The impact of anti-endotoxin core antibodies on endotoxin and cytokine release and ventilation time after cardiac surgery.

OBJECTIVES: We hypothesized that a temporary cardiopulmonary bypass (CPB)-induced reduction of endotoxin antibody levels contributes to elevated endotoxin levels and the associated inflammatory consequences, with a significant influence on the postoperative ventilation time period. BACKGROUND: Cardiac surgery using CPB induces a systemic inflammatory response syndrome with an associated risk of increased postoperative morbidity and mortality. METHODS: A total of 100 consecutive patients undergoing elective coronary artery bypass graft surgery using CPB were prospectively investigated. Endotoxin core antibodies (immunoglobulin [Ig] M/IgG against lipid A and lipopolysaccharide), endotoxin, interleukin (IL)-1-beta, IL-6, IL-8 and tumor necrosis factor-alpha were measured serially from 24 h preoperatively until 72 h postoperatively. RESULTS: Eighty-five patients had no complications (group 1), whereas 15 patients required prolonged ventilation (group 2). In both groups, there was a decrease of all antibodies 5 min after CPB onset, compared with baseline values (p < 0.001), an increase of endotoxin and IL-8 peaking at 30 min postoperatively (p < 0.001) and an increase of IL-6 peaking 3 h postoperatively (p < 0.001). In group 2, preoperative antibody levels were lower (p < 0.01)--specifically, the decrease in IgM was significantly stronger and of longer duration (p < 0.002)--and levels of endotoxin (p < 0.001) and IL-8 (p < 0.001) were higher at 30 min postoperatively. CONCLUSIONS: We conclude that an CPB-associated temporary reduction of anti-endotoxin core antibody levels contributes to elevated endotoxin and IL-8 release. Furthermore, lower levels of IgM anti-endotoxin core antibodies were associated with a greater rise in endotoxin and IL-8, as well as prolonged respirator dependence.

Prediction of clinical outcome after cardiac surgery: the role of cytokines, endotoxin, and anti-endotoxin core antibodies.

Coronary artery bypass grafting (CABG) using cardiopulmonary bypass (CPB) can lead to a systemic inflammatory response syndrome with organ failure and increased morbidity and mortality. The mechanisms of these findings are still under discussion. We investigated whether anti-endotoxin core antibodies, endotoxin, and proinflammatory cytokines influence the clinical course after cardiac surgery. Seventy-eight patients undergoing CABG using CPB were investigated. Anti-endotoxin core antibodies, endotoxin, interleukin (IL)-6, IL-8, IL-1beta, and TNF-alpha were measured 24 h preoperatively and up to 72 h postoperatively. Patients with a postoperative mechanical ventilation time below 24 h (n = 65; Group A) were compared to patients with prolonged respirator therapy (>24 h; n = 13; Group B). Preoperative antibody levels were significantly lower in Group B (P < 0.001). In this group, antibody levels remained decreased during the observation period (P < 0.001). Endotoxin significantly increased 30' postoperatively in both groups (P < 0.002). The increase in Group B was 3-fold higher (P< 0.001). IL-8 increased postoperatively in both groups, peaking 3 h after surgery (P < 0.001). In Group B, the IL-8 release was significantly higher than in Group A (P < 0.001). IL-6 significantly increased in both groups, reaching its maximum 24 h postoperatively (P < 0.001). No differences between groups were observed. No significant changes of IL-1beta and TNF-alpha were observed. We conclude that anti-endotoxin core antibodies may be predictive of adverse outcome after cardiac surgery. The imbalance between antibodies and endotoxin results in an exaggerated increase in endotoxin and IL-8 with an impact on clinical outcome.

[Rational diagnosis and surgical therapy of renal cell carcinoma with tumor thrombosis in the vena cava]. / Rationelle Diagnostik und operative Therapie des Nierenzellkarzinoms mit Tumorthrombus in der V. cava.

Venous involvement in renal cell carcinoma (RCC) represents an advanced state of disease. Nonetheless, its influence on survival is rather secondary compared with that of local tumor growth, grading and metastasis. Since conservative treatment in advanced RCC is mainly ineffective, surgical management offers the most promising approach for potential cure. Only patients without metastasis, however, seem to benefit from an aggressive surgical intervention. The surgical technique itself is determined by the vena caval extent of the tumor thrombus. Preferably, noninvasive imaging techniques should provide information about metastasis and the extent of the tumor thrombus. Diagnostic efforts should be adapted to therapeutic feasibility and prognosis in every individual patient in order to avoid fatiguing and costly over-examination. The standards requested above can be realized by use of modern sonographic and computed-tomographic imaging techniques or by magnetic resonance imaging alone. Thus, nowadays, the essential diagnostics in RCC with vena caval involvement may dispense with angiographic examinations.

[Proinflammatory cytokines and cardiac pump function]. / Proinflammatorische Zytokine und kardiale Pumpfunktion.

In situations of depressed myocardial function, the role of immunological mechanisms has been studied recently. In different pathophysiological situations, such as chronic heart failure, open heart surgery with extracorporal circulation, cardiac transplantation, myocardial infarction and angina pectoris, patterns have been described with elevation of proinflammatory cytokines, such as tumor necrosis factor-alpha, interleukin-1, interleukin-6, and reversible myocardial dysfunction, which may represent a final common pathway. The available data suggest a modulation of important determinants of pump function, i.e., contractility, preload, afterload, and heart rate, by cytokines. Potential mechanisms include the beta-adrenoceptor- and nitric oxide pathway, as well as a direct impact on intracellular calcium homeostasis. Interventional strategies based on this understanding are beginning to emerge.

Aprotinin diminishes inflammatory processes.

Many of the recent reports concerning cytokine levels in cardiopulmonary bypass have documented changes in the levels of these trauma indicators. In the present report, we also document their levels but in the presence of Aprotinin. Aprotinin is a protease inhibitor used not only to diminish bleeding, but also to diminish elements of the diffuse inflammatory response associated with this type of surgery. We report in plasma obtained from 20 patients that initially interleukin-8 (IL-8) levels (53.4 +/- 7 pg/ml) plasma to 185.5 +/- 30 pg/ml) increased 20 min from the start of surgery. This is followed by IL-6 (5.3 +/- 1.1 to 200 +/- 50 pg/ml) peaking 15 h post surgery. These levels return to normal by day 3 postop. IL-1 beta and tumour necrosis factor (TNF) levels remained at baseline for the observation period. Associated with these changes in cytokine levels is the activity state of immunocytes (granulocytes and monocytes) noted by conformational changes obtained from computer-assisted microscopy. The cells exhibited an ameboid conformation and became mobile (67%), peaking at 120 min after surgery began and returned to a more rounded conformation with only 6% exhibiting the ameboid conformation by day three. In in-vitro experiments, where immunocytes not exposed to cardiopulmonary bypass were exposed to plasma obtained from patients having undergone this surgery, their activity level rose to 65%. In the same experiment, when Aprotinin was added to the cell-plasma mixture, the level of activation dramatically dropped to 25%. Thus, aprotinin was found at high doses to lower cytokine and cellular activation associated with the acute inflammatory responses of cardiopulmonary bypass, suggesting that this may be initiated by hyperstimulated immunocytes.

[Operations in limited left ventricular pump function]. / Operationen bei eingeschränkter linksventrikulärer Pumpfunktion.

The proportion of patients with left ventricular dysfunction (LVD) undergoing open heart surgery is increasing. In this patient group, the perioperative risk is elevated because of the preexisting pathophysiology. Detailed evaluation, interdisciplinary differential therapeutic considerations on the basis of the comparative benefit rationale as well as hemodynamic, antiischemic and antiarrhythmic optimization is mandatory. To plan the operation in patients with coronary artery disease, the issue of reversibility of LVD has to be resolved by sophisticated viability testing. The ultimate decision on revascularization versus aneurysmectomy and scar excision has to be met by the operating surgeon. If the patient's hemodynamics is severely compromised, the perioperative risk may be too high and cardiac transplantation, possibly with mechanical bridging, should be considered. If, in addition, intractable malignant tachyarrhythmias are encountered, antitachycardia operation and defibrillator implantation may be performed. During extracorporeal circulation which is associated with a systemic inflammatory response syndrome the compensatory potential is reduced in patients with LVD, and therefore, the risk of complications such as low-output syndrome, respiratory and renal failure is elevated. Advances in the understanding of pathophysiological mechanisms, an individualized preoperative tailored medical and mechanical therapy for preparation of the operation, anesthesiologic management, cardioprotection and postoperative intensive care have contributed to improvement of outcome in this patient group. Specifically patients with documented evidence of myocardial viability such as angina have profited from surgical revascularization as compared to medical therapy in large scale prospective trials. Perioperative mortality has been lowered to 2-20%. In the absence of angina and presence of overt heart failure and arrhythmias, however, the postoperative 3- and 5-year prognosis of 60% and 35%, respectively, continues to be reduced. Improvement of ejection fraction, angina class, functional capacity and quality of life has been documented in all studies. In conclusion, cardiac operations in patients with left ventricular dysfunction can nowadays be performed with a reasonable risk-benefit ratio, if a careful individualized preoperative evaluation and optimal pre-, intra-and postoperative management is performed.

Reconstructive vascular surgery in rotationplasty for malignant tumors of the femur.

The rotationplasty procedure of the femur, as first described by Borrgreve, is the functional improvement of an abnormally shortened lower limb. In the last 15 years this procedure has been used in its original form and as modification for tumors of the femur and proximal tibia. The reconstruction of the femoral vessels as an important part of the operation has not enough been accentuated. Principally two types of reconstructions can be performed: the vessels are dissected in the adductor canal or a segmental resection and reanastomosis are performed. Between January 1990 and April 1993 classical and modified rotationplasties were performed for malignant tumors in 34 patients in our institution. In all cases a segmental femoral vessel resection with end-to-end anastomosis were performed. No intra- and postoperative vascular related complications occurred. The authors emphasize the advantage of this method: reanastomosing resected femoral vessels by experienced vascular surgeons is a save, time-saving method. In addition, the radicality of the operation increases in order to obtain excellent long term results.

[Surgical treatment of dissecting aneurysms of the aortic arch].

Since May 1987 to May 1988, 8 cases of dissecting aneurysms of the aortic arch were treated surgically at the Department of Cardiovascular Surgery. Justus-Liebig University. Four cases were Standford A type and 4 were Stanford B type. All the patients were operated on under deep hypothermia (20 degrees C) and circulatory arrest, and aneurysms were repaired using pre-clotting graft without clamping the aortic arch. Bleeding from anastomosis line was controlled by fibrin coagulum. In addition, the auto-blood transfusion was applied using the cell saver system. This procedure could be performed in a short circulatory arrest and cardiac ischemic time. Seven patients were alive and discharged without neurological complication. Only one patient died because of the carotid artery dissection to the aortic dissection on the 2nd. post-operative days the clinical results were almost satisfactory. It appeared that surgical repair for dissecting aneurysm of the aortic arch could be performed safely and easily by this surgical technique and the know-how.

Implantable cardioverter/defibrillators (ICD): a new lead-system using transvenous-subcutaneous approach in patients with prior cardiac surgery.

The current approach in cardioverter-defibrillator implantation requires placement of epicardial leads which may lead to pericardial and/or pleural effusion and pneumonia during the perioperative period. Although ICD implantation is less invasive than other surgical techniques for the treatment of rhythm disturbances, the perioperative mortality must be considered. Minimizing the operative procedure could lead to a reduction in perioperative mortality. Therefore, we investigated an approach without the need for thoracotomy using a transvenous/subcutaneous lead system. In nine patients with prior cardiac surgery, defibrillator implantation was performed by a transvenous/subcutaneous approach. There was no perioperative mortality. In all patients, a sufficient defibrillation threshold was achieved. The defibrillation pulses were delivered as two sequential pulses between a right ventricular electrode (cathode) and a coronary sinus or superior caval vein electrode (anode 1) and a subcutaneous patch electrode (anode 2). Intubation of the coronary sinus was necessary in 4 patients in order to obtain satisfactory defibrillation thresholds. These data demonstrate that a transvenous/subcutaneous approach is feasible in patients with prior cardiac surgery obviating the need for thoracotomy. Sensing function of the RV-electrode, intubation of the coronary sinus and the intraoperative use of an epicutaneous patch electrode are current problems of this new technique.