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This study evaluated the effect of varying the synthesis of nitric oxide with sodium nitroprusside or N-nitro-L-arginine methyl ester (L-NAME) in a pancreatitis-lung injury model. Rats (n = 45) were randomized to control or caerulein-induced pancreatitis groups, treated with saline, sodium nitroprusside (0·4 μg/kg) or l-NAME (10 mg/kg). Myeloperoxidase activity was used as a measure of neutrophil infiltration. Wet to dry (W:D) lung weight and bronchoalveolar lavage (BAL) protein concentrations were used to assess vascular leakage. Pancreatitis was shown to induce pulmonary neutrophil influx: mean(s.e.m.) myeloperoxidase activity 6·79(0·5) units/g in caerulein-treated animals versus 2·08(0·5) units/g in controls (P < 0·001). Animals with pancreatitis showed increased microvascular leakage compared with controls (mean(s.e.m.) W:D lung weight 7·01(0·5) versus 2·85(0·2), P < 0·001; BAL protein concentration 2539(222) versus 347(32) μg/ml, P < 0·001). Compared with the saline-treated pancreatitis group, these changes were reduced by sodium nitroprusside (mean(s.e.m.) myeloperoxidase activity to 2·5(0·4) units/g, P < 0·001; W:D lung weight to 3·8(0·37), P < 0·001; BAL protein concentration 1389(182) μg/ml, P < 0·05). L-NAME exacerbated the pancreatitis-induced pulmonary oedema (W:D lung weight increased to 11·96(0·6), P < 0·001), protein leakage (BAL protein concentration rose to 3707(309) μg/ml, P < 0·05) and neutrophil infiltration (myeloperoxidase activity increased to 9·01(0·3) units/g, P < 0·05). These data suggest that, in vivo, nitric oxide inhibits pancreatitis-induced lung injury, possibly in part by inhibiting pulmonary neutrophil influx.

Background An increased plasma level of homocysteine has been proposed as an independent risk factor for atherosclerosis; this review examines the evidence. Methods A Medline search was undertaken for English language articles on homocysteine and vascular disease. Further papers were identified by cross-referencing from the reference lists of relevant major articles. Results Although much interest has been generated about homocysteine and atherosclerotic disease, contradictory data exist regarding its role in disease progression. There is insufficient current evidence to regard increased homocysteine level as a causative factor in atherosclerotic disease. Conclusion It is not known whether lowering plasma homocysteine concentration will reduce cardiovascular risk in the long term. Until such data become available, there is no evidence for the widespread use of folic acid therapy to reduce cardiovascular disease risk.

Background The pathogenesis of interleukin (IL) 2-induced vascular leak syndrome may be related to neutrophil-mediated endothelial injury. Nitric oxide inhibits neutrophil superoxide anion synthesis and adherence to endothelial cells. The role of systemic nitric oxide in preventing IL-2-induced lung injury was studied in an experimental model. Methods Sprague-Dawley rats (seven per group) were randomized to control, IL-2 treatment (1 × 106 units), and IL-2 with sodium nitroprusside 0.2 mg/kg. Lung injury was measured by estimation of extravascular lung water (wet:dry weight) and bronchoalveolar lavage (BAL) protein concentration, and by histological findings. Neutrophil infiltration was evaluated by measuring myeloperoxidase activity and BAL neutrophil concentration. Results IL-2 produced significant lung damage characterized by leucocyte sequestration (increased myeloperoxidase and BAL neutrophil concentrations), pulmonary congestion and microvascular protein leakage (increased wet: dry weight ratio and BAL protein concentration). This injury was reduced significantly by the addition of sodium nitroprusside, the nitric oxide donor. Conclusion Nitric oxide reduces IL-Zinduced lung injury.

BackgroundSurgery depresses host tumoricidal activity and may increase tumour growth. This study compared the effects of laparoscopy with laparotomy on extraperitoneal tumour growth and immune function in a murine model.MethodsC57BL/6 female mice aged 8–10 weeks had tumours induced in the right flank (n = 45) and were randomized to undergo halothane anaesthesia only, laparoscopy or laparotomy. Flank tumour volume was assessed over 10 days. A second group of animals (n = 540) were randomized to undergo the same procedures and killed at 24, 48 and 96 h. Splenocytes were harvested for natural killer (NK) cell and lymphokine activated killer (LAK) cell cytotoxicity studies.ResultsThere was a significant increase in flank tumour growth in the first 48 h after laparotomy and laparoscopy compared with controls (PConclusionExtraperitoneal tumour growth was significantly accelerated after laparotomy and correlated with significantly suppressed NK and LAK cytotoxicity for at least 4 days after operation. Laparoscopy had a shorter, less profound effect on tumour growth and immune function.

Background Ischaemia–reperfusion injury is mediated by neutrophil–endothelial interaction. Induction of heat shock proteins attenuates neutrophil–endothelial interactions. The aim of this study was to determine whether thermal preconditioning could have a protective effect on neutrophil-mediated lung injury in an animal model of lower torso ischaemia–reperfusion. Methods Sprague-Dawley rats were randomized into: control, ischaemia–reperfusion, and ischaemia–reperfusion preconditioned with hyperthermia groups. Ischaemia–reperfusion injury was induced by infrarenal aortic clamping for 30 min and reperfusion for 120 min. Thermotolerance was induced by raising the core body temperature to 40·5–41·5°C for 15 min, 18 h before ischaemia–reperfusion. Wet:dry lung (W:D) weight ratio, bronchoalveolar lavage protein (BALprot) concentration, tissue myeloperoxidase (MPO) activity and bronchoalveolar lavage polymorphonuclear neutrophil (BAL PMN) count were measured. Heat shock protein 72 (hsp72) expression in lung, intestine and mesentery was measured using Western immunoblotting. Results Ischaemia–reperfusion resulted in a significant increase in tissue oedema (W:D weight ratio) and BALprot concentration. In addition there was a marked increase in tissue neutrophil infiltration (MPO activity, BAL PMN concentration). Preconditioning with hyperthemia resulted in increased expression of hsp72 and significantly reduced tissue oedema and neutrophil infiltration. Conclusion Thermal preconditioning protects against neutrophil-mediated ischaemia–reperfusion-induced lung injury, possibly by increasing the expression of heat shock proteins.

Background The aims of this study were to evaluate the effects of aortic clamping and unclamping on neutrophil and monocyte activation and release of plasma mediators in 2() patients undergoing elective aortic aneurysm surgery, and to correlate these findings with pulmonary haemodynamics and gas exchange. Methods Simultaneous arterial and mixed venous samples were obtained during and after aortic damping and unclamping. Results Neutrophil respiratory burst activity in mixed venous samples increased significantly during the period of aortic clamping. An initial increase in neutrophil CD11b expression in venous blood 5 min after clamp removal was followed by a significant decrease in level of expression. Plasma tumour necrosis factor levels increased at the end of the cross-clamp period and reached a maximum 60 min following reperfusion. There was a significant and sustained rise in plasma thromboxane B 2 levels following clamp removal. This increase correlated with the development of increased pulmonary vascular resistance. Conclusion This study confirms the central role played by activated neutrophils in the early stages of reperfusion injury and also suggests a role for plasma mediators in mediating cardiopulmonary dysfunction during major vascular surgery.

The aim of this study was to determine whether glyceryl trinitrate (GTN) has a protective effect on neutrophil- mediated lung injury in a model of aortic occlusion (30 min) and reperfusion (120 min). Sprague-Dawley rats were randomized into control (n = 11), ischaemia-reperfusion (IR) (n = 12), and IR treated with GTN (2 μg kg−1 min−1) during reperfusion (n = 10). Myeloperoxidase (MPO) activity measured pulmonary neutrophil influx. Pulmonary endothelial permeability was measured by wet:dry weight ratio, bronchoalveolar lavage (BAL) protein and neutrophil counts. Neutrophil superoxide release was measured by flow cytometry in a further IR versus GTN experiment (n = 6 in each group). The significant increase in MPO activity produced by IR to a level of 7·99 units g−1 was prevented by GTN which reduced the level to 4·73 units g−1. The increase in pulmonary microvascular leakage after reperfusion was also prevented by GTN: BAL protein without GTN was 992 μg ml−1 and with GTN 579 μg ml−1; BAL neutrophil count without GTN was 3219 cells mm−3 and with GTN 820 cells mm−3; the wet:dry lung weight ratio without GTN was 3·8 and with GTN 3·3. Neutrophil superoxide release increased significantly after 40 min of reperfusion in the untreated IR group (P < 0·05). This increase was prevented in the GTN-treated group. GTN administration had no effect on plasma thromboxane production during revascularization. These data suggest that GTN administration during the reperfusion phase has the potential to decrease pulmonary microvascular injury.

Suture line recurrence is an important cause of failure after potentially curative resection for colonic carcinoma. Our aim was to determine whether suture technique affected the incidence of perianastomotic tumours in experimentally induced colonic cancer. Sprague-Dawley rats were randomized into three groups. A 1 cm longitudinal colotomy was repaired with four interrupted 6/0 polypropylene monofilament sutures, using either a transmural technique (n = 18) or a seromuscular technique (n = 18). Control animals (n = 18) had a sham laparotomy. All animals received nine, weekly, subcutaneous injections of azoxymethane (total dose 90 mg/kg) starting 6 weeks after laparotomy. Surviving animals were killed 32 weeks after laparotomy. Five animals from each group were given intraperitoneal bromodeoxyuridine (100 mg/kg) 1 h before being killed. At death, perianastomotic tumours occurred more frequently in animals with transmural sutures than in either controls or those with seromuscular sutures. This difference was associated with a greater mucosal bromodeoxyuridine crypt cell labelling index in the transmural suture group. We conclude that a transmural anastomotic suture technique promotes the development of experimental perianastomotic colonic tumours.

Transabdominal exposure is the most widely used surgical approach to the infrarenal aorta. Over the last 30 years a number of surgeons have championed the retroperitoneal approach for repair of abdominal aortic aneurysms and aortoiliac occlusive disease using a variety of incisions. Several studies attest to the clinical superiority of this approach over the transabdominal route and recent evidence demonstrates reduced physiological disturbance with this technique. The retroperitoneal approach is suitable for all elective operations on the abdominal aorta, particularly in patients with high-risk aneurysms and in selected patients with symptomatic and ruptured aneurysms.

Leg swelling is a significant problem following ankle fracture. Venous pump function and femoral and popliteal venous patency were assessed prospectively in 26 patients with ankle fractures requiring open reduction, internal fixation and immobilization in plaster. Functional venous volume, venous filling index (VFI), ejection volume fraction (EVF) and residual volume fraction (RVF) were measured using air plethysmography at 5 days and at 6, 12 and 18 weeks after fracture. The uninjured leg was used as a control. Popliteal and femoral venous patency was determined using duplex ultrasonography. No patient developed deep vein thrombosis during the study. At 5 days after fracture there was a significant reduction in mean(s.d) EVF, 18·2(12·1) versus 55·9(19·5) percent, and increase in RVF, 87·0(14·3) versus 42·5(22·2) per cent (both P < 0·001). Analogous values were similar at 6 weeks, EVF 28·5(21·2) versus 55·6(21·9) per cent, RVF 82·2(16·8) versus 48·5(23·8) per cent (both P < 0·001), and at 12 weeks, EVF 39·1(16·0) versus 60·3(14·9) per cent, RVF 64·7(18·8) versus 38·8(13·2), per cent (both P < 0·001). However, by 18 weeks there was no significant difference in venous function between fractured and control limbs. It is concluded that there is a significant and prolonged impairment in venous pump function following ankle fracture.