Effect of Acute Sublethal Endotoxaemia onIn VitroDigital Vascular Reactivity in Horses

Abstract

Endotoxaemia is a syndrome linked to the development of equine laminitis; however, the relationship between them is uncertain. The aim of this experiment was to evaluate the effect of an experimental acute sublethal endotoxaemia model on in vitro equine palmar digital vascular reactivity. Rings of arteries and veins of each forelimb were obtained from 11 clinically healthy horses submitted to two surgical procedures, 3 weeks apart. Before the second surgery, 0.25 microg/kg of lipopolysaccharide from Escherichia coli O55:B5 in saline, was administered i.v. in 30 min. After 3 h, the vessels were harvested and submitted to in vitro vascular reactivity experiments and histopathology. The response to depolarizing Krebs solution (DKS, 40 mm), phenylephrine (PHE), acetylcholine (ACh) and sodium nitroprusside (SNP) were evaluated. All horses showed colic pain and watery diarrhoea, tachycardia, tachypnea, hyperthermia and leucopenia. Concentration-response curve (CRC) to PHE was shifted to the left in arteries rings from endotoxemic horses without any effect on vein rings. The CRC to ACh was shifted to the right with a reduction in the maximal response. The response to SNP and DKS was similar between groups. There was no evidence of histopathological effects. The increased response to PHE in digital arteries together with a reduction of the endothelium-dependent response to ACh in arteries and veins, confirm the existing reports where endotoxaemia was found to modify the digital vascular reactivity during the acute phase. As the digital endothelial function is impaired, there may be an increased potential to develop a digital prothrombotic state with a reduced vasodilatory capacity.

A comparative study between responses of isolated bovine and equine digital arteries to vasoactive mediators

“…CARB proved more potent in the EDA than in the BDA, which is in line with the observation by other authors of high EDA sensitivity to cholinergic vasodilator agonists (Baxter, ; Baxter, Tackett et al., ; Cogswell et al., ; Schneider et al., ; Zerpa et al., ). This might involve a higher muscarinic receptor density and/or coupling efficiency in the EDA as compared to BDA.…”

Alterações morfológicas de tecido laminar do casco e parâmetros clínicos e laboratoriais de equinos com síndrome cólica letal

“…Esta alteração pode estar associada à ativação inflamatória sistêmica causada pela endotoxemia, com sequestro tecidual de leucócitos (Zerpa et al 2005, Campebell et al 2007). Fernandes et al (2003) associaram a leucopenia com a severidade do quadro endotoxêmico em cavalos com duodenojejunite.…”

“…Alguns trabalhos demonstram que existem técnicas mais precisas para demonstrar a presença do infiltrado inflamatório no tecido laminar , Loftus et al 2006, as quais não foram realizadas neste estudo. No entanto, a presença da leucopenia aqui observada sugere infiltração tecidual leucocitária (Zerpa et al 2005). Segundo Hurley et al (2006), a presença de leucócitos no interstício laminar é coincidente com a leucopenia na laminite induzida por extrato de nogueira preta.…”

“…Com o mesmo modelo, Galey et al (1991), constataram redução de leucócitos duas horas antes do aparecimento dos sinais clínicos da enfermidade podal. Desta forma, semelhante à falência orgânica observada na sepse humana, a injúria laminar pode ser causada pela liberação de numerosos mediadores inflamatórios pelos leucó-citos, como espécies reativas de oxigênio e metaloproteinases (Belknap & Black 2005, Zerpa et al 2005, Loftus et al 2006. Um achado importante que contribui para a ocorrência de lesões graves no tecido laminar de equinos é a ausência da enzima superóxido dismutase (SOD) nesse tecido, a qual promove proteção contra os efeitos deleté-rios das espécies reativas de oxigênio, agindo como antioxidante (Loftus et al 2007b).…”

“…A trombocitopenia relaciona-se com o aparecimento de tromboembolia e com a diátese hemorrágica presente na sepse (Dong et al 2005, Koury et al 2006, Campebell et al 2007), sendo identificada também em animais durante a indução de laminite (Moore et al 1981). A leucopenia, causada pela migração e ativação de leucócitos nos tecidos, pode levar a liberação de metaloproteinases que causam lesão tecidual (Zerpa et al 2005).…”