The Experimental Research On Artificial Aortic Arch Stent-grafts

Background:Acute type A aortic dissection(ATAAD) remains a life threatening disease. It ischaracterized by sudden onset, rapid progression and high mortality. Without timelydiagnosis and treatment, the fatality rate was from1%to4%per hour within the first48hours after the onset of Stanford type A aortic dissection, and the natural mortality up to50%within48hours.Timely surgical treatment can prevent fatal complications such as cardiac tamponade,heart failure, and aortic rupture. The current treatment methods include the traditionalsurgical treatment, the treatment combining traditional surgery frozen elephant trunktechnology and endovascular repair. However, the traditional surgery accompaniescomplex surgical techniques, slow anastomosis, a long period of cardiopulmonary bypass(CPB) and deep hypothermic circulatory arrest (DHCA), and postoperative anastomoticbleeding. The overall in-hospital mortality and complications following conventionalsurgical treatment of acute Stanford type A dissection remains high, despite theimprovements in surgical techniques and perioperative care. Endovascular therapy islimited by many anatomic factors when it was applied in patients with Stanford Adissection. Recently, several studies have been performed and reported the initialencouraging results of hybrid aortic arch repair in small series. But because of theparticularity of the anatomical structure of the aortic arch and the complexity ofhemodynamic, we couldn’t find a kind of specifically stent targeted hybrid surgicaltreatment of aortic arch disease at home and abroad.The purpose of this topic is to develop an artificial aortic arch stent-graft with newstructures. After passing the in vitro testing, the stent grafts were used in experimentalresearchs to test the feasibility and safety of clinical application in animal experiments. Wehope that the artificial aortic arch grafts could greatly simplify the surgical process, shortenthe operation time, reduce complications and improve patient survival, and moreeffectively relieve the pain of the patients with aortic arch diseases, while the quality of thesurgery must be guaranteed.Methods:1. Design and ex vivo test of the artificial aortic arch prosthesis 1) Basic structure of the artificial aortic arch prosthesis.The main part of the device consists of a stent-graft and a delivery system, thestent-graft consists of bare Nitinol stent, ePTFE membrane and the polyester suture portion.The ePTFE membrane covers on the two sides of the metal skeleton and the polyestersuture portion located in the proximal end of the stent-grafts. The stent-grafts enabledself-expansion. The overall structure of the stent is designed to be consistent with aorticarch morphology structure, including a main body, and1to3branches. The main bodycorresponds to the aortic arch, the branches correspond to the left subclavian artery, leftcommon carotid artery and brachiocephalic trunk, respectively. The delivery systemconsists of the handle member, the fixed rod and the sheath core member, the mainenvelope and the wire member, Tip and the sheath core member, branch envelope and thebranch pull member and guidewire. Fixed rod and handle are fixed together, the core of thesheath passes through from the handle middle. The pull member and fixed blocks areconnected together, and the pull member could be deprived through a fixed block. Theguide wire passes through the middle of Tip and sheath core. The main body of stent-graftis fixed with the fixed rod and covered with the main envelope, and the branches areloaded into the branch envelopes.2) Ex vivo test of the artificial aortic arch prosthesisA. The appearance and size testing of the artificial aortic arch stent-graft: thestent-grafts and delivery system are check through visual and electronic microscope (2.5times zoom): check if the bracket is broken, dust, dirt, loose; if the graft surface is smoothand clean, if there are holes, cracks and scratches. Check if the outer surface of the deliverysystem is clean and smooth, no creases, no hard bends, no stains, no cracks, no glitches, noprocessing defects. The size of the artificial aortic arch prosthesis is detect by verniercaliper and ruler.B. Physical performance testing of artificial aortic arch graft: a) The detection ofphysical mechanics including the strength of the stent-graft connection, the connectionstrength between the tectorial membrane and the metal stent, the stent radial force and thelamination rupturing force was tested by the tensile machine and the mold; b) Injecting intothe stent lumen with room temperature distilled water via pressure pump, to test thepermeation amount of the stent graft; c) The vessel model whose diameter is10-20%smaller than the stent is on the water bath, releasing the stent into the vessel model with the delivery system, checking the flexibility and adherent of the stent-graft underdirect vision; d) Release the stent-graft into water bath under the conditions of30-37℃bythe delivery system to check the outer surface of the stent, for testing the reboundresilience; e) The silicone tube fixed with the stent-graft is installed into fatigue machine,opening test switch, to test fatigue strength in accordance with a good tune frequency,amplitude, and zero points; f) The stent-graft is placed directly on the X-ray imagingapparatus, for rays detect testing.C. Chemical properties testing of the artificial aortic arch graft: the sterilizedstent-graft and stent system were sampled to product testing liquids separately, check thereducing substances, pH, fat residue, the total content of heavy metals, ultravioletabsorbance, ethylene oxide residues.D. Physical performance testing of delivery system: a) The fixed rod and the handleare respectively fixed to the upper and lower jig in the tensile machine, setting the tensilemachine to be stretched under a certain speed, testing connecting force between the fixedrod and the handle. b) The connecting force between the sheath core and the fixed rod, thecore of the sheath and the Tip head as well as the cable and fixed block were tested in thesame way; c) Cable and fixed block are fixed to the upper and lower jig in the tensilemachine respectively, testing connecting force between; d) The sample was pre-degreasingcleaned, and then was immersed into20℃±5℃0.5mol/L sodium chloride solution,keeping168h. Signs of corrosion of the specimen surface were enlarged and observed witha microscope (10times), to test the corrosion resistance of the metal transported system.E. Microstructure testing of the delivery system: a sample after carefully polished, nocorroded was performed to observe the morphology and quantity of inclusions, quantitativeanalysis of the percentage of the area of the inclusions was performing using professionalmetallographic analysis software Image Plus Pro6.0; a sample after polished andcorroded(4%nitric acid), on the mirror phase under the microscope to observe themicrostructure, and quantitative statistics crystallite size.2.Animal Experiments of the artificial aortic arch prosthesis1)20adult German sheepdogs were used as surgical objects in our experiments.Incising distal ascending aorta under deep hypothermic circulatory arrest, introducing theguide wires of the stent system, advancing the main body and the branches carefully intothe proximal descending aorta, left subclavian artery, and brachiocephalic artery along individual guide wires, deploying the stent-graft when the main body and branches of thisstent graft system were satisfactorily positioned, suturing the suturing portion to thetransected distal stump of the ascending aorta, and proximal ascending aorta in end-to-endanastomosis fashion. Clinical observation of peroperative period and the short and mediumterm (6months) was performed. We observed operation time, circulatory arrest time,operative bleeding, postoperative drainage, postoperative mortality, complications rate andso on.2) CTA and DSA were performed on the animals6months after the surgery.3)Animals were sacrificed after imaging test and the specimen were removed.Hematoxylin-eosin (HE) staining and Victoria Blue (VB) were performed to observe theorganizational structure of the body.Results:1. Appearance and size of the stent graft system is qualified. The connection strength of allthe stents were much larger than5N; stent radial force was greater than4N; the connectionstrength between the ePTFE tectorial membrane and the metal stent is much greater than15N; permeation amount of the tectorial membrane coating penetration volume is far lessthan100ml/cm2/min; membrane rupture force is much greater than10N. All stent-graftswere described with good flexibility, without kinking phenomenon, no bending, with goodadherence, good rebound resilience, being able to restore the original shape; the connectionbetween all stents and tectorial membrane was intact after fatigue test, tectorial membranewith no holes or cracks, the suture without shedding, wire without fracture, wireconnection point with no loose; observation of X-ray images confirmed good stentdetectability. All tests were confirmed stent physical properties to meet product designrequirements. Sample test solution of the stent-graft and the delivery system showedreducing substances <2ml, pH <1.5, fat residue <2mg, total content of heavy metals<1μg/ml, ultraviolet absorbance <0.1, and unmeasured ethylene oxide residues. All testswere confirmed chemical properties of the stent to meet product design requirements. Theconnection force between the fixed rod and the handle, the core of the sheath and the fixedrod, the core of the sheath and the Tip head was much larger than15N; there was nocorrosion on the surface of all the metal part, as a class. All tests were confirmed physicalconnection force properties of the delivery system to meet product design requirements.The crystallite size of the NiTi wire and the steel sleeve is not thicker than4; inclusions particles in NiTi wire and steel sets in all samples does not exceed39μm; area percentagedoes not exceed2.8%, to meet the requirements.2. Two cases died in experiemental group (mortality of10%), the mean cardiopulmonarybypass time, circulatory arrest time were80.2±7.54and10.7±1.94min, respectively.The surviving animals recovered well with no significant complications.Aortic imaging including CTA and DSA6months after surgery indicated that the mainbody and branches of the stent grafts were of normal morphology, no thrombus and narrow,no stent displacement, no internal leakage was observed. The luminal surface of theendoprosthesis had a thin but full coverage layer of uniform white neointima, without anyloosely attached mural thrombus. Histologic sections with H&E stain displayed a normalarrangement of the media and adventitia and exuberant circumferential intimalproliferation with or without neo-microvessels, compared with the control sections.Histologic sections with VB stain showed a normal distribution pattern and density of theelastic fibers and collagen bundles in the medial and adventitial layer, and the integrity ofinternal elastic lamina in the experiment group was moderately destoried by the extrusionof proliferated intima.Conclusions:1. The new type of artificial aortic arch stent-grafts we designed have qualified appearanceand size. And physical properties, chemical properties, and microscopic examination of thegrafts as well as their delivery system complied with requirements.2. The animal experiments show that the new artificial aortic arch grafts meet the basicrequirements of artificial vascular substitutes. It is safe and reliable and has real clinicalvalue.3. Compared with traditional open surgery and endovascular exclusion technology, thestudy shows that our new artificial aortic arch stent-grafts combining hybrid surgicaltechnique simplifies the surgical procedure, reduces the surgical time and surgical trauma,and brings down surgical mortality and incidence of postoperative complications.4. This experiment is only a small sample of the animal experiment, the clinical effects ofthe products requires a large sample, long-term follow-up and clinical trials to confirm.