Johann Meinhart

Clinical autologous in vitro endothelialization of infrainguinal ePTFE grafts in 100 patients: a 9-year experience.

BACKGROUND Clinical in vitro endothelialization was assessed for its ability to improve the long-term patency of prosthetic femoropopliteal bypass grafts. METHODS Between June 1989 and May 1998, 100 patients received 113 in vitro endothelialized expanded polytetrafluoroethylene grafts (ePTFE). Bilateral implantations were performed in 13 patients. In phase 1 of the study, 24 patients received 27 endothelialized grafts and 16 patients received 17 untreated grafts. In phase 2, endothelialization was offered to all patients who did not have a suitable saphenous vein available. Phase 2 began in June 1993 and included 76 patients who received 86 endotheliazed ePTFE grafts. In all, 100 patients had autologous endothelial cells harvested from 4- to 5-cm segments of a subcutaneous vein. In phase 1, the external jugular vein was used. In phase 2, the cephalic vein was used. These cells were grown to first-passage mass cultures and were lined confluently onto 6-mm ePTFE grafts, pre-coated with fibrin glue. Patency assessment for Kaplan-Meier survivorship analysis was determined by using duplex sonography and angiography. RESULTS In phase 1, the Kaplan-Meier method revealed a primary 9-year patency rate for 65% for the endothelialized group, versus 16% for the control group (log-rank test, P = .002; Wilcoxon test, P = .003). In phase 2, the 5-year primary patency rate for all in vitro endothelialized infrainguinal reconstructions was 68% (66% for above-the-knee grafts and 76% for below-the-knee grafts). CONCLUSIONS Nine years of clinical in vitro endothelialization provided strong evidence that autologous endothelial cell lining improves the patency of small-diameter vascular grafts and that a cell culture-dependent procedure can be used in a clinical routine.

Clinical autologous in vitro endothelialization of 153 infrainguinal ePTFE grafts

BACKGROUND Over the past 17 years, our group has developed and clinically applied an in vitro endothelialization procedure whereby infrainguinal expanded polytetrafluoroethylene (ePTFE) prostheses are confluently lined with cultured autologous endothelial cells before implantation. After a successful randomized pilot study from 1989 to 1993, the procedure was adopted for routine operations. METHODS Since June 1993, 153 endothelialized ePTFE grafts were implanted in the infrainguinal position in 136 patients (102 above knee (AK) and 51 below knee (BK), 89 men and 47 women, mean age 64.7+/-9.4 years). Seventeen patients received an endothelialized prosthesis bilaterally. Autologous endothelial cells were harvested from 4- to 5-cm segments of a subcutaneous vein (in 86% the cephalic vein), grown to first-passage mass cultures and confluently lined onto 6- (n = 113) or 7-mm (n = 40) inner diameter (ID) ePTFE grafts, precoated with fibrin glue. The observation period for 6-mm grafts was 7 years, and for 7-mm grafts was 4 years. Patency assessment for Kaplan-Meier survivorship analyses was based on duplex sonography and angiography. RESULTS Kaplan-Meier survivorship function revealed a primary patency rate of 62.8% after 7 years (SE = 0.05) for all infrainguinal reconstructions (60% AK/70.8% BK). The primary patency for stage II and III patients was 64.4% after 7 years. The more recent group of 7-mm ID grafts showed a primary patency of 83.7% after 4 years. CONCLUSIONS Our data provide strong evidence that autologous endothelial cell lining distinctly improves the patency of small diameter vascular grafts.

Long-term experience in autologous in vitro endothelialization of infrainguinal ePTFE grafts

OBJECTIVE Based on a previous randomized study showing significantly superior patency rates for in vitro endothelialized expanded polytetrafluoroethylene (ePTFE) grafts we investigated whether it was feasible for a nontertiary institution to offer autologous in vitro endothelialization to all elective infrainguinal bypass patients who had no suitable saphenous vein available. METHODS Over a period of 15 years, 310 out of 318 consecutive nonacute patients (age 64.7 +/- 8.6) received 341 endothelialized ePTFE grafts (308 femoropopliteal: 153 above knee [AK] and 155 below knee [BK] and 33 femorodistal). Autologous endothelial cells were harvested from short segments (3.9 +/- 1.1 cm) of subcutaneous veins (80% cephalic, 11% basilic, 2% external jugular, and 7% saphenous) and grown to mass cultures within 18.9 +/- 4.5 days before being confluently lined onto fibrin glue-coated ePTFE grafts. The graft diameter was 6 mm (64%) or 7 mm (36%). The overall procedure-related delay for graft implantation was 27.6 + 7.8 days. Growth failure prevented 2.5% of patients from receiving an endothelialized graft. The mean observation period was 9.6 years. Primary patencies were obtained from Kaplan-Meier survivorship functions. Explants for morphological analysis were obtained from eight patients. RESULTS The overall primary patency rate of femoropopliteal grafts was 69% at 5 years (68% [AK] vs 71% [BK]) and 61% at 10 years (59% [AK] vs 64% [BK]). Primary patency of 7 mm vs 6 mm grafts was 78%/62% at 5 years and 71%/55% at 10 years. The difference between the two groups was statistically significant (log rank test P = .023; Breslow test P = .017). Stage I vs II/III patients showed 5-year patencies of 67% vs 73% (N.S.) and 10-year patencies of 61%% vs 53% (N.S.). The primary patency of femorodistal grafts was 52% at 5 years and 36% at 10 years. The limb salvage rate was 94% (fempop) vs 86% (femdistal) at 5 years and 89% vs 71% at 10 years. All retrieved samples showed the presence of an endothelium after 38.9 +/- 17.8 months. CONCLUSION Autologous in vitro endothelialization was shown to be a feasible routine procedure at a nontertiary hospital. Explants confirmed the presence of an endothelium years after implantation while the primary patency in the particularly challenging subgroup of patients without a suitable saphenous vein resembles that of vein grafts.

In vitro endothelialization of expanded polytetrafluoroethylene grafts: A clinical case report after 41 months of implantation

PURPOSE Forty-one months after we performed bilateral implantation of in vitro endothelialized femoropopliteal bypass grafts in a 69-year-old patient, we obtained a central graft segment for histologic and ultrastructural investigation. METHODS Before implantation the grafts were confluently lined with autologous first passage mass cultures of pure cephalic vein endothelial cells. The precoating of the expanded polytetrafluoroethylene prosthesis was done with fibrinolytically inhibited fibrin glue. Reoperation became necessary because of symptomatic unilateral atherosclerotic lesions located in the center of one of the two in vitro lined grafts. A 21 cm long graft segment was removed and replaced by a new in vitro endothelialized expanded polytetrafluoroethylene graft. RESULTS On scanning electron microscopy a confluently covering mature endothelium was found throughout the whole length of the removed prosthesis. The endothelial identity was confirmed by a positive immunohistochemical CD 34, von Willebrand factor-staining, and the ultrastructural demonstration of Weibel Pallade bodies. The endothelium rested on a collagen IV positive basement membrane. Histologic cross sections revealed uniformly developed subintimal tissue of 1.21 +/- 0.19 mm thickness, which was separated from the intima by a distinct internal elastic membrane. The cells of this cell-rich matrix stained strongly positive for actin. Ultrastructurally, this matrix was dominated by highly contractile myofibroblasts loaded with peripherally located well-developed actin fillaments. A number of these cells also showed signs of secretory cells with a distinct endoplasmic reticulum and a Golgi complex. In areas of atherosclerotic lesions the subendothelial matrix was partially exposed, and the internal elastic membrane had to a certain extent disintegrated. Only in these areas KP-1 and MG-M1 positive foamy macrophages and CD 34 positive capillaries were found. The myofibroblasts of this diseased part of the subintimal tissue contained large lipid vacuoles. CONCLUSIONS We conclude that the confluent in vitro lining of synthetic vascular grafts with pure autologous endothelial cells facilitates graft healing, which may result in a hybrid structure with features of a native vessel.

Translumbar treatment of type II endoleaks after endovascular repair of abdominal aortic aneurysm

The modality of treatment and the appropriate time point to treat type II endoleaks after endovascular repair of abdominal aortic aneurysms (EVAR) remain controversial issues. The purpose of the present study was to assess the efficacy of translumbar embolization of type II endoleaks after endovascular repair of aortic aneurysm repair. Eighty-four consecutive patients after EVAR were analyzed for the onset of type II endoleaks. Of these, five patients had experienced translumbar embolization after ineffective intraartrial approach to exclude the endoleak. A combination of several liquid embolic agents was used as sealant. Post-procedural contrast-enhanced ultrasound (CEUS) was used to document the outcome of the embolization. Translumbar embolization was successful in four patients. Complete sealing of the nidus was seen on CEUS 24 h after the procedure. In one patient with a duplication of the inferior vena cava, the procedure was aborted because an additional type Ib endoleak was found. The procedure was well tolerated by all patients. The translumbar approach to treat growing aneurysm sacs in patients with persistent type II endoleaks is safe and well tolerated. The immediate post-interventional outcome as documented on CEUS is promising. Long-term follow-ups are yet to be performed.

In vitro endothelialization of a mesosystemic shunt: A clinical case report

The existence of a confluently covering endothelium that is free of any thrombotic appositions can be proved 30 days after clinical implantation of an in vitro endothelialized expanded polytetrafluoroethylene graft. The recipient of the mesosystemic H-graft was a 69-year-old man who had a thrombosed portal vein following pancreatitis. Autologous endothelial cells were obtained from the external jugular vein under local anesthesia, applying the in situ cannulation technique. After low-density plating, first-passage mass cultures of 1.22 x 10(6) endothelial cells were obtained 14 days after vein excision. After precoating was accomplished with fibrinolytically inhibited fibrin glue, a 10 mm expanded polytetrafluoroethylene graft was confluently lined with the autologous endothelial cells at a seeding density of 1.2 x 10(5) cells/cm2. After a maturation period of an additional 9 days and the microbiologic exclusion of a possible infection, an 11 cm graft segment was implanted between the superior mesenteric vein and the inferior vena cava. In spite of a patent shunt the patient had a repeat bleeding episode, needed parenteral nutrition, and died of sepsis on day 30. Immediately after the graft had been taken out, specimens were processed by scanning electron microscopy and light microscopy for the immunohistochemical proof of the endothelial nature of the surface-covering cell layer. The entire graft surface displayed a confluent cell lining that was free of any thrombotic appositions. A strongly positive stain result for both factor VIII-related antigen and the fixation-resistant CD34 molecule identified these cells as endothelial. No alpha-actin-positive cells could be detected. The underlying protein matrix was well preserved and unaltered in thickness and appearance, compared with preimplantation samples. None of the specimens showed any evidence of infection. This human demonstration of an intact endothelium on a patent venous prosthesis further establishes in vitro lining as a method that actually creates a persistent and functioning endothelium on a synthetic graft surface.

Fate of the False Lumen After Combined Surgical and Endovascular Repair Treating Stanford Type A Aortic Dissections

BACKGROUND The purpose of this study was to evaluate the alterations of the aorta by using a new combined surgical and endovascular technique for the treatment of aortic type A dissections. The diameter of the descending aorta, the implanted stent graft, and the false lumen were evaluated. METHODS Between August 2005 and February 2009, 14 patients (aged 49 +/- 13 years; 11 men, 3 women) with type A dissection in the aorta were operated on the thoracic aorta by the frozen elephant trunk technique. The size dynamics of the false lumen were analyzed by deducting the diameter of the stent graft obtained on computed tomography from the maximum dimension of the aorta. RESULTS The technical success rate was 100%. All patients survived during the follow-up period. The mean follow-up period was 21.4 months. No redisection or aortic rupture occurred during the follow-up period. Postoperative computed tomography scans showed complete thrombus formation of the false lumen in the perigraft space within the entire zone of the stented segment of the hybrid prosthesis during the first 2 weeks after surgery in 12 patients (86%), whereas all patients showed complete obliteration of the false lumen at the 3-month control. The follow-up computed tomography scan obtained after 12 months revealed shrinkage of the false lumen in 9 patients (64%). CONCLUSIONS The combined surgical and endovascular technique described in this report proved effective for the treatment of extended aortic lesions. The perigraft space thrombosed completely and had shrunken after successful placement of the stent graft.

Changes in Serum Levels of Myokines and Wnt-Antagonists after an Ultramarathon Race.

Background Regular physical activities have a positive effect on the muscular skeletal system but overstrenuous exercise may be different. Transiently suppressed bone formation and increased bone resorption after participation in a 246-km ultradistance race has been demonstrated. Purpose The aim of this study was to analyze effects of the Spartathlon race on novel musculoskeletal markers. Methods Venous blood samples were obtained before and immediately after the race from 19 participants of the Spartathlon. From 9 runners who were available 3 days after the start blood was drawn for a third time. Serum levels of myostatin, an inhibitor of myogenic differentiation, and its opponent follistatin as well as sclerostin and dickkopf-1, both of them inhibitors of the wnt signaling pathway, and markers of bone turnover were determined. Results Serum levels of myostatin were significantly higher after the race. Serum follistatin only showed a transient increase. Sclerostin levels did not significantly differ before and after the race, whereas dickkopf-1 levels were significantly decreased. At follow-up a decrement of sclerostin and dickkopf-1 levels was seen. Serum cathepsin K levels did not change. Conclusion The increase of serum levels of myostatin appears to reflect muscle catabolic processes induced by overstrenuous exercise. After the short-term uncoupling of bone turnover participation in an ultradistance race seems to initiate a long-term positive effect on bone indicated by the low-level inhibition of the Wnt/β-catenin signaling pathway.

A newly designed thorax support vest prevents sternum instability after median sternotomy

OBJECTIVE Sternum infection remains one of the primary causes of postoperative morbidity and mortality after median sternotomy. We report the clinical efficacy for primary reinforcement of the sternum with a new design of thorax support vest. METHODS A prospective randomized study including 455 patients was started in September 2007 to evaluate the effectiveness of the Posthorax sternum vest (Epple Inc., Vienna, Austria). One hundred and seventy five patients were treated with the sternum dressing postoperatively (group A), 227 patients did not receive the vest (group B) and 53 patients refused it (group C). Several clinical and operative data were evaluated. All patients were recorded using the STS risk scoring analysis for mediastinitis after cardiac surgery. RESULTS The median age and gender distribution were comparable in both groups. Preoperative data like renal failure, chronic obstructive pulmonary disease, peripheral artery disease, and myocardial infarction were not significant. There were more patients with diabetes in group A and C (A: 39.4%, B: 29.1%, C: 43.4%, p = 0.036). A total of 55.8% underwent coronary bypass grafting, 15.4% aortic valve replacement, 7.7% mitral valve repair and 21.1% concomitant cardiac procedures. The median risk factor analysis and body mass index were comparable. In the follow-up period up to 90 days, in group A we observed 0.6% sternum wound complications, in group B 4.9%, and in group C 9.4% (group A vs B: Fishers exact test p = 0.0152 and group A vs C: p = 0.0029). CONCLUSIONS The use of the Posthorax sternum vest shows a favourable outcome to prevent sternum instability after cardiac surgery. There was one reoperation in patients treated with this sternum vest compared to 16 in the control groups.

A prospective randomized multicenter trial shows improvement of sternum related complications in cardiac surgery with the Posthorax® support vest

Sternal instability, dehiscence and mediastinitis are major causes of morbidity and mortality in cardiac surgery. The aim of this analysis is to determine the effect of a Posthorax support vest (Epple Inc, Vienna, Austria) after median sternotomy. One thousand five hundred and sixty cases were included in a prospective randomized multicenter trial. Patients were randomized as follows: 905 received a flexible dressing postoperatively (group A) and 655 patients were given a Posthorax support vest (group B). Patients in groups A and B were well matched. Their mean age was 68 years (range: 34-87 years). The patient characteristics and operative data were equally distributed in both groups. The mean total hospital stay was significantly shorter in group B than in group A (A: 17.33+/-17.5; B: 14.76+/-7.7; P=0.04). Sternal wound complications necessitating reoperation during the 90 days follow-up period were observed in 4.5%. Reoperation rates were as follows: 3.9% in group A and 0.6% in group B (P<0.05). The use of the Posthorax sternum support vest is a valuable adjunct to prevent sternum-related complications after cardiac surgery. In the 90 days follow-up period, additional surgical procedures were significantly reduced by the use of the support vest.