Search

Mechanical thrombectomy to treat large vessel occlusions (LVO) causing a stroke is one of the most effective treatments in medicine, with a number needed to treat to improve clinical outcomes as low as 2.6. As the name implies, it is a mechanical solution to a blocked artery and modeling these mechanics preclinically for device design, regulatory clearance and high-fidelity physician training made clinical applications possible. In vitro simulation of LVO is extensively used to characterize device performance in representative vascular anatomies with physiologically accurate hemodynamics. Embolus analogues, validated against clots extracted from patients, provide a realistic simulated use experience. In vitro experimentation produces quantitative results such as particle analysis of distal emboli generated during the procedure, as well as pressure and flow throughout the experiment. Animal modeling, used mostly for regulatory review, allows estimation of device safety. Other than one recent development, nearly all animal modeling does not incorporate the desired target organ, the brain, but rather is performed in the extracranial circulation. Computational modeling of the procedure remains at the earliest stages but represents an enormous opportunity to rapidly characterize and iterate new thrombectomy concepts as well as optimize procedure workflow. No preclinical model is a perfect surrogate; however, models available can answer important questions during device development and have to date been successful in delivering efficacious and safe devices producing excellent clinical outcomes. This review reflects on the developments of preclinical modeling of mechanical thrombectomy with particular focus on clinical translation, as well as articulate existing gaps requiring additional research.

Introduction La diversion de flux est une technique efficace pour le traitement des anevrismes intracrâniens, avec des taux d’occlusion eleves au long terme. Toutefois, certains anevrismes ne vont jamais cicatriser et d’autres vont s’occlure de facon retardee. De nombreuses donnees precliniques montrent que la bonne apposition a la paroi est un facteur fondamental a l’occlusion anevrismale. Nous avons compare les taux d’occlusion a moyen terme avec ou sans angioplastie apres la pose d’un stent a diversion de flux. Methodes Entre octobre 2011 et septembre 2016, tous les patients traites a l’aide d’un stent Pipeline pour un anevrisme de la circulation anterieure ont ete inclus. Les criteres d’exclusion etaient l’absence de suivi angiographique (6–24 mois) et l’utilisation concomitante d’un autre type de stent. La presentation clinique, les informations techniques et le suivi etaient conserves dans une banque de donnees prospective. Resultats Au total, 144 anevrismes ont ete inclus, avec un taux d’angioplastie de 52 %. Les caracteristiques demographiques, anevrismales et le suivi angiographique moyen (12 mois) n’etaient pas differents entre les deux groupes. Le taux d’occlusion complete etait plus eleve dans le groupe angioplastie (89 %) que dans le groupe controle (71 %), p = 0,006. L’angioplastie n’a pas entraine de complication hemorragique ni n’etait associe a une utilisation plus frequente d’inhibiteurs de la GPIIb/IIIa (p = 0,2). Lors du suivi il n’y a pas eu d’augmentation de score mRs dans le groupe angioplastie. Conclusion La bonne apposition a la paroi arterielle est un facteur important pour l’occlusion arterielle precoce apres traitement par stent a diversion de flux.

The investigation of two Bejaranoa species from South America yielded, in addition to known sesquiterpene lactones and some other widespread metabolites, six new furanoheliangolides and a new pyranoheliangolide.

The aerial parts of Olearia teretifolia afforded, in addition to two known diterpenes, 39 new ones, 20 ent -clerodanes and 19 ent -labdanes. Furthermore, a new enediynediene and coniferyl acetate were present. The structures were elucidated by high field NMR techniques. Chemotaxonomic aspects are discussed briefly.

The aerial parts of Chrysocephalum ambiguum afforded, in addition to two known diterpenes, 28 new ones, 22 ent-labdanes, four ent-manoyloxide derivatives and two monocyclic diterpenes derived from helipterol. The structures were elucidated by high field 1H NMR spectroscopy.

From 12 Ursinia species, in addition to known compounds, 31 new sesquiterpene lactones, 10 being germacranolides, 19 guaianolides, one eudesmanolide and a rearranged one, were isolated. Furthermore, seven sesquiterpene acids and methyl esters, including two fulvenes and a rearranged eudesmane, a nerolidol and seven farnesol derivatives, a furosesquiterpene derived from dehydrolasiospermane, three eudesmane and three eremophilane derivatives as well as a triynene were present. The structures were elucidated by high field NMR techniques. The chemistry supports the placement of the genus in the tribe Anthemideae, probably as a subtribe, together with related South African genera.

Investigation of 11 Aspilia species afforded several known kaurane derivatives and other diterpenes. From A. eenii a highly oxygenated germacrane bisepoxide was isolated. Comparison of the 1 H NMR data with those of several germacrane derivatives from Senecio and Ligularia species, spin decoupling and NOED led to corrections of the structures of several compounds.

The aerial parts of D. floribundum afforded, in addition to known compounds, 10 new clerodane derivatives while D. ericoides gave 2β-hydroxyhardwickiic acid and widespread compounds. The structures were elucidated by high field NMR spectroscopy. The chemotaxonomic aspects are discussed briefly.

From the aerial parts of Siegesbeckia orientalis , in addition to a known sesquiterpene lactone, nine new germacranolides, three melampolides, three geranylnerol derivatives and three ent -pimarenes were isolated. From Guizotia scabra a new eudesmanolide was obtained. The structures were elucidated by high field NMR techniques. The chemotaxonomic aspects are discussed briefly.

A reinvestigation of Aristeguetia buddleaefolia gave 16 new labdanes and two nor -labdanes, while A. glutinosa afforded, in addition to large amounts of 8,15-dihydroxylabdane, three new nor -labdanes. Badillao salicina gave six new cis -clerodanes and Grosvenoria rimbachii , guaianolides and tremetone derivatives, four of which were new. The structures were elucidated by high field NMR techniques and a few chemical transformations. The chemotaxonomy is discussed briefly.

The aerial parts of Brickellia californica afforded in addition to widespread compounds seven guaianolides, three of them not reported previously, and a germacranolide. From B. lemmonii 11 new ent -labdanes and three known ones were isolated. Structures were elucidated by high field NMR techniques.

The aerial parts of Cronquistia pringlei afforded, in addition to some known germacranolides and guaianolides, four new guainolides a lactone with a new carbon skeleton, i.e. a heliangolide with a cyclopropane ring. The structures were elucidated by high field NMR techniques. The chemotaxonomy is discussed briefly.

The aerial parts of Apalochlamys spectabilis gave in addition to known compounds seven costic acid derivatives, two guaianolides a nor -eudesmane derivative. From Cassinia longifolia a new isoalantolactone derivative was isolated while C. aculeata gave three atisirene derivatives, two of them not previously isolated. The structures were elucidated by high field NMR techniques some chemical transformations. Chemotaxonomic aspects are discussed briefly.

The aerial parts of Palafoxia arida gave in addition to a known ent -pimarene derivative 10 further ones, a manoyl oxide derivative and a new geranyl ester. From P. texana var. ambigua three known E -biformene derivatives were isolated. The structures were elucidated by high field NMR spectroscopy and the chemotaxonomy of the difficult genus Palafoxia is discussed briefly.

Five new furanoeremophilanes were isolated from three Gynoxys species. The structures of three 3α,6β-diacyloxyfuranoeremophilanes previously isolated from G. sancto-antonii have to be revised to the corresponding 1β,6β derivatives.

Tamaulipa azurea gave two new seco -labdanes. Bishopiella elegans gave a known nerolidol derivative and a guaianolide. Campuluclinium megacephalum gave a tremetone derivative while Asanthus solidaginifolius afforded, in addition to polyalthic acid, two known germacranolides and large amounts of a cyclopropanogermacranolide, so far only isolated in trace amounts from a Cronquistia species. Cronquistianthus trianae also afforded germacranolides.

Investigation of seven Australian Senecio species indicated that the constituents are similar as those from South Africa. The co-occurrence of a pyrrolizidine alkaloid (acetylsenecionin) and the corresponding acylpyrrol is reported for the first time.

The aerial parts of Flourensia macrophylla afforded, in addition to compounds similar to those from other Flourensia species, four new eudesman

The investigation of five representatives of Australian Gnaphaliinae species afforded in addition to several known compounds 17 new sesquiterpene lactones, 13 eudesmane derivatives derived from costic acid, ten further various sesquiterpenes and an unusual ester. The structures were elucidated by high field NMR techniques. The chemotaxonomic situation is discussed briefly.

The investigation of two further Senecio species and the re-investigation of S. inaequidens afforded, in addition to known compounds, seven new furanoeremophilane derivatives. Six of these are closely related to cacalol, a sesquiterpene type which predominates in the species investigated.

An investigation of the aerial parts of Chromolaena chasleae afforded a prostaglandin-like acid, whose structure followed from the 1H NMR spectral data and from the reaction with periodate, which afforded a hemiacetal. From a new Chromolaena species, three novel cadinene derivatives were isolated, which were closely related to those isolated previously from this genus.

The investigation of Dimerostemma asperatum afforded four new eudesmanolides, two unusual acetylenic esters and two diterpene lactones related to g

Re-investigation of Wunderlichia mirabilis afforded three new modified eudesmanolides of the same type isolated previously from an Onoseris species, and minute amounts of a germacranolide for which a structure only could be proposed. Actinoseris polymorpha also contained a new germacranolide, the angetate of desacetyllaurenobiolide. Structures were elucidated by spectroscopic methods and by some chemical transformations. The significance of these findings is discussed briefly.

The roots of C. rugosa afforded, in addition to known compounds, a C 17 -acetylenic epoxide and five new guaianolides, four of them being hydroperoxides. The structures were elucidated by extensive NMR studies. The aerial parts only contain triterpene mixtures, as those of C. hieronymi . The compounds isolated confirm that Cacosmia is unrelated chemically to true members of the tribe Senecioneae.

Investigation of six species, all belonging to the Vernonieae, afforded in addition to known compounds seven new guaianolides five of them related to eremanthine, one of the lactones which may be typical of the tribe. The structures were elucidated by spectroscopic methods. Chemotaxonomic aspects are discussed briefly.

The investigation of the aerial parts of Eupatorium altissimum from a collection in West Virginia gave three new guaianolides, six heliangolides and a costunolide all closely related to lactones isolated previously from the tribe Eupatorieae.

The investigation of eight Baccharis species afforded, in addition to known compounds, five new clerodanes, three labdane derivatives and a nor-diterpene as well as one hydroperoxide derived from 4α-hydroxygermacra-1(10), 5-diene. The structures were elucidated by spectroscopic methods. The structures of esters isolated previously from B. cassinaefolia have to be revised. Chemotaxonomic aspects are discussed briefly.

The investigation of seven Verbesina species afforded, in addition to known compounds, several new eudesmane and germacrane derivatives, all bearing a cinnamate or derivatives as residue. Furthermore, a new bisabolene aldehyde and two acetophenone derivatives were isolated. The structures were elucidated mainly by spectroscopic methods and some chemical transformations. The chemotaxonomic situation is discussed briefly.

The aerial parts of Blainvillea dichotoma afforded, in addition to known compounds, seven new sesquiterpene lactones, four related to elephantin, two melampolides and a further cis,cis-germacranolide. The chemotaxonomic situation is discussed briefly.

An investigation of Brickellia diffusa afforded three new dehydronerolidol derivatives and five new labdane derivatives, all highly oxygenated. The structures were elucidated by spectroscopic methods and a few chemical transformations. The compounds isolated showed close relationships to those isolated from Brickellia sp.

The investigation of Encelia canescens afforded, in addition to several known compounds, four new dimeric p -hydroxyacetophenone derivatives, two epimeric chromene dimers and two epimeric mixed dimers of euparin and encecalin. Furthermore, derivatives of tremetone and of encecalin were present. The structures were elucidated hy high field 1 H NMR spectroscopy.

An investigation of three Grazielia species afforded, in addition to known compounds, several new sesquiterpene lactones, eight germacranolides, two melampolides and one guaianolide as well as three diterpenes, two geranylgeraniol derivatives and a labda-diene. Three of the sesquiterpene lactones had an additional β-lactone ring, one an acid function, and two others unusual ester functions. The structures were elucidated by spectroscopic methods and some chemical transformations. The chemotaxonomic situation is discussed briefly.

The reinvestigation of the roots of Liabum eggersii afforded, in addition to compounds reported before, several sesquiterpene hydrocarbons with unusual carbon skeletons and the first derivative of the propellane modhephene which itself is also present. The roots of L. floribundum contain a tricyclic sesquiterpene with three five-membered rings. This ketone most probably is a derivative of the sesquiterpene silphiperfolene. The structures of the new compounds were elucidated by extensive NMR studies and by some chemical transformations. Two further species only afforded known compounds. The chemotaxonomic situation is discussed briefly.

The investigation of four South American species of the tribe Heliantheae afforded in addition to known compounds 14 new sesquiterpene lactones, mostly belonging to the melampolides, but four being further examples of cis , cis -germacranolides. The stereochemistry is established by intensive 1 H-NMR studies and some chemical transformations. Some of the new lactones were only obtainable as inseparable mixtures of 2-methylbutyric and isovaleric esters. Furthermore a new acetylenic aldehyde was isolated. The chemotaxonomic situation is discussed especially with regard to the position of the genus Smallanthus .

Resume Aus Praxelis clematidea wird ein Phenylalanin-Derivat isoliert, dessen Struktur durch spektroskopische Methoden geklart und durch Synthese sichergestellt wird.

The investigation of four further Mikania species afforded several diterpenes, four geranylgeraniol derivatives and three kaurane epoxides. The structures were elucidated by spectroscopic methods and a few chemical transformations.

The aerial parts of Trichogonia salviaefolia afforded a new ent -kaurenic acid derivative and a germacranolide which, most likely, is the precursor of the trichosalviolides. The aerial parts of Liatris spicata gave 1α-hydroxybacchotricuneatin A and a guaianolide, which may be the precursor of spicatin. From Brickellia vernicosa some further dehydronerolidol derivatives were isolated.

From the aerial parts of Chiliotrichium rosmarinifolium in addition to known compounds nine diterpenes were isolated, three isolabdanes, three seco-isolabdanes, a cis-clerodane, a rearranged dilactone and a geranyl geraniol derivative. The aerial parts of Nardophyllum lanatum gave two of the new diterpenes and three further diterpenes which are closely related to those of the Chiliotrichium species. Further-more two new geranyl geraniol derivatives were present. The structures were elucidated by highfield NMR spectroscopy.

A reinvestigation of Ageratum fastigiatum afforded, in addition to known compounds, several new farnesene derivatives including some tetrahydropyrane derivatives. Furthermore a sesquiterpene lactone derived from daucane and a minor derivative of the ent -labdanes isolated previously were isolated. The structures were elucidated by spectroscopic methods.

Investigation of seven Bolivian Baccharis species afforded in addition to known compounds 17 ent -clerodane, 10 ent -labdane, two bisabolene, a germacrane, a cadinane, a guaiane and a p -coumaric acid derivative. In one case the ent -labdane was linked with a bisabolene derivative via a malonate group. The structures were elucidated mainly by high field NMR techniques.

From the aerial parts of Wedelia hookeriana eight new eudesmanolides, all derivatives of ivangustin, and a new ent-kaurenic acid derivative togethe

The aerial parts of Gutierrezia lucida afforded three new diterpenic acids, all closely related to agathic acid and those of G. mandonii also three diterpenic acids, which again are labdane derivatives. The structures were elucidated by spectroscopic methods and some chemical transformations. The roots of these species and of a further one only contain triterpenes and no acetylenes. The chemotaxonomic situation is briefly discussed.

The investigation of six Zinnia species afforded in addition to already known compounds two eudesmanolides, five guaianolides, three germacranolides, five elemanolides and a dihydroxygeranylgeraniol. The structures were elucidated by spectroscopic methods and some chemical transformations. The chemotaxonomic situation is discussed briefly.

The investigation of Dimerostemma brasilianum afforded, in addition to known compounds, 18 new eudesmanolides and a new diterpene lactone derived f

Rugelia nudicaulis afforded, in addition to known compounds, three new highly oxygenated oplopanone derivatives and a bisabolone derivative. The structures were elucidated by high field 1 H NMR spectroscopy. The chemotaxonomic situation is discussed briefly.

The aerial parts of two Gaillardia species afforded in addition to known sesquiterpene lactones 23 new pseudoguaianolides, two dugaldiolide derivatives and two seco-neopulchellin derivatives. The structures were elucidated by spectroscopic methods. Biogenetic relationships are discussed briefly.

The investigation of Eremanthus crotonoides afforded in addition to known compounds three new furanoheliangolides, while from E. glomerulatus six new furanoheliangolides and eremantholides were isolated. From the aerial parts of Chresta sphaerocephala a new guaianolide was obtained, while the roots contained known furanoheliangolides. The chemotaxonomy of the subtribe Lychnophorinae is discussed briefly.

The investigation of Lasiolaena morii afforded in addition to known compounds four new guaianolides, three diterpenes derived from geranyl nerol in

The investigation of Vernonia compactiflora afforded in addition to known compounds a hirsutinolide and a glaucolide; the latter is most probably the direct precursor of the former. The aerial parts of V. monocephala contain the same hirsutinolide as well as the corresponding acetate, while those of V. chalybaea afforded glaucolide B. A reinvestigation of the aerial parts of V. cotoneaster gave in addition to the allenic lactone isolated before two further known ones as well as a new glaucolide. The structures of the lactones were elucidated by spectroscopic methods and some chemical transformations. The erroneously assigned stereochemistry at C-10 in the hirsutinolides has been revised. The biogenetic relationship of the Vernonia lactones is discussed briefly.