[Integration of surgical research into the education and continuing education of the surgeon].
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Biomedical subjects
Publications and source records attributed to E Wolner.
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Pulmonary surfactant during lung transplantation was investigated in the control group of a canine single lung transplantation model by measuring dipalmitoyl-phosphatidylcholine, the main phosphocholine fraction of surfactant in bronchoalveolar lavage. In a second group of dogs, L-carnitine, an essential cofactor for transfer of long-chain fatty acids into the mitochondria, was applied. Organ function after pulmonary artery flushing with modified Euro-Collins solution and hypothermic storage for 4 hours was adequate in both groups, with significantly higher arterial oxygen pressure levels in the L-carnitine group after 12 (p less than 0.05) and 24 (p less than 0.025) hours, respectively. In the control group, a reduction of the dipalmitoyl-phosphotidylcholine portion on total phosphotidylcholines was observed 4 and 12 hours after transplantation of the left lung (p less than 0.005 and p less than 0.01, respectively, both specified by Student's t test for dependent data, not significant by Bonferroni correction). In the simultaneously stored right lungs, a constant fall of the dipalmitoyl-phosphotidylcholine portion was demonstrated. In the L-carnitine group, significantly higher dipalmitoyl-phosphotidylcholine levels were observed in the transplanted left lungs after 4 hours (p less than 0.01) and in the continuously stored right lungs after 24 hours (p less than 0.005), when compared with the control group. These results suggest that dipalmitoyl-phosphotidylcholine portion on total phosphotidylcholine decreases parallel to the extent of the ischemic damage. Furthermore, the application of L-carnitine improved pulmonary function after transplantation, possibly by reducing the impairing effect of ischemia on alveolar type II cell metabolism and thereby on pulmonary surfactant system.
Between March 1984 and August 1988, 89 orthotopic cardiac transplants were performed in 87 patients at the Second Department of Surgery, University of Vienna. 2 patients underwent retransplantation and 3 patients received previously a total artificial heart bridge. Recipients were immunosuppressed with low dose cyclosporine, azathioprine and since May 1986 with additional low dose prednisolone; all patients were supplemented perioperatively with either ATG or OKT3. 1-year survival rates continuously increased from 33% in 1984 to 88% in 1987 (p = 0.07). The one-year survival rate in recipients given double drug therapy (cyclosporine and azathioprine) was 43% as compared with 77% on triple therapy (cyclosporine, azathioprine and prednisolone, p = 0.003). Acute rejection was the leading cause of death. These data indicate that the substantial improvement in survival rates is attributable to augmented immunosuppression and to improved patient management and recipient selection.
One hundred and ninety six thoracotomies were performed on 152 patients with pulmonary metastases up to 1988 in the Second Surgical Department, University of Vienna. Age ranged from 2 to 78 years, 13 patients were younger than 18 years. The primary tumour was carcinoma in 103 cases, sarcoma in 38 cases and melanoma in 11 cases. The primary tumour in young patients was osteosarcoma in 7 cases, Ewing sarcoma in 2 and Wilms tumour in 2 cases. With a minimal follow-up period of 2.5 years the actuarial 5 years survival rate of 37% was observed for carcinoma, and 29% for sarcoma patients. A statistical difference was found between the carcinoma and sarcoma groups with respect to survival rate; the prognosis for patients with melanoma was markedly worse. A prognostic factor was the duration of disease-free interval in carcinoma patients. Actuarial post-thoracotomy survival in patients with osteogenic sarcoma was 32% at 5 years and only 10% in the soft-tissue sarcoma group. Size of lesions, vitality of the metastases and disease-free interval correlated with survival in the osteogenic group, whilst the number of lesions was of importance in the soft-tissue group. On account of the lesser functional morbidity and the ability to assess both lungs for exploration, palpation and resections, the importance of median sternotomy is constantly increasing for the treatment of pulmonary metastatic disease and the results justify an aggressive approach. In those cases which the primary tumour is sensitive to chemotherapy the procedure of metastatic resection must be incorporated into the general scheme of oncological therapy.
Glutaraldehyde (GA) and formaldehyde (FA) were shown to be released from 1 cm2 fixed pericard patches into 2-mL storage solutions after three 2-min washings in concentrations of about 1 mg/L. The cytotoxicity of these aldehyde concentrations on bovine aortic endothelial cells (BAECs) was evaluated in vitro, by proliferation capacity, cellular ATP content, PGI2 release and cyclic AMP synthesis. Continuous incubation of BAECs with GA greater than 0.1 mg/L and FA greater than 0.5 mg/L resulted in a significantly inhibited proliferation and in an increase of the intracellular Ca2+ triggered parameters, PGI2 and cyclic AMP, up to three fold. This strongly suggests an aldehyde-induced inhibition of the plasma-membrane bound Ca2+-ATPase, an enzyme which normally maintains low intracellular Ca2+-level. From these findings there is evidence that aldehydes released from bioprosthetic valve tissue may contribute to the lack of endothelial cell coverage in human implants.
Prostacyclin (PGI2) has proven beneficial effects on organ preservation. Iloprost (ZK 36 374), a stable synthetic analogue with a longer half-life of 14 minutes is reported to have less hypotensive effects than PGI2 while offering increased cytoprotective and antiaggregation action. In this study its effects on lung-preservation were investigated. The heart lung block of 12 Beagle dogs was harvested after flushing of the pulmonary artery with 60 ml/kg modified Eurocollins (MEC) solution, the left lung was stored for 4 hours and then transplanted into 12 weight-matched dogs. Prior to operation the animals were randomized into two groups with MEC solution as the only preservative in group A and an additional i.v. infusion of 1 microgram/kg/min Iloprost during 15 minutes prior to flushing and 15 micrograms/kg Iloprost administered to the perfusate in group B. Arterial pO2, alveolo-arterial oxygen difference (AaDO2) and pulmonary artery pressure (PAP) of the transplanted lungs were measured 1, 4, 12, and 24 hours after transplantation during occlusion of the contralateral pulmonal artery. The application of Iloprost resulted in a significant improvement of pO2 (p = 0.047), AaDO2 (p = 0.002) and PAP (p = 0.018) after 1 hour. Results in group B at later time points were improved without reaching statistical significance. Iloprost therefore showed beneficial effects on pulmonary function early after lung preservation with MEC.
Worldwide the clinical use of total artificial hearts (TAH) for bridging the time until heart transplantation (HTX) has become part of HTX programs. At our clinic, TAH bridging has been performed in five deteriorating HTX candidates since 1986. Four patients suffered from dilative CMP and one patient from a large anterior wall infarction. Three times the ellipsoid heart and twice the Berlin TAH were implanted. After TAH implantation, the conditions of all patients improved. The accompanying dysfunctions of kidneys and other vital organs, which were due to cardiogenic shock, could be restored in the three patients who underwent subsequent HTX. Bridging periods lasted from 9 to 13 days. Two patients, however, could not be transplanted because of infection. Although three patients could be bridged until transplantation and were in good clinical conditions, the longest survival following two-stage HTX was 40 days. In the future, complications like infection, bleeding, and transplant rejection have to be prevented to improve the long-term results of Viennese TAH bridging.
Control strategies for total artificial heart application have generally been based on experience with healthy animals. Human patients in a bad state of health who have impaired organ functions and who are subjected to intensive care procedures can develop atypical hemodynamic behavior. In these patients, both unstable and hyperstable behavior of the vascular resistance were observed. Therefore, regulation of cardiac output (CO) by pressure parameters only was avoided and CO was adjusted to obtain an appropriate O2-utilization (O2U). Intending to keep the O2U within ranges of 20-25%, we obtained cardiac indexes between 3.3 and 4.4 L/m2/min (CO 6-8 L/min), which is higher than other cardiac indexes reported. A CO of 10.5 L/min was even necessary to obtain an O2U of 30% in a septic patient. This strategy caused a stable driving management and led to a rapid hemodynamic stabilization and general improvement of the patients' condition. Results indicate that it is also very important to monitor metabolic parameters for appropriate driver adjustment as well, especially in the early postoperative phase, and that O2-U is a sensitive and useful parameter for this purpose.
To study the hemodynamic side effects of mexiletine and disopyramide when administered before cardioplegic arrest 15 dogs underwent sham cardiac surgery with a 90-min period of aortic cross-clamping. 5 dogs served as control, 5 were given 8 mg/kg/day mexiletine and another five 11 mg/kg/day disopyramide for 1 week before surgery. On the day of surgery a continuous infusion was started. After reperfusion treated animals exceeded their preischemic blood pressure and regained their preoperative cardiac output. Compared to control animals left ventricular work was higher in the treated animals after reperfusion. The two tested type I antiarrhythmics tend to add to myocardial protection when given before cardioplegic arrest and do not exhibit negative inotropic side effects.
To assess independent risk factors predicting the occurrence of clinically significant acute rejection episodes in the first 6 months after cardiac transplantation, we performed a multivariate stepwise logistic regression analysis. Forty-three recipients, undergoing transplantation between September 1986 and May 1988, were eligible for analysis and received standardized, low-dose triple drug maintenance immunosuppression with cyclosporine, azathioprine, and prednisolone. Immunoprophylaxis was supplemented perioperatively with either a polyclonal (antithymocyte globulin, N = 26) or a monoclonal (OKT3, N = 17) anti-T-cell antibody. Investigated, conceivable risk factors comprised recipient and donor age, ischemic time, perioperative anti-T-cell antibody prophylaxis, recipient preoperative status, underlying disease, previous cardiac operation, and histocompatibility parameter (mismatches for HLA-A, HLA-B, HLA-DR, HLA-B+DR, HLA-A+B+DR, and Rh0[D] antigen, HLA-DRw6 positive recipient, and identify for ABO system). Univariate analysis suggested significant influence of the type of antibody used perioperatively (p = 0.0024) and the number of mismatches for HLA-A+B+DR (p = 0.0037) and for HLA-B+DR (p = 0.0043). Stepwise logistic regression yielded the number of mismatches for HLA-B+DR (p = 0.0029) and the type of antibody used perioperatively (p = 0.0031) as being highly significant predictors of acute cardiac rejection. Six-month freedom from rejection was 100%, 41%, and 27% for recipients with two, three, and four mismatches for HLA-B+DR and 59% versus 22% for recipients with polyclonal versus monoclonal antibody prophylaxis. Similar to results with kidney transplantation, these results indicate that a poor donor/recipient match for combined HLA-B+DR loci constitutes an independent risk factor for acute graft rejection in low-dose triple drug immunosuppressed cardiac recipients, which stimulates the potential concept of prospective HLA matching. In our experience OKT3 prophylaxis provides significantly less effective prevention of acute rejection than a comparable course of antithymocyte globulin.
The skeletal muscle has the capacity to respond adaptively to increased use. This observation could open up the feasibility of constructing pumping chambers to support or even replace cardiac work. We investigated the changes in enzyme activity due to chronic stimulation in an animal skeletal muscle. In 5 adult sheep the psoas muscle of one side was electrically stimulated through the muscle nerves, with an implantable stimulation unit for 5 weeks. The activity of the hexokinase (E.C.2.7.1.1.), lactate dehydrogenase (E.C.1.1.1.27), malate dehydrogenase (E.C.1.1.1.37), creatine kinase (E.C.2.7.3.2.) choline acetyltransferase and the contents of adenosine triphosphate and adenosine diphosphate were determined in bioptic specimen. The use of only 15 Hertz as a stimulation frequency led to a transformation of an originally fast-twitch muscle into a slow-twitch muscle with reduced susceptibility to fatigue. These results indicate a potential role of the skeletal muscle as an ideal myocardial substitute with the ability to perform hemodynamic work.
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The beginning of angioplasty dates back to the turn of this century. Two lines of research were pursued over the past 40 years, organic and synthetic replacements of vessels. Autologous replacement, using an endogenous extremity vein, proved to be the most favourable variant. It was found to be not applicable to about 20 per cent of all patients, so that allogenic, semixenogenic or synthetic substitutes were required. Synthetic replacement was found to be characterised by a high rate of longtime closure, attributable to good biocompatibility of synthetic prostheses and low thrombogenic property of their inner surfaces. Endothelialisation of the prosthesis would be a possibility to improve the rate of success in bypass vascular surgery.
Between 1971 and 1988 74 operations for intestinal complications following radiotherapy were performed on 67 patients at the Second Surgical Department, University of Vienna. The lesions were located in the small bowel (n = 41) and in the sigmoid colon/rectum (n = 33). 98.5% of the patients were females, the most frequent cause for irradiation being ovarian cancer. Bowel stenosis with resultant chronic or acute ileus was the most frequent indication for operation, occurring in 31 cases (76%) of the small bowel lesions and in 15 cases (46%) of the colon lesions. Percutaneous irradiation resulted in a significantly higher proportion of small bowel lesions (77%, p = 0.001), whilst endocavitary irradiation was followed in 67% of cases by colorectal lesions. Different application modality of irradiation also resulted in completely different symptoms for small and large bowel lesions. The operative mortality was 9.5%. Peritonitis following anastomotic leakage was the cause of death in 6 of 7 cases. In the treatment of small bowel ileus mortality following bowel resection (9%, one of 11 cases) was comparable to that of the bypass operation (6%, one of 18 cases). Both operation methods seem to be justified. Single-layer anastomosis resulted in zero mortality (21 cases) for ileus operation compared with 19% mortality (16 cases) in double-layer anastomosis and should be preferred for operations on the irradiated bowel.
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Two cases of leaflet fracture in the Edwards-Duromedics valve at 36 and 38 months after implantation are reported. Both patients were immediately reoperated on and recovered well. In one valve an older housing fracture with partial tissue ingrowth was noted beside a recent transverse leaflet fracture. In the other valve the leaflet was fractured near the pivot mechanism. All larger embolized parts were detected in the iliac artery region by computed tomographic scan and were subsequently removed. Problems in diagnosis and the importance of immediate reoperation, even without exact diagnosis, are discussed. Technical evaluation of the valve revealed crack growth and arrest, giving evidence of fatigue fracture. Scanning electron microscopic examination revealed several areas of pitting and erosion. Although the exact cause of mechanical disruption remains speculative, pyrolytic carbon seems to have the characteristic of fatigue fracture as well as erosion damage. A connection between the two might exist.