Effects of dopexamine on the intestinal microvascular blood flow and leucocyte activation in a sepsis model in rats (original) (raw)
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Critical care (London, England), 2006
The administration of dopexamine may constitute a therapeutical option to improve hepatosplanchnic perfusion in sepsis. In order to verify this hypothesis, we administered dopexamine in an experimental sepsis model in rats. This prospective, randomized, controlled laboratory study was conducted in 42 Wistar rats. The animals were divided into 3 groups. Group 1 (CON group) served as control group. The Animals of groups 2 (LPS Group) and 3 received an endotoxin infusion (20 mg/kgfor 15 min). In addition, in group 3 (DPX group) dopexamine was administered 0.5 microg/kg/minover 4 hours. One half of the animals of each group underwent studies of intestinal microvascular blood flow (IMBF) using laser Doppler fluxmetry. In the other half an intravital microscopic evaluation of the leukocyte endothelium cell interaction in the intestinal microcirculation was performed. Functional capillary denstity (FCD) in the intestinal mucosaand the circular as well as the longitudinal muscle layer was e...
Dopexamine reverses colonic but not gastric mucosal perfusion defects in lethal endotoxin shock
British Journal of Anaesthesia, 2003
Background. Whilst dopexamine appears to increase overall splanchnic blood¯ow in postoperative and septic patients, the effects on gastric mucosal perfusion are controversial and based on concomitantly increasing mucosal to arterial PCO 2 gradients (PdCO 2 ). We hypothesized that dopexamine alters splanchnic blood¯ow distribution and metabolism during experimental endotoxin shock and modi®es the in¯ammatory response induced by endotoxin.
Critical Care, 2013
Introduction: The effects of dopexamine, a β2-agonist, on perioperative and sepsis-related hemodynamic, microvascular, immune, and organ dysfunction are controversial and poorly understood. We investigated these effects in a rodent model of laparotomy and endotoxemia. Methods: In two experiments, 80 male Wistar rats underwent laparotomy. In 64 rats, this was followed by administration of endotoxin; the remainder (16) underwent sham endotoxemia. Endotoxemic animals received either dopexamine at 0.5, 1, or 2 μg/kg/min or 0.9% saline vehicle (controls) as resuscitation fluid. The effects of dopexamine on global hemodynamics, mesenteric regional microvascular flow, renal and hepatic function and immune activation were evaluated.
Anesthesiology, 2004
Background Insufficient blood flow to the splanchnic organs is believed to be an important contributory factor for the development of organ failure after septic shock. It has been suggested that increasing systemic flow also may improve splanchnic blood flow in septic patients. The aim of this study was to compare the effects of three commonly used inotropic agents, dopamine, dobutamine, and dopexamine, on systemic (cardiac index), regional (superior mesenteric artery), and local (micro-circulatory) blood flow during septic shock in pigs. Methods Eight pigs were intravenously anesthetized, mechanically ventilated, and exposed to sepsis induced by fecal peritonitis. Cardiac index was measured with thermodilution, superior mesenteric artery flow was measured with ultrasound transit time flowmetry, and microcirculatory blood flow was continuously measured with a six-channel laser Doppler flowmetry in the gastric, jejunal, and colon mucosa as well as in the kidney, pancreas, and jejunal...
Shock, 2013
Dobutamine is recommended for the treatment of sepsis-related circulatory failure in international guidelines. Furthermore, dobutamine has been demonstrated to improve liver function and hepatic perfusion after experimental hemorrhagic shock. Yet, it is unknown whether dobutamine may also induce hepatoprotective effects in sepsis. This study was designed to investigate the effect of dobutamine on survival, hepatic function, and microcirculation after polymicrobial sepsis in rat. Under general anesthesia, male Sprague-Dawley rats (n = 25/group) underwent pretreatment with dobutamine (10 2g/kg per minute) in the presence or absence of "1-receptor antagonist esmolol (500 2g/kg per minute), esmolol alone, or vehicle for 6 h, before induction of sepsis (cecal ligation and incision [CLI]). Sham-operated animals were treated likewise but underwent no CLI. Five hours after CLI, either liver function was assessed by plasma disappearance rate of indocyanine green (n = 5/group), or intravital microscopy was performed (n = 5/group) for evaluation of hepatic perfusion index and hepatic integrity (as propidium iodideYstained cells per field). Alternatively, survival time after induction of CLI was monitored under general anesthesia (n = 15/group). Compared with controls, dobutamine pretreatment significantly improved plasma disappearance rate of indocyanine green (13.8% T 4.1% vs. 20.6% T 4.6%; P = 0.029), hepatic perfusion index (275.0 T 126.1 vs. 703.5 T 177.4 pL/s per mm; P G 0.001), hepatocellular injury (22.2 T 6.7 vs. 6.4 T 3.1 cells per field; P G 0.001), and survival time (326 T 20 vs. 603 T 41 min; P G 0.001). Coadministration of esmolol abolished the protective effect of dobutamine completely. Our results indicate that pretreatment with dobutamine may improve survival, liver function, and hepatic microcirculation after polymicrobial sepsis in rat via "1-adrenoceptor activation. Dobutamine could therefore play a relevant role for hepatoprotection under septic conditions.
Intensive Care Medicine, 2007
Objective: To test the hypothesis that levosimendan increases systemic and intestinal oxygen delivery (DO 2) and prevents intramucosal acidosis in septic shock. Design: Prospective, controlled experimental study. Setting: University-based research laboratory. Subjects: Nineteen anesthetized, mechanically ventilated sheep. Interventions: Endotoxin-treated sheep were randomly assigned to three groups: control (n = 7), dobutamine (10 µg/kg/min, n = 6) and levosimendan (100 µg/kg over 10 min followed by 100 µg/kg/h, n = 6) and treated for 120 min. Measurements and main results: After endotoxin administration, systemic and intestinal DO 2 decreased (24.6 ± 5.2 vs 15.3 ± 3.4 ml/kg/min and 105.0 ± 28.1 vs 55.8 ± 25.9 ml/kg/min, respectively; p < 0.05 for both). Arterial lactate and the intramucosal-arterial PCO 2 difference (∆PCO 2) increased (1.4 ± 0.3 vs 3.1 ± 1.5 mmHg and 9 ± 6 vs 23 ± 6 mmHg mmol/l, respectively; p < 0.05). Systemic DO 2 was preserved in the dobutamine-treated group (22.3 ± 4.7 vs 26.8 ± 7.0 ml/min/kg, p = NS) but intestinal DO 2 decreased (98.9 ± 0.2 vs 68.0 ± 22.9 ml/min/kg, p < 0.05) and ∆PCO 2 increased (12 ± 5 vs 25 ± 11 mmHg, p < 0.05). The administration of levosimendan prevented declines in systemic and intestinal DO 2 (25.1 ± 3.0 vs 24.0 ± 6.3 ml/min/kg and 111.1 ± 18.0 vs 98.2 ± 23.1 ml/min/kg, p = NS for both) or increases in ∆PCO 2 (7 ± 7 vs 10 ± 8, p = NS). Arterial lactate increased in both the dobutamine and levosimendan groups (1.6 ± 0.3 vs 2.5 ± 0.7 and 1.4 ± 0.4 vs. 2.9 ± 1.1 mmol/l, p = NS between groups). Conclusions: Compared with dobutamine, levosimendan increased intestinal blood flow and diminished intramucosal acidosis in this experimental model of sepsis.
Annals of Surgery, 1998
Objective To determine the early effects of therapy of endotoxin (ET) shock with epinephrne, norepinephrine, or dopexamine on splanchnic circulation, oxygen metabolism, sigmoid mucosal pHi, bacterial translocation, and morphologic integrity of the ileal, colonic, and sigmoid mucosa. Summary Background Data Conflicting concepts exist conceming the catecholamine therapy of septic shock, but little is known about the effects of catecholamine treatment on splanchnic circulation and mucosal integrity. Methods ET shock was induced in pigs by ET infusion over 30 minutes, and animals were studied for 4 hours. All animals were resuscitated with fluid. To mimic the treatment of septic shock in humans, mean arterial pressure was maintained in two groups at >70 mm Hg with the administration of epinephrine or norepinephrine. A third group of animals received dopexamine at 7 ,ug/kg per minute. Systemic and splanchnic blood flow and oxygen metabolism were studied, sigmoid colon mucosal pHi was obtained tonometrically, and bacterial translocation was determined by culture of portal venous blood, mesenteric lymph nodes, liver, spleen, and lung specimens. Histologic sections of ileal, colonic, and sigmoid mucosa were morphometrically examined for therapy effects.
Nutrition (Burbank, Los Angeles County, Calif.), 2012
Intestine Leukocyte adhesion a b s t r a c t Objective: The administration of glutamine (Gln), which is depleted in critical illness, is associated with an improvement of gut metabolism, structure, and function. The aim of the present study was to evaluate the effects of intravenous Gln and its galenic formulation, L-alanyl-L-glutamine dipeptide (AlaGln), on the intestinal microcirculation during experimental endotoxemia using intravital fluorescence microscopy. Gln or AlaGln administration was performed as pretreatment or post-treatment, respectively. To identify further the underlying mechanisms, amino acid levels were studied. Methods: Sixty male Lewis rats were randomly divided into six groups (n ¼ 10/group): control, LPS (lipopolysaccharide 5 mg/kg intravenously), Gln/LPS (LPS animals pretreated with Gln 0.75 g/kg Gln intravenously), AlaGln/LPS (LPS animals pretreated with AlaGln intravenously, 0.75 g/kg Gln content), LPS/Gln (LPS animals post-treated with Gln 0.75 g/kg intravenously), and LPS/AlaGln (LPS animals post-treated with AlaGln intravenously, 0.75 g/kg Gln content). Two hours after the endotoxin challenge, the microcirculation of the terminal ileum was studied using intravital fluorescence microscopy. Blood samples were drawn at the beginning, during, and the end of the experiment to determine the amino acid levels. Results: The Gln and AlaGln pre-and post-treatment, respectively, prevented the LPS-induced decrease in the functional capillary density of the intestinal muscular and mucosal layers (P < 0.05). The number of adherent leukocytes in the submucosal venules was significantly attenuated after the Gln and AlaGln pre-and post-treatment (P < 0.05). Conclusion: The Gln and AlaGln administrations improved the intestinal microcirculation by increasing the functional capillary density of the intestinal wall and decreasing the submucosal leukocyte activation.