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.

Pharmacokinetics, immunogenicity, and efficacy of dimeric TNFR binding proteins in healthy and bacteremic baboon.

Immunogenicity, pharmacokinetics, and therapeutic efficacy of three novel dimeric soluble tumor necrosis factor (TNF)-receptor I constructs [TNF-binding protein (bp)] were evaluated in 28 baboons, 12 of which were healthy and 16 were challenged with a lethal Escherichia coli bacteremia. The three constructs differed only in the number of extracellular domains of the TNF receptor I and were dimerized with polyethylene glycol. Although all three constructs had generally similar pharmacokinetics when administered to a naive animal, they differed quantitatively in their immunogenicity. Antibodies were detected more frequently, and titers were significantly higher (P < 0.05) in both healthy and septic baboons that received the 4.0-domain TNF-bp construct, compared with animals receiving the 2.6-domain construct. When the TNF-bp constructs were administered a second time (21 days later), the half-lives of the three constructs were significantly shorter in animals that had an antibody response after the first injection. In contrast, all three TNF-bp constructs were equally effective at improving outcome, blocking a systemic TNF-alpha response, and attenuating the cytokine responses when administered at a dose of 1.0 mg/kg body wt 1 h before a lethal E. coli infusion. The findings suggest that immunogenicity of TNF-bp constructs can be altered by changing the number of functional domains, without affecting their capacity to neutralize TNF-alpha and to abrogate TNF-mediated pathology.

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.

Exogenous human recombinant interleukin-10 attenuates hindlimb ischemia-reperfusion injury.

Proinflammatory cytokines have been found to mediate part of the local and distant organ injury after ischemia and reperfusion (I/R). The anti-inflammatory cytokine interleukin-10 (IL-10) inhibits both TNF-alpha and IL-1, and we hypothesized that exogenous human IL-10 may decrease lung and soleus muscle injury after hindlimb I/R. Male Sprague-Dawley rats were randomly assigned to I/R (n = 10); I/R+IL-10 (10 micrograms i.v., n = 10), SHAM (n = 4); or SHAM+IL-10 (10 micrograms i.v., n = 4). Bilateral hindlimb ischemia was produced by tourniquet occlusion for 4 hr and all animals were sacrificed after 4 hr of reperfusion or at comparable times for the SHAMs. Soleus muscle cellular injury was determined by uptake of 99Tc pyrophosphate while soleus muscle capillary permeability, and lung capillary permeability were assessed by uptake of 125I-labeled albumin. Soleus muscle and lung neutrophil infiltration were measured with the myeloperoxidase assay. Serum samples were assessed for TNF-alpha production with the WEHI bioassay. Hindlimb I/R caused significant soleus muscle cellular injury, soleus muscle capillary injury, lung capillary injury, and lung neutrophil infiltration, Pretreatment with exogenous IL-10 significantly reduced soleus muscle capillary permeability and also reduced soleus muscle cellular injury, but not to a statistically significant degree. IL-10 administration also reduced pulmonary capillary permeability despite significantly increased lung neutrophil infiltration. Elevated TNF-alpha levels were found in 66% (4/6) rats in the I/R group versus 30% (3/10) rats in the I/R+IL-10 group. Exogenous IL-10 attenuates both local and distant organ injury after hindlimb I/R potentially independent of neutrophil infiltration.

Involvement of 26-kDa cell-associated TNF-alpha in experimental hepatitis and exacerbation of liver injury with a matrix metalloproteinase inhibitor.

TNF-alpha is a pleiotropic cytokine that exists both as a 26-kDa cell-associated and a 17-kDa soluble form. Recently, a class of matrix metalloproteinase inhibitors has been identified that can prevent the processing by TNF convertase of 26-kDa TNF-alpha to its 17-kDa form and can reduce mortality from normally lethal doses of D-galactosamine plus LPS (D-GalN/LPS). Here we report that a matrix metalloproteinase inhibitor, GM-6001, improves survival but does not protect against liver injury from D-GalN/LPS-induced shock in the mouse. In Con A-induced hepatitis, GM-6001 actually exacerbates hepatocellular necrosis and apoptosis despite greater than 90% reduction in plasma TNF-alpha concentrations. Treatment with GM-6001 also has minimal effect on the concentration of membrane-associated TNF-alpha in the livers of animals with Con A induced hepatitis. In contrast, a TNF binding protein (TNF-bp), which neutralizes both membrane-associated and soluble TNF-alpha, prevents D-GalN/LPS- and Con A-induced hepatitis. Our studies suggest that cell-associated TNF-alpha plays a role in the hepatocellular necrosis and apoptosis that accompany D-GalN/LPS- or Con A-induced hepatitis, and that matrix metalloproteinase inhibitors are ineffective in preventing this hepatic injury.

"Half and half" woven and knitted Dacron grafts in the aortoiliac and aortofemoral positions: seven and one-half years follow-up.

One-hundred fifty-eight patients received specially manufactured aortoiliac or aortofemoral bifurcated grafts with one limb woven, the other knitted from Dacron. During an observation period ranging from 1,567 to 2,555 days (average 2,130 days) no statistically significant difference was found in either platelet adherence (30 patients studied) or in clinical patency. According to the results of the study, the type of graft (woven or knitted) did not seem to influence either platelet adherence or patency rate in the aortoiliac or aortofemoral positions.

Traumatic tears of the thoracic aorta: improved results using the Bio-Medicus pump.

Traumatic disruption of the descending thoracic aorta is a relatively rare but dramatic injury. Controversy remains regarding the use of shunts during operative repair. Discouraged by our results using the "no shunt" technique, we adopted the recently reported technique using the Bio-Medicus pump for left atrium-femoral artery bypass without heparin sodium. At Charlotte Memorial Hospital and Medical Center, 39 patients were treated for tears of the descending thoracic aorta between January 1979 and October 1988. Eight patients died before repair could be completed. Four patients underwent repair using femorofemoral bypass with 1 death and no instances of paraplegia. Fifteen patients had repair using the no-shunt technique with 4 deaths and three instances of paraplegia. Since January 1986, 12 patients have been treated using the Bio-Medicus heparinless pump with no deaths and no instances of paraplegia. We present our experience to confirm the reports of others regarding the efficacy of this technique. We believe it reduces the morbidity and mortality associated with this serious injury and aids in the hemodynamic management of the patient during aortic clamping.

Balloon valvuloplasty in calcified aortic stenosis: a cause for caution and alarm.

Balloon dilation by the percutaneous route has recently been recommended as an alternative to surgical intervention in the management of calcified aortic valvular stenosis. To investigate the validity of balloon valvuloplasty, this procedure was carried out in the operating room under direct vision in 30 patients just prior to excision and replacement of the ossified aortic valve. Changes induced by balloon dilation were evaluated by visual inspection as well as by geometric measurements. By visual observation, balloon valvuloplasty did not have a detectable impact on the valvular anatomy in about 19 of the patients and induced enlargement of the functional aortic orifice judged as "minimal" or "moderate" in only 11. In no patient was there a substantial increase in the functional orifice size. These findings were supported by geometrical measurements. Therefore, we believe that the virtues of this procedure have been grossly overstated by its proponents and that it should be offered only to patients who present a truly forbidding risk by standards of modern surgery.

Indium 111-labeled platelet deposition in woven and knitted Dacron bifurcated aortic grafts with the same patient as a clinical model.

A study was designed to compare platelet deposition between knitted and woven Dacron grafts in the same patient. Twenty patients received aortoiliac or aortofemoral bifurcated Dacron grafts, each composed of one woven and one double-velour knitted limb. External nuclear graft imaging was carried out after injection of autologous platelets labeled with indium 111. The patients were studied postoperatively in time periods ranging from 6 days to 42 months. Platelet accumulation was almost identical in knitted and woven limbs in all patients. This study appears to indicate that there is no difference in thrombogenicity between knitted and woven bifurcated Dacron grafts in the aortoiliac or aortofemoral positions measured by platelet accumulation.

Patency rate of bifurcated aortic grafts: comparative analysis of woven versus knitted prostheses in the same patient.

To investigate the difference in patency rate between woven and knitted aortofemoral or aortoiliac prosthetic grafts, a special vascular prosthesis was manufactured with one limb of the graft knitted and the other, woven. The prosthesis was implanted in 143 consecutive patients with occlusive aortoiliac arteriosclerotic disease or aneurysms. Detailed statistical analysis failed to reveal any difference in the patency rate between the woven and knitted limbs of the grafts during an observation period ranging from one month to two years.

The value of thermography in the early diagnosis of postoperative sternal wound infections.

Peristernal skin temperatures were recorded postoperatively by infrared thermography in 150 patients. Persistent elevation of peristernal skin temperature during the 3rd and 4th post-operative week was found in 5 patients, all of whom developed sternal wound infection. A further group of 18 patients, all suspected to have occult wound infection, showed persistent temperature elevation in 7 patients, 6 of these patients were proven later to have manifest infection and needed treatment. Close thermographic scruting of the incision in patients with suspected but not proven infection appears to be useful in deleting early stages of deep seated infections.

Ascending-distal abdominal aorta bypass for treatment of hypoplastic aortic arch and atypical coarctation in the adult.

Repair of aortic coarctation is usually an easy operation. However, it can be very difficult under certain circumstances. These include operating on an adult or operating when specific anatomical variations, such as hypoplasia of the transverse aortic arch or calcification of the coarctation area, are present. We recommend that in such cases the situation be handled using ascending aorta-lower abdominal aorta bypass grafts rather than conventional resection and anastomosis of the coarctation itself. The cases of 2 patients are presented in whom a hypoplastic aortic arch associated with atypical coarctation was repaired using such a procedure.

Technical options in repairing the diseased ascending aorta with aortic valve involvement.

Operative repair of the diseased ascending aorta with aortic valve involvement consists of replacement of the ascending aorta and the aortic valve plus reconstitution of coronary arterial flow. Two basic techniques are presently available. The conventional technique involves separate replacement of the aorta and valve above and below a small segment of retained aorta including the coronary orifices. The second method consists of replacement of the entire ascending aorta and aortic valve with reconstitution of coronary flow by approximation of the coronary orifices to the Dacron conduit or with saphenous vein bypasses. Each method has its merits depending on the exact pathological anatomy encountered near the coronary orifices. Other pathological variables exist that demand additional intraoperative choices in technique. The present report details the operative repair of this lesion and outlines the technical options available for solution of the various problems encountered.

Simultaneous revascularization for complex brachiocephalic and coronary artery disease.

We have recently encountered two patients with significant coronary artery disease in addition to complex and extensive brachiocephalic occlusive disease. Both were operated upon successfully with simultaneous repair of both anatomic areas. These cases form the basis of this article. Fourteen additional patients with combined coronary and conventional carotid disease have been operated upon successfully with a simultaneous approach to both lesions. We conclude, until convincing prospective data are available possibly indicating otherwise, that a simultaneous approach to these combined lesions is indicated.

Post-traumatic intracardiac shunts. Report of two cases and review of the literature.

Intracardiac shunts consequent to penetrating thoracic injury have been reported in 94 patients. Two additional cases are reported emphasizing the frequently complex anatomic abnormalities, the variability in clinical course, and the favorable outcome of repair. From a review of the literature, it is apparent that most such lesions should be corrected, since patients are at a continual risk of symptomatic cardiac dysfunction and repair offers an excellent prognosis with minimal morbidity.

Chylopericardium with cardiac tamponade after cardiovascular surgery in two patients.

Two patients developed postoperative chylopericardium leading to acute cardiac tamponade. Delayed diagnosis and urgent throacotomy did not prevent death in three-month-old patient after the Glenn anastomosis of the superior vena cava to the right pulmonary artery, whereas early recognition of chylopericardium following repair of an interrupted aortic arch in an 11-week-old patient was successfully treated by tube pericardiostomy. The literature is reviewed, and an anatomic predisposition for post-surgical chylopericardium is proposed.