Metabolic and calorigenic effects of dopexamine in healthy volunteers.

OBJECTIVE To evaluate metabolic and calorigenic effects of dopexamine in healthy volunteers. DESIGN Prospective, randomized trial. SETTING Laboratory of the University Department of Anesthesiology. SUBJECTS Eight volunteers. INTERVENTIONS After a control period, dopexamine was administered using four infusion rates (0.75, 1.5, 3.0, and 6.0 microg/kg/min). MEASUREMENTS AND MAIN RESULTS Blood pressure, heart rate, oxygen consumption (VO2), and the plasma concentration of potassium, glucose, lactate, and norepinephrine were measured. Typical hemodynamic responses were seen. VO2 increased from 122 +/- 11 (SD) to 150 +/- 9 mL/min/m2 during the highest dopexamine infusion rate. Plasma potassium concentration decreased only during the highest infusion rate. Plasma glucose concentration increased during infusion rates of 3 and 6 microg/kg/min of dopexamine, from 90 +/- 5 to 99 +/- 5 mg/dL (5.0 +/- 0.3 to 5.5 +/- 0.3 mmol/L), and from 87 +/- 7 to 103 +/- 11 mg/dL (4.8 +/- 0.4 to 5.7 +/- 0.6 mmol/L), respectively. Lactate did not increase during dopexamine infusion. Plasma norepinephrine concentration increased during all four infusion rates. 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. 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.

[1]  A. Webb,et al.  Goal-directed therapy with dopexamine, dobutamine, and volume expansion: effects of systemic oxygen transport on hepatic ultrastructure in porcine sepsis. , 1995, Critical care medicine.

[2]  S. Toubro,et al.  Contribution of beta 3-adrenoceptor activation to ephedrine-induced thermogenesis in humans. , 1995, International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity.

[3]  M. Georgieff,et al.  Oxygen uptake and metabolic changes during infusion of dobutamine in comparison to fenoterol and phenylephrine in volunteers , 1995 .

[4]  R. Beale,et al.  Protecting the gut and the liver in the critically ill: Effects of dopexamine , 1994, Critical care medicine.

[5]  E. Bennett,et al.  A randomized clinical trial of the effect of deliberate perioperative increase of oxygen delivery on mortality in high-risk surgical patients. , 1993, JAMA.

[6]  F. Lönnqvist,et al.  Evidence for a functional β3‐adrenoceptor in man , 1993 .

[7]  K. Lindner,et al.  Effects of norepinephrine, epinephrine, and dopamine infusions on oxygen consumption in volunteers. , 1993 .

[8]  K. Lindner,et al.  Adrenaline: relationship between infusion rate, plasma concentration, metabolic and haemodynamic effects in volunteers. , 1992, European journal of anaesthesiology.

[9]  H. Ensinger,et al.  Relationship between infusion rates, plasma concentrations, and cardiovascular and metabolic effects during the infusion of norepinephrine in healthy volunteers , 1992, Critical care medicine.

[10]  T. Oh,et al.  EFFECT OF DOBUTAMINE ON OXYGEN SUPPLY AND UPTAKE IN HEALTHY VOLUNTEERS , 1992 .

[11]  K. Frayn,et al.  Metabolic effects of low-dose dopamine infusion in normal volunteers. , 1990, Clinical science.

[12]  N. Morgan,et al.  Differential effects of β-adrenergic agonists on insulin secretion from pancreatic islets isolated from rat and man , 1990 .

[13]  J. Takala,et al.  Measurement of gas exchange in intensive care: laboratory and clinical validation of a new device. , 1989, Critical care medicine.

[14]  W. Shoemaker,et al.  Prospective trial of supranormal values of survivors as therapeutic goals in high-risk surgical patients. , 1988, Chest.

[15]  J. Carroll,et al.  Role of the beta 2 adrenoceptor in mediating positive inotropic activity in the failing heart and its relation to the hemodynamic actions of dopexamine hydrochloride. , 1988, The American journal of cardiology.

[16]  R. Foulds Clinical development of dopexamine hydrochloride (Dopacard) and an overview of its hemodynamic effects. , 1988, The American journal of cardiology.

[17]  P. Binkley,et al.  Cardiovascular pharmacology of dopexamine in low output congestive heart failure. , 1988, The American journal of cardiology.

[18]  M. Rosen,et al.  Comparison of the effects of dopamine, dobutamine, and dopexamine upon renal blood flow: a study in normal healthy volunteers. , 1988, British journal of clinical pharmacology.

[19]  A. Grünert,et al.  Basal plasma-catecholamine-level determination using HPLC-ED and different sample cleanup techniques , 1988 .

[20]  George W. Smith,et al.  Inhibition of Uptake1 by dopexamine hydrochloride in vitro) , 1987, British journal of pharmacology.

[21]  W. Littler,et al.  Beneficial Haemodynamic Effects of Intravenous Dopexamine in Patients with Low‐Output Heart Failure , 1987, Journal of cardiovascular pharmacology.

[22]  R. Wolfe,et al.  Effect of severe burn injury on substrate cycling by glucose and fatty acids. , 1987, The New England journal of medicine.

[23]  J. B. Farmer,et al.  The cardiovascular actions of dopexamine hydrochloride, an agonist at dopamine receptors and β2‐adrenoceptors in the dog , 1987, The Journal of pharmacy and pharmacology.

[24]  W. Shoemaker,et al.  Hemodynamic and oxygen transport effects of dobutamine in critically ill general surgical patients , 1986, Critical care medicine.

[25]  L. Erhardt,et al.  Short-term haemodynamic effects of dopexamine in patients with chronic congestive heart failure. , 1986, European heart journal.

[26]  E. Horton,et al.  Metabolic studies in human obesity during overnutrition and undernutrition: thermogenic and hormonal responses to norepinephrine. , 1986, Metabolism: clinical and experimental.

[27]  M. Webb-Peploe,et al.  Acute haemodynamic and metabolic effects of dopexamine, a new dopaminergic receptor agonist, in patients with chronic heart failure. , 1985, British heart journal.

[28]  J. B. Farmer,et al.  Dopexamine: a novel agonist at peripheral dopamine receptors and β2‐adrenoceptors , 1985, British journal of pharmacology.

[29]  J. B. Farmer,et al.  The effects of dopexamine on the cardiovascular system of the dog , 1985, British journal of pharmacology.

[30]  M. Brown,et al.  Hypokalemia from beta 2-receptor stimulation by circulating epinephrine. , 1983, The American journal of cardiology.

[31]  H. Sarau,et al.  Characterization of the peripheral and central effects of SK&F 82526, a novel dopamine receptor agonist. , 1982, The Journal of pharmacology and experimental therapeutics.

[32]  P. Cryer,et al.  Epinephrine plasma thresholds for lipolytic effects in man: measurements of fatty acid transport with [l-13C]palmitic acid. , 1981, The Journal of clinical investigation.

[33]  P. Cryer,et al.  Epinephrine plasma metabolic clearance rates and physiologic thresholds for metabolic and hemodynamic actions in man. , 1980, The Journal of clinical investigation.

[34]  G. Corso,et al.  Influence of epinephrine, norepinephrine, and isoproterenol on glucose homeostasis in normal man. , 1980, The Journal of clinical endocrinology and metabolism.

[35]  C. Dollery,et al.  Interindividual variation in kinetics of infused epinephrine , 1979, Clinical pharmacology and therapeutics.

[36]  A. Mason,et al.  Catecholamines: Znediator of the Hypermetabolic Response to Thermal Injury , 1974, Annals of surgery.

[37]  N. Svedmyr Studies on the Mechanism for the Calorigenic Effect of Adrenaline in Man , 1966 .

[38]  D. MacGregor,et al.  Relative efficacy and potency of beta-adrenoceptor agonists for generating cAMP in human lymphocytes. , 1996, Chest.

[39]  M. Georgieff,et al.  Metabolic and haemodynamic effects of dopamine plus domperidone in volunteers , 1993, Research in experimental medicine. Zeitschrift fur die gesamte experimentelle Medizin einschliesslich experimenteller Chirurgie.

[40]  F. Amenta,et al.  Dopexamine hydrochloride in the human kidney: localization, receptor binding and effect on 3'-5'-cyclic adenosine monophosphate generation. , 1993, Nephron.

[41]  I. Campbell,et al.  Metabolic effects of dobutamine in normal man. , 1992, Clinical science.

[42]  W. Shoemaker,et al.  Sequential cardiorespiratory patterns associated with outcome in septic shock. , 1984, Chest.

[43]  S. Holm A Simple Sequentially Rejective Multiple Test Procedure , 1979 .