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METABOLIC CHANGES DURING DOPAMINE INFUSION IN DOGS
Br.J. Anaesth. (1979), 515 1021
METABOLIC CHANGES DURING DOPAMINE INFUSION IN DOGS G. M. HALL, C. YOUNG AND A. SCOTT SUMMARY
It is well known that the inotropic agents adrenaline, noradrenaline and isoprenaline stimulate various aspects of metabolism (Himms-Hagen, 1967). Recent studies have shown also that salbutamol, administered i.v. in small doses to produce bronchodilatation, has significant metabolic activity (Neville et al., 1977). Goldberg (1977) claimed that dopamine has less effect on metabolism than adrenaline or isoprenaline, although no evidence was given to support this contention. In this study we have examined the effects of the infusion in dogs of dopamine 10 and 30 jxg kg" 1 min" 1 on circulating glucose, glycerol, lactate and potassium concentrations. Such information is relevant to the management of patients receiving dopamine infusions, and is also of value in attempting to define the adrenoreceptor agonist activity of dopamine.
The results from the sample collected after 30 min of the initial saline infusion were used as the control values and statistical analysis of the results was undertaken as described previously (Scott, Chakrabarti and Hall, 1979). RESULTS
The infusion of dopamine both 10 and 30 jj.g kg^ 1 min- 1 produced a biphasic change in blood glucose concentration (fig. 1). There was an initial increase in glucose values after 45 min (P<0.05) followed by a decrease to control values. During the subsequent saline infusion, the glucose was decreased significantly (P<0.05) below control values. Dopamine 10 [xg kg" 1 min" 1 produced a significant increase (P<0.05) in plasma glycerol concentration after 60, 75 and 90 min (fig. 2). There was an even greater response to dopamine 30 jxg kg" 1 min" 1 , with a three-fold increase in glycerol concentration METHODS after 60 min (P<0.01). Furthermore, the stimulation The details of the anaesthetic technique and surgical of lipolysis with the larger dose of dopamine persisted preparation of the dogs, and the experimental pro- into the second period of saline infusion, so that there cedure for the infusion of dopamine 10 and 30 fxg was still a significant increase (P<0.05) in plasma kg" 1 min" 1 , have been described in detail in the glycerol concentration 45 min after the dopamine was previous paper (Scott, Chakrabarti and Hall, 1979). discontinued. Blood lactate concentration increased slightly with Central venous blood samples were analysed in duplicate for blood glucose (Werner, Rey and both doses of dopamine (fig. 3), but this was statisticWielinger, 1970), plasma glycerol (Eggstein and ally significant (P<0.05) only with dopamine 10 (j.g 1 1 Kuhlmann, 1974), blood lactate (Hohorst, 1962) and kg" min" in the latter half of the period of infusion plasma potassium concentrations (flame photometry). of catecholamine. Plasma potassium concentration decreased by only G. M. HALL, M.B., B.S., PH.D., M.I.BIOL., F.F.A.R.C.S.; 0.25 mmol litre" 1 during the infusion of the small CAROL YOUNG, B.SC.; ANDREW SCOTT, M.B., B.S., F.F.A.R.C.S.; dose of dopamine and 0.5 mmol litre" 1 with 30 (xg Department of Anaesthetics, Royal Postgraduate Medical kg" 1 min" 1 (fig. 4). Neither change was statistically School, Hammersmith Hospital, London W12 0HS. significant. Correspondence to G. M. H. © Macmillan Journals Ltd 1979 0007-0912/79/111021-05 $01.00
Downloaded from http://bja.oxfordjournals.org/ at University of Bath Library & Learning Centre on June 20, 2015
The effects were investigated, in 12 dogs, of the infusion of dopamine 10 or 30 (ig kg" 1 min" 1 on circulating glucose, glycerol, lactate and potassium concentrations. Both doses of dopamine produced an initial increase in blood glucose concentration (P < 0.05) followed by hypoglycaemia (P<0.05). Lipolysis was stimulated as shown by an increase in plasma glycerol concentrations with dopamine 10 (ig kg" 1 min- 1 (P<0.05) and dopamine 30 [igkg- 1 min~ 1 (P<0.01). Blood lactate concentrations increased slightly in both groups, but this was significant (P < 0.05) only in the dogs infused with dopamine 10 [*g kg- 1 min" 1 . Dopamine had no significant effect on the plasma potassium concentration.
BRITISH JOURNAL OF ANAESTHESIA
1022
* *
8
§
m Dopamine
Saline 30
Saline
60
120
90
150
Time (min)
FIG. 1. Mean ( + SEM) blood glucose concentration (mmol litre"1) in dogs infused with dopamine 30 [igkg-'min- 1 (closed circles) and dopamine 10 |ig kg" 1 min" 1 (open circles). *P<0.05 compared with 30-min sample.
0.6 r 0.5
S =
0.4 0.3
to
0.2
is 0.1 Dopamine
Saline 30
Saline
60
90
120
150
Time (min)
FIG. 2. Mean ( + SEM) plasma glycerol concentration (mmol litre"1) in dogs infused with dopamine 30 (ig kg" 1 min" 1 (closed circles) and dopamine 10 ng kg" 1 min" 1 (open circles). *P<0.05; **P<0.01 compared with 30-min sample.
Downloaded from http://bja.oxfordjournals.org/ at University of Bath Library & Learning Centre on June 20, 2015
1'
0)
~ 4
1023
METABOLIC EFFECTS OF DOPAMINE 4.0 r
3.0
1.0
Dopamine
Saline 30
60
Saline
90
120
150
Time (min)
FIG. 3. Mean ( ± SEM) blood lactate concentration (mmol litre"1) in dogs infused with dopamine 30 (igkg- 1 min- 1 (closed circles) and dopamine 10 (ig kg" 1 min- 1 (open circles). *P<0.05 compared with 30-min sample.
TO
CL
Saline
Dopamine
Saline 30
60
90
120
150'
Time (min)
FIG. 4. Mean ( + SEM) plasma potassium concentration (mmol litre-1) in dogs infused with dopamine 30 |ig kg~ l min" 1 (closed circles) and dopamine 10 |ig kg"1 min"1 (open circles).
Downloaded from http://bja.oxfordjournals.org/ at University of Bath Library & Learning Centre on June 20, 2015
2.0
BRITISH JOURNAL OF ANAESTHESIA
1024 DISCUSSION
ACKNOWLEDGEMENTS
We thank the M.R.C. for financial support, Mr Chakrabarti and Miss Barbara Curruthers for technical assistance and Mrs Shirley Richens for expert secretarial assistance.
REFERENCES
Brody, T. M., and McNeill, J. H. (1970). Adrenergic receptors for metabolic responses in skeletal and smooth muscles. Fed. Proc, 29, 1375. Chauve, A., Castro, A., and Fontan, F. (1977). Effect of dopamine in cardiac patients after open heart surgery. Proc. R. Soc. Med., 70, (Suppl. 2), 51. Chideckel, E. W., Goodner, C. J., Koerker, D. J., Johnson, D. G., and Ensinck, J. W. (1977). Role of glucagon in mediating metabolic effects of epinephrine. Am. J. Physiol., 232, E464.
Downloaded from http://bja.oxfordjournals.org/ at University of Bath Library & Learning Centre on June 20, 2015
The biphasic response of the blood glucose concentration to infusion of dopamine (fig. 1) has not been reported previously. Leblanc and others (1977) showed that, in man, the glycaemic response was not sustained when dopamine 4 (xg kg" 1 min - 1 was infused i.v. for 2 h, but they failed to continue their observations after the dopamine was discontinued. However, their results suggested a possible mechanism for the biphasic response. Dopamine was found to stimulate a rapid but transient increase in glucagon secretion from the a cells of the pancreas, followed by a slower but more sustained secretion of insulin. Thus, the increase in blood glucose is probably caused by the effect of glucagon in stimulating hepatic glycogenolysis, although it is not possible to exclude a direct action of dopamine on glycogenolysis. The failure to sustain the hyperglycaemia and the occurrence of subsequent hypoglycaemia are the results of the persistent hyperinsulinaemia. Chideckel and others (1977) have suggested that the effect of catecholamines on hepatic glucose metabolism is always mediated indirectly via changes in secretion of pancreatic glucagon and insulin. This indirect effect of catecholamines may explain the difficulty in ascribing the stimulation of hepatic glycogenolysis to either a or p adrenoreceptors. It is possible that the results obtained in the dog may not be applicable directly to man, but the results of Leblanc and others (1977) and our findings of unstable glucose values during infusions of dopamine (authors' unpublished observations) suggest that the biphasic glucose response has important clinical implications. We recommend that frequent monitoring of the blood glucose concentration is undertaken not only during the infusion of dopamine but also after the catecholamine is discontinued, to detect possible hypoglycaemia. We chose to measure plasma glycerol rather than plasma free fatty acid (FFA) concentrations to indicate changes in fat metabolism, as we consider the former to be a more accurate indicator of lipolysis (Hall et ah, 1978). The significant increase in lipolysis observed with both doses of dopamine (fig. 2) showed that the catecholamine was a potent stimulator of the adrenoreceptors in the adipose tissue. Fain (1973) has demonstrated that lipolysis is subserved by Pj-adrenoreceptors in all animal species, so that we would predict similar changes in man. Random estimations of plasma FFA values in the dogs confirmed the increase in lipolysis, and when dopamine 30 jxg kg- 1 min" 1 was infused individual values
greater than 2 mmol litre" 1 were found. It is possible that high FFA values predispose to cardiac arrhythmias (Oliver, 1972), although this is disputed by most cardiologists (Opie, 1972). It is usually considered that the infusion of dopamine has little effect on heart rate or myocardial irritability, but recent studies by Chauve, Castro and Fontan (1977) and Miller (1977) have reported the occurrence of tachyarrhythmias. Although it has been assumed that this represents a direct effect of dopamine on the myocardium, a secondary effect from the stimulation of lipolysis may be contributory. The cause of the statistically significant, but metabolically small, increase in lactate concentration observed with the administration of dopamine 10 (xg k g - 1 min" 1 (fig. 3) is obscure, particularly as oxygen availability increased more than oxygen consumption (Scott, Chakrabarti and Hall, 1979). However, the failure of the larger dose of dopamine to increase blood lactate concentration significantly showed that there was unlikely to be an important contribution from the stimulation of p2-adrenoreceptors responsible for lactate production in muscle (Brody and McNeill, 1970). Dopamine had little effect on plasma potassium concentration (fig. 4), but if the associated haemoconcentration was a result of a diuresis (Scott, Chakrabarti and Hall, 1979) this may prevent the full extent of the hypokalaemic response from being recorded. We conclude that the administration of dopamine i.v. is associated with significant changes in glucose and fat metabolism. The stimulation of lipolysis shows that dopamine is an agonist for (3j-adrenoreceptors and this catecholamine appears to be unique in stimulating a, px and dopaminergic receptors.
METABOLIC EFFECTS OF DOPAMINE
CHANGEMENTS METABOLIQUES PENDANT L'INFUSION DE DOPAMINE A DES CHIENS RESUME
On a etudie sur 12 chiens, les effets de l'infusion de dopamine, a raison de 10 et de 30 [ig kg- 1 min"1, sur les concentrations de glucose, de glycerol, de lactate et de potassium dans la
85
circulation. Ces deux doses de dopamine ont produit a l'origine une augmentation de la concentration de glucose dans le sang (P<0,05) et celle-ci a ete suivie d'une hypoglycemie (/><0,05). La lipolyse a ete stimulee, comme on a pu le voir par une augmentation des concentrations de glycerol dans le plasma, par de la dopamine a 10 |ig kg- 1 min' 1 (/><0,05) et de la dopamine a 30 |ig kg"1 min' 1 (P<0,01). Les concentrations de lactate dans le sang ont augmente legerement dans chacun des deux groupes, mais cela n'a ete significatif (P < 0,05) que chez les chiens soumis a une infusion ce 10 jig kg"1 min"1. La dopamine n'a eu aucun effet sur les concentrations de potassium dans le plasma. STOFFWECHSELANDERUNGEN WAHREND DOPAMIN-INFUSION BEI HUNDEN ZUSAMMENFASSUNG
Bei 12 Hunden wurden die Wirkungen einer Infusion von 10 oder 30 (ig Dopamin auf zirkulierende Konzentrationen von Glukose, Glyzerol, Laktat und Kalium untersucht. Dopamin bewirkte einen anfanglichen Anstieg der Blut-Glukosekonzentration (/><0,05), gefolgt von Hypoglykamie (P<0,05). Lipolyse wurde stimuliert, wie durch einen Anstieg der Blut-Glyzerolkonzentrationen mit Dopamin 10 [ig kg- 1 min"1 (P<0,05) und Dopamin 30 (ig kg- 1 min- 1 (p <0,01) gezeigt wurde. Blut-Laktatkonzentrationen stiegen leicht, doch war dies nur bei Hunden wesentlich (P<0,05), die eine Infusion von lOjigkg- 1 min- 1 erhalten hatten. Auf die Plasma-Kalium-konzentrationen hatte Dopamin keinen Einfluss. CAMBIOS METABOLICOS DURANTE LA INFUSION DE DOPAMINA EN PERROS SUMARIO
En 12 perros, se averiguaron los efectos de la infusi6n de 10 y 30 (ig kg- 1 min- 1 de dopamina en las concentraciones circulantes de glucosa, glicerol, lactato y potasio. Ambas dosis de dopamina causaron un aumento inicial de la concentraci6n de glucosa en la sangre (P<0,05), seguids por hipoglicemia (P<0,05). Se estimul6 la Iip61isis, tal como indicado por un aumento en las concentraciones de glicerol en el plasma, con 10 (xg kg" 1 min- 1 (P<0,05) y 30 (ig kg- 1 min" 1 de dopamina (P<0,01). Las concentraciones de lactato en la sangre aumentaron ligeramente en ambos grupos, pero fueron significantes unicamente (P<0,05) en perros infusados con 10 (ig kg- 1 min" 1 de dopamina. La dopamina no tuvo ningun efecto significativo en la concentracidn de potasio en la sangre.
Downloaded from http://bja.oxfordjournals.org/ at University of Bath Library & Learning Centre on June 20, 2015
Eggstein, M., and Knhlmann, E. (1974). Triglycerides and glycerol. Determination after alkaline hydrolysis; in Methods of Enzymatic Analysis, 3rd edn (ed. H. U. Bergmeyer), p. 1825. New York and London: Academic Press. Fain, J. N. (1973). Biochemical aspects of drug and hormone action on adipose tissue. Pharmacol. Rev., 25, 67. Goldberg, L. I. (1977). Dopamine in the treatment of heart failure. Proc. R. Soc. Med., 70, (Suppl. 2), 24. Hall, G. M., Young, C , Holdcroft, A., and AlaghbandZadeh, J. (1978). Substrate mobilization during surgery. A comparison between halothane and fentanyl anaesthesia. Anaesthesia, 33, 924. Himms-Hagen, J. (1967). Sympathetic regulation of metabolism. Pharmacol. Rev., 19, 367. Hohorst, H. J. (1962). L-lactate. Determination with lactate dehydrogenase and NAD; in Methods of Enzymatic Analysis, 1st edn (ed. H. U. Bergmeyer), p. 622. Berlin: Springer-Verlag. Leblanc, H., Lachelin, G. C. L., Abu-Fadil, S., and Yen, S. S. C. (1977). The effect of dopamine infusion on insulin and glucagon secretion in man. J. Clin. Endocrinol. Metab., 44, 196. Miller, A. J. (1977). Dopamine in the treatment of heart failure. Proc. R. Soc. Med., 70, (Suppl. 2), 16. Neville, A., Palmer, J. B. D., Gaddie, J., May, C. S., Palmer, K. N. V., and Murchison, L. E. (1977). Metabolic effects of salbutamol: comparison of aerosol and intravenous administration. Br. Med. J., I, 413. Oliver, M. F. (1972). Metabolic response during impending myocardial infarction. II: Clinical implications. Circulation, 45, 491. Opie, L. H. (1972). Metabolic response during impending myocardial infarction. I: Relevance of studies of glucose and fatty acid metabolism in animals. Circulation, 45, 483. Scott, A., Chakrabarti, M. K., and Hall, G. M. (1979). Oxygen transport during dopamine infusion in dogs. Br.J.Anaesth.,51,1011. Werner, W., Rey, H. G., and Wielinger, H. (1970). A micro-method for the determination of the blood glucose concentration. Z. Analyt. Chem., 252, 224.
1025
METABOLIC CHANGES DURING DOPAMINE INFUSION IN DOGS G. M. HALL, C. YOUNG AND A. SCOTT SUMMARY
It is well known that the inotropic agents adrenaline, noradrenaline and isoprenaline stimulate various aspects of metabolism (Himms-Hagen, 1967). Recent studies have shown also that salbutamol, administered i.v. in small doses to produce bronchodilatation, has significant metabolic activity (Neville et al., 1977). Goldberg (1977) claimed that dopamine has less effect on metabolism than adrenaline or isoprenaline, although no evidence was given to support this contention. In this study we have examined the effects of the infusion in dogs of dopamine 10 and 30 jxg kg" 1 min" 1 on circulating glucose, glycerol, lactate and potassium concentrations. Such information is relevant to the management of patients receiving dopamine infusions, and is also of value in attempting to define the adrenoreceptor agonist activity of dopamine.
The results from the sample collected after 30 min of the initial saline infusion were used as the control values and statistical analysis of the results was undertaken as described previously (Scott, Chakrabarti and Hall, 1979). RESULTS
The infusion of dopamine both 10 and 30 jj.g kg^ 1 min- 1 produced a biphasic change in blood glucose concentration (fig. 1). There was an initial increase in glucose values after 45 min (P<0.05) followed by a decrease to control values. During the subsequent saline infusion, the glucose was decreased significantly (P<0.05) below control values. Dopamine 10 [xg kg" 1 min" 1 produced a significant increase (P<0.05) in plasma glycerol concentration after 60, 75 and 90 min (fig. 2). There was an even greater response to dopamine 30 jxg kg" 1 min" 1 , with a three-fold increase in glycerol concentration METHODS after 60 min (P<0.01). Furthermore, the stimulation The details of the anaesthetic technique and surgical of lipolysis with the larger dose of dopamine persisted preparation of the dogs, and the experimental pro- into the second period of saline infusion, so that there cedure for the infusion of dopamine 10 and 30 fxg was still a significant increase (P<0.05) in plasma kg" 1 min" 1 , have been described in detail in the glycerol concentration 45 min after the dopamine was previous paper (Scott, Chakrabarti and Hall, 1979). discontinued. Blood lactate concentration increased slightly with Central venous blood samples were analysed in duplicate for blood glucose (Werner, Rey and both doses of dopamine (fig. 3), but this was statisticWielinger, 1970), plasma glycerol (Eggstein and ally significant (P<0.05) only with dopamine 10 (j.g 1 1 Kuhlmann, 1974), blood lactate (Hohorst, 1962) and kg" min" in the latter half of the period of infusion plasma potassium concentrations (flame photometry). of catecholamine. Plasma potassium concentration decreased by only G. M. HALL, M.B., B.S., PH.D., M.I.BIOL., F.F.A.R.C.S.; 0.25 mmol litre" 1 during the infusion of the small CAROL YOUNG, B.SC.; ANDREW SCOTT, M.B., B.S., F.F.A.R.C.S.; dose of dopamine and 0.5 mmol litre" 1 with 30 (xg Department of Anaesthetics, Royal Postgraduate Medical kg" 1 min" 1 (fig. 4). Neither change was statistically School, Hammersmith Hospital, London W12 0HS. significant. Correspondence to G. M. H. © Macmillan Journals Ltd 1979 0007-0912/79/111021-05 $01.00
Downloaded from http://bja.oxfordjournals.org/ at University of Bath Library & Learning Centre on June 20, 2015
The effects were investigated, in 12 dogs, of the infusion of dopamine 10 or 30 (ig kg" 1 min" 1 on circulating glucose, glycerol, lactate and potassium concentrations. Both doses of dopamine produced an initial increase in blood glucose concentration (P < 0.05) followed by hypoglycaemia (P<0.05). Lipolysis was stimulated as shown by an increase in plasma glycerol concentrations with dopamine 10 (ig kg" 1 min- 1 (P<0.05) and dopamine 30 [igkg- 1 min~ 1 (P<0.01). Blood lactate concentrations increased slightly in both groups, but this was significant (P < 0.05) only in the dogs infused with dopamine 10 [*g kg- 1 min" 1 . Dopamine had no significant effect on the plasma potassium concentration.
BRITISH JOURNAL OF ANAESTHESIA
1022
* *
8
§
m Dopamine
Saline 30
Saline
60
120
90
150
Time (min)
FIG. 1. Mean ( + SEM) blood glucose concentration (mmol litre"1) in dogs infused with dopamine 30 [igkg-'min- 1 (closed circles) and dopamine 10 |ig kg" 1 min" 1 (open circles). *P<0.05 compared with 30-min sample.
0.6 r 0.5
S =
0.4 0.3
to
0.2
is 0.1 Dopamine
Saline 30
Saline
60
90
120
150
Time (min)
FIG. 2. Mean ( + SEM) plasma glycerol concentration (mmol litre"1) in dogs infused with dopamine 30 (ig kg" 1 min" 1 (closed circles) and dopamine 10 ng kg" 1 min" 1 (open circles). *P<0.05; **P<0.01 compared with 30-min sample.
Downloaded from http://bja.oxfordjournals.org/ at University of Bath Library & Learning Centre on June 20, 2015
1'
0)
~ 4
1023
METABOLIC EFFECTS OF DOPAMINE 4.0 r
3.0
1.0
Dopamine
Saline 30
60
Saline
90
120
150
Time (min)
FIG. 3. Mean ( ± SEM) blood lactate concentration (mmol litre"1) in dogs infused with dopamine 30 (igkg- 1 min- 1 (closed circles) and dopamine 10 (ig kg" 1 min- 1 (open circles). *P<0.05 compared with 30-min sample.
TO
CL
Saline
Dopamine
Saline 30
60
90
120
150'
Time (min)
FIG. 4. Mean ( + SEM) plasma potassium concentration (mmol litre-1) in dogs infused with dopamine 30 |ig kg~ l min" 1 (closed circles) and dopamine 10 |ig kg"1 min"1 (open circles).
Downloaded from http://bja.oxfordjournals.org/ at University of Bath Library & Learning Centre on June 20, 2015
2.0
BRITISH JOURNAL OF ANAESTHESIA
1024 DISCUSSION
ACKNOWLEDGEMENTS
We thank the M.R.C. for financial support, Mr Chakrabarti and Miss Barbara Curruthers for technical assistance and Mrs Shirley Richens for expert secretarial assistance.
REFERENCES
Brody, T. M., and McNeill, J. H. (1970). Adrenergic receptors for metabolic responses in skeletal and smooth muscles. Fed. Proc, 29, 1375. Chauve, A., Castro, A., and Fontan, F. (1977). Effect of dopamine in cardiac patients after open heart surgery. Proc. R. Soc. Med., 70, (Suppl. 2), 51. Chideckel, E. W., Goodner, C. J., Koerker, D. J., Johnson, D. G., and Ensinck, J. W. (1977). Role of glucagon in mediating metabolic effects of epinephrine. Am. J. Physiol., 232, E464.
Downloaded from http://bja.oxfordjournals.org/ at University of Bath Library & Learning Centre on June 20, 2015
The biphasic response of the blood glucose concentration to infusion of dopamine (fig. 1) has not been reported previously. Leblanc and others (1977) showed that, in man, the glycaemic response was not sustained when dopamine 4 (xg kg" 1 min - 1 was infused i.v. for 2 h, but they failed to continue their observations after the dopamine was discontinued. However, their results suggested a possible mechanism for the biphasic response. Dopamine was found to stimulate a rapid but transient increase in glucagon secretion from the a cells of the pancreas, followed by a slower but more sustained secretion of insulin. Thus, the increase in blood glucose is probably caused by the effect of glucagon in stimulating hepatic glycogenolysis, although it is not possible to exclude a direct action of dopamine on glycogenolysis. The failure to sustain the hyperglycaemia and the occurrence of subsequent hypoglycaemia are the results of the persistent hyperinsulinaemia. Chideckel and others (1977) have suggested that the effect of catecholamines on hepatic glucose metabolism is always mediated indirectly via changes in secretion of pancreatic glucagon and insulin. This indirect effect of catecholamines may explain the difficulty in ascribing the stimulation of hepatic glycogenolysis to either a or p adrenoreceptors. It is possible that the results obtained in the dog may not be applicable directly to man, but the results of Leblanc and others (1977) and our findings of unstable glucose values during infusions of dopamine (authors' unpublished observations) suggest that the biphasic glucose response has important clinical implications. We recommend that frequent monitoring of the blood glucose concentration is undertaken not only during the infusion of dopamine but also after the catecholamine is discontinued, to detect possible hypoglycaemia. We chose to measure plasma glycerol rather than plasma free fatty acid (FFA) concentrations to indicate changes in fat metabolism, as we consider the former to be a more accurate indicator of lipolysis (Hall et ah, 1978). The significant increase in lipolysis observed with both doses of dopamine (fig. 2) showed that the catecholamine was a potent stimulator of the adrenoreceptors in the adipose tissue. Fain (1973) has demonstrated that lipolysis is subserved by Pj-adrenoreceptors in all animal species, so that we would predict similar changes in man. Random estimations of plasma FFA values in the dogs confirmed the increase in lipolysis, and when dopamine 30 jxg kg- 1 min" 1 was infused individual values
greater than 2 mmol litre" 1 were found. It is possible that high FFA values predispose to cardiac arrhythmias (Oliver, 1972), although this is disputed by most cardiologists (Opie, 1972). It is usually considered that the infusion of dopamine has little effect on heart rate or myocardial irritability, but recent studies by Chauve, Castro and Fontan (1977) and Miller (1977) have reported the occurrence of tachyarrhythmias. Although it has been assumed that this represents a direct effect of dopamine on the myocardium, a secondary effect from the stimulation of lipolysis may be contributory. The cause of the statistically significant, but metabolically small, increase in lactate concentration observed with the administration of dopamine 10 (xg k g - 1 min" 1 (fig. 3) is obscure, particularly as oxygen availability increased more than oxygen consumption (Scott, Chakrabarti and Hall, 1979). However, the failure of the larger dose of dopamine to increase blood lactate concentration significantly showed that there was unlikely to be an important contribution from the stimulation of p2-adrenoreceptors responsible for lactate production in muscle (Brody and McNeill, 1970). Dopamine had little effect on plasma potassium concentration (fig. 4), but if the associated haemoconcentration was a result of a diuresis (Scott, Chakrabarti and Hall, 1979) this may prevent the full extent of the hypokalaemic response from being recorded. We conclude that the administration of dopamine i.v. is associated with significant changes in glucose and fat metabolism. The stimulation of lipolysis shows that dopamine is an agonist for (3j-adrenoreceptors and this catecholamine appears to be unique in stimulating a, px and dopaminergic receptors.
METABOLIC EFFECTS OF DOPAMINE
CHANGEMENTS METABOLIQUES PENDANT L'INFUSION DE DOPAMINE A DES CHIENS RESUME
On a etudie sur 12 chiens, les effets de l'infusion de dopamine, a raison de 10 et de 30 [ig kg- 1 min"1, sur les concentrations de glucose, de glycerol, de lactate et de potassium dans la
85
circulation. Ces deux doses de dopamine ont produit a l'origine une augmentation de la concentration de glucose dans le sang (P<0,05) et celle-ci a ete suivie d'une hypoglycemie (/><0,05). La lipolyse a ete stimulee, comme on a pu le voir par une augmentation des concentrations de glycerol dans le plasma, par de la dopamine a 10 |ig kg- 1 min' 1 (/><0,05) et de la dopamine a 30 |ig kg"1 min' 1 (P<0,01). Les concentrations de lactate dans le sang ont augmente legerement dans chacun des deux groupes, mais cela n'a ete significatif (P < 0,05) que chez les chiens soumis a une infusion ce 10 jig kg"1 min"1. La dopamine n'a eu aucun effet sur les concentrations de potassium dans le plasma. STOFFWECHSELANDERUNGEN WAHREND DOPAMIN-INFUSION BEI HUNDEN ZUSAMMENFASSUNG
Bei 12 Hunden wurden die Wirkungen einer Infusion von 10 oder 30 (ig Dopamin auf zirkulierende Konzentrationen von Glukose, Glyzerol, Laktat und Kalium untersucht. Dopamin bewirkte einen anfanglichen Anstieg der Blut-Glukosekonzentration (/><0,05), gefolgt von Hypoglykamie (P<0,05). Lipolyse wurde stimuliert, wie durch einen Anstieg der Blut-Glyzerolkonzentrationen mit Dopamin 10 [ig kg- 1 min"1 (P<0,05) und Dopamin 30 (ig kg- 1 min- 1 (p <0,01) gezeigt wurde. Blut-Laktatkonzentrationen stiegen leicht, doch war dies nur bei Hunden wesentlich (P<0,05), die eine Infusion von lOjigkg- 1 min- 1 erhalten hatten. Auf die Plasma-Kalium-konzentrationen hatte Dopamin keinen Einfluss. CAMBIOS METABOLICOS DURANTE LA INFUSION DE DOPAMINA EN PERROS SUMARIO
En 12 perros, se averiguaron los efectos de la infusi6n de 10 y 30 (ig kg- 1 min- 1 de dopamina en las concentraciones circulantes de glucosa, glicerol, lactato y potasio. Ambas dosis de dopamina causaron un aumento inicial de la concentraci6n de glucosa en la sangre (P<0,05), seguids por hipoglicemia (P<0,05). Se estimul6 la Iip61isis, tal como indicado por un aumento en las concentraciones de glicerol en el plasma, con 10 (xg kg" 1 min- 1 (P<0,05) y 30 (ig kg- 1 min" 1 de dopamina (P<0,01). Las concentraciones de lactato en la sangre aumentaron ligeramente en ambos grupos, pero fueron significantes unicamente (P<0,05) en perros infusados con 10 (ig kg- 1 min" 1 de dopamina. La dopamina no tuvo ningun efecto significativo en la concentracidn de potasio en la sangre.
Downloaded from http://bja.oxfordjournals.org/ at University of Bath Library & Learning Centre on June 20, 2015
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