Acta anaestli. scand. 1977, 21, 374-378
A Comparison between the Influence of Halothane or Fentanyl and Droperidol Anaesthesia on the Adrenergic Receptor Response in Human Adipose Tissue in vitro U. ROSENQVIST, M. LINDHOLM and J. EKLUNU Departments of Internal Medicine and Anaesthesiology, Karolinska Hospital, Stockholm, Sweden
A comparison was made between the adrenergic receptor response in vitro in human adipose tissue obtained under halothane and neuroleptanaesthesia. In both groups the net release of glycerol was significantly stimulated (Pc0.01) by the combined alpha- and beta-adrenergic agonist, I-noradrenaline. In the halothane group, the lipolysis was further increased by the addition of phentolamine (an alpha-adrenergic blocking agent). No such effect could be demonstrated in specimens from the fentanyl/droperidol group. This difference in response was most probably explained by the fact that droperidol had quite a long-lasting alpha-adrenergic blocking property, which totally obliterated the effect of another alpha-adrenergic blocking agent. The findings stress the importance of using a standardized procedure, including the choice of anaesthetic agents, when human adipose tissue is sampled for metabolic studies in vitro. The results also indicate the possibility of a difference in metabolic effects in vivo between the two procedures.
Received 3 November, accepted for publication 16 December 1976
Human adipose tissue is an easily accessible in vitro adrencrgic receptor response of suborgan which has been used extensively for cutaneous adipose tissue. metabolic studies in vitro (BURNS& LANGLEY 1970, EFENDIC 1970, BJORNTORP & OSTMAN 1971, RODISON et al. 1972, ROSENQVIST 1972, METHODS ARNER1976). Since specimens are often Twenty-four subjects were studied. In 14, anaesthesia obtained from subjects under general anaes- was induced by a short-acting barbiturate, and by halothane and N 2 0 and 02.T h e thesia, we found it important to evaluate maintained remaining 10 subjects were operated on under neurothe effect of two commonly used anaesthetic lept anaesthesia (fentanyl and droperidol) with N 2 0 procedures on lipolysis and tissue response to and 02.Muscle relaxation was achieved either by adrenergic stimulation. An increased know- succinylcholine or pancuronium, and normoventilaledge of the effects of the two different anaes- tion was achieved by the use of a n Engstrom Ventilator (Jungner Medical, Sweden). The choice between the thetic procedures on the adrenergic receptor different anaesthetics was based upon the patients’ response might help to increase understanding physical condition. Halothane anaesthesia was used as of the metabolic changes observed in patients the routine method, while neurolept anaesthesia was during operation and in the postoperative preferred when the patients had a history of liver period. I n the present investigation, a comp- disease (including obstructive jaundice), had had a recent halothane anaesthetic or else were considered to arison was made between the effects of halo- be high risk patients due to heart or lung disease. All thane anaesthesia and so-called neurolept subjects were scheduled for elective surgery for either anaesthesia (fentanyl and droperidol) on the gall-bladder disease or peptic ulcers. At the time of
ANAESTHESIA AND ADRENERGIC RESPONSE
Anaesthetic procedure
n
Halothane
14
Fentanyldroperidol
Female
% of ideal
male
body weight
Age
50.3+ 1.6
10 -
-
10
53.1k2.6
5
I-noradrenaline plus 5 pg/ml phentolamine (Ph) or 5 pg/ml phentolamine alone (Mean+s.e. mean). Glycerol release (pmol/g ww/2h) Halothane Fentanyl-droperidol N = 14 N = 10
96.4k2.3
4 5
100.5+3.8
375
0.694k 0.133 0.974k 0.280 1.532k0.239 2.153k0.464 0.838 k 0 ~ 6 3 ~1.178 k 0.2 12’ 0.602 k0.212 0.986k0.227
Basal NA NA-basal Ph
~~~
~~
The P-values were calculated from the paired differences: 1) n.s. 2) P< 0.01 3) P< 0.001.
Net glycerol release
Net glycerol release
( p moles/g ww/2 h)
Ip
moles/g w w / 2 h )
4,
3
! A
0
0.02
0.2
2 NA x 10’
14 NA x lo5[M
Figs. 1 and 2. Lipolytic effect of different concentrations of I-noradrenaline (NA) in presence (0-0) and absence of 5 pg/ml phentolamine (0-0). Adipose tissue specimens were obtained from five subjects undergoing halothane anaesthesia (Fig. I ) and five subjects exposed to fentanyl-droperidol (Fig. 2) (Meanfsx. mean).
376
U . ROSENQVIST, M. LINDH0I.M A N D J. EKLUND
operation, all patients were in good health without signs of liver or metabolic disorders, and, in addition, all patients were drug-free. Subcutaneous adipose tissue was obtained from the abdominal wall at the beginning of the operation and transported in physiological saline a t 37°C to the laboratory. The tissue was then divided into 50-100 mg pieces and preincubated for 1 h at 37°C in KrebsHenseleit bicarbonate (KHB) buffer, p H 7.4, containing 1% bovine albumin (Fraction V, Armour Pharmaceutical Division). Separate pieces were then transferred to plastic vials containing 1.5 ml incubation medium made of KHB with 3% albumin, 1 mg/ml glucosc ( p H 7.4). Incubations were then carried out 1970). Glycerol for 2 h using air as gas phase (EFENDIC was determined fluorometrically according to CHERNICK (1969). The following agents were used: l-noradrenaline bitartrate (Astra, Sweden) and phentolamine (Regitine" Ciba, Switzerland).
Net glycerol release
( p moles/g ww/2 h)
7 2
1
b 0
I
1
0.02
0.2
2
A
14
NA x lo5[iv13
RESULTS The mean ages and percentages of' ideal body weights of the two groups of patients are shown in Table 1. There were no significant differences regarding these parameters between the groups. The proportion of female subjects was higher in the halothane group. The lipolytic response to the combined alpha- and beta-adrenergic agonist 1-noradrenaline (NA) is shown in Table 2. The net release of glycerol was significantly ( P < 0.00 1 ) stimulated in both groups. Phentolamine (Ph), an alpha-adrenergic blocking agent, did not by itself change the rate of lipolysis; however, in the presence of 1-noradrenaline [(NA+ Ph)-NA] it significantly (Pc0.01) increased lipolysis in the halothane group, while no such effect of alpha-adrenergic blockade could be demonstrated in specimens from the fentanyl-droperidol group. This finding was further explored by a doseresponse curve of 1-noradrenaline in the presence or absence of 5 pg/ml phentolamine. It has previously been shown that this concentration of the alpha-adrenergic antagonist completely blocks the alpha response of the tissue (EFENDIC1970). As seen in Figure 1, phentolamine markedly potentiated the lipolytic response to 1-noradrenaline in specimens from subjects undergoing halothane anaesthesia, while in the fentanyl-
L
Fig. 3. Net effect of 5 ,ug/ml of phentolamine in presence of different concentrations of 1-noradrenaline (NA) on specimens from subjects undergoing anacsthesia with halothane (0-0, N = 5) and fentanyldroperidol (0-0,N = 5) (Meanfs.e. mean).
droperidol group no significant effects of phentolamine were observed (Fig. 2). The net effect ofphentolamine [(NA+ Ph)-NA] in both groups of subjects is shown in Figure 3. It seems that the dose-response curve was shifted to the right in specimens from the fentanyl-droperidol group (Fig. 3). DISCUSSION The present study emphasized the necessity of controlling the anaesthetic procedures when studying human adipose tissue. Fentanyldroperidol anaesthesia obliterated the alphaadrenergic response in vitro in subcutaneous adipose tissue. O n the other hand, human adipose tissue obtained during halothane anaesthesia responded to both alpha- and beta-adrenergic stimulation. Alpha stimulation inhibits both basal and stimulated lipolysis (BURNS& LANCLEY1970, EFENDXC 1970) by suppression of the cyclic AMP production (ROBISON et al. 1972, GRILL& ROSENQVIST 1975), a process which seems to involve intracellular C a + + (ROSENQVIST 1974a,b). Beta-
ANAESTHESIA AND ADRENERGlC RESPONSE
377
adrenergic stimulation, 011 the other hand, In conclusion, the present investigation has stimulates the formation of cyclic AMP, and demonstrated that the alpha-antagonistic thereby the rate of lipolysis (BURNS & LANG- property of phentolamine in vitro is obliterated LEY 1970, EFENDIC 1970, ROBISON et al. 1972, in adipose tissue specimens from subjects GRILL& ROSENQVIST 1975). undergoing fentanyl-droperidol anaesthesia I n the course of these studies, we obtained when compared with specimens from subjects specimens from subjects operated upon under undergoing anaesthesia with halothane. This fentanyl-droperidol anaesthesia. The alpha- study stresses the importance of controlling receptor response could then no longer be the conditions for analgesia or anaesthesia and demonstrated. Droperidol is a potent neuro- of standardizing the procedure when using leptical agent with alpha-adrenergic blocking human adipose tissue for metabolic studies. properties (YELNOSKY et al. 1964, WHITWAM & RUSSEL1971). It is the recommended complement to the potent analgesic fentanyl. ACKNOWLEDGMENTS Droperidol has a relatively long biological This study was supported in part by grants from the half life, and, as shown in the present study, Swedish Medical Research Council 04223 and the its alpha-antagonistic effect remains in the Nordic Insulin Foundation. tissue after at least 1 h of preincubation. The effect of halothane on adipose tissue metabolism and the response to noradrenaline has REFERENCES been studied by BENNIS & SMITH( 1 973). They ARNER,P. (1976) Studies on the metabolism of human found that the basal release of glycerol was adipose tissue with special reference to the adrenergic significantly diminished, and that the anticontrol of lipolysis and the metabolism of partial acylgycerols.Thesis, Karolinska Institute, Stockholm. lipolytic effect of insulin was slightly less J. & SMITH,U.(1973) Effect of halothane on pronounced in specimens exposed to halo- BENNIS, lipolysis and lipogenesis in human adipose tissue. thane. O n the other hand, MAKELAINEN et Acta anaesth. scand. 17, 76. al. (1973a,b) found a stimulated lipolysis BJORNTORP, J. (1971) Human adipose P. & OSTMAN, after halothane exposure in rats both in vivo tissue dynamics and regulation. Advances in Metabolic Disorders, Vol. 5, ed. LEVINE,R. & LUFT,R. Acaand in vitro. They found, further, that this demic Press, New York and London, p. 277. lipolysis could be blocked by a beta-blocking BURNS,T. W. & LANGLEY, P. E. (1970) Lipolysis by agent (propanolol). human adipose tissue. The role of cyclic 3’, 5’Anaesthetic agents, therefore, can proadenosine monophosphate and adrenergic receptor foundly influence the susceptibility of tissue sites. 1.lab. Clin. Med. 75, 983. S.S. (1969) Determination of glycerol in to hormonal effects. Thus the choice of CHERNICK, Methods in Enzymologv, Lipids, Vol. 4, acyl glycerols. procedure has to be determined by the metaJ. M. Academic Press, New York ed. LOWENSTEIN, bolic parameters which are to be studied. and London, p. 627. Trauma and surgical stress certainly EFENDIC, S. (1970) Studies on the effect of catecholastimulate the sympathetic nervous system. mines on human adipose tissue metabolism. Thesis, Karolinska Institute, Stockholm. The metabolic consequences are numerous GRILL, V. & ROSENQVIST, U. (1975) Dynamics of alpha and include mobilization of free fatty acids, adrenergic inhibition of the adenyl cyclase-cyclic increased gluconeogenesis and glycolysis (cf. AMP system in human adipose tissue. Acta med. THORBN 1974). The present finding of a scand. 197, 283. marked inhibition of the alpha-adrenergic MAKELAINEN, A., NIKKI,P. & VAPAATALO, H. (1973a) Halothane-induced lipopolysis in rats. Acta anaesth. response in vitro by fentanyl-doperidol anaesscand. 17, 170. thesia raises the question of how the metaMAKELAINEN, A., VAPAATALO, H. & NIKKI,P. (1973b) bolism is affected during the operation and Halothane-induced lipolysis in uitro in the rat. Acta the post-operative period when neurolept anaesth. scand. 17, 179. anaesthesia is used. To our knowledge this ROBISON, G. A., LANGLEY, P. E. & BURNS, T. W. (1972) Adrenergic receptors in human adipocytes, divergent has not been fully explored.
378
U. ROSENQVIST, M . LINDHOLhf AND J . EKLUND
effects on adenosine 3', 5' monophosphate and lipolysis. Biochem. Pharmacol. 21, 589. ROSENQVIST, U. (1972) Inhibition of noradrenalineinduced lipolysis in hypothyroid subjects by increased alpha adrenergic responsiveness. Acta med. scand. 192, 535. ROSENQVIST, U. (1974a) Effect of bicarbonate and phosphate on the adrenergic receptor response in human adipose tissue in uitro. Acta med. scand. 195, 345. ROSENQVIST, U. (1974b) Demonstration of an enhanced alpha adrenergic receptor in human adipose tissue when incubated in presence of Li+ instead of N a + . Acta. med. scand. 196, 69. TITORBN, L. (1974) General metabolic response to trauma including pain influence. Acta arraesth. scand., Suppl. 55, 9.
J. G . & RUSSEL, b'.Y. (1971) 'The acute cardiovascular changes and adrenergic blockade by droperidol in man. Brif.3. Anaesth. 43, 581. YELNOSKY, J., KATZ, R. & DIETKICH, E. V. (1964) A study of some of the pharmacological actions 01' droperidol. Toxicol. appl. Pharniacol. 6, 37. WHITWAM,
Address: Jan Eklutid, M.D.
Department of Anaesthesiology Karolinska Hospital S-104-01 Stockholm 60 Sweden
A Comparison between the Influence of Halothane or Fentanyl and Droperidol Anaesthesia on the Adrenergic Receptor Response in Human Adipose Tissue in vitro U. ROSENQVIST, M. LINDHOLM and J. EKLUNU Departments of Internal Medicine and Anaesthesiology, Karolinska Hospital, Stockholm, Sweden
A comparison was made between the adrenergic receptor response in vitro in human adipose tissue obtained under halothane and neuroleptanaesthesia. In both groups the net release of glycerol was significantly stimulated (Pc0.01) by the combined alpha- and beta-adrenergic agonist, I-noradrenaline. In the halothane group, the lipolysis was further increased by the addition of phentolamine (an alpha-adrenergic blocking agent). No such effect could be demonstrated in specimens from the fentanyl/droperidol group. This difference in response was most probably explained by the fact that droperidol had quite a long-lasting alpha-adrenergic blocking property, which totally obliterated the effect of another alpha-adrenergic blocking agent. The findings stress the importance of using a standardized procedure, including the choice of anaesthetic agents, when human adipose tissue is sampled for metabolic studies in vitro. The results also indicate the possibility of a difference in metabolic effects in vivo between the two procedures.
Received 3 November, accepted for publication 16 December 1976
Human adipose tissue is an easily accessible in vitro adrencrgic receptor response of suborgan which has been used extensively for cutaneous adipose tissue. metabolic studies in vitro (BURNS& LANGLEY 1970, EFENDIC 1970, BJORNTORP & OSTMAN 1971, RODISON et al. 1972, ROSENQVIST 1972, METHODS ARNER1976). Since specimens are often Twenty-four subjects were studied. In 14, anaesthesia obtained from subjects under general anaes- was induced by a short-acting barbiturate, and by halothane and N 2 0 and 02.T h e thesia, we found it important to evaluate maintained remaining 10 subjects were operated on under neurothe effect of two commonly used anaesthetic lept anaesthesia (fentanyl and droperidol) with N 2 0 procedures on lipolysis and tissue response to and 02.Muscle relaxation was achieved either by adrenergic stimulation. An increased know- succinylcholine or pancuronium, and normoventilaledge of the effects of the two different anaes- tion was achieved by the use of a n Engstrom Ventilator (Jungner Medical, Sweden). The choice between the thetic procedures on the adrenergic receptor different anaesthetics was based upon the patients’ response might help to increase understanding physical condition. Halothane anaesthesia was used as of the metabolic changes observed in patients the routine method, while neurolept anaesthesia was during operation and in the postoperative preferred when the patients had a history of liver period. I n the present investigation, a comp- disease (including obstructive jaundice), had had a recent halothane anaesthetic or else were considered to arison was made between the effects of halo- be high risk patients due to heart or lung disease. All thane anaesthesia and so-called neurolept subjects were scheduled for elective surgery for either anaesthesia (fentanyl and droperidol) on the gall-bladder disease or peptic ulcers. At the time of
ANAESTHESIA AND ADRENERGIC RESPONSE
Anaesthetic procedure
n
Halothane
14
Fentanyldroperidol
Female
% of ideal
male
body weight
Age
50.3+ 1.6
10 -
-
10
53.1k2.6
5
I-noradrenaline plus 5 pg/ml phentolamine (Ph) or 5 pg/ml phentolamine alone (Mean+s.e. mean). Glycerol release (pmol/g ww/2h) Halothane Fentanyl-droperidol N = 14 N = 10
96.4k2.3
4 5
100.5+3.8
375
0.694k 0.133 0.974k 0.280 1.532k0.239 2.153k0.464 0.838 k 0 ~ 6 3 ~1.178 k 0.2 12’ 0.602 k0.212 0.986k0.227
Basal NA NA-basal Ph
~~~
~~
The P-values were calculated from the paired differences: 1) n.s. 2) P< 0.01 3) P< 0.001.
Net glycerol release
Net glycerol release
( p moles/g ww/2 h)
Ip
moles/g w w / 2 h )
4,
3
! A
0
0.02
0.2
2 NA x 10’
14 NA x lo5[M
Figs. 1 and 2. Lipolytic effect of different concentrations of I-noradrenaline (NA) in presence (0-0) and absence of 5 pg/ml phentolamine (0-0). Adipose tissue specimens were obtained from five subjects undergoing halothane anaesthesia (Fig. I ) and five subjects exposed to fentanyl-droperidol (Fig. 2) (Meanfsx. mean).
376
U . ROSENQVIST, M. LINDH0I.M A N D J. EKLUND
operation, all patients were in good health without signs of liver or metabolic disorders, and, in addition, all patients were drug-free. Subcutaneous adipose tissue was obtained from the abdominal wall at the beginning of the operation and transported in physiological saline a t 37°C to the laboratory. The tissue was then divided into 50-100 mg pieces and preincubated for 1 h at 37°C in KrebsHenseleit bicarbonate (KHB) buffer, p H 7.4, containing 1% bovine albumin (Fraction V, Armour Pharmaceutical Division). Separate pieces were then transferred to plastic vials containing 1.5 ml incubation medium made of KHB with 3% albumin, 1 mg/ml glucosc ( p H 7.4). Incubations were then carried out 1970). Glycerol for 2 h using air as gas phase (EFENDIC was determined fluorometrically according to CHERNICK (1969). The following agents were used: l-noradrenaline bitartrate (Astra, Sweden) and phentolamine (Regitine" Ciba, Switzerland).
Net glycerol release
( p moles/g ww/2 h)
7 2
1
b 0
I
1
0.02
0.2
2
A
14
NA x lo5[iv13
RESULTS The mean ages and percentages of' ideal body weights of the two groups of patients are shown in Table 1. There were no significant differences regarding these parameters between the groups. The proportion of female subjects was higher in the halothane group. The lipolytic response to the combined alpha- and beta-adrenergic agonist 1-noradrenaline (NA) is shown in Table 2. The net release of glycerol was significantly ( P < 0.00 1 ) stimulated in both groups. Phentolamine (Ph), an alpha-adrenergic blocking agent, did not by itself change the rate of lipolysis; however, in the presence of 1-noradrenaline [(NA+ Ph)-NA] it significantly (Pc0.01) increased lipolysis in the halothane group, while no such effect of alpha-adrenergic blockade could be demonstrated in specimens from the fentanyl-droperidol group. This finding was further explored by a doseresponse curve of 1-noradrenaline in the presence or absence of 5 pg/ml phentolamine. It has previously been shown that this concentration of the alpha-adrenergic antagonist completely blocks the alpha response of the tissue (EFENDIC1970). As seen in Figure 1, phentolamine markedly potentiated the lipolytic response to 1-noradrenaline in specimens from subjects undergoing halothane anaesthesia, while in the fentanyl-
L
Fig. 3. Net effect of 5 ,ug/ml of phentolamine in presence of different concentrations of 1-noradrenaline (NA) on specimens from subjects undergoing anacsthesia with halothane (0-0, N = 5) and fentanyldroperidol (0-0,N = 5) (Meanfs.e. mean).
droperidol group no significant effects of phentolamine were observed (Fig. 2). The net effect ofphentolamine [(NA+ Ph)-NA] in both groups of subjects is shown in Figure 3. It seems that the dose-response curve was shifted to the right in specimens from the fentanyl-droperidol group (Fig. 3). DISCUSSION The present study emphasized the necessity of controlling the anaesthetic procedures when studying human adipose tissue. Fentanyldroperidol anaesthesia obliterated the alphaadrenergic response in vitro in subcutaneous adipose tissue. O n the other hand, human adipose tissue obtained during halothane anaesthesia responded to both alpha- and beta-adrenergic stimulation. Alpha stimulation inhibits both basal and stimulated lipolysis (BURNS& LANCLEY1970, EFENDXC 1970) by suppression of the cyclic AMP production (ROBISON et al. 1972, GRILL& ROSENQVIST 1975), a process which seems to involve intracellular C a + + (ROSENQVIST 1974a,b). Beta-
ANAESTHESIA AND ADRENERGlC RESPONSE
377
adrenergic stimulation, 011 the other hand, In conclusion, the present investigation has stimulates the formation of cyclic AMP, and demonstrated that the alpha-antagonistic thereby the rate of lipolysis (BURNS & LANG- property of phentolamine in vitro is obliterated LEY 1970, EFENDIC 1970, ROBISON et al. 1972, in adipose tissue specimens from subjects GRILL& ROSENQVIST 1975). undergoing fentanyl-droperidol anaesthesia I n the course of these studies, we obtained when compared with specimens from subjects specimens from subjects operated upon under undergoing anaesthesia with halothane. This fentanyl-droperidol anaesthesia. The alpha- study stresses the importance of controlling receptor response could then no longer be the conditions for analgesia or anaesthesia and demonstrated. Droperidol is a potent neuro- of standardizing the procedure when using leptical agent with alpha-adrenergic blocking human adipose tissue for metabolic studies. properties (YELNOSKY et al. 1964, WHITWAM & RUSSEL1971). It is the recommended complement to the potent analgesic fentanyl. ACKNOWLEDGMENTS Droperidol has a relatively long biological This study was supported in part by grants from the half life, and, as shown in the present study, Swedish Medical Research Council 04223 and the its alpha-antagonistic effect remains in the Nordic Insulin Foundation. tissue after at least 1 h of preincubation. The effect of halothane on adipose tissue metabolism and the response to noradrenaline has REFERENCES been studied by BENNIS & SMITH( 1 973). They ARNER,P. (1976) Studies on the metabolism of human found that the basal release of glycerol was adipose tissue with special reference to the adrenergic significantly diminished, and that the anticontrol of lipolysis and the metabolism of partial acylgycerols.Thesis, Karolinska Institute, Stockholm. lipolytic effect of insulin was slightly less J. & SMITH,U.(1973) Effect of halothane on pronounced in specimens exposed to halo- BENNIS, lipolysis and lipogenesis in human adipose tissue. thane. O n the other hand, MAKELAINEN et Acta anaesth. scand. 17, 76. al. (1973a,b) found a stimulated lipolysis BJORNTORP, J. (1971) Human adipose P. & OSTMAN, after halothane exposure in rats both in vivo tissue dynamics and regulation. Advances in Metabolic Disorders, Vol. 5, ed. LEVINE,R. & LUFT,R. Acaand in vitro. They found, further, that this demic Press, New York and London, p. 277. lipolysis could be blocked by a beta-blocking BURNS,T. W. & LANGLEY, P. E. (1970) Lipolysis by agent (propanolol). human adipose tissue. The role of cyclic 3’, 5’Anaesthetic agents, therefore, can proadenosine monophosphate and adrenergic receptor foundly influence the susceptibility of tissue sites. 1.lab. Clin. Med. 75, 983. S.S. (1969) Determination of glycerol in to hormonal effects. Thus the choice of CHERNICK, Methods in Enzymologv, Lipids, Vol. 4, acyl glycerols. procedure has to be determined by the metaJ. M. Academic Press, New York ed. LOWENSTEIN, bolic parameters which are to be studied. and London, p. 627. Trauma and surgical stress certainly EFENDIC, S. (1970) Studies on the effect of catecholastimulate the sympathetic nervous system. mines on human adipose tissue metabolism. Thesis, Karolinska Institute, Stockholm. The metabolic consequences are numerous GRILL, V. & ROSENQVIST, U. (1975) Dynamics of alpha and include mobilization of free fatty acids, adrenergic inhibition of the adenyl cyclase-cyclic increased gluconeogenesis and glycolysis (cf. AMP system in human adipose tissue. Acta med. THORBN 1974). The present finding of a scand. 197, 283. marked inhibition of the alpha-adrenergic MAKELAINEN, A., NIKKI,P. & VAPAATALO, H. (1973a) Halothane-induced lipopolysis in rats. Acta anaesth. response in vitro by fentanyl-doperidol anaesscand. 17, 170. thesia raises the question of how the metaMAKELAINEN, A., VAPAATALO, H. & NIKKI,P. (1973b) bolism is affected during the operation and Halothane-induced lipolysis in uitro in the rat. Acta the post-operative period when neurolept anaesth. scand. 17, 179. anaesthesia is used. To our knowledge this ROBISON, G. A., LANGLEY, P. E. & BURNS, T. W. (1972) Adrenergic receptors in human adipocytes, divergent has not been fully explored.
378
U. ROSENQVIST, M . LINDHOLhf AND J . EKLUND
effects on adenosine 3', 5' monophosphate and lipolysis. Biochem. Pharmacol. 21, 589. ROSENQVIST, U. (1972) Inhibition of noradrenalineinduced lipolysis in hypothyroid subjects by increased alpha adrenergic responsiveness. Acta med. scand. 192, 535. ROSENQVIST, U. (1974a) Effect of bicarbonate and phosphate on the adrenergic receptor response in human adipose tissue in uitro. Acta med. scand. 195, 345. ROSENQVIST, U. (1974b) Demonstration of an enhanced alpha adrenergic receptor in human adipose tissue when incubated in presence of Li+ instead of N a + . Acta. med. scand. 196, 69. TITORBN, L. (1974) General metabolic response to trauma including pain influence. Acta arraesth. scand., Suppl. 55, 9.
J. G . & RUSSEL, b'.Y. (1971) 'The acute cardiovascular changes and adrenergic blockade by droperidol in man. Brif.3. Anaesth. 43, 581. YELNOSKY, J., KATZ, R. & DIETKICH, E. V. (1964) A study of some of the pharmacological actions 01' droperidol. Toxicol. appl. Pharniacol. 6, 37. WHITWAM,
Address: Jan Eklutid, M.D.
Department of Anaesthesiology Karolinska Hospital S-104-01 Stockholm 60 Sweden
