Manfred Prager

Endovascular Stent Grafting Versus Open Surgical Operation in Patients With Infrarenal Aortic Aneurysms

Background— Although transfemoral endovascular aneurysm management (TEAM) of infrarenal abdominal aortic aneurysms (AAA) is widely performed, open graft replacement is still considered the standard of care. The aim of this study was to investigate whether clear indications for TEAM can be established in patients with significant comorbidities without investigating differences in relative procedure efficacy or durability. Methods and Results— A propensity score–based analysis of 454 consecutive patients treated electively for AAA from January 1995 through December 2000 was performed. Of those 454 patients, 248 received open surgery and 206 received TEAM. In-hospital mortality rates (MRs) were compared. After adjusting for propensity scores, a Cox proportional hazard model (COX) was employed to test the influence of the respective treatment on postoperative 900-day survival estimates (SEs). Several potential preoperative risk factors were used as covariates. The MR of all patients was 3.7%. Explorative anal...

Prostaglandin-J2 induces synthesis of interleukin-8 by endothelial cells in a PPARγ-independent manner

PPARgamma is a transcription factor of nuclear receptor superfamily, involved in the regulation of inflammation. We investigated the influence of PPARgamma-ligands, 15-deoxy-delta12,14 prostaglandin-J2 (15d-PGJ2), and ciglitazone, on the generation of interleukin-8 (IL-8) by the human microvascular endothelial cell line (HMEC- 1). Expression of PPARgamma in HMEC-1 was confirmed by RT-PCR. Both PPARgamma-ligands tested induced the activation of PPAR, but the potency of ciglitazone was higher, as evidenced by luciferase assay. Resting HMEC-1 released about 150 pg/ml of IL-8 protein. Treatment with LPS increased the IL-8 secretion up to 1 ng/ml. 15d-PGJ2 potently and dose-dependently increased both the steady-state and LPS-induced generation of IL-8 mRNA and IL-8 protein. In contrast, neither basal nor LPS-elicited expression of IL-8 was influenced by ciglitazone. We conclude, that 15d-PGJ2 is a potent inducer of IL-8 production and can be a mediator of inflammatory response, but this effect is independent of PPARgamma activation.

Chlamydia pneumoniae in Carotid Artery Atherosclerosis A Comparison of Its Presence in Atherosclerotic Plaque, Healthy Vessels, and Circulating Leukocytes From the Same Individuals

Background and Purpose— There is growing clinical and experimental evidence that infections with Chlamydia pneumoniae might contribute to the development and progression of atherosclerosis. However, studies detecting the pathogen in atherosclerotic lesions examined either only atherosclerotic vessels or control vessels without atherosclerosis obtained from a different group of individuals. We analyzed atherosclerotic plaques of the carotid artery, samples of apparently healthy greater saphenous veins, and circulating leukocytes from the same individual patients for the presence of C pneumoniae. Methods— From each of 46 patients undergoing carotid endarterectomy for symptomatic carotid artery stenosis, these samples were analyzed by nested polymerase chain reaction for C pneumoniae–specific DNA. Furthermore, we determined IgA and IgG titers specific for the pathogen and plasma levels of C-reactive protein in these patients. Results— C pneumoniae DNA was detected in 86.9% of the leukocytes and in 82.6% of the atherosclerotic plaques but in only 6.5% of the saphenous veins. In 85% of patients who also had leukocytes positive for C pneumoniae, the atherosclerotic plaques were positive and the saphenous veins were negative. The presence of C pneumoniae–specific DNA in leukocytes significantly coincided with the presence of the respective DNA in the plaques of the carotid arteries (P =0.0002). No association between the presence of C pneumoniae and specific IgA or IgG levels was seen. C-reactive protein levels were significantly higher in patients with chlamydia-positive atherosclerotic plaques and with positive leukocytes than in patients with negative plaques of the carotid arteries or negative leukocytes, respectively (P <0.01, P <0.05). Conclusions— Our observation of >80% incidence of C pneumoniae in atherosclerotic plaques of the carotid artery does not prove causality between an infection with the pathogen and the development of atherosclerosis. It must be emphasized, however, that >90% of apparently healthy saphenous veins were negative for C pneumoniae. Given the structural and functional differences between veins and arteries, careful interpretation of our results regarding a possible causative role of C pneumoniae seems warranted.

Prostaglandin E1 reduces ischemia/reperfusion injury by normalizing nitric oxide and superoxide release.

To test the effects of prostaglandin E1 on 2.5 h of ischemia followed by 2 h of reperfusion, continuous nitric oxide measurements (electrochemical) were correlated with intermittent assays of superoxide and peroxynitrite levels (chemiluminescence) and ischemia/reperfusion injury in rabbit adductor magnus muscle. Administering prostaglandin E1 (1 microg/kg) before or during ischemia/reperfusion caused normalization of the release of nitric oxide, superoxide, and peroxynitrite to slightly above preischemic levels. This pattern was dramatically different from that observed during ischemia/reperfusion alone, where nitric oxide concentration increased three times above its basal level. Normalization of constitutive nitric oxide synthase activity in the presence of prostaglandin E1 was associated with a significant reduction of superoxide and peroxynitrite production and subsequent reduction of ischemia/reperfusion injury. At 2 h of reperfusion, vasoconstriction associated with ischemia/reperfusion injury was eliminated, and edema was significantly mollified but still apparent. Prostaglandin E1 treatment does not directly inhibit constitutive nitric oxide synthase, like the inhibitor N(omega)-monomethyl-L-arginine. Some phenomenon associated with ischemia turns on endothelial constitutive nitric oxide synthase to start transforming L-arginine and oxygen into nitric oxide, but prostaglandin E1 seems to inhibit this phenomenon. Thus, essential local L-arginine pools are not depleted, and normal basal levels of essential nitric oxide are maintained, whereas cytotoxic superoxide and peroxynitrite production by L-arginine-deficient constitutive nitric oxide synthase is prevented.

Patency Rate of Implantable Devices During Long-Term Intraaterial Chemotherapy

Intrarterial implantable drug delivery systems have been considered as an alternative method for treating patients with unresectable liver malignancies. However, catheter problems with external implanted devices have resulted in limited application of chemotherapy. The introduction of subcutaneous devices offers an opportunity for long-term locoregional chemotherapy. Twelve external intraarterial catheters were implanted into 12 patients and 52 subcutaneously placed devices into 51 patients, all with various hepatic malignancies. Retrospec tive analyses comparing those two intraarterial systems were conducted taking into account the function and complication rate (hepatic artery thrombosis, infection, leaking, hemorrhage, and dislocation). The follow-up time for the external system was two to eight months (median five weeks), the thrombosis rate 33.3%, and the infection rate 25%. One instance of severe bleeding from the hepatic artery occurred during chemotherapy. One catheter dislocated. For the subcutaneously implanted intraarterial devices the follow-up time was five to forty-one months (median sixteen months), the thrombotic complication rate 17.3%, and the infection rate 7.6% (all patients with simultaneous bowel sur gery). Catheter dislocation one year later required reimplantation; in 1 patient therapy had to be discontinued because of a catheter leak. The overall function rate was 71.3% with a median follow-up time of eight months. Anticoagulation therapy for subcutaneously implanted devices starting from the beginning of intraarterial chemotherapy is recommended to achieve long-term patency. No implantation should be performed simultaneously with bowel surgery. The sub cutaneously placed intraarterial devices had a higher function rate and were available for a longer period as compared with external implanted catheters.

Endovascular treatment of a multimorbid patient with late AAA rupture after stent-graft placement: 1-year follow-up.

Purpose: To report successful endovascular management of a ruptured abdominal aortic aneurysm (AAA) in a multimorbid patient 40 months after primary stent-grafting. Case Report: A 64-year-old man presented with hypotension, severe back pain, and abdominal distension. Immediate computed tomography revealed a proximal type I endoleak due to distal migration of the stent-graft with subsequent rupture of the aneurysm. The patient was hemodynamically unstable, and open surgery was refused because of severe comorbidities that were the indications for initial endovascular repair. The diameter of the proximal aneurysm neck required the use of a thoracic stent-graft that was overly long, which led to occlusion of the contralateral stent-graft limb supplying not only the left leg but also a left kidney transplant. A crossover bypass was implanted to revascularize both. Conclusions: Minimally invasive strategies, even when challenged by complex vascular reconstructions, offer the possibility of managing ruptured aortic aneurysms in patients unsuitable for open surgery.

No evidence for a direct role of Helicobacter pylori and Mycoplasma pneumoniae in carotid artery atherosclerosis

Background: That infections with certain pathogens, by initiating an inflammatory response, may contribute to the development of atherosclerosis is suggested by clinical and experimental evidence. Aim: To analyse atherosclerotic plaques of the carotid artery, samples of apparently healthy greater saphenous veins and circulating leucocytes from the same individual patients for the presence of Helicobacter pylori and Mycoplasma pneumoniae. Methods: Samples from 36 patients undergoing carotid endarterectomy for symptomatic carotid artery stenosis were analysed by polymerase chain reaction for the presence of DNA specific for H pylori and M pneumoniae. IgG antibody titres against H pylori and M pneumoniae and plasma levels of soluble E-selectin, soluble intercellular adhesion molecule-1 and soluble vascular cell adhesion molecule-1 were determined. Results:M pneumoniae-specific DNA was detected in the atherosclerotic plaques of 13 of 36 (36.1%) patients, in the saphenous veins of 9 of 36 (25%) patients and in the leucocytes of 27 of 36 (75%) patients. No salient association was observed between the presence of M pneumoniae-specific DNA in leucocytes and atherosclerotic plaques or veins. A marked correlation between the presence of M pneumoniae in the respective specimens and the studied inflammatory markers or the presence of anti-M pneumoniae antibodies was not observed. H pylori-specific DNA could not be detected in the specimens tested. Conclusions: The absence of H pylori and the random distribution of M pneumoniae in tissue samples obtained from patients with symptomatic carotid artery stenosis do not support a role for these pathogens in the development of atherosclerosis due to a direct interaction of the bacteria with the vasculature.

Der Vena-saphena-magna-Bypass

ZusammenfassungGrundlagenAnhand einer retrospektiven Analyse eigener Ergebnisse soll der Stand der chirurgischen Technik diskutiert werden. Grundlage für die Diskussion sind die am Workshop “Der Venenbypass” 1991 in Linz gehaltenen Referate.MethodikZwischen 1970 und 1991 wurden an der I. Chirurgischen Universitätsklinik Wien 590 reversierte Venenbypässe angelegt. Anschlußgefäß war in 39% die supragenuale, in 31% die infragenuale A. poplitea, in 30% ein krurales Gefäß.ErgebnisseDie 30-Tage-Letalität betrug 2%, die mediane Nachbeobachtungszeit 65 Monate. Die Gesamtfunktionsrate nach 60 Monaten betrug 55%, die sekundäre Funktionsrate 70% für alle Patienten. Die primäre Funktionsrate für supragenuale Venenbypässe betrug 61%, für infragenuale 49% und für krurale 52%. Der Beinerhalt nach 60 Monaten war in 88% gewährleistet.SchlußfolgerungenEin Literaturüberblick diskutiert die verschiedenen Trends auf dem Gebiet der Venenbypasschirurgie zur Revaskularisation der unteren Extremität. Große prospektive, randomisierte Studien werden benötigt, um die beste Technik für distale Rekonstruktionen der unteren Extremität zu evaluieren, daher muß die Wahl des Vorgehens derzeit der Präferenz des Chirurgen überlasen werden.SummaryBackgroundDuring a 20-year period between 1970 and 1991 590 reversed vein bypass grafts were performed for claudication (40%) and for limb salvage (60%).MethodsOutflow anastomoses were constructed to the suprageniculate popliteal (39%), infrageniculate popliteal (31%) and crural arteries; the technique was reversed vein bypass graft.ResultsThe 30-day mortality rate was 2%, the median fllow-up 65 months. At 60 months primary graft patency was 55% overall; secondary graft patency was 70%, respectively. Primary cumulative patency rates at 60 months depending on the outflow site were as follows: suprageniculate popliteal 61%, infrageniculate popliteal 49% and crural 52%. Cumulative limb salvage at 60 months was 88% overall. A literature review on current trends in lower limb vein bypass surgery is given.ConclusionsA 5-year graft patency rate of 55% and a limb salvage rate of 88% were achievable with the reversed vein bypass. Literature shows, that the performance of the reversed vein graft and the in situ technique yield similar results. Further prospective randomized studies are needed to find out the superior technique for lower limb revascularization.

Gutless Adenoviral Vectors – Promising Tools for Gene Therapy

SummaryBackground: Progress in gene therapy depends on establishing the appropriate gene transfer methods. The most efficient vehicles for the delivery of foreign genes to the target tissues are modified adenoviruses. Methods: Adenoviral vectors of the first generation despite the high infection efficiency, have an essential drawback: They induce a strong immune response, which excludes them from clinical trials. Results: In the past few years, there have been substantial efforts to improve adenoviral vectors with particular emphasis on reducing immunological effects in the host organism. Conclusions: In this review we describe the preparation and application of gutless vectors, the most advanced and promising type of adenoviral vehicles so far.ZusammenfassungGrundlagen: Der Erfolg einer Gentherapie hängt von der Etablierung geeigneter Gentransfermethoden ab. Die effektivsten Transportmittel für Fremdgene zum Zielgewebe vermitteln modifizierte Adenoviren. Methodik: Die erste Generation von adenoviralen Vektoren haben ungeachtet der hohen Infektiosität einen essentiellen Nachteil: sie induzieren eine starke Immunantwort, die sie von klinischen Versuchen ausschließt. Ergebnisse: In den letzten Jahren gab es verstärkte Bemühungen, die adenoviralen Vektoren zu verbessern und im Besonderen die immunologischen Effekte an dem Empfängerorganismus zu reduzieren. Schlußfolgerungen: Hier beschreiben wir die Präparation und Applikation von „Gutless“-Vektoren, den bisher bestentwickelten und vielversprechendsten adenoviralen Vektoren.

α‐Tocopherol Pretreatment Reduces Ischaemia/Reperfusion Injury in Rabbit Skeletal Muscle

SummaryBackground: Ischaemia/reperfusion (I/R) injury is characterized by the production of oxygen free radicals and the loss of high energy phosphates. α-Tocopherol (vitamin E) has been reported to play a protective role against free radical damage. Therefore, its i. v. supplementation prior to onset of ischaemia was investigated in an established I/R injury model.Methods: New Zealand white rabbits were subjected to a bilateral hind limb ischaemia/reperfusion of 2.5 h/2 h without any treatment (IR group), whereas in the VE group the vitamin E emulsion Tocovenös® was given i. v. for 10 min in a dose of 3 mg/kg bw. A SHAM group served as a control. Intramuscular phosphocreatine (PCr) and adenosine triphosphate (ATP), muscle interfibre area (MIFA), and microvessel cross-sectional area (MVCSA) were determined and electron microscopy was performed.Results: In the IR group, PCr decreased by 65 % of the initial level after 2.5 h of ischaemia and a further depletion was noticed after 2 h of reperfusion (20.9±1.1 vs 6.3±3.0 µmol/g wet wt,P<0.01). By contrast, ATP remained stable after ischaemia but dropped dramatically after reperfusion (6.5±0.2 vs 2.1±8.0 µmol/g wet wt,P<0.05). In the VE group, PCr and ATP did not differ significantly from the SHAM group at the end of reperfusion. Consequently, ATP in this group was significantly higher as compared with the IR group (4.9±0.9 vs 2.1±8.0 µmol/g wet wt,P<0.05). In the IR group, prominent interstitial oedema formation was found after reperfusion expressed by the increase in MIFA (28.2±4.2 vs 13.7±1.6 %,P<0.05). In the VE group, only a moderate interstitial oedema was found (18.7±3.4 %). Severe microvessel constriction was observed after reperfusion in both experimental groups. Electron microscopy revealed fewer tissue changes in the VE group as compared with the IR group.Conclusions: α-Tocopherol pretreatment had a protective effect on I/R injury in skeletal muscle expressed by recovery of PCr after reperfusion and by prevention of ATP depletion. Although microvascular constriction could not be prevented, antioxidative treatment reduced interstitial oedema and preserved muscle morphology.ZusammenfassungGrundlagen: Der Ischämie/Reperfusions (I/R)-Schaden ist durch die Produktion freier Sauerstoffradikale und den Verlust energiereicher Phosphate charakterisiert. Es ist bekannt, daß α-Tocopherol (Vitamin E) eine Schutzfunktion bei Schäden durch freie Radikale hat. Deshalb wurde eine i. v. Supplementation vor Beginn der Ischämie an einem etablierten I/R-Modell untersucht.Methodik: An weißen New Zealand Kaninchen wurde eine beidseitige Ischämie/Reperfusion von 2,5 h/2 h an den hinteren Extremitäten durchgeführt: in Gruppe I/R ohne Behandlung. In der VE-Gruppe wurde die Vitamin-E-Emulsion Tocovenös® i. v. für 10 min in einer Dosierung von 3 mg/kg gegeben. Eine SHAM-Gruppe diente als Kontrolle. Intramuskuläres Phosphokreatin (PCr), Adenosin Triphosphat (ATP), die Fläche zwischen den Muskelfasern (MIFA) und die Mikrogefäßfläche (MVCSA) wurden bestimmt und elektronenmikroskopische Aufnahmen ausgewertet.Ergebnisse: In der IR-Gruppe verringerte sich das PCr nach 2,5 h Ischämie um 65 % im Verhältnis zum Ausgangswert. Nach 2 h Reperfusion wurde eine weitere Absenkung gemessen (20,9±1,1 vs 6,3±3,0 µmol/g wet wt,P<0,01). Im Gegensatz dazu blieb der ATP-Spiegel während der Ischämie stabil, fiel aber stark nach der Reperfusion (6,5±0,2 vs 2,1±8,0 µmol/g wet wt,P<0,05). In der VE-Gruppe veränderten sich PCr und ATP nicht signifikant zur SHAM-Gruppe am Ende der Reperfusion und ATP war im Vergleich zur IR-Gruppe signifikant höher (4,9±0,9 vs 2,1±8,0 µmol/g wet wt,P<0,05). In der IR-Gruppe zeigte sich am Ende der Reperfusion ein deutliches interstitielles Ödem (Anstieg der MIFA) im Vergleich zur SHAM-Gruppe (28,2±4,2 vs 13,7±1,6 %,P<0,05). In der VE-Gruppe wurde nur ein geringes interstitielles Ödem gemessen (18,7±3,4 %). In beiden experimentellen Gruppen wurde eine deutliche Konstriktion der Mikrogefäße beobachtet. Die Elektronenmikroskopie zeigte in der VE Gruppe geringere Gewebsveränderungen als in der IR-Gruppe.Schlußfolgerungen: Eine α-Tocopherol-Vorbehandlung hat einen protektiven Effekt auf die Skelettmuskulatur beim I/R-Schaden, erkennbar an der Normalisierung des PCr nach Reperfusion und der Vorbeugung eines ATP-Abfalls. Obwohl eine Konstriktion der Mikrogefäße nicht verhindert werden konnte, reduzierte die antioxidative Behandlung das interstitielle Ödem und bewahrte die Muskelmorphologie.