We have previously produced an experimental model of ischemic bowel necrosis in the rat by injecting platelet activating factor (PAF) (7 micrograms/kg) into the mesenteric vascular bed. The dose of PAF required to produce necrosis could be reduced to 50% if the animal was pretreated with bacterial endotoxin (lipopolysaccharide) (20 micrograms/rat). The mechanism of this potentiating effect of lipopolysaccharide is unclear, but activation of the complement system may be one of the contributing factors. To investigate the role of the complement system, we injected cobra venom factor (CVF) (1 unit/kg) to activate the complement system before injection of PAF (2 micrograms/kg) into the superior mesenteric artery. CVF and PAF were also injected separately at the same dosage to other groups of rats. CVF activated the complement system, but by itself did not produce gross necrosis of the bowel. PAF alone caused 3 out of 9 rats treated to develop bowel necrosis. In contrast, combination of the two produced bowel necrosis in all 6 rats thus treated. CVF did not enhance the effects of PAF on hemoconcentration and leukopenia, but aggravated the hypotension caused by PAF. PAF, on the other hand, also enhanced activation of the complement system by CVF. To investigate the specificity of PAF on complement activation, lyso-PAF was used in combination with CVF. It was found that lyso-PAF did not have a significant potentiating effect on CVF-induced complement activation and, by itself, it had no effect on complement activation, blood pressure, white blood cell count or hematocrit. Lyso-PAF, with or without CVF, also failed to produce bowel necrosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

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Genetic discoveries as the basis of personalized therapy: rosiglitazone treatment of Alzheimer's disease.

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Alzheimer Disease↗

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Role of asphyxia and feeding in a neonatal rat model of necrotizing enterocolitis.

Necrotizing enterocolitis (NEC) is a common gastrointestinal disorder affecting premature infants. To investigate critically the importance of the purported risk factors of NEC (formula feeding, asphyxia, bacteria, and prematurity), we developed a neonatal rat model that closely mimics the human disease. Full-term and premature newborn rats were stressed with formula feeding, asphyxia, and/or exogenous bacterial colonization and subsequently evaluated grossly and histologically for the development of intestinal injury. We found that most animals treated with asphyxia, formula feeding, and bacteria developed NEC (77%) and died (86%) by 96 h. All maternally fed animals treated with asphyxia and bacterial colonization survived and had normal intestinal histology. Furthermore, asphyxia was a critical instigating factor, because formula and bacterial exposure without asphyxia resulted in normal intestine and minimal mortality (12%). Enteral bacterial colonization was not a significant determinant of NEC in this model. We conclude that the neonatal rat model is an excellent test system for the study of NEC. As in the human disease, asphyxia and formula feeding play an important role in the pathophysiology of experimental NEC.

Animal Nutritional Physiological Phenomena↗