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The Effect of Ketalar on the Adrenal Gland of Young White Leghorn Cockerels
1014
T. F. SHARBY, G. E. TEMPLETON, J. N. BEASLEY AND E. L. STEPHENSON
toxicosis of certain fungi in chickens. Avian Dis. 9: 57-66. Duncan, D. B., 1955. Multiple range and multiple F tests. Biometrics, 11: 1-42. Forgacs, J., 1966. Mycoses and mycotoxicosis in poultry. Part II. Feedstuffs, 38(11): 26, 30, 71. Lovett, Jr., 1972. Toxigenic fungi from poultry feed and litter. Poultry Sci. 51: 309-313. Meronuck, R. A., K. H. Garren, C. M. Christensen, G. H. Nelson and F . Bates, 1970. Effects on
turkey poults and chicks of rations containing corn invaded by Penicillium and Fusarium species. Amer. J. Vet. Res. 31: 551-555. Richardson, L. R., S. Wilkes, J. Godwin and K. R. Pierce, 1962. Effect of moldy diet and moldy soybean meal on the growth of chicks and poults. J. Nutr. 78: 301-306. Steel, R. G. D., and J. H. Torrie, 1960. Principles and Procedures of Statistics. McGraw-Hill Book Co., Inc., New York, New York.
ROBERT B. CHIASSON, ALFRED S. EGGE 1 AND BURTON LYNCH JR. 2 Department of Biological Sciences, University of Arizona, Tucson, Arizona 85721 (Received for publication September 6, 1972) ABSTRACT Intramuscular injection of the non-barbiturate anesthetic Ketamine Hydrochloride produces rapid atrophic effects in the adrenal gland of young White Leghorn cockerels. Signs of recovery from the atrophic effects are recorded five days following injection of the drug. POULTRY SCIENCE 52: 1014-1018, 1973
INTRODUCTION
T
HE fine review by Frankel (1970) of the avian adrenal gland clearly points out the need for much additional work before we have as clear an understanding of adrenal function in birds as we have in mammals. Literature supporting a functional zonation in the avian adrenal is far more convincing than a morphological zonation; neither zonation is as clearly defined as it is in mammals. Studies reporting adrenal hypertrophy or adrenal atrophy (Miller and Riddle, 1942; Brown et al., 1958; and Frankel et al., 1967) have described these conditions in terms of adrenal weight or histo-
1 Department of Biology, California State College San Bernardino, California 92407 2 Fellow N.I.D.R. Trgn. Grant 5TIDE184 University of Arizona 85721.
logical appearance. A hypertrophic gland is reported to have a relatively large weight compared to a normal one, while an atrophic gland is reported to have a lighter weight than a normal one. Miller and Riddle (1942) describes the atrophic adrenal as one consisting of "reduced central strands of cortex (interrenal tissue) . . ." that the ". . . atrophy is the result of reduced volume of cortical cells and a smaller total number of cells, diminished by death and a lower rate of replacement." The data reported in this paper is concerned with the atrophic effects in the avian adrenal with the use of the nonbarbiturate anesthetic Ketalar. This is the Park-Davis brand name for Ketamine Hydrochloride, which is chemically designated dl 2-(o-chloro-phenyl)-2-(methylamino) cyclohexanone hydrochloride.
Downloaded from http://ps.oxfordjournals.org/ at D H Hill Library - Acquis Dept S on March 16, 2015
The Effect of Ketalar on the Adrenal Gland of Young White Leghorn Cockerels
1015
KETALAR AND THE ADRENAL EXPERIMENTAL PROCEDURE
T™„(m » Treatment % Adrenal wt. (mg.)
A (4) Normal, n0
treatment 13.5 + 0.7
B (5) Chloroform
a n d s h a m-
lesion
C (8) Ketalar and shamlesion
13.4 + 0. o 11.1 ± 0 . 3 *
Eody weight (gm.) * Reduction statistically significant, p < 0.005.
Ketalar per kilogram body weight of the bird. Both groups were maintained on a normal diet for five days. At the end of this period the animals were killed and their adrenals were prepared as in group A. The adrenals of all birds were embedded in paraffin and stained with hematoxylin and eosin. RESULTS AND DISCUSSION
The adrenal weights of group C birds
PIG. 1. Sections of cockerel adrenals through the peripheral region of the glands. Magnification = 153X. A. adrenal of a normal, untreated bird. B. adrenal of a sham operated bird anesthetized with Ketalar.
Downloaded from http://ps.oxfordjournals.org/ at D H Hill Library - Acquis Dept S on March 16, 2015
Young (5-6 weeks old) White Leghorn cockerels raised by the University of Arizona Poultry F a r m were used for this study. Body weights ranged from 411 to 692 grams. Adrenal weights and histological d a t a were collected from three groups designated A, B, and C. Group A consisted of untreated normal cockerels. Four animals were randomly selected and then killed. Their adrenals were immediately removed, weighed, and fixed in Bouin's solution. Groups B and C were diencephalic sham lesioned in a stereotaxic instrument. The groups differed from one another only in the kind of anesthetic used to prepare them for the sham lesion surgery. Group B was anesthetized with chloroform (through inhalation), while group C was anesthetized with 100 mg. of
TAHI.K 1. Effect of two anesthetics on adrenal weight. Values are means±standard errors. Figures in parentheses indicate number of animals tested
1016
R. B. CHIASSON, A. S. E G G E AND B. L Y N C H , J R .
B
FIG. 2. Sections of cockerel adrenals through the central region of the glands. Magnification = 153X. A. adrenal of a normal, untreated animal. B. adrenal of a sham operated bird anesthetized with Ketalar. were significantly lower t h a n either of the other two groups of birds (see Table 1). Although group C has an obviously lower number of cells compared to either group A or B, the cells present appear to be more characteristic of hypertrophied cells than of atrophic ones (see Figs. 1 and 2). The interrenal cords in the subcapsular region are large with round distinct nuclei surrounded by a well defined cytoplasm. The interrenal tissue in the mid-zone of the gland is likewise large and well defined rather than thin and pycnotic as is characteristic of an atrophic gland (Fig. 3). The chromaffin tissue is easily differentiated from the interrenal tissue and is scattered throughout the gland (see Fig.
4). This seemingly paradoxical situation of an atrophic gland with what appears to be hypertrophic cells can probably be explained as a short term effect of Ketalar. The initial effect may be an acute atrophic one, followed by a reactivation of the gland once the Ketalar is metabolized or eliminated from the body. The histological appearance of group B was similar to that of group A (see Fig. 4A and 4B). Both the reduced weight and the obviously lower number of cells throughout the interrenal tissue of birds anesthetized with Ketalar suggests t h a t their adrenals have become atrophic. Unlike reports in the literature concerning atrophic adrenal
Downloaded from http://ps.oxfordjournals.org/ at D H Hill Library - Acquis Dept S on March 16, 2015
A
KETALAR AND THE ADRENAL
The dramatic histologic changes that occur in the young cockerel adrenal glands following injection of Ketalar suggests that one might find some dramatic physiological changes in adrenal function with
the use of this anesthetic. Although this paper does not provide data as to where the site of action for Ketalar is in the bird, it is our hope that it will contribute to future studies dealing with the problem of pituitary a n d / o r extrapituitary regulation of avian adrenal function. ACKNOWLEDGMENTS
This study was supported in p a r t by N . I . D . R . Training Grant 5-T 1-DE 184 (Program Director R. B . Chiasson). Cockerels used in this study were supplied through the generosity of Dr. B. L. Reid, D e p a r t m e n t of Poultry Science, University of Arizona. Ms. Lacey Scanlan performed the histological techniques and Dr. W. R. Ferris and Ms. Mardi Wolford
#
*
FIG. 3. Normal A, and Ketalar treated (B) adrenals. Note the greater amount of cytoplasm and the increased reticulation of the Ketalar treated gland. Magnification = 604X-
Downloaded from http://ps.oxfordjournals.org/ at D H Hill Library - Acquis Dept S on March 16, 2015
glands (Miller and Riddle, 1942; Brown el al., 1958; and Frankel el al., 1967), (he interrenal tissue throughout the gland appeared more normal or hypertrophic than atrophic. Since the data reported here represents an effect five days following the intramuscular injection of Ketalar, it is quite possible t h a t the atrophic influence of Ketalar had terminated and the glands were beginning to recover. This could explain the active-looking cell structure in the otherwise small atrophic appearing gland.
1017
1018
R. B. CHIASSON, A. S. EGGE AND B. LYNCH, J R .
\
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FIG. 4. Whole cross sections of adrenal glands of White Leghorn cockerels magnified 2X. A. h from a normal, untreated bird, B, section from a chloroform anesthetized, sham operated bird, and C is from a Ketalar anesthetized, sham operated cockerel.
are gratefully acknowledged for their assistance in the preparation of photomicrographs. REFERENCES Brown, K. I., D. Brown and R. Meyer, 1958. Effect of surgical trauma, ACTH, and adrenal cortical hormones on electrolytes, water balance, and gluconeogensis in male chickens. Amer. J. Physiol. 192:43-50.
Frankel, A., J. W. Graber and A. V. Nalbandov, 1967. The effect of hypothalamic lesions on adrenal function in intact and adenohypophysectomized cockerels. Gen. Comp. Endocrinol. 8: 387-396. Frankel, A., 1970. Neurohumoral control of the avian adrenal: a review. Poultry Sci. 49: 869-921. Miller, R. A., and 0 . Riddle, 1942. The cytology of the adrenal cortex of normal pigeons and in experimentally induced atrophy and hypertrophy. Amer. J. Anat. 71:311-341.
AUGUST 11-16, 1974. CONGRESS, WORLD'S POULTRY SCIENCE ASSOCIATION, NEW ORLEANS, LOUISIANA, U.S.A. SEPTEMBER 22-27, 1974. IV INTERNATIONAL CONGRESS OF FOOD SCIENCE AND TECHNOLOGY, MADRID, SPAIN AUGUST 6-10, 1973 SIXTY-SECOND ANNUAL MEETING POULTRY SCIENCE ASSOCIATION, SOUTH DAKOTA STATE UNIVERSITY, BROOKINGS
Downloaded from http://ps.oxfordjournals.org/ at D H Hill Library - Acquis Dept S on March 16, 2015
\
T. F. SHARBY, G. E. TEMPLETON, J. N. BEASLEY AND E. L. STEPHENSON
toxicosis of certain fungi in chickens. Avian Dis. 9: 57-66. Duncan, D. B., 1955. Multiple range and multiple F tests. Biometrics, 11: 1-42. Forgacs, J., 1966. Mycoses and mycotoxicosis in poultry. Part II. Feedstuffs, 38(11): 26, 30, 71. Lovett, Jr., 1972. Toxigenic fungi from poultry feed and litter. Poultry Sci. 51: 309-313. Meronuck, R. A., K. H. Garren, C. M. Christensen, G. H. Nelson and F . Bates, 1970. Effects on
turkey poults and chicks of rations containing corn invaded by Penicillium and Fusarium species. Amer. J. Vet. Res. 31: 551-555. Richardson, L. R., S. Wilkes, J. Godwin and K. R. Pierce, 1962. Effect of moldy diet and moldy soybean meal on the growth of chicks and poults. J. Nutr. 78: 301-306. Steel, R. G. D., and J. H. Torrie, 1960. Principles and Procedures of Statistics. McGraw-Hill Book Co., Inc., New York, New York.
ROBERT B. CHIASSON, ALFRED S. EGGE 1 AND BURTON LYNCH JR. 2 Department of Biological Sciences, University of Arizona, Tucson, Arizona 85721 (Received for publication September 6, 1972) ABSTRACT Intramuscular injection of the non-barbiturate anesthetic Ketamine Hydrochloride produces rapid atrophic effects in the adrenal gland of young White Leghorn cockerels. Signs of recovery from the atrophic effects are recorded five days following injection of the drug. POULTRY SCIENCE 52: 1014-1018, 1973
INTRODUCTION
T
HE fine review by Frankel (1970) of the avian adrenal gland clearly points out the need for much additional work before we have as clear an understanding of adrenal function in birds as we have in mammals. Literature supporting a functional zonation in the avian adrenal is far more convincing than a morphological zonation; neither zonation is as clearly defined as it is in mammals. Studies reporting adrenal hypertrophy or adrenal atrophy (Miller and Riddle, 1942; Brown et al., 1958; and Frankel et al., 1967) have described these conditions in terms of adrenal weight or histo-
1 Department of Biology, California State College San Bernardino, California 92407 2 Fellow N.I.D.R. Trgn. Grant 5TIDE184 University of Arizona 85721.
logical appearance. A hypertrophic gland is reported to have a relatively large weight compared to a normal one, while an atrophic gland is reported to have a lighter weight than a normal one. Miller and Riddle (1942) describes the atrophic adrenal as one consisting of "reduced central strands of cortex (interrenal tissue) . . ." that the ". . . atrophy is the result of reduced volume of cortical cells and a smaller total number of cells, diminished by death and a lower rate of replacement." The data reported in this paper is concerned with the atrophic effects in the avian adrenal with the use of the nonbarbiturate anesthetic Ketalar. This is the Park-Davis brand name for Ketamine Hydrochloride, which is chemically designated dl 2-(o-chloro-phenyl)-2-(methylamino) cyclohexanone hydrochloride.
Downloaded from http://ps.oxfordjournals.org/ at D H Hill Library - Acquis Dept S on March 16, 2015
The Effect of Ketalar on the Adrenal Gland of Young White Leghorn Cockerels
1015
KETALAR AND THE ADRENAL EXPERIMENTAL PROCEDURE
T™„(m » Treatment % Adrenal wt. (mg.)
A (4) Normal, n0
treatment 13.5 + 0.7
B (5) Chloroform
a n d s h a m-
lesion
C (8) Ketalar and shamlesion
13.4 + 0. o 11.1 ± 0 . 3 *
Eody weight (gm.) * Reduction statistically significant, p < 0.005.
Ketalar per kilogram body weight of the bird. Both groups were maintained on a normal diet for five days. At the end of this period the animals were killed and their adrenals were prepared as in group A. The adrenals of all birds were embedded in paraffin and stained with hematoxylin and eosin. RESULTS AND DISCUSSION
The adrenal weights of group C birds
PIG. 1. Sections of cockerel adrenals through the peripheral region of the glands. Magnification = 153X. A. adrenal of a normal, untreated bird. B. adrenal of a sham operated bird anesthetized with Ketalar.
Downloaded from http://ps.oxfordjournals.org/ at D H Hill Library - Acquis Dept S on March 16, 2015
Young (5-6 weeks old) White Leghorn cockerels raised by the University of Arizona Poultry F a r m were used for this study. Body weights ranged from 411 to 692 grams. Adrenal weights and histological d a t a were collected from three groups designated A, B, and C. Group A consisted of untreated normal cockerels. Four animals were randomly selected and then killed. Their adrenals were immediately removed, weighed, and fixed in Bouin's solution. Groups B and C were diencephalic sham lesioned in a stereotaxic instrument. The groups differed from one another only in the kind of anesthetic used to prepare them for the sham lesion surgery. Group B was anesthetized with chloroform (through inhalation), while group C was anesthetized with 100 mg. of
TAHI.K 1. Effect of two anesthetics on adrenal weight. Values are means±standard errors. Figures in parentheses indicate number of animals tested
1016
R. B. CHIASSON, A. S. E G G E AND B. L Y N C H , J R .
B
FIG. 2. Sections of cockerel adrenals through the central region of the glands. Magnification = 153X. A. adrenal of a normal, untreated animal. B. adrenal of a sham operated bird anesthetized with Ketalar. were significantly lower t h a n either of the other two groups of birds (see Table 1). Although group C has an obviously lower number of cells compared to either group A or B, the cells present appear to be more characteristic of hypertrophied cells than of atrophic ones (see Figs. 1 and 2). The interrenal cords in the subcapsular region are large with round distinct nuclei surrounded by a well defined cytoplasm. The interrenal tissue in the mid-zone of the gland is likewise large and well defined rather than thin and pycnotic as is characteristic of an atrophic gland (Fig. 3). The chromaffin tissue is easily differentiated from the interrenal tissue and is scattered throughout the gland (see Fig.
4). This seemingly paradoxical situation of an atrophic gland with what appears to be hypertrophic cells can probably be explained as a short term effect of Ketalar. The initial effect may be an acute atrophic one, followed by a reactivation of the gland once the Ketalar is metabolized or eliminated from the body. The histological appearance of group B was similar to that of group A (see Fig. 4A and 4B). Both the reduced weight and the obviously lower number of cells throughout the interrenal tissue of birds anesthetized with Ketalar suggests t h a t their adrenals have become atrophic. Unlike reports in the literature concerning atrophic adrenal
Downloaded from http://ps.oxfordjournals.org/ at D H Hill Library - Acquis Dept S on March 16, 2015
A
KETALAR AND THE ADRENAL
The dramatic histologic changes that occur in the young cockerel adrenal glands following injection of Ketalar suggests that one might find some dramatic physiological changes in adrenal function with
the use of this anesthetic. Although this paper does not provide data as to where the site of action for Ketalar is in the bird, it is our hope that it will contribute to future studies dealing with the problem of pituitary a n d / o r extrapituitary regulation of avian adrenal function. ACKNOWLEDGMENTS
This study was supported in p a r t by N . I . D . R . Training Grant 5-T 1-DE 184 (Program Director R. B . Chiasson). Cockerels used in this study were supplied through the generosity of Dr. B. L. Reid, D e p a r t m e n t of Poultry Science, University of Arizona. Ms. Lacey Scanlan performed the histological techniques and Dr. W. R. Ferris and Ms. Mardi Wolford
#
*
FIG. 3. Normal A, and Ketalar treated (B) adrenals. Note the greater amount of cytoplasm and the increased reticulation of the Ketalar treated gland. Magnification = 604X-
Downloaded from http://ps.oxfordjournals.org/ at D H Hill Library - Acquis Dept S on March 16, 2015
glands (Miller and Riddle, 1942; Brown el al., 1958; and Frankel el al., 1967), (he interrenal tissue throughout the gland appeared more normal or hypertrophic than atrophic. Since the data reported here represents an effect five days following the intramuscular injection of Ketalar, it is quite possible t h a t the atrophic influence of Ketalar had terminated and the glands were beginning to recover. This could explain the active-looking cell structure in the otherwise small atrophic appearing gland.
1017
1018
R. B. CHIASSON, A. S. EGGE AND B. LYNCH, J R .
\
\
\
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FIG. 4. Whole cross sections of adrenal glands of White Leghorn cockerels magnified 2X. A. h from a normal, untreated bird, B, section from a chloroform anesthetized, sham operated bird, and C is from a Ketalar anesthetized, sham operated cockerel.
are gratefully acknowledged for their assistance in the preparation of photomicrographs. REFERENCES Brown, K. I., D. Brown and R. Meyer, 1958. Effect of surgical trauma, ACTH, and adrenal cortical hormones on electrolytes, water balance, and gluconeogensis in male chickens. Amer. J. Physiol. 192:43-50.
Frankel, A., J. W. Graber and A. V. Nalbandov, 1967. The effect of hypothalamic lesions on adrenal function in intact and adenohypophysectomized cockerels. Gen. Comp. Endocrinol. 8: 387-396. Frankel, A., 1970. Neurohumoral control of the avian adrenal: a review. Poultry Sci. 49: 869-921. Miller, R. A., and 0 . Riddle, 1942. The cytology of the adrenal cortex of normal pigeons and in experimentally induced atrophy and hypertrophy. Amer. J. Anat. 71:311-341.
AUGUST 11-16, 1974. CONGRESS, WORLD'S POULTRY SCIENCE ASSOCIATION, NEW ORLEANS, LOUISIANA, U.S.A. SEPTEMBER 22-27, 1974. IV INTERNATIONAL CONGRESS OF FOOD SCIENCE AND TECHNOLOGY, MADRID, SPAIN AUGUST 6-10, 1973 SIXTY-SECOND ANNUAL MEETING POULTRY SCIENCE ASSOCIATION, SOUTH DAKOTA STATE UNIVERSITY, BROOKINGS
Downloaded from http://ps.oxfordjournals.org/ at D H Hill Library - Acquis Dept S on March 16, 2015
\