Disease relevance of FPL 60278

• In this multicenter, parallel design, placebo-controlled study, 45 patients with functional class III or IV chronic congestive heart failure were randomized to receive a placebo infusion or one of three different doses of dopexamine [1].
• During this 6-h period, dopexamine was infused at rates of 1, 2 and 4 micrograms/kg body weight per min in the low, intermediate and high dose groups, respectively [1].
• Abnormalities of gastric mucosal oxygenation in septic shock: partial responsiveness to dopexamine [2].
• Protecting the gut and the liver in the critically ill: effects of dopexamine [3].
• The main effect of dopexamine infusion in the sepsis group was the attenuation of the rhythmic blood flow patterns (flow motion) observed during saline infusion [4].

High impact information on FPL 60278

• To study vessel relaxation, segments were again preconstricted with phenylephrine 10(-5) mol/L and concentration-relaxation responses to dopamine, dobutamine, and dopexamine (10(-8) to 10(-4) mol/L) were obtained [5].
• Fluid and dopexamine administration resulted in a dose dependent improvement in flow, independent of blood pressure [6].
• Measurements (perfusion units (PU)) were documented prior to implantation, post-reperfusion, postoperatively, during graft ischaemia, and in response to therapeutic interventions (dopexamine and phenylephrine infusions) [6].
• In patients receiving high dose infusion, dopexamine produced a 78% increase in cardiac index associated with a 43% decrease in systemic vascular resistance and 24% increase in heart rate (p less than 0.05 vs. placebo for all three variables) [1].
• Efficacy and safety of a short-term (6-h) intravenous infusion of dopexamine in patients with severe congestive heart failure: a randomized, double-blind, parallel, placebo-controlled multicenter study [1].

Chemical compound and disease context of FPL 60278

• In patients with septic shock and ongoing noradrenaline treatment dopexamine seems to have no preferential effects on hepatosplanchnic hemodynamics, O(2) exchange, or energy balance [7].
• CONCLUSIONS: In our model of endotoxemia, dobutamine and dopexamine preserved systemic and hepatic blood flow [8].
• Unlike dopamine and salbutamol, dopexamine does not cause arrhythmias in the guinea-pig isolated perfused heart at doses of up to 10(-5) mol, which is a thousand times the minimum cardiostimulant dose [9].
• INTERVENTIONS: Rats given endotoxin (Escherichia coli lipopolysaccharide [LPS]; 1.5 mg/kg i.v. over 60 mins) were treated with a continuous infusion of dopexamine (DPX; 2.5 microg/kg/min, n = 7, group LPS + DPX) or 0.9% saline (n = 7, group LPS) during a study period of 120 mins [10].
• CONCLUSIONS: Dopexamine protects against cerebral edema formation in sepsis by stimulation of beta2-adrenergic receptors, whereas the alpha1 adrenoceptor agonist methoxamine induces cerebral microvessel endothelial cell swelling [11].

Biological context of FPL 60278

• In patients randomized to receive dopexamine, right atrial, systemic arterial, pulmonary artery and pulmonary capillary wedge pressures showed minimal change from baseline and did not differ statistically from the placebo response [1].
• Then dopexamine infusion was titrated (1-4 microg x kg(-1) x min(-1)) to increase cardiac output by approximately 25% (20-30%) [7].
• The study demonstrates the mechanism of action of dopexamine on cardiac function and peripheral perfusion during cardiac surgery and shows that the inodilator properties during cardiac surgery are useful haemodynamically and facilitate early reversal of tissue hypoperfusion and oxygen debt in this environment [12].
• The study demonstrated that dopexamine significantly increased cardiac index compared with the control group (P < 0.05) and that this effect was mediated through an increase in both left ventricular stroke volume index and heart rate (P < 0.05) [12].
• Dopexamine increased mean arterial pressure, heart rate, and hindlimb blood flow during anaesthesia in controls, but not in CHF [13].

Anatomical context of FPL 60278

• The haemodynamic effect of prophylactic peri-operative dopexamine in coronary artery bypass patients [12].
• The pharmacological profile and anatomical localization of dopexamine binding were investigated in sections of right and left ventricle using [3H]-dopexamine and ligand techniques associated with light microscope autoradiography [14].
• Dopexamine increased mucosal tissue PO2 by 89% (20-microg dose, p < .01) and mucosal hemoglobin oxygen saturation by 26% (2.5-microg dose, p < .05) and 35% (5-, 10-, and 20-microg dose, p < .05) [15].
• The purpose of this study was to assess the effect of the synthetic catecholamine, dopexamine, on the mucosal microcirculation of the septic rat ileum [4].
• Dopexamine attenuated both the increase in leukocyte adherence and vascular permeability during endotoxemia [16].

Associations of FPL 60278 with other chemical compounds

• In contrast, both felodipine as well as dopexamine prevented any increases in PLP, normalized blood gas profile, and significantly increased survival rate to 80 to 90% [17].
• CONCLUSIONS: Both enalaprilat and dopexamine increased renal blood flow in the control and CHF groups [13].
• Baseline measurements were made and cardiac output was increased by > 25% by administering either dobutamine (10 micrograms/min), dopexamine (10 micrograms/kg/min), or colloid [18].
• OBJECTIVE: To compare the effects of dopamine and dopexamine on gastric mucosal oxygenation during mechanical ventilation without and with positive end-expiratory airway pressure (PEEP) and after compensation of the PEEP-induced hemodynamic suppression [19].
• CONCLUSION: It was not possible to differentiate the adrenergic receptor subtype responsible for the calorigenic and metabolic effects, since the putative beta2 adrenergic-receptor agonist, dopexamine, caused an increase in the plasma concentration of the beta1 adrenergic-receptor agonist, norepinephrine [20].

Gene context of FPL 60278

• Since beta2 adrenergic receptor-mediated effects such as hypokalemia were found only at infusion rates > or = 3 microg/kg/min, the effects of dopexamine at infusion rates < 3 microg/kg/min may be mainly mediated by stimulation of dopaminergic receptors and the indirect sympathomimetic action [20].
• SAA and CRP increases during the postoperative period were less pronounced with dopexamine throughout the study [21].
• Dobutamine decreased interleukin-10 expression, whereas dopexamine did not [22].
• Dopexamine did not modify the inflammatory response as evaluated by arterial IL-1beta and IL-6 concentrations [23].
• Postoperative increases in IL-6 were smallest in patients who received 2.0 micrograms.kg-1.min-1 dopexamine (P < or = 0.02) [21].

Analytical, diagnostic and therapeutic context of FPL 60278

• The aim of our study was to evaluate the short-term haemodynamic effects of dopexamine administered by intravenous infusion at different dosage rates [24].
• Liver tissue oxygen tension increased well above baseline during resuscitation in the dopexamine group, and liver tissue oxygen tension was significantly higher than in the control group [25].
• Dopexamine (8 microg/kg/min) and saline were infused intravenously into each rat using a randomized crossover design [4].
• In endotoxemic mice, both dobutamine and dopexamine decreased induction of macrophage inflammatory protein-2 mRNA (P < 0.05) and reduced the fraction of neutrophils in lung lavage fluid (P < 0.05) [22].
• The chronotropic response to dopexamine was significantly reduced after cardiac denervation [26].

References