C.V. Soong

Endotoxaemia, the generation of the cytokines and their relationship to intramucosal acidosis of the sigmoid colon in elective abdominal aortic aneurysm repair

Ischaemia of the large bowel occasionally occurs following abdominal aortic aneurysm repair and may lead to multiple system organ failure (MSOF). Intramucosal acidosis of the sigmoid colon is a good indicator of sigmoid colonic ischaemia. Intramucosal pH of the sigmoid colon was measured using the silicone tonometer in 21 patients undergoing abdominal aortic aneurysmectomy. Samples were taken for plasma endotoxin, tumour necrosis factor (TNF) and interleukin-6 (IL-6) measurements preoperatively, half-hourly during the operation, 2-hourly for the next 12 h, 4-hourly for a further 48 h and 8-hourly thereafter until the fifth day. The intramucosal pH of the sigmoid colon fell to less than 7.00 peri-operatively in 10 patients, four of whom developed diarrhoea; in comparison, this did not occur in any of the 11 whose pH remained greater than 7.00 (p = 0.036). Higher peak concentrations of endotoxin, TNF and IL-6 were found in those patients whose intramucosal pH fell to less than 7.00 compared to those whose pH remained greater than 7.00 (mean +/- S.E.M. pg/ml, endotoxin = 112 +/- 24 vs. 58 +/- 6, p < 0.05; TNF = 26 +/- 8 vs. 7 +/- 2, p < 0.05; IL-6 = 213 +/- 59 vs. 87 +/- 12, p = 0.09). In the two patients who died, both from the group with pH level less than 7.00, concentrations of IL-6 were considerably higher than that in most of the other patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Intramucosal acidosis and systemic host responses in abdominal aortic aneurysm surgery

OBJECTIVESnTo assess the specific host responses to systemic endotoxemia and tumor necrosis factor (TNF) activation after abdominal aortic aneurysm surgery by measuring antiendotoxin core antibodies (EndoCab) immunoglobulin (Ig)G and IgM, and soluble p55TNF receptor concentrations. The role of the gut in initiating these immune responses was evaluated by correlating the systemic markers to changes in the intramucosal pH of the sigmoid colon.nnnDESIGNnRetrospective, reevaluation study.nnnSETTINGnVascular unit of a university hospital.nnnPATIENTSnEleven patients who underwent abdominal aortic aneurysm repair surgery were selected from a larger patient cohort (n = 42) on the basis of their clinical outcome (four patients had fatal complications and seven patients had an uneventful recovery).nnnINTERVENTIONSnAfter induction of anesthesia, intramucosal pH of the sigmoid colon was measured using tonometry. Blood samples were obtained from indwelling catheters or direct venipuncture preoperatively, during surgery, and daily until postoperative day 5.nnnMEASUREMENTS AND MAIN RESULTSnThose patients who died developed intramucosal acidosis of the sigmoid colon intraoperatively. Significant consumption of both IgG and IgM EndoCab antibodies was found in all patients. By measuring the concentration of antibodies to a neutral antigen, i.e., tetanus toxoid, the consumption of IgG EndoCab antibody concentrations was shown to be a specific host response. In all patients, reciprocal changes in the serum concentrations of p55TNF receptor and interleukin (IL)-6 were observed. The percentage increase in p55TNF receptor and the concentration of IL-6 were significantly higher in the nonsurvivor group by 48 hrs. There were significant correlations between, intramucosal pH and EndoCab antibodies, intramucosal pH and p55 TNF receptor, and p55 TNF receptor and IL-6.nnnCONCLUSIONSnThe development of colonic ischemia is associated with a significant consumption of IgG EndoCab antibodies and a simultaneous increase in soluble p55TNF receptor. This study provides further support for the concept that gut-derived endotoxin and the generation of TNF may play a role in the pathogenesis of complications after abdominal aortic aneurysm surgery.

Reduction of free radical generation minimises lower limb swelling following femoropopliteal bypass surgery

Oxygen-derived free radicals have been implicated as contributors to the development of lower limb oedema observed after femoropopliteal bypass grafting. This study investigates the occurrence of free radical-induced lipid peroxidation after this operation and the possible effects of allopurinol (xanthine oxidase inhibitor) in reducing free radical injury in order to minimise lower leg oedema. Twenty-nine patients undergoing femoropopliteal bypass surgery were randomised in a double blind fashion into two groups; those in one were given allopurinol 200 mg orally (n = 15) at 24 h and 2 h preoperatively and again at 24 h postoperatively, while those in the second group received a placebo (n = 14). Daily lower limb volume was calculated to assess swelling. Blood samples were taken from the femoral vein for measurements of malondialdehyde (MDA), an end product of lipid peroxidation, before the application of the femoral artery clamp, just prior to and immediately after clamp release, and at 20 minute intervals thereafter for 1 hour. The increase in lower limb volume in the placebo group was almost twice (8.9 +/- 1.6%) that of the allopurinol group (4.6 +/- 1%; p = 0.02). Six out of the 14 patients receiving placebo suffered swelling of 10% or more of original lower limb volume in comparison to only one out of 15 in those given allopurinol (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Intramucosal acidosis and the inflammatory response in acute pancreatitis

OBJECTIVE:The aim of this study was to assess the host response and diminished bowel perfusion during acute pancreatitis.METHODS:A total of 19 patients admitted with established diagnoses of acute pancreatitis on the basis of clinical findings, elevated serum amylase to more than four times the upper limit or by contrast radiology. Patients were stratified into mild and severe pancreatitis using the Atlanta criteria. Blood samples were obtained from in-dwelling lines or direct venipuncture within 12 h of admission and 24 hourly thereafter for measurements of plasma endotoxin, EndoCab immunoglobulin (Ig)G and IgM antibodies, tumor necrosis factor (TNF), p55 TNF receptor, and IL-6. A gastric tonometer was inserted in place of a nasogastric tube for intramucosal pH evaluation.RESULTS:Episodes of endotoxaemia were more common and endotoxin concentration significantly higher at presentation in the severe group compared to the mild group of patients. A greater consumption of IgM antibody was found in those with severe disease. The decrease in IgM antibody concentration was shown to be a specific host response, as a fall in concentration of antibodies to a neutral antigen, tetanus toxoid, was not observed. Significantly greater elevations were found in p55 TNF receptor and IL-6 concentrations in the severe group in comparison to those suffering mild pancreatitis. Significant correlations were found between gastric intramucosal pH and EndoCab IgM antibody, p55 TNF receptor, and IL-6.CONCLUSIONS:These results suggest that endotoxemia, an acute inflammatory response, and a reduction in bowel perfusion may occur in severe acute pancreatitis. The endotoxemia and inflammatory response may be due to the permeation of bacteria and their breakdown products across a disrupted bowel mucosal barrier.

The generation of byproducts of lipid peroxidation following carotid endarterectomy

The aim of this study was to determine whether free radical-induced lipid peroxidation occurs following transient carotid clamping. Jugular vein plasma levels of malondialdehyde (MDA) and diene conjugates (DC) were estimated in 24 patients undergoing carotid endarterectomy, at the beginning of the operation (To), just prior to clamping the carotid artery before the shunt was removed for closure of the arteriotomy (Ts), and at 30 (T30), 60 (T60), 120 (T120), 180 (T180) and 300 (T300) seconds after the clamps were released. Carotid clamp times were recorded. Significant elevations in the concentrations of both MDA and DC were observed at T60 after clamp release (MDA = 559 +/- 64 pmol/ml, DC = 428 +/- 32 units/ml), in comparison to concentrations at To (MDA = 408 +/- 34 pmol/ml, p < 0.01; DC = 374 +/- 28 units/ml, p < 0.05), returning to baseline at T300. There was a significant correlation between the percentage rise in MDA concentration and the duration of clamp-induced ischaemia (r = 0.45, p = 0.03). The significance of this burst of MDA and DC is unclear especially as the one patient who sustained a postoperative neurological deficit displayed no rise in the concentration of either. If this rise is related to free radical generation following ischaemia-reperfusion injury it may play an important role in influencing the clinical outcome in the patients.

Lipid peroxidation as a cause of lower limb swelling following femoro-popliteal bypass grafting.

We examined the role of free radical induced lipid peroxidation in lower limb swelling in patients following femoro-popliteal bypass grafting. In 20 patients undergoing this operation blood samples were taken from the femoral vein via a cannula before the femoral artery clamp was applied, just prior to and immediately after clamp release and at 10 min intervals thereafter for 1 h for measurements of malondialdehyde (MDA) and vitamin E. The concentration of MDA was significantly elevated at 40 min after reperfusion (mean +/- S.E.M., 573 +/- 83 pmol/ml) compared to just before clamp release (359 +/- 41 pmol/ml; p < 0.01). This was associated with a corresponding fall in the concentration of vitamin E at the time of peak MDA rise (5.68 +/- 0.28 to 5.29 +/- 0.28 mumol/mM cholesterol, p < 0.05) suggesting its utilisation as an antioxidant. The degree of oedema was related to the changes in MDA and vitamin E. Thus, in the 15 patients with greater than 10% increase in lower limb volume the rise in the concentration of MDA was 364 +/- 44 to 693 +/- 76 pmol/ml (p = 0.0001) while that in the five, whose swelling was less than 10%, was 344 +/- 40 to 559 +/- 243 pmol/ml (p = 0.25). A significant fall in vitamin E was found only in the group with greater than 10% lower limb oedema (5.90 +/- 0.33 to 5.40 +/- 0.34 mumol/mM cholesterol, p < 0.01), in comparison to those with less than 10% swelling (5.01 +/- 0.35 to 5.04 +/- 0.50 mumol/mM cholesterol).(ABSTRACT TRUNCATED AT 250 WORDS)

The use of tonometry to predict mortality in patients undergoing abdominal aortic aneurysm repair

OBJECTIVEnTo assess the reliability of intramucosal pH (pHi) of the sigmoid colon, IL-6 concentration and the APACHE II score in predicting outcome in patients undergoing elective abdominal aortic aneurysm repair.nnnDESIGNnProspective study.nnnMETHODSnIn 42 patients, measurements were made of the sigmoid pHi with the silicone tonometer and plasma IL-6 by enzyme linked immuno-sorbent assay (ELISA). The daily postoperative APACHE II scores were also calculated. In 29 patients a preoperative left ventricular ejection fraction was determined by gated radionuclide angiography.nnnRESULTSnFour out of 42 patients who were studied died. The lowest perioperative pHi, the peak postoperative IL-6 concentration and APACHE II scores were significantly different in the survivors in comparison to the non-survivors. In the non-survivors, the fall in pHi preceded the time of patients demise by at least 4 days. Significant correlations were observed between changes in pHi, IL-6 and APACHE II. Using receiver operating characteristic curves, pHi was shown to be the most predictive of mortality compared to the other variables. The simplicity, speed and practicality of using the tonometer adds to its superiority over the latter measurements. No relationship was found between ventricular ejection fraction, pHi and outcome.nnnCONCLUSIONnAlthough the number of patients is small, these results support pHi as a valuable predictor of outcome and also suggest a role for the gut in initiating the IL-6 and physiological responses.

Lower limb oedema following distal arterial bypass grafting

Lower-limb oedema following arterial bypass surgery for ischemia is a common sequela which can complicate wound healing or delay resumption of mobility. Its exact pathogenesis remains uncertain but many theories have been proposed. Lymphatic disruption during arterial exposure, and endothelial damage from atrophy of the media and oxygen-derived free radical release are currently favoured hypotheses. Infrequently, deep vein thrombosis follows surgery and may exacerbate the condition. Efforts aimed at reducing the oedema, such as the use of lymphatic preserving incisional approaches or the use of antioxidants, have given conflicting results. The use of compression hosiery and leg elevation appear to be the most effective measures in reducing postoperative lower limb oedema.