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Braz Dent J(1998) 9(1): 33-37 ISSN 0103-6440
Blood Glucose Determination
In
Normal and
Alloxan-Diabetic Rats After Administration of Local
Anesthetics Containing Vasoconstrictors
Luís A
.
ESMERINO
José RANALI
Antonio L
.
RODRIGUES Jr
.
Departamento de Ciências Fisiológicas, Faculdade de Odontologia de Piracicaba, UNICAMP, Piracicaba, SP, Brasil
Normal and alloxan-diabetic rats were injected submucously in the posterior region of the upper jaw with bupivacaine (1.28 mg/kg) containing adrenaline (0.0012 mg/kg), or lignocaine (5.14 mg/kg) containing noradrenaline (0.005 mglkg). Blood glucose was determined at zero (before adrninistration),0.5,1,2,3 and 4 hours after the administration ofthe anesthetics.Statistical analysis (ANOVA and Tukey's test, P<0.05) showed significant differences between treatments at 1 hour in normal rats.Bupivacaine with adrenaline induced a significantly greater blood glucose levei than lignocaine with noradrenaline. The effect was significant but of short duration. ln alloxan-diabetic rats, anesthetics containing adrenaline or noradrenaline did not induce increased blood glucoselevels,
Key Words: catecholamines,local anesthetics, vasoconstrictor agents.
Introduction
Adrenaline or other catecholamines are used as vasoconstrictors toincrease the efficiency of local anesthetic solutions. Vasoconstrictors promote longer lasting anesthe-sia (Keesling and Hinds, 1963), diminish the toxic effects by delaying absorption (Cannel et al., 1975; Caruana et al., 1982), and reduce blood loss in surgical procedures (Jastak and Yagiela, 1983).
However, catecholamines are involved in integrated metabolic alterations which affect carbohydrates, proteins and lipids(Cryer, 1984). Hyperglycemia may result from both direct and indirect action of adrenaline (Rizza et al., 1980a,b). Indirect hyperglycemic actions include suppression of insulin secretion. Direct hyperglycemic actions result from stimulation of hepatic glucose release and limitation of glucose utilization (Cryer and Gerich, 1983). A physiological rise in adrenaline can stimulate both glycogenolysis and gluconeogenesis (Cherrington et al., 1984). Although its effect on glycogenolysis wanes rapidly, hyperglycemia continues because of gluconeogenesis (Sherwin and Sacca, 1984).
An increase in blood glucose levels due to vasoconstrictors used with local anesthetics may be insignificant in normal patients, but can be relevant in diabetic patients.
The metabolic changes observed in untreated diabetics are, in many aspects, similar to those produced by infusion of catecholamines (Christensen, 1979). According to Sherwin
34 L.A.Esmerino et aI.
et aI.(1980), the hyperglycemic effects of adrenaline arenotably increased indiabetics. Experiments in dogs showed that administration of adrenaline increased blood
glucose to levelsmuch higher in diabetic dogs than in normal ones (Vranic et aI.,1984).Berk etal. (1982) observed similareffects in humans.
With increasing numbers of diabetic patients presenting for dental treatment, perhaps because of their improved longevity (Osie, 1990), it is important to investigate alterations in blood glucose levels in normal and diabetic rats treated with local anesthetics containing vasoconstrictors.
Material and Methods
AnimaIs
Sixty male Wistar rats weighing approximately 250 g, fed a balanced dietand water
ad libitum were used in the experiments. The rats were randomly divided into two groups:
30 normal rats and 30 alloxan-diabetic rats.
lnduction of diabetes
Diabetes was produced byasingle dose ofalloxan (150 mg/kg ip)after a 24-hour
fast. Two days after the administration of alloxan, blood glucose concentration was determined. AnimaIs having blood glucose concentration over 13.8 mmol/l were consi
d-ered diabetic. Hyperglycemic rats were given daily doses of 2 units of protamine zinc
insulin administered in the late afternoon, for a period not less than I week before being used in the experiment. AnimaIs with blood glucose levels between 8.3 and 19.4 mmol/l,
after a12-hour fast, were selected for use(Woodson and Potter, 1979).
Experimental procedures
Normal and diabetic rats were subdivided into 3 groups of 10 rats each. After a 12
-hour fast, they received submucous injections in the posterior region of the upper jaw of one of the following drugs: bupivacaine (1.28 mglkg) with adrenaline (0.0012 mglkg), lignocaine (5.14 mg/kg) with noradrenaline (0.005 mglkg), or saline (150 mmol/l),
Blood glucose determination
Blood samples were collected from the tail vein. To minimize stress, the animaIs were anesthetized with sodium pentobarbital (30 mg/kg ip), 15 minutes before the first sample. Collections weremade atO,0.5,1,2 and 3 hours afterthe administration ofthe drugs. From the diabetic rats one more sample was collected at 4 hours. Blood glucose concentration wasdetermined by the Haemo-Glukotest20-800-R and measurements read with a Reflolux"
test(Boehringer-Mannheim) (BrodricketaI., 1987).
Local anesthetics and blood glucose 35
Statistical analysis
Homogeneity of the data was verified by the "F-max" test.Afterwards, analysis of variance (ANOV A) was used in a completely randomized design, in which treatments were compared, considering each period separately. Each individual comparison was evaluated by Tukey's test (P<O.05).
Results
Mean blood glucose levels for the different treatments of normal rats are given in Table 1.The "F-max" testconfirmed homogeneity ofvariance allowing the use of ANOV A.
This revealed statistically significant differences between treatments at I hour. Tukey's test (P<O.05) showed that adrenaline containing local anesthetics induced a significantly greater blood glucose levei than the other injections at 1hour.
Mean blood glucose levels for the different treatments of alloxan-diabetic rats are given in Table 1.There were no statistically significant differences between the treatment groups.
Table I-Blood glucose concentration in normal and diabetic rats injected submucously with bupivacaine containing adrenaline, lignocaine containing noradrenaline, or saline.
AnimaIs and drugs
Blood glucose (mmolll)
o
h 0.5 h I h 2 h 3 h 4 h Normal rats Bupivacaine/ 4.34 ±0.11 4.55 ±0.24 4.73 ±0.13* 4.20 ±0.14 3.99 ±0.12 Adrenaline Lignocaine/ 4.60 ± 0.20 4.21 ±0.14 4.10 ± 0.19 4.30 ±0.25 3.98 ±0.16 Noradrenaline Saline 4.68 ±0.16 4.26 ± 0.12 3.87 ±0.11 3.97 ±0.13 3.61 ±0.11 Diabetic rats Bupivacaine/ 14.1 ± 1.9 16.5 ± 1.5 15.6 ± 1.7 15.6 ± 1.4 17.2 ±1.7 19.5±1.8 Adrenaline Lignocaine/ 14.0 ± 1.5 15.6 ± 1.5 15.2 ± 1.3 16.2 ±1.4 17.8 ± 1.2 18.6 ± 1.2 Noradrenaline Saline 15.2 ± 1.5 16.7 ± 1.3 16.5 ±1.4 17.5 ±1.5 18.0 ± 1.3 17.9± 1.4 *P<0.05 compared with lignocaine and salineMean±SE
36 L.A.Esmerino et ai.
Discussion
At 1 hour, normal rats showed statisticaIly significant differences between treat-ments. Tukey's test showed that bupivacaine with adrenaline induced a significantly greater blood glucose leveI than lignocaine with noradrenaline and saline at I hour. The increase in blood glucose at I hour with adrenaline is probably due to glycogenolysis (Sacca et aI., 1980). The effect was significant but of short duration. Another factor that might have contributed to raise the glucose levels at 1 hour is the antagonistic effect of adrenaline at the periphery and in the liver (Sherwin and Sacca, 1984). According to Robertson and Potter (1973), the potent anti-insulin effects of adrenaline invivo may be explained by itsunique capacity to interfere with insulin action as well as insulin secretion.
The lack of effect at 2 and 3 hours may be due to a lack of gluconeogenesis,
although Sherwin and Sacca (1984) reported that an accentuated adrenaline-induced
hyperglycemia is observed with gluconeogenesis. This observation suggests that hyper-glycemia· induced by local anesthetic solutions containing catecholamines is not very significant in normal animaIs. It should also be noted that we used very high doses.
Blood glucose levels in alloxan-diabetic rats showed great variation (8.3 to 19.4 mmol/l). There was no statistically significant difference between experimental groups at time O(zero), showing that glycemia in diabetic animaIs was similar at the beginning of the experiment.
The anesthetics containing adrenaline or noradrenaline used did not modify glu-cose levels in diabetic rats. This was unexpected since the effects of catecholamines in diabetics are moreevident (Vranic et aI., 1984).
Although anesthetized, the animaIs might have altered blood glucose levels due to stress during blood sampling. Furthermore, the 12-hour fast and the duration of the experiment could have led to a greater requirement for insulin, because animais had been controlled with daily doses of insulin previously. Blood glucose levels may have risen due to gluconeogenesis (Sherwin and Sacca, 1984), in theabsence ofinsulin.
As there was no statistical difference in blood glucose levels in diabetic rats at all times tested, there was possibly no glycogenolysis or gluconeogenesis. Therefore, it was concluded that in the experimental model used, local anesthetics containing adrenaline or noradrenaline did not increase blood glucose levels in alloxan-diabetic rats,
Bra:DentJ 9(1) J998
References
Berk MA,Clutter WE,Skor D,Sharh SD:Enhanced glycemic responsivenessto epinephrine in ins ulin-dependent diabetes mellitus is the result of the inability of secrete insulin. J Clin Invest 75:
1842-1851, 1982
Brodrick JM,Colloby PS,Legg EI:Comparison of twonewward-basedglucosemeters.Prat Diabetes4:
170-172, 1987
CannelL, Beckett AH,Walters H,SaundersA:Circulatinglevelsof lignocaineafter peri-oral injections. Br Dent J 138: 87-93, 1975
Local anesthetics and blood glucose 37
anaesthesia. J Dent 10: 140-143, 1982
Cherrington AD, Fucks H, Stevenson RW, Williams PE, Alberti KGMM, Steiner KE: Effect of epinephrine on glycogenolysis and gluconeogenesis in conscious overnight-fasted dogs. Am J
Physiol 247: EI37-144, 1984
Christensen Nl: Catecholamines and diabetes mellitus. Diabetologia 16:211-224, 1979 Cryer PE: Catecholamines and metabolism. Am 1Physiol 247: EI-3, 1984
Cryer PE, Gerich JE: Relevance of glucose counterregulatory system to patients with diabetes: Critical roles of glucagon and epinephrine. Diabetes Care 6: 95-99, 1983
lastak JT, Yagiela JA:Vasoconstrictors and localanesthesia: A review and rationale for use. J AmDent Assoe 107: 623-630, 1983
Keesling GR, Hinds EC: Optimal concentrationsofepinephrine in lidocaine solutions.J Am Dent Assoe 66: 337-340, 1963
Osie AM: Management of diabetic dental patient. Quintessence Int 21: 491-494, 1990
RizzaRA,Cryer PE,Haymond MW,Gerich JE: Adrenergic mechanisms for the effects ofepineprine on
glucose production and cJearancein mano1Clin Invest 65: 682-689, 1980a
Rizza RA, Haymond MW, Miles 1M, Verdonk CA, Cryer PE, Gerich JE: Effect of a-adrenergic stimulation and itsblockade on glucose turnover in manoAm J Physiol 238: E466-472, 1980b Robertson RP, Potter DI: Adrenergic modulation of basal insulin secretion in manoDiabetes 22: 1-8,
1973
Sacca L, Morrone G, Cicala M, Corso G, Ungaro B: Influence of epinephrine, norepinephrine, and isoproterenol on glucose homeostasis in normal mano1Clin Endocr Metab 50: 680-684, 1980 Sherwin SR,SaccaL:Effect ofepinephrineon glucosemetabolism in humans:contribution of liver.Am
1 Physiol 247: EI57-165, 1984
Sherwin RS, Sharmoon H, Hendler R, Sacca L, Eigler N, Walesky M:Epinephrine and regulation of glucose metabolism: Effect of diabetes and hormonal interaction. Metabolism 29: 1146-1154, 1980
Vranic M,Gauther C,Bilinski D,Wasserman D,Tayer REL,Hetenyil E,LickeleyHLA:Catecholamine responses and their interactions with other glucoregulatory hormones. Am J Physiol 247: E145
-156, 1984
Woodson LC, Potter DE:The influenceofendogenous glucagon release on hyperglycemic responsesto catecholamines in normal fed and diabetic rats.J Pharmacol Exp Ther 210: 458-464, 1979 Correspondence: Dr.José Ranali, Departamento de CiênciasFisiológicas, Faculdade de'Odontologia de Piracicaba, UNICAMP, Av. Limeira 901, 13414-018 Piracicaba, SP, Brasil.
Accepted January 4, 1998
