Effects of dopexamine on the intestinal microvascular blood flow and leucocyte activation in a sepsis model in rats

Birnbaum, Jürgen; Klotz, Edda; Spies, Claudia; Lorenz, B; Stuebs, Patrick; Hein, Ortrud Vargas; Gründling, Matthias; Pavlović, Dragan; Usichenko, Taras; Wendt, Michael; Kox, Wolfgang J.; Lehmann, Christian

doi:10.1186/cc5011

Cited by 24 publications

(19 citation statements)

References 35 publications

(26 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As a consequence, leukocyte-endothelial adhesion and transmigration into tissues is decreased, with a reduction in organ injury. This suggestion is consistent with the findings of previous studies indicating that catecholamines can inhibit cytokine release [16,22]. Although not intrinsically chemotactic, TNF-α and IL-1β upregulate endothelial and leukocyte expression of adhesion molecules [23,24], and hence promote leukocyte-endothelial adhesion and migration into tissues.…”

Section: Discussionsupporting

confidence: 92%

“…It is also reassuring that many of the findings from the current experiments are consistent with those of previous work, such as the reduction in regional microvascular flux seen with LPS, as well as the amelioration of renal dysfunction and downregulation of CD11b integrins caused by dopexamine [16,25,29]. Many methods have been used to evaluate the microcirculation in vivo , each of which has limitations.…”

Section: Discussionsupporting

confidence: 88%

“…Although not intrinsically chemotactic, TNF-α and IL-1β upregulate endothelial and leukocyte expression of adhesion molecules [23,24], and hence promote leukocyte-endothelial adhesion and migration into tissues. Previous work also showed that adrenergic agents can decrease leukocyte expression of adhesion molecules [25], whereas in vivo microscopy suggests that dopexamine may decrease leukocyte-endothelial adhesion in the mesenteric circulation [16,17]. Dopexamine has been shown to decrease free radical-mediated tissue injury in other animal models [26,27], whereas the β2-agonist terbutaline reduced nitric oxide and superoxide levels in endotoxemic rats [28].…”

Section: Discussionmentioning

confidence: 99%

“…It has been suggested that anti-inflammatory actions may be beneficial [13,15]. Previous work indicated that dopexamine may decrease leukocyte-endothelial adhesion in mesenteric venules [16,17], a phenomenon dependent on CD11a and CD11b integrins [18]. Other adrenergic agents have also been shown to exert antiinflammatory actions on cytokine responses in immune cells [15,19,20].…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Dopexamine can attenuate the inflammatory response and protect against organ injury in the absence of significant effects on hemodynamics or regional microvascular flow

et al. 2013

View full text Add to dashboard Cite

IntroductionThe 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.MethodsIn 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.ResultsEndotoxin administration was associated with a systemic inflammatory response (increased plasma levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and IL-10, as well as cell-adhesion molecules CD11a and CD11b), and increased pulmonary myeloperoxidase (MPO) activity (indicating pulmonary leukocyte infiltration), whereas biochemical changes demonstrated lactic acidosis with significant renal and hepatic injury. Dopexamine administration was associated with less-severe lactic acidosis (pooled dopexamine versus controls, (lactate, 2.2 mM ± 0.2 mM versus 4.0 mM ± 0.5 mM; P < 0.001) and reductions in the systemic inflammatory response (pooled dopexamine versus control, 4 hour (TNF-α): 324 pg/ml ± 93 pg/ml versus 97 pg/ml ± 14 pg/ml, p < 0.01), pulmonary myeloperoxidase (MPO) activity, and hepatic and renal injury (pooled dopexamine versus control (ALT): 81 IU/L ± 4 IU/L versus 138 IU/L ± 25 IU/L; P < 0.05; (creatinine): 49.4 μM ± 3.9 μM versus 76.2 μM ± 9.8 μM; P < 0.005). However, in this study, clinically relevant doses of dopexamine were not associated with clinically significant changes in MAP, CI, or gut regional microvascular flow.ConclusionsIn this model, dopexamine can attenuate the systemic inflammatory response, reduce tissue leukocyte infiltration, and protect against organ injury at doses that do not alter global hemodynamics or regional microvascular flow. These findings suggest that immunomodulatory effects of catecholamines may be clinically significant when used in critically ill surgical patients and are independent of their hemodynamic actions.

show abstract

Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Dopexamine can attenuate the inflammatory response and protect against organ injury in the absence of significant effects on hemodynamics or regional microvascular flow

et al. 2013

View full text Add to dashboard Cite

show abstract

“…The required dopamine dosage during ES resuscitation was also higher than in HS resuscitation. Certain studies have shown that the use of dopamine may improve alveolar fluid re-absorption (27,28), intestinal microcirculation and renal β-2-microglobulin excretion (21), as well as reduce intestinal inflammation (29). The results of the current study indicate that the use of dopamine may alleviate lung and intestinal injury and aggravate renal injury.…”

Section: Discussionmentioning

confidence: 99%

Tidal volume in animal models of hemorrhagic and endotoxic shock

Liu

2013

Experimental and Therapeutic Medicine

View full text Add to dashboard Cite

The aim of this study was to examine the characteristics of lung, kidney and small intestine injury caused by early resuscitation from hemorrhagic shock (HS) and endotoxic shock (ES) when ventilating with different tidal volumes (Vts). The study also considered the determination of the appropriate Vt for use in mechanical ventilation (MV) during treatment for shock. Resuscitated rabbits were ventilated with varying Vts for 120 min following 60 min of HS or ES. The histopathology, ultrastructure and apoptotic index (AI) of the lung, kidney and small intestine were then measured. Organs from the high-Vt groups (VT=12–15 ml/kg) showed the highest pathological scores (PSs; P<0.05). For HS, the renal PS and AI of the HS-M group (Vt=8–10 ml/kg)were lower than those of the HS-L group (Vt=4–6 ml/kg) and the lung PS and AI of the HS-C (control) group were lower compared with those of the HS-M group. For ES, the lung PS of the ES-L group was lower compared with that of the ES-M group (Vt=8–10 ml/kg) and the lung AI of the ES-C (control) group was lower compared with that of the ES-L group (Vt=4–6 ml/kg). When ventilated with the same Vt, ES resulted in higher PSs in the lung and intestine and a lower renal PS (P<0.05) than HS. MV was not recommended for either shock type. When it was necessary for MV to be applied, low Vt (4–6 ml/kg) protected the lung in ES. Moderate Vt (8–10 ml/kg) may be relatively safe to use for HS.

show abstract

Dopamine and Renal Function and Blood Pressure Regulation

Armando

Villar

José

2011

Comprehensive Physiology

105

215

View full text Add to dashboard Cite

Dopamine is an important regulator of systemic blood pressure via multiple mechanisms. It affects fluid and electrolyte balance by its actions on renal hemodynamics and epithelial ion and water transport and by regulation of hormones and humoral agents. The kidney synthesizes dopamine from circulating or filtered L-DOPA independently from innervation. The major determinants of the renal tubular synthesis/release of dopamine are probably sodium intake and intracellular sodium. Dopamine exerts its actions via two families of cell surface receptors, D1-like receptors comprising D1R and D5R, and D2-like receptors comprising D2R, D3R, and D4R, and by interactions with other G protein-coupled receptors. D1-like receptors are linked to vasodilation, while the effect of D2-like receptors on the vasculature is variable and probably dependent upon the state of nerve activity. Dopamine secreted into the tubular lumen acts mainly via D1-like receptors in an autocrine/paracrine manner to regulate ion transport in the proximal and distal nephron. These effects are mediated mainly by tubular mechanisms and augmented by hemodynamic mechanisms. The natriuretic effect of D1-like receptors is caused by inhibition of ion transport in the apical and basolateral membranes. D2-like receptors participate in the inhibition of ion transport during conditions of euvolemia and moderate volume expansion. Dopamine also controls ion transport and blood pressure by regulating the production of reactive oxygen species and the inflammatory response. Essential hypertension is associated with abnormalities in dopamine production, receptor number, and/or posttranslational modification.

show abstract

Effects of dopexamine on the intestinal microvascular blood flow and leucocyte activation in a sepsis model in rats

Abstract: Introduction Dopexamine may be a therapeutic option to improve hepatosplanchnic perfusion in sepsis. To investigate this possibility, we administered dopexamine in an experimental sepsis model in rats.

Cited by 24 publications

References 35 publications

Dopexamine can attenuate the inflammatory response and protect against organ injury in the absence of significant effects on hemodynamics or regional microvascular flow

Dopexamine can attenuate the inflammatory response and protect against organ injury in the absence of significant effects on hemodynamics or regional microvascular flow

Tidal volume in animal models of hemorrhagic and endotoxic shock

Dopamine and Renal Function and Blood Pressure Regulation

Contact Info

Product

Resources

About