Lack of gamma delta T cells ameliorates inflammatory response after acute intestinal ischemia reperfusion in mice.

T-cells have been demonstrated to modulate ischemia-reperfusion injury (IRI) in the kidney, lung, liver, and intestine. Whereas most T-cell subpopulations contribute primarily to the antigen-specific effector and memory phases of immunity, γδ-T-cells combine adaptive features with rapid, innate-like responses that can place them in the initiation phase of immune reactions. Therefore, we aimed to clarify the role of γδ-T-cells in intestinal IRI. Adult wild-type (WT) and γδ-T-cell-deficient mice were subjected to acute intestinal IRI. Gene expression of pro-inflammatory cytokines and influx of leukocyte subpopulations in the gut were assessed by qPCR and flow cytometry. Serum transaminases were measured as an indicator of distant organ IRI. Intestinal IRI led to increased influx of neutrophils, pro-inflammatory cytokine expression and LDH/ALT/AST elevation. Selective deficiency of γδ-T-cells significantly decreased pro-inflammatory cytokine levels and neutrophil infiltration in the gut following IRI compared to controls. Furthermore, γδ-T-cell deficiency resulted in decreased LDH and transaminases levels in sera, indicating amelioration of distant organ injury. Increasing evidence demonstrates a key role of T-cell subpopulations in IRI. We demonstrate that γδ-T-cell deficiency ameliorated pro-inflammatory cytokine production, neutrophil recruitment and distant organ injury. Thus, γδ-T-cells may be considered as mediators contributing to the inflammatory response in the acute phase of intestinal IRI.

Systemic and regional cerebral perfusion in small infants undergoing minor lower abdominal surgery under awake caudal anaesthesia: An observational study.

BACKGROUND: Infants undergoing general anaesthesia have an increased risk of severe respiratory and cardiovascular critical events. Awake caudal anaesthesia is an alternative for small infants undergoing minor lower abdominal surgery. While clinical experience has shown stable intra-operative haemodynamic conditions, there are no studies evaluating systemic and regional cerebral perfusion during such a procedure. OBJECTIVES: The purpose of this study was to evaluate the effects of awake caudal anaesthesia on systemic and regional cerebral perfusion in small infants. DESIGN: A prospective observational cohort study. SETTING: Clinic of Anaesthesiology, University Children's Hospital, between November 2017 and June 2018. PATIENTS: Twenty small infants (postmenstrual age 36 to 54 weeks, weight 1800 to 5700 g) scheduled for lower abdominal surgery under awake caudal anaesthesia were enrolled in this study. INTERVENTION: Standard monitoring was expanded to include cardiac index using electrical velocimetry and regional cerebral oxygen saturation using near infrared spectroscopy. The caudal block was performed with 0.3% ropivacaine 1 ml kg Hypotension was defined as mean arterial blood pressure (BP) less than 35 mmHg and regional cerebral desaturation as regional cerebral oxygen saturation less than 80% of baseline. MAIN OUTCOMES: Mean arterial BP, cardiac index and regional cerebral oxygen saturation parameters under awake caudal anaesthesia. RESULTS: Mean arterial BP, cardiac index and regional cerebral oxygen saturation remained above the predefined lower limits. No episodes of hypotension or regional cerebral desaturation were observed. Operation time was 35 ±â€Š13 (range 20 to 71) min. The infants were discharged to the neonatal ward after the end of surgery, and milk was fed 22 ±â€Š15 (range 6 to 55) min thereafter. Five preterm infants experienced self-limiting episodes of apnoea intra-operatively. CONCLUSION: The current study shows that awake caudal anaesthesia does not impair systemic and regional cerebral perfusion in small infants. TRIAL REGISTRATION: German registry of clinical studies (DRKS-ID: 800015742).

Conventional alpha beta (αß) T cells do not contribute to acute intestinal ischemia-reperfusion injury in mice.

PURPOSE: Ischemia-reperfusion injury (IRI) is associated with significant patient mortality and morbidity. The complex cascade of IRI is incompletely understood, but inflammation is known to be a key mediator. In addition to the predominant innate immune responses, previous research has also indicated that αß T cells contribute to IRI in various organ models. The aim of this study was to clarify the role αß T cells play in IRI to the gut. METHODS: Adult wild-type (WT) and αß T cell-deficient mice were subjected to acute intestinal IRI with 30min ischemia followed by 4h reperfusion. The gene expression of pro-inflammatory cytokines was measured by qPCR, and the influx of leukocyte subpopulations in the gut was assessed via flow cytometry and histology. Pro-inflammatory cytokines in the serum were measured, and transaminases were assessed as an indicator of distant organ IRI. RESULTS: Intestinal IRI led to an increased expression of pro-inflammatory cytokines in the gut tissue and an influx of leukocytes that predominantly consisted of neutrophils and macrophages. Furthermore, intestinal IRI increased serum IL-6, TNF-α, and ALT/AST levels. The αß T cell-deficient mice did not exhibit a more significant increase in pro-inflammatory cytokines in the gut or serum following IR than the WT mice. There was also no difference between WT- and αß T cell-deficient mice in terms of neutrophil infiltration or macrophage activation. Furthermore, the increase in transaminases was equal in both groups indicating that the level of distant organ injury was comparable. CONCLUSION: An increasing body of evidence demonstrates that αß T cells play a key role in IRI. In the gut, however, αß T cells are not pivotal in the first hours following acute IRI as deficiency does not impact cytokine production, neutrophil recruitment, macrophage activation, or distant organ injury. Thus, αß T cells may be considered innocent bystanders during the acute phase of intestinal IRI.

Laparoscopy vs minilaparotomy and full laparotomy preserves circulatory but not peritoneal and pulmonary immune responses.

PURPOSE: Laparoscopy has been associated with lower inflammatory responses. However, it has been postulated that minilaparotomy, in contrast to full laparotomy, is equally minimally invasive. OBJECTIVE: The aim of this study was to investigate local, systemic, and distant organ immune responses after different surgical approaches to the abdominal cavity, such as minilaparotomy, full laparotomy, and laparoscopy, in a small animal model. METHODS: Male Lewis rats received a permanent central venous catheter and were randomized to 4 groups (n = 6 per group). The animals were subjected to anesthesia alone (control), minilaparotomy (1 cm), full laparotomy (7 cm), or laparoscopy for 60 minutes. Blood was collected via the central venous catheter before as well as 1 hour and 6 hours after the start of intervention. Peritoneal and bronchoalveolar lavages, as well as heart puncture, were performed after 24 hours. RESULTS: All surgical interventions led to a significant migration of polymorphonucleocytes into the abdominal cavity. Full laparotomy resulted in a significant increase in nitric oxide production by peritoneal macrophages as compared with control. Macrophage nitric oxide production after laparoscopy and minilaparotomy was not significantly different. A shift in the expression of OX-6 and CD54 was only detected after full laparotomy. Systemically, O(2)(-) release by circulating mononuclear cells was significantly increased after minilaparotomy and full laparotomy, but not after laparoscopy. The systemic levels of IL6 were significantly accelerated only after full laparotomy, with a maximum after 6 hours. In the lungs, function of alveolar macrophages was not altered in any group. CONCLUSIONS: Any approach to the peritoneal cavity causes local inflammatory responses. Full laparotomy alters peritoneal macrophage functions more pronouncedly than does minilaparotomy or laparoscopy. Systemic inflammatory responses, such as free oxygen radical release, are significantly increased by both minilaparotomy and full laparotomy, whereas laparoscopy preserves systemic immune function. Our results may lead to further preference for the laparoscopic approach over minilaparotomy and full laparotomy.