Oprettelse af to saccular elastase-fordøjede aneurismer med forskellig hæmodynamik i en kanin
Summary
Denne protokol beskriver trinene til oprettelse af en kaninmodel med to elastasefordøjede aneurismer med forskellig hæmodynamik (stub- og bifurcationskonstellation). Dette gør det muligt at teste nye endovaskulære enheder i aneurismer med forskellige angioarkitektur og hæmodynamiske tilstande inden for et enkelt dyr.
Abstract
Prækliniske dyremodeller med hæmodynamiske, morfologiske og histologiske egenskaber tæt på humane intrakranielle aneurismer spiller en central rolle i forståelsen af de patofysiologiske processer og udvikling og test af nye terapeutiske strategier. Denne undersøgelse har til formål at beskrive en ny kaninaneurismemodel, der gør det muligt at skabe to elastasefordøjede saccular aneurismer med forskellige hæmodynamiske tilstande inden for samme dyr.
Fem kvindelige newzealandske hvide kaniner med en gennemsnitsvægt på 4,0 (± 0,3) kg og gennemsnitsalder på 25 (±5) uger gennemgik mikrokirurgisk stub- og bifurcationaneurismedannelse. En aneurisme (stub) blev skabt ved højre fælles halspulsåre (CCA) eksponering ved dens oprindelse ved brachiocephalic trunk. Et midlertidigt klip blev påført ved CCA-oprindelsen og et andet, 2 cm over. Dette segment blev behandlet med en lokal injektion på 100 U elastase i 20 min. En anden aneurisme (bifurcation) blev skabt ved at suturere en elastasebehandlet arteriel pose i ende-til-side anastomose af højre CCA til venstre CCA. Patency blev kontrolleret af fluorescens angiografi umiddelbart efter oprettelsen.
Den gennemsnitlige varighed af operationen var 221 min. Oprettelsen af to aneurismer i samme dyr var vellykket hos alle kaniner uden komplikationer. Alle aneurismer blev patenteret umiddelbart efter operationen bortset fra en bifurcation-aneurisme, som viste en ekstrem vævsreaktion på grund af elastaseinkubation og en øjeblikkelig intraluminal trombose. Der blev ikke observeret dødelighed under operationen og op til en måneds opfølgning. Morbiditet var begrænset til et forbigående vestibulært syndrom (en kanin), som kom sig spontant inden for en dag.
Demonstreret her for første gang er muligheden for at skabe en to-aneurisme kaninmodel med stump og bifurcation hæmodynamiske egenskaber og stærkt degenererede vægforhold. Denne model gør det muligt at studere det naturlige forløb og potentielle behandlingsstrategier på grundlag af aneurismebiologi under forskellige strømningsforhold.
Introduction
Intrakraniel aneurisme er en alvorlig tilstand med en dødelighed efter brud, der når 50% og langvarig invaliditet hos 10-20% af patienterne1. Det sidste årti har set en hurtig udvikling af endovaskulære behandlingsmuligheder, men samtidig også en stigende gentagelsesrate med op til 33% af aneurisme recanalisering efter coiling 2,3. For bedre at forstå den patofysiologi, der ligger til grund for aneurismeokklusion og recanalisering samt til udvikling og test af nye endovaskulære enheder, er der i øjeblikket behov for pålidelige prækliniske modeller, hvis hæmodynamiske, morfologiske og histologiske egenskaber efterligner dem af humane intrakranielle aneurismer 4,5,6 . Fra i dag er der ingen defineret model som standard for prækliniske forsøg, og en lang række arter og teknikker er tilgængelige for forskere 7,8.
Kaninen er imidlertid en art af særlig interesse på grund af størrelsen og hæmodynamiske ligheder mellem dens halsarterier og de menneskelige cerebrale fartøjer samt dens lignende koagulations- og trombolyseprofiler. Flere modeller med elastasefordøjede saccular aneurismer på de fælles halspulsårer (CCA’er) har vist kvalitative og kvantitative ligheder med humane intrakranielle aneurismer med hensyn til strømningsbetingelser, geometriske træk og vægegenskaber 9,10,11,12. Denne undersøgelse har til formål at beskrive en teknik til at skabe en ny kaninaneurismemodel med både stub- og bifurcation elastasefordøjede aneurismer i samme dyr. De kirurgiske teknikker er inspireret af Hoh et al.13 og Wanderer et al.14 med små ændringer for at give en god standardisering og reproducerbarhed og for at sikre lav dødelighed og sygelighed.
Protocol
Representative Results
Discussion
Den mest almindelige teknik til oprettelse af aneurisme involverer oprettelsen af en stubaneurisme ved oprindelsen af den rigtige CCA, enten gennem en åben eller en endovaskulær metode. Modellen er blevet valideret til at være en stabil ikke-voksende aneurisme, der forbliver åben med tiden20,21. Den anden mulige teknik involverer mikrokirurgisk dannelse af en arteriel bifurcationaneurisme ved at anastomosere den højre CCA på venstre og suturere en aneurisme…
Declarações
The authors have nothing to disclose.
Acknowledgements
Forfatterne takker professor Hans Rudolf Widmer, dr. Luca Remonda og professor Javier Fandino for deres videnskabelige støtte og tekniske bidrag til dette arbejde. En særlig tak til Olgica Beslac for hendes råd under procedurerne og Kay Nettelbeck for hans hjælp. Desuden takker vi Daniela Casoni DVM, ph.d. og med. dyrlæge. Luisana Garcia, PD Dr. Alessandra Bergadano og Dr. Carlotta Detotto for deres dedikerede veterinære støtte.
Materials
| 4-0 resorbable suture | Ethicon Inc., USA | VCP292ZH | |
| 4-0 resorbable suture | Ethicon Inc., USA | VCP304H | |
| 6-0 non absorbable suture | B. Braun, Germany | C0766070 | |
| 9-0 non absorbable suture | B. Braun, Germany | G1111140 | |
| Adrenaline | Amino AG | 1445419 | any generic |
| Amiodarone | Helvepharm AG | 5078567 | any generic |
| Anesthesia machine | Dräger | any other | |
| Aspirin | Sanofi-Aventis (Suisse) SA | 622693 | any generic |
| Atropine | Labatec Pharma SA | 6577083 | any generic |
| Bandpass filter blue | Thorlabs | FD1B | any other |
| Bandpass filter green | Thorlabs | FGV9 | any other |
| Biemer vessel clip (2x) | B. Braun Medical AG, Aesculap, Switzerland | FD560R | any other |
| Bipolar forceps | any other | ||
| Bispectral index (neonatal) | any other | ||
| Blood pressure cuff (neonatal) | any other | ||
| Bycilces spotlight | any other | ||
| Clamoxyl | GlaxoSmithKline AG | 758808 | any generic |
| Dexmedetomidine | Ever Pharma | 136740-1 | any generic |
| Elastase | Sigma Aldrich | E7885 | |
| Electrocardiogram electrodes | |||
| Ephedrine | Amino AG | 1435734 | |
| Esmolol | OrPha Swiss GmbH | 3284044 | |
| Fentanyl (intravenous use) | Janssen-Cilag AG | 98683 | |
| Fentanyl (transdermal) | Mepha Pharma AG | 4008286 | |
| Fluoresceine | Curatis AG | 5030376 | |
| Fragmin | Pfizer PFE Switzerland GmbH | 1906725 | |
| Heating pad or heating forced-air warming system | |||
| Isotonic sodium chloride solution (0.9%) | Fresenius KABI | 336769 | |
| Ketamine | Pfizer PFE Switzerland GmbH | 342261 | |
| lid retractor | Approach | ||
| Lidocaine | Streuli Pharma AG | 747466 | |
| Longuettes | |||
| Metacam | Boehringer Ingelheim | P7626406 | Medication |
| Methadone | Streuli Pharma AG | 1084546 | Sedaton |
| Micro-forceps curved | Ulrich Swiss, Switzerland | U52-015-15 | |
| Micro-forceps straight 2x | Ulrich Swiss, Switzerland | U52-010-15 | |
| Microscissors | Ulrich Swiss , Switzerland | U52-327-15 | |
| Midazolam | Accord Healthcare AG | 7752484 | |
| Needle 23 G | arteriotomy | ||
| Needle holder | |||
| O2-Face mask | |||
| Operation microscope | Wild Heerbrugg | ||
| Papaverin | Bichsel | topical application | |
| Povidone iodine | Mundipharma Medical Company | any generic | |
| Prilocaine-lidocaine creme | Emla | ||
| Propofol | B. Braun Medical AG, Switzerland | General anesthesia | |
| Pulse oxymeter | |||
| Rectal temperature probe (neonatal) | |||
| Ringer Lactate | Bioren Sintetica SA | Infusion | |
| Ropivacain | Aspen Pharma Schweiz GmbH | 1882249 | Local anesthesia |
| Scalpell | Swann-Morton | 210 | |
| Small animal shaver | |||
| Soft tissue forceps | |||
| Soft tissue spreader | |||
| Stainless steel sponge bowls | |||
| Sterile micro swabs | |||
| Stethoscope | |||
| Surgery drape | |||
| Surgical scissors | |||
| Syringes 1 mL, 2 mL, and 5 mL | |||
| Tris-Buffer | Sigma Aldrich | 93302 | Elastase solution |
| Vascular clip applicator | B. Braun, Germany | FT495T | |
| Vein and arterial catheter 22 G | |||
| vessel loop | Approach | ||
| video camera or smartphone | |||
| Vitarubin | Streuli Pharma AG | 6847559 | |
| Yasargil titan standard clip (2x) | B. Braun Medical AG, Aesculap, Switzerland | FT242T |
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