Neutrophil-mediated mycobacteriocidal immunity in the lung during Mycobacterium bovis BCG infection in C57BL/6 mice.

Although neutrophils have been identified as sources of inflammatory cytokines and chemokines, little is known about their immunologic function during mycobacterial infection in the lungs. In this study, we examined the growth of Mycobacterium bovis BCG in the lungs under experimental conditions that altered neutrophil recruitment to the lungs. Depletion and recruitment of neutrophils was associated with respective increases and decreases in M. bovis BCG growth. Thus, neutrophils may enhance mycobacteriocidal immunity in the lungs.

Intravenous immunoglobulin in neurological disease: a specialist review.

Treatment of neurological disorders with intravenous immunoglobulin (IVIg) is an increasing feature of our practice for an expanding range of indications. For some there is evidence of benefit from randomised controlled trials, whereas for others evidence is anecdotal. The relative rarity of some of the disorders means that good randomised control trials will be difficult to deliver. Meanwhile, the treatment is costly and pressure to "do something" in often distressing disorders considerable. This review follows a 1 day meeting of the authors in November 2000 and examines current evidence for the use of IVIg in neurological conditions and comments on mechanisms of action, delivery, safety and tolerability, and health economic issues. Evidence of efficacy has been classified into levels for healthcare interventions (tables 1 and 2).

Comparison of milrinone versus nitroglycerin, alone and in combination, on grafted internal mammary artery flow after cardiopulmonary bypass: effects of alpha-adrenergic stimulation.

OBJECTIVES: To compare changes in blood flow in a grafted internal mammary artery (IMA) after cardiopulmonary bypass (CPB) in response to the administration of milrinone or nitroglycerin and to establish the effects of alpha-adrenergic stimulation. DESIGN: Randomized study. SETTING: A university medical center hospital and a Veterans Affairs Medical Center hospital. PARTICIPANTS: Thirty consenting adults scheduled for elective coronary artery bypass graft surgery. INTERVENTIONS: Patients were randomized to receive a 2 microg/kg/min infusion of nitroglycerin (n = 10), a loading dose of 50 microg/kg of milrinone (n = 10), or both drugs combined (n = 10) shortly after CPB. Intravenous phenylephrine was administered to increase mean arterial pressure by 20%. IMA flow was measured with a calibrated laser Doppler flow probe. Hemodynamic and flow measurements were obtained before and after every intervention. MEASUREMENTS AND MAIN RESULTS: Nitroglycerin and milrinone increased mean IMA flow, but the increase was greater with milrinone. Both drugs combined were superior to nitroglycerin alone but not to milrinone. The addition of phenylephrine to nitroglycerin increased IMA flow in 6 of 10 patients. IMA flow decreased in 4 of 10 patients, however. Phenylephrine significantly increased IMA blood flow in patients receiving milrinone or in those given both drugs combined. CONCLUSION: After CPB, milrinone and nitroglycerin vasodilate the IMA; however, the combination of both drugs was not superior to milrinone alone. When using alpha-adrenergic stimulation, milrinone proved superior to nitroglycerin in preserving IMA flow.

Single-stage transmediastinal replacement of the ascending, arch, and descending thoracic aorta.

BACKGROUND: Aneurysms of the ascending, arch, and descending thoracic aorta are typically managed with two operations. The first stage involves replacement of the ascending and arch aorta leaving a segment of graft in the proximal descending aorta with a mortality and stroke risk of 8%. The second stage involves replacement of the descending aorta with a mortality of 5% and a paraplegia risk of 5% to 10%. Some patients refuse surgical completion and others are at increased risk to undergo the second stage thoracotomy, leaving them with untreated descending thoracic aortic aneurysms vulnerable to rupture. A single-stage transmediastinal operation used in 14 patients is described. METHODS: Under circulatory arrest, the descending thoracic aorta is opened. A wire is passed up to the arch and a graft is brought down and secured excluding the descending thoracic aneurysm. The arch vessels are attached as a single patch and the graft is brought forward, replacing the ascending aorta. RESULTS: Fourteen patients have undergone single-stage replacement of the ascending, arch, and descending aorta with a 14% mortality rate and 14% incidence of paraplegia. CONCLUSIONS: Patients with aneurysms of the ascending, arch, and descending thoracic aorta can be managed with a single operation with comparable mortality and morbidity of the two-stage approach.

Inhibition of phosphodiesterase type III before aortic cross-clamping preserves intramyocardial cyclic adenosine monophosphate during cardiopulmonary bypass.

UNLABELLED: Inotropes are often used to treat myocardial dysfunction shortly after cardiopulmonary bypass (CPB). beta-Adrenergic agonists improve contractility, in part by increasing cyclic adenosine monophosphate (cAMP) production, whereas phosphodiesterase type III inhibitors prevent its breakdown. CPB is associated with abnormalities at the beta-receptor level and diminished adenyl cyclase activity, both of which tend to decrease cAMP. These effects may be increased in the presence of preexisting myocardial dysfunction. We tested the hypothesis that inhibition of phosphodiesterase type III before global myocardial ischemia and pharmacologic arrest results in the preservation of intramyocardial cAMP concentration during CPB. Twenty adult patients undergoing coronary artery bypass grafting with CPB were studied. After CPB was instituted, a myocardial biopsy was obtained from the apex of the left ventricle. Patients were randomized to receive either placebo or milrinone (50 micro/kg) through the bypass pump 10 min before aortic cross-clamping. Another myocardial biopsy was performed adjacent to the left ventricular apex just before weaning from CPB. Myocardial cAMP concentration was determined by radioimmunoassay. Myocyte protein content was determined by the Bradford method by using a commercial kit. There were no significant demographic differences between the groups; however, patients in the Milrinone group had a lower left ventricular ejection fraction than placebo (41% +/- 13% vs 53% +/- 7%; P < 0.05). Patients who received milrinone had larger cAMP concentrations at the end of CPB compared with placebo (21 +/- 12.5 pmol/mg protein versus 12.8 +/- 2.2 pmol/mg protein; P < 0.05). The administration of milrinone before aortic cross-clamping is associated with increased intramyocardial cAMP concentration at the end of CPB. IMPLICATIONS: The administration of a single dose of milrinone before aortic cross-clamping resulted in significantly larger intramyocardial cyclic adenosine monophosphate concentration in myocardial biopsy specimens compared with controls.

A dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN)-related protein is highly expressed on human liver sinusoidal endothelial cells and promotes HIV-1 infection.

The discovery of dendritic cell (DC)-specific intercellular adhesion molecule (ICAM)-3-grabbing nonintegrin (DC-SIGN) as a DC-specific ICAM-3 binding receptor that enhances HIV-1 infection of T cells in trans has indicated a potentially important role for adhesion molecules in AIDS pathogenesis. A related molecule called DC-SIGNR exhibits 77% amino acid sequence identity with DC-SIGN. The DC-SIGN and DC-SIGNR genes map within a 30-kb region on chromosome 19p13.2-3. Their strong homology and close physical location indicate a recent duplication of the original gene. Messenger RNA and protein expression patterns demonstrate that the DC-SIGN-related molecule is highly expressed on liver sinusoidal cells and in the lymph node but not on DCs, in contrast to DC-SIGN. Therefore, we suggest that a more appropriate name for the DC-SIGN-related molecule is L-SIGN, liver/lymph node-specific ICAM-3-grabbing nonintegrin. We show that in the liver, L-SIGN is expressed by sinusoidal endothelial cells. Functional studies indicate that L-SIGN behaves similarly to DC-SIGN in that it has a high affinity for ICAM-3, captures HIV-1 through gp120 binding, and enhances HIV-1 infection of T cells in trans. We propose that L-SIGN may play an important role in the interaction between liver sinusoidal endothelium and trafficking lymphocytes, as well as function in the pathogenesis of HIV-1.

Latency-associated peptide of transforming growth factor beta enhances mycobacteriocidal immunity in the lung during Mycobacterium bovis BCG infection in C57BL/6 mice.

Latency-associated peptide of transforming growth factor beta (TGF-beta) (LAP) was used to determine whether in vivo modulation of TGF-beta bioactivity enhanced pulmonary immunity to Mycobacterium bovis BCG infection in C57BL/6 mice. LAP decreased BCG growth in the lung and enhanced antigen-specific T-cell proliferation and gamma interferon mRNA expression. Thus, susceptibility of the lung to primary BCG infection may be partially mediated by the immunosuppressive effects of TGF-beta.

The relationship between visceral ischemia, proinflammatory cytokines, and organ injury in patients undergoing thoracoabdominal aortic aneurysm repair.

OBJECTIVES: Plasma proinflammatory, anti-inflammatory cytokine, and soluble tumor necrosis factor (TNF) receptor concentrations were examined in hospitalized patients after abdominal and thoracoabdominal aortic aneurysm (TAAA) repair, with and without left atrial femoral bypass. Changes in plasma cytokine concentrations were related to the duration of visceral ischemia and the frequency rate of postoperative, single, or multiple system organ dysfunction (MSOD). DESIGN: Prospective, observational study. SETTING: Two academic referral centers in the United States and The Netherlands. PATIENTS: We included 16 patients undergoing TAAA repair without left atrial femoral bypass, 12 patients undergoing TAAA repair with left atrial femoral bypass, and nine patients undergoing infrarenal aortic aneurysm repair. MEASUREMENTS AND MAIN RESULTS: Timed, arterial blood sampling for proinflammatory and anti-inflammatory cytokine and soluble TNF receptor concentrations (p55 and p75), and prospective assessment of postoperative single and MSOD. Plasma appearance of TNF-alpha, interleukin (IL)-6, IL-8, and IL-10 peaked 1 to 4 hrs after TAAA repair, and concentrations were significantly elevated compared with infrarenal abdominal aortic aneurysm repair (p < .05). Left atrial femoral bypass significantly reduced the duration of visceral ischemia (p < .05) and the systemic TNF-alpha, p75, and IL-10 responses (p < .05). Plasma TNF-alpha concentrations >150 pg/mL were more common in patients with extended visceral ischemia times (>40 mins). Additionally, patients with early peak TNF-alpha concentrations >150 pg/mL and IL-6 levels >1,000 pg/mL developed MSOD more frequently than patients without these elevated plasma cytokine levels (both p < .05). CONCLUSIONS: Thoracoabdominal aortic aneurysm repair results in the increased plasma appearance of TNF-alpha, IL-6, IL-8, IL-10, and shed TNF receptors. The frequency and magnitude of postoperative organ dysfunction after TAAA repair is associated with an increased concentration of the cytokines, TNF-alpha, and IL-6 and the increased plasma levels of these cytokines appear to require extended visceral ischemia times.

Milrinone, not epinephrine, improves left ventricular compliance after cardiopulmonary bypass.

OBJECTIVE: To compare the effects of milrinone versus epinephrine administered after cardiopulmonary bypass (CPB) on left ventricular compliance. DESIGN: Prospective and randomized. SETTING: University-affiliated hospital. PARTICIPANTS: Twenty consenting adult patients. INTERVENTIONS: Patients undergoing aortocoronary bypass surgery were randomized to receive 50 microg/kg of milrinone (group M; n = 10) or 0.03 microg/kg/min of epinephrine (group E; n = 10) shortly after separation from CPB. Left ventricular compliance was assessed by observing changes in left ventricular end-diastolic area (LVEDA) in the short-axis view with transesophageal echocardiography, while maintaining a constant left atrial pressure. Measurements were performed (1) before CPB, (2) after separation from CPB, and (3) after either milrinone or epinephrine. MEASUREMENTS AND MAIN RESULTS: Baseline LVEDA decreased by 20% after CPB in the milrinone group (from 16.6 +/- 3.1 cm2 to 14.3 +/- 2.4 cm2; p < 0.05) and by 22% in the epinephrine group (from 19.4 +/- 4.1 cm2 to 17.2 +/- 3.8 cm2; p < 0.05). LVEDA increased by 15% after milrinone (from 14.3 +/- 2.4 cm2 to 15.6 +/- 2.8 cm2; p < 0.05) but remained unchanged after epinephrine (from 17.2 +/- 3.8 cm2 to 17.1 +/- 4.2 cm2; p = ns). CONCLUSIONS: Left ventricular compliance was decreased after CPB. The administration of milrinone, but not epinephrine, was associated with a partial return to prebypass values. The exact mechanism of action remains to be determined.

Interleukin-10 appearance following thoraco-abdominal and abdominal aortic aneurysm repair is associated with the duration of visceral ischaemia.

OBJECTIVES: to evaluate the plasma IL-10 levels during elective operative repair of thoraco-abdominal and abdominal aortic aneurysm repair. To study whether IL-10 plasma levels are associated with the duration of cross-clamping (ischaemia) and clinical outcome. MATERIALS: fifteen consecutive patients undergoing surgery for TAAA and 10 consecutive patients undergoing surgical repair of AAA were included. METHODS: plasma concentrations of IL-10 were measured by ELISA technique. Clinical outcome of the TAAA patients was prospectively analysed. RESULTS: during aortic clamping IL-10 was produced in both populations. The plasma IL-10 peak (934+/-172 pg/ml) of the TAAA group was seen at 4 h after declamping and remained detectable after 48 h. The plasma IL-10 peak (212+/-32 pg/ml) of the AAA group was seen 30 min after declamping and fell to undetectable levels by 24 h. These data show that the peak IL-10 plasma levels in TAAA repair are significantly (p<0.05) higher compared to the peak IL-10 plasma levels as seen during AAA repair. A positive correlation was seen between cross-clamping and peak plasma IL-10 and organ dysfunction. CONCLUSIONS: IL-10 plasma concentrations appear higher, later and are longer detectable in patients undergoing TAAA. Correlations were seen with duration of cross-clamping and MSOD.

Pulmonary immune responses during primary mycobacterium bovis- Calmette-Guerin bacillus infection in C57Bl/6 mice.

Mechanisms of protective immunity to mycobacterial infection in the lung remain poorly defined. In this study, T-cell subset expansion and cytokine expression in bronchoalveolar spaces, lung parenchyma, and mediastinal lymph nodes of mice infected intratracheally with Mycobacterium bovis-Calmette-Guerin bacillus (BCG) were analyzed in parallel with histopathology and bacterial burden. M. bovis-BCG was cleared rapidly from bronchoalveolar spaces without evidence for persistence. In lung parenchyma bacteria grew during the first 4 wk followed by gradual clearance with less than 0.1% of the original inoculum persisting for more than 8 mo. Clearance of M. bovis-BCG from bronchoalveolar lavage was associated with recruitment of both neutrophils and lymphocytes. Lung CD4(+), CD8(+), and gammadelta T-cell receptor-positive T cells expanded maximally by Week 4, and declined by Week 8 to control values despite bacterial persistence. Both CD4(+) and CD8(+) lung T cells produced interferon (IFN)-gamma in response to M. bovis-BCG. Four distinct pathologic states of lung parenchymal infection were noted. Early focal sub-bronchial inflammation with transmigration of cells into airways was followed by diffuse peribronchitis, perivasculitis, and alveolitis with activated macrophages, lymphoblasts, and occasional giant cells. The latter stage corresponded to maximal M. bovis-BCG growth. Resolving infection consisted of small lymphocytes and foamy macrophages, which coincided with decreasing M. bovis-BCG colony-forming units, T-cell infiltration, and IFN-gamma expression. A final quiescent phase consisted of residual lymphoid aggregates and perivasculitis associated with persistent spontaneous IFN-gamma production. Bacterial dissemination to lymph node and spleen occurred by Week 4 and declined in parallel to lung. In contrast to lung, IFN-gamma secretion was detected only late despite early expansion of CD4(+) and CD8(+) T cells. By reverse transcriptase/polymerase chain reaction, IFN-gamma and interleukin (IL)-12 p40 messenger RNA (mRNA) in lung paralleled IFN-gamma protein production. Tumor necrosis factor-alpha, IL-4 and IL-10 mRNA expression was not increased during M. bovis-BCG lung infection. Thus, protective immunity to M. bovis-BCG in the lung evolved differently in air space, lung, and lymph node.

Effects of calcium chloride on grafted internal mammary artery flow after cardiopulmonary bypass.

OBJECTIVE: To examine the effects of calcium chloride (CaCl2) administration on blood flow through the grafted left internal mammary artery (IMA) after cardiopulmonary bypass (CPB). DESIGN: Single-arm prospective study. SETTING: University-affiliated hospital operating room. PARTICIPANTS: Twenty adult patients scheduled for coronary artery bypass graft surgery with IMA graft. INTERVENTIONS: IMA flow was measured noninvasively with a laser Doppler flow probe placed around the IMA, and measurements were recorded for 10 seconds and averaged. After separation from CPB under stable hemodynamics, baseline IMA flow was measured. CaCl2, 15 mg/kg, was administered intravenously over 1 minute. Blood pressure, left atrial pressure, heart rate, and IMA flow were then measured at 1, 5, and 10 minutes. Coronary perfusion pressure and IMA vascular resistance were calculated. MEASUREMENTS AND MAIN RESULTS: After CaCl2 administration, IMA blood flow significantly decreased from baseline at 1, 5, and 10 minutes (from 28+/-9 mL/min to 19+/-8 mL/min, 22+/-6 mL/min, and 25+/-4 mL/min), with gradual return toward baseline over time. Blood pressure, coronary perfusion pressure, and IMA vascular resistance significantly increased at 1 and 5 minutes after CaCl2. Left atrial pressure and heart rate remained unchanged. No systolic regional wall motion abnormalities were detected on transesophageal echocardiography. CONCLUSIONS: CaCl2, administered as a bolus dose after separation from CPB, transiently but significantly reduces IMA flow and can potentially trigger vasospasm, increasing the risk for myocardial ischemia or infarction in susceptible patients. Further studies are needed to determine whether this effect also occurs with nitrosodilators or phosphodiesterase inhibitors.

Effects of milrinone versus epinephrine on grafted internal mammary artery flow after cardiopulmonary bypass.

OBJECTIVE: To compare changes on grafted internal mammary artery (IMA) flow after cardiopulmonary bypass in response to the administration of milrinone or epinephrine. DESIGN: Prospective and randomized. SETTING: University-affiliated hospital. PARTICIPANTS: Twenty consenting, adult patients undergoing CABG. INTERVENTIONS: Patients were randomized to receive either milrinone, 50 microg/kg, or epinephrine, 0.03 microg/kg/min, immediately after cardiopulmonary bypass. IMA flow was measured with a laser Doppler flow probe before and after the administration of either drug. MEASUREMENTS AND MAIN RESULTS: Baseline grafted IMA flow was similar for both groups (milrinone, 38+/-14 mL/min; epinephrine, 33+/-10 mL/min). In patients who received milrinone, flow increased by 24% to 50+/-17 mL/min, p<0.05; whereas with epinephrine, it remained essentially unchanged (33+/-10 v. 31+/-11 mL/min). CONCLUSIONS: This study confirms that the vasodilatory effect of milrinone on the IMA is also present after its anastomosis, whereas low-dose epinephrine exhibits neither beneficial nor adverse effects. It is suggested that in the absence of excessive vasodilation, milrinone should be considered as a first-line inotrope after coronary artery bypass graft surgery, to achieve an increase in contractility and IMA artery flow.

Coordinate regulation of lipogenesis, the assembly and secretion of apolipoprotein B-containing lipoproteins by sterol response element binding protein 1.

Stable plasmid-driven expression of the liver-specific gene product cholesterol 7alpha-hydroxylase (7alpha-hydroxylase) was used to alter the cellular content of transcriptionally active sterol response element binding protein 1 (SREBP1). As a result of stable expression of 7alpha-hydroxylase, individual single cell clones expressed varying amounts of mature SREBP1 protein. These single cell clones provided an opportunity to identify SREBP1-regulated genes that may influence the assembly and secretion of apoB-containing lipoproteins. Our results show that in McArdle rat hepatoma cells, which normally do not express 7alpha-hydroxylase, plasmid-driven expression of 7alpha-hydroxylase results in the following: 1) a linear relationship between (i) the cellular content of mature SREBP1 and 7alpha-hydroxylase protein, (ii) the relative expression of 7alpha-hydroxylase mRNA and the mRNA's encoding the enzymes regulating fatty acid, i.e. acetyl-CoA carboxylase and sterol synthesis, i.e. HMG-CoA reductase, (iii) the relative expression of 7alpha-hydroxylase mRNA and microsomal triglyceride transfer protein mRNA, a gene product that is essential for the assembly and secretion of apoB-containing lipoproteins; 2) increased synthesis of all lipoprotein lipids (cholesterol, cholesterol esters, triglycerides, and phospholipids); and 3) increased secretion of apoB100 without any change in apoB mRNA. Cells expressing 7alpha-hydroxylase contained significantly less cholesterol (both free and esterified). The increased cellular content of mature SREBP1 and increased secretion of apoB100 were concomitantly reversed by 25-hydroxycholesterol, suggesting that the content of mature SREBP1, known to be decreased by 25-hydroxycholesterol, mediates the changes in the lipoprotein assembly and secretion pathway that are caused by 7alpha-hydroxylase. These data suggest that several steps in the assembly and secretion of apoB-containing lipoproteins by McArdle hepatoma cells may be coordinately linked through the cellular content of mature SREBP1.

Exogenously administered interleukin-10 decreases pulmonary neutrophil infiltration in a tumor necrosis factor-dependent murine model of acute visceral ischemia.

INTRODUCTION: Visceral ischemia and reperfusion associated with thoracoabdominal aortic aneurysm (TAAA) repair results in lung injury, which appears to be mediated in part by proinflammatory cytokines. The purpose of this study was to determine the effect of exogenous administration of the antiinflammatory cytokine, recombinant human IL-10 (rhIL-10), on proinflammatory cytokine production (IL-6 and TNF alpha) and pulmonary neutrophil infiltration after acute visceral ischemia-reperfusion. METHODS: Two hours before 25 minutes of supraceliac aortic occlusion, 80 C57BL/6 mice (20 to 22 g) received an intraperitoneal injection of rhIL-10 (0.2 microgram [n = 20], 2 micrograms [n = 20], 5 micrograms [n = 25], or 20 micrograms [n = 15]), and 16 mice received murine anti-IL-10 IgM 200 micrograms. Twenty-five additional mice underwent visceral ischemia-reperfusion without treatment (controls), and 16 mice underwent laparotomy without aortic occlusion (sham). RESULTS: Pretreatment with exogenous rhIL-10 resulted in significant reductions in lung neutrophil infiltration with 0.2 microgram, 2 micrograms, and 5 micrograms per mouse of rhIL-10 compared with lung neutrophil levels in control mice that underwent acute visceral ischemia-reperfusion alone (p < 0.05). In addition, serum TNF alpha was detected in 50% of control mice and in 75% of mice that received murine anti-IL-10, but in none of the mice that received rhIL-10 (2 micrograms per mouse) or the mice that underwent sham operative procedures (p < 0.05 by chi 2 analysis). CONCLUSION: Exogenous IL-10 limits pulmonary neutrophil recruitment and the appearance of TNF alpha in this model of visceral ischemia-reperfusion injury. Thus the use of exogenous IL-10 may offer a novel therapeutic approach to decrease the complications that are associated with TAAA repair.

The effect of temperature management during cardiopulmonary bypass on neurologic and neuropsychologic outcomes in patients undergoing coronary revascularization.

Several studies suggest that normothermic ("warm") bypass techniques may improve myocardial outcomes for patients undergoing cardiac operations. Normothermic temperatures during cardiopulmonary bypass may, however, decrease the brain's tolerance to the ischemic insults that accompany all cardiac procedures. To assess the effect of bypass temperature management strategy on central nervous system outcomes in patients undergoing coronary revascularization, 138 patients were randomly assigned to two treatment groups: (1) hypothermia (n = 70), patients cooled to a temperature less than 28 degrees C during cardiopulmonary bypass, or (2) normothermia (n = 68), patients actively warmed to a temperature of at least 35 degrees C. Patients underwent detailed neurologic examination before the operation, on postoperative days 1 to 3 and 7 to 10, and at approximately 1 month after operation. In addition, a battery of five neuropsychologic tests was administered before operation, on postoperative days 7 to 10, and at the 4- to 6-week follow-up visit. Patients in the normothermic treatment group were older (65 +/- 10 vs 61 +/- 11 years in the hypothermic group), had statistically less likelihood of preexisting cerebrovascular disease, and had higher bypass blood glucose values (276 +/- 100 mg/% vs. 152 +/- 66 mg/% in the hypothermic group). All other patient characteristics and intraoperative variables were similar in the two treatment groups. Seven of 68 patients in the normothermic group were found to have a central neurologic deficit, compared with none of the patients cooled to 28 degrees C (p = 0.006). Performance on at least one neuropsychologic test deteriorated in the immediate postoperative period in more than one half of all patients in both treatment groups but returned to preoperative levels approximately 1 month after the operation in most (85%). This pattern was not related to bypass temperature management strategy. We conclude that active warming during cardiopulmonary bypass to maintain systemic temperatures > or = 35 degrees C increases the risk of perioperative neurologic deficit in patients undergoing elective coronary revascularization.

Visceral ischemia and organ dysfunction after thoracoabdominal aortic aneurysm repair. A clinical and cost analysis.

OBJECTIVE: Repair of thoracoabdominal aortic aneurysms (TAAAs) is associated with significant postoperative morbidity and mortality. Reperfusion of acutely ischemic abdominal viscera in animals leads to release of multiple factors that cause local and distant organ damage, and similar phenomena occurring in humans after TAAA repair could contribute to the high morbidity/mortality and cost associated with this procedure. METHODS: Twenty-nine patients undergoing elective TAAA repair were studied prospectively. Preoperative organ dysfunction and intraoperative risk factors (cross-clamp time, blood loss, operative time) were assessed and compared with postoperative organ dysfunction (defined as: pulmonary, positive pressure ventilation for > 7 days; renal, increase in serum creatinine > 2.0 mg/dL over baseline; hepatic, lactate dehydrogenase > 500 international units and total bilirubin > 3.0 mg/dL or serum transaminase level > 200 international units; hematopoietic, platelet count > 50 K or leukocyte count > 4.5 K, mortality, and costs. RESULTS: No relationship between preoperative organ dysfunction, blood loss, or operative time and postoperative organ dysfunction or mortality was seen; however, cross-clamp times > 40 minutes were associated with a significantly greater incidence of pulmonary (59%), renal (47%), hepatic (35%), and hematopoietic (47%) dysfunction. In addition, multiple-organ dysfunction (> 2 organ systems) was more common after > 40 minutes of visceral ischemia and led to significantly greater overall hospital ($88,465 + $76,155 vs. $41,782 + $31,244) and intensive care unit ($26,726 + $28,256 vs. $11,234 + $12,146) costs (p < 0.01, Mann-Whitney U test). Mortality associated with leukopenia was 67% compared with 4% without leukopenia (p < 0.01). CONCLUSION: Increasing durations of acute visceral ischemia led to significant multiple organ dysfunction after TAAA repair. Methods of limiting visceral ischemia or the systemic effects of visceral ischemia may decrease both the morbidity and mortality and the overall hospital cost associated with this procedure.

Increased soluble interleukin-1 type II receptor concentrations in postoperative patients and in patients with sepsis syndrome.

Plasma interleukin-1 (IL-1) activity is modulated in part through the simultaneous appearance of several inhibitors of IL-1 action, including interleukin-1 receptor antagonist (IL-1ra) and the soluble IL-1 type II receptor (IL-1RII). However, little is known concerning the plasma appearance of these inhibitors in patients following operative trauma or those with sepsis syndrome. In the present report, plasma IL-1beta, IL-1ra, and soluble IL-1RI and IL-1RII concentrations were evaluated in 118 patients with sepsis syndrome or after elective operative trauma. Plasma concentrations of IL-1ra increased significantly following elective operative repair of thoraco-abdominal and abdominal aortic aneurysms, and after bowel resection for inflammatory bowel disease, but did not increase after laparoscopic cholecystectomy. Plasma IL-1ra levels were also elevated in patients with sepsis syndrome. In contrast, soluble IL-1RII levels were only increased in patients after operative repair of thoraco-abdominal aortic aneurysms and in sepsis syndrome, whereas concentrations were unaffected by the other more modest surgical procedures. Plasma IL-1RI concentrations decreased in all postoperative patients in the first 24 hours after surgery. We conclude that both plasma IL-1ra and soluble IL-1RII concentrations often increase in sepsis and following some operative trauma. Less severe operative trauma increases the plasma concentration of only IL-1ra, whereas both IL-1ra and soluble IL-1RII are increased in patients with sepsis syndrome or following thoraco-abdominal aneurysm repair.