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1.
Med Sci Monit ; 15(2): BR37-42, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19179959

RESUMO

BACKGROUND: Dobutamine is the agent of choice for increasing cardiac output during myocardial depression in humans with septic shock. Studies have shown that beta-adrenoceptor agonists influence nitric oxide generation, probably by modulating cyclic adenosine monophosphate. We investigated the effects of dobutamine on the systemic and luminal gut release of nitric oxide during endotoxic shock in rabbits. MATERIAL/METHODS: Twenty anesthetized and ventilated New Zealand rabbits received placebo or intravenous lipopolysaccharide with or without dobutamine (5 micro g/kg/min). Ultrasonic flow probes placed around the superior mesenteric artery and the abdominal aorta continuously estimated the flow. A segment from the ileum was isolated and perfused, and serum nitrate/nitrite levels were measured in the perfusate solution and the serum every hour. RESULTS: The mean arterial pressure decreased with statistical significance in the lipopolysaccharide group but not in the lipopolysaccharide/dobutamine group. The abdominal aortic flow decreased statistically significantly after lipopolysaccharide administration in both groups but recovered to baseline in the lipopolysaccharide/dobutamine group. The flow in the superior mesenteric artery was statistically significantly higher in the lipopolysaccharide/dobutamine group than in the lipopolysaccharide group at 2 hours. The serum nitrate/nitrite levels were higher in the lipopolysaccharide group and lower in the lipopolysaccharide/dobutamine group than those in the control group. The gut luminal perfusate serum nitrate/nitrite level was higher in the lipopolysaccharide group than in the lipopolysaccharide/dobutamine group. CONCLUSIONS: Dobutamine can decrease total and intestinal nitric oxide production in vivo. Those effects seem to be inversely proportional to the changes in blood flow.


Assuntos
Dobutamina/farmacologia , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Óxido Nítrico/biossíntese , Choque Séptico/metabolismo , Animais , Circulação Coronária/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Ácido Láctico/sangue , Lipopolissacarídeos/administração & dosagem , Lipopolissacarídeos/farmacologia , Nitratos/sangue , Nitritos/sangue , Perfusão , Coelhos , Choque Séptico/fisiopatologia
2.
J Appl Physiol (1985) ; 95(5): 2047-54, 2003 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-12923122

RESUMO

Whether the gut alterations seen during sepsis are caused by microcirculatory hypoxia or disturbances in cellular metabolic pathways associated with mitochondrial respiration remains controversial. We hypothesized that hypoperfusion or hypoxia and local production of nitric oxide might play an important role in the development of gut mucosal injury during endotoxic shock and investigated their roles by using differing levels of fluid resuscitation and occlusion of the superior mesenteric artery (SMA). Anesthetized New Zealand rabbits were allocated to group I (sham, n = 8); group II [low-dose endotoxin (LPS, Escherichia coli-055:B5, 150 microg/kg)/fluid resuscitation (12 ml x kg(-1) x h(-1)); n = 8]; group III [high-dose LPS (1 mg/kg)/fluid resuscitation (12 ml x kg(-1) x h(-1)); n = 8]; group IV [high-dose LPS (1 mg/kg)/hypovolemia (4 ml x kg-1 x h(-1) fluids); n = 8]; and group V [SMA ligation/fluid resuscitation (12 ml x kg(-1) x h(-1)); n = 4]. Luminal gut lactate concentrations and PCO2 gap increased in groups IV and V (P < 0.05), reflecting alterations in gut perfusion. Interestingly, significant histological alterations were observed in all LPS groups but not in group V. Blood and luminal gut nitrate/nitrite concentrations increased only in group IV. The mechanism of gut injury in endotoxic shock seems unrelated to hypoxia and release of nitric oxide. Gut dysfunction may occur as a result of so-called "cytopathic hypoxia."


Assuntos
Mucosa Intestinal/patologia , Isquemia/patologia , Choque Séptico/patologia , Animais , Pressão Sanguínea , Dióxido de Carbono/sangue , Íleo/irrigação sanguínea , Íleo/metabolismo , Íleo/patologia , Mucosa Intestinal/irrigação sanguínea , Mucosa Intestinal/metabolismo , Isquemia/metabolismo , Ácido Láctico/sangue , Lipopolissacarídeos/farmacologia , Nitratos/sangue , Óxido Nítrico/metabolismo , Nitritos/sangue , Coelhos , Fluxo Sanguíneo Regional , Sepse/metabolismo , Sepse/patologia , Choque Séptico/metabolismo , Organismos Livres de Patógenos Específicos
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