A model of bridging angiogenesis in the rat

Theile, David E.; Kane, Anthony J.; Romeo, Rosalind; Mitchell, Geraldine M.; Crowe, Daniel; Stewart, Alastair G.; Morrison, Wayne A.

doi:10.1016/s0007-1226(98)80016-7

Cited by 15 publications

(16 citation statements)

References 23 publications

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“…Therefore, we used the iNOS KO mouse (MacMicking et al, 1995) to provide a more de®nite examination of the role of iNOS in functional angiogenesis. The time course of¯ap survival in wild-type mice (Figure 2) was similar to that observed in rats (Theile et al, 1998). In iNOS KO mice,¯ap survival remained below 30% for 21 days and was signi®cantly less than that in wildtype controls, which showed a progressive increase in survival to approximately 85% by 21 days.…”

Section: Effect Of Targeted Inos Gene Disruption On Angiogenesis-depesupporting

confidence: 69%

“…In an in vivo model which incorporates a pathophysiological type of angiogenesis in the adult (Theile et al, 1998), we have provided pharmacological and genetic evidence that iNOS activity enhances skin¯ap survival, and by direct inference, angiogenesis. Three lines of evidence implicated iNOS as proangiogenic.…”

Section: Discussionmentioning

confidence: 99%

“…In saline-treated rats in which 7 days was allowed for bridging angiogenesis, there was a signi®cant¯ap survival of 39+7% (n=17, P50.05 compared with 0% survival when no time was allowed for angiogenesis) (Theile et al, 1998). Treatment with the NOS inhibitors had a distinct eect depending on the inhibitor selectivity (Figure 1).…”

Section: Effect Of Nos Inhibitors On Rat Angiogenic Pediclesmentioning

confidence: 96%

“…The surgical technique for the creation of the model of angiogenesis has been characterized and described in detail (Theile et al, 1998). Brie¯y, in the ®rst operation adult male Sprague-Dawley rats (200 ± 250 g) were anaesthetized by intra-peritoneal injection of sodium pentobarbitone (30 ± 45 mg kg 71 ), the right and left inferior epigastric vascular pedicles were isolated and the artery and nerve cauterized to create a gap of 7 mm between the ends of the artery.…”

Section: Surgical Procedures and Drug Treatment In Ratsmentioning

confidence: 99%

“…A new model of angiogenesis has been developed to avoid confounding in¯uences, such as developmental angiogenesis in foetal tissue or vessel growth into a normally avascular area, that are associated with other models of angiogenesis (Theile et al, 1998). In this new model, the developing vessels are required to provide blood¯ow to a skin/muscle¯ap, mimicking the clinical process of angiogenesis in reconstructive surgery.…”

Section: Introductionmentioning

confidence: 99%

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Inducible nitric oxide synthase (iNOS) activity promotes ischaemic skin flap survival

Kane

Barker

Mitchell

et al. 2001

British J Pharmacology

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1 We have examined the role of nitric oxide (NO) in a model of functional angiogenesis in which survival of a skin¯ap depends entirely on angiogenesis to provide an arterial blood supply to maintain tissue viability. 2 The dierent eects of nitric oxide synthase (NOS) inhibitors on rat skin¯ap survival appeared to be explained on the basis of their NOS isoform selectivity. Skin¯ap survival was decreased by iNOS-selective (inducible NOS) inhibitors, S-methyl-isothiourea, aminoguanidine and aminoethylthiorea; unaected by the non-selective inhibitor nitro-imino-L-ornithine; and enhanced by the cNOS (constitutive NOS, that is endothelial NOS (eNOS) and neuronal NOS (nNOS)) inhibitor, nitro-L-arginine methyl ester. 3 Skin¯ap survival was reduced in mice with targeted disruption of the iNOS gene (iNOS knockout mice), and the administration of nitro-L-arginine methyl ester signi®cantly increased¯ap survival in iNOS knockout mice (P50.05). 4 iNOS immunoreactivity was identi®ed in mast cells in the angiogenic region. Immunoreactive vascular endothelial growth factor (VEGF) and basic ®broblast growth factor were also localized to mast cells. 5 The combination of interferon-g and tumour necrosis factor-a induced NO production and increased VEGF levels in mast cells cultured from bone marrow of wild-type, but not iNOS KO mice. 6 The increased tissue survival associated with the capacity for iNOS expression may be related to iNOS-dependent enhancement of VEGF levels and an ensuing angiogenic response. Our results provide both pharmacological and genetic evidence that iNOS activity promotes survival of ischaemic tissue.

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Section: Effect Of Targeted Inos Gene Disruption On Angiogenesis-depesupporting

confidence: 69%

Section: Discussionmentioning

confidence: 99%

Section: Effect Of Nos Inhibitors On Rat Angiogenic Pediclesmentioning

confidence: 96%

Section: Surgical Procedures and Drug Treatment In Ratsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations