RESUMO
BACKGROUND: Resistance to r-tPA (recombinant tissue-type plasminogen activator) is a well-known but poorly understood phenomenon that hampers successful recanalization in patients with acute ischemic stroke. Using clinically relevant thrombi from patients with acute ischemic stroke, we investigated if and how thrombus composition impacts r-tPA-mediated lysis. In addition, we explored strategies to overcome r-tPA resistance. METHODS: Thrombi were split into 2 parts, 1 of which was used for thrombolysis and the other for detailed histological analysis. Thrombolysis was performed in normal human plasma using r-tPA alone, using r-tPA in combination with DNase-1 or using r-tPA in combination with N,N'-diacetyl-l-cystine. Thrombus lysis was calculated as the percentage of residual thrombus weight compared with its initial weight and the degree of lysis was linked to thrombus composition determined via histology. RESULTS: Interestingly, we found that the efficacy of r-tPA-mediated thrombolysis was strongly correlated with the composition of the thrombi. Thrombi containing high amounts of red blood cells and low amounts of DNA and von Willebrand Factor were efficiently degraded by r-tPA, whereas thrombi containing low amounts of red blood cells and higher amounts of DNA and von Willebrand Factor were resistant to r-tPA. Importantly, combination of r-tPA with DNase-1 or N,N'-diacetyl-l-cystine significantly and specifically improved the lysis of these r-tPA-resistant thrombi. CONCLUSIONS: Using patient thrombus material, our results for the first time show that the composition of stroke thrombi largely determines their susceptibility to r-tPA-mediated thrombolysis. Red blood cell-poor thrombi have a specific resistance to r-tPA, which can be overcome by targeting nonfibrin components using DNase-1 or N,N'-diacetyl-l-cystine.
RESUMO
OBJECTIVE: To report the long-term outcome of patients presenting with an aortic, aortoiliac, or isolated common iliac aneurysm treated with the bifurcated EXCLUDER Endoprosthesis. Furthermore, potential differences in late outcome results between the original- and low-permeability endoprosthesis were analyzed. METHODS: A retrospective analysis of prospectively collected data of 182 patients who underwent endovascular aneurysm repair with the EXCLUDER Endoprosthesis between June 1998 and October 2015 in an academic, tertiary care center for aortic disease was performed. Patient follow-up was from 3 to 20 years (mean follow-up of 6.9 years). Primary end points were overall survival and reintervention-free survival. Secondary end points were device-related complications, endoleaks, and reinterventions. RESULTS: Overall survival at 5, 10, and 15 years was 72.8%, 42.1%, and 12.2%, respectively, with no aneurysm-related mortality and no difference in overall survival between the original- vs low-permeability endoprosthesis group (P = .617). Freedom from type I endoleak at 5 years was 94.8%. No new type I endoleak was detected beyond the 5-year follow-up mark. No type III endoleak was identified. Reintervention-free survival was 83.6%, 66.7%, and 66.7% at 5-, 10-, and 15-year follow-up, respectively. There was a significant difference in intervention-free survival between the original- vs low-permeability endoprosthesis group (P = .029) and after the 5-year follow-up mark. In addition, patients with the low-permeability endoprosthesis showed significantly fewer device-related complications (P = .002) and endoleaks (P = .005). CONCLUSIONS: Endovascular aneurysm repair using the EXCLUDER Endoprosthesis is effective and durable on long-term follow-up, with acceptably low device-related complications and reinterventions. The low-permeability endoprosthesis was associated with significantly fewer new device-related complications and endoleaks after 5 years of follow-up.