. Dose and timing study.

OBJECTIVES: Opiates, which serve an integral role in anesthesia, suppress immune function, particularly natural killer cell cytotoxicity (NKCC). NK cells play an important role in tumor and metastasis surveillance. We reported that large-dose fentanyl anesthesia induced prolonged suppression of NKCC in patients undergoing abdominal surgery. The immune modulatory effects of opiates may depend on the interaction between dose and time of administration. The present study examined the effects of different doses of fentanyl, administered at different time points relative to tumor inoculation, on NKCC and on experimental tumor metastasis in rats. METHODS: Fischer 344 rats were injected with low or high doses of fentanyl, 6 or 2 h before, simultaneously with or 1 h after being inoculated intravenously with MADB106 tumor cells. Lung tumor retention (LTR) was assessed 4 h after, and lung tumor metastases were counted 3 weeks after tumor inoculation. NKCC was assessed 1 h after the fentanyl injection. RESULTS: At all time points, except 6 h before tumor inoculation, fentanyl (0.1-0.3 mg/kg) induced a dose-dependent increase in MADB106 LTR (2.3- to 74-fold). An intermediate dose of fentanyl (0.15 mg/kg) doubled the number of lung metastasis, and, within animal, suppressed NKCC and increased MADB106 LTR in a correlated manner. CONCLUSION: These findings indicate that fentanyl suppresses NKCC and increases the risk of tumor metastasis. Suppression of NK cells at a time when surgery may induce tumor dissemination can prove to be critical to the spread of metastases. It is suggested that the acute administration of a moderate dose of opiates during surgery should be applied cautiously, particularly in cancer patients.