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Role of taurine in furazolidone-induced cardiomyopathy
Comp.Biochrm. Physiol. Vol. 72C, NO. I. pp. 137-140. 1982 Printed in Great Britain
030~4492182/030137-04u)3.00/0 Q 1982Pergamon Press Ltd
ROLE OF TAURINE IN FURAZOLIDONE-INDUCED CARDIOMYOPATHY STEPHEN W. SCHAFFER.’CAROLINE M. CZARNECKI~ and JAMES MCCLUNE’ ‘University of South Alabama. College of Medicine. Department of Pharmacology. Mobile. AL 36688. U.S.A.: and ‘Department of Veterinary Biology. College of Veterinary Medicine. University of Minnesota. St Paul. MN 55108. U.S.A. (Receiwd 14 Srptenther 1981) Abstract--l. Taurine levels were determined in the heart. brain. and red and white muscle of turkey poults fed furazolidone (FZ) at a dose of 700 ppm from 2 to 5 weeks of age and/or 0.1 M taurine from 1 to 5 weeks of age. 2. In FZ-fed poults. taurine levels in the myocardium decreased significantly (P < 0.001). but not in brajn or muscle indicating a specific effect of FZ on the heart. 3. Exogenous administration of taurine significantly (P < 0.001) increased taurine content of brain and muscle in all poults. 4. Myocardial taurine levels were significantly elevated (P c 0.01) in poults fed a normal ration. but not in those fed FZ. 5. Although taurine treatment restored myocardial taurine to normal levels in the FZ-fed poults. the treatment did not decrease the incidence of FZ-induced cardioyopathy. 6. Since taurine is a membrane stabilizer and protects against calcium overload. our data suggests that sarcolemmal damage leading to tissue calcium overload is not the mechanism of the furazolidonemediated syndrome.
INTRODUCl.ION
Round heart is an avian cardiomyopathy which occurs either spontaneously in turkeys or can be induced by inclusion of the antibiotic furazolidone (FZ) in the animals feed (Czamecki er al.. 1973; Jankus et al., 1972). The syndrome is characterized by ventricular hypertrophy and dilatation, marked loss of contractile elements, dilatation of the sarcoplasmic reticulum and massive accumulation of glycogen (Czarnecki, 1980; Sautter et a/., 1968; Staley et al., 1978; Wilson & Siller, 1954). Similar degenerative changes have been described for other cardiomyopathies, such as the Syrian hamster (Lochner et al., 1970). Based on evidence that calcium regulators, such as taurine and verapamil prevent both massive accumulation of calcium by the heart and the development of myocardial lesions (Azari er al.. 1980; Jasmin & Bajusz, 1975), it has been proposed that disturbed myocardial calcium metabolism is a decisive pathogenetic factor in the cardiomyopathic hamster. Welty & Welty (1981) have reported that taurine protects against calcium overload in the Syrian hamster by preventing gross sarcolemmal dysfunction. Since defects in sarcolemmal function were also observed in round heart (Schaffer et al., 1981), it was felt that the basis for the two syndromes may be similar. This hypothesis was tested in this study. METHODSAND MATERIALS Broad-Breasted White Turkey poults were obtained from a single hatch of a large breeder strain. At 1 week of age, the poults were placed in one of two groups. One group of 40 poults was maintained on a normal ration and water ad lib while a second group of 40 poults was maintained on a normal ration and 0.1 M taurine ad lib. At 2 137
weeks of age, the poults were screened utilizing the electrocardiographic (ECG) technique developed by Jankus et al. (1971) and modified by Czarnecki & Good (1980). Poults from each group were placed randomly in one of two pens: Group I: control pen-normal ration and water ad lib, FZ pen-FZ at 700ppm and water ad lib; Group II: taurine pen-normal ration and 0.1 M taurine daily ad lib, FZtaurine pen-FZ at 700 ppm and 0.1 M taurine daily ad lib. At 4 and 5 weeks of age, six poults from each of the pens were selected for sacrifice by cervical dislocation. At sacrifice tissue samples from the right ventricular free wall, brain. and tibialis anterior and pectoralis major muscles were excised quickly. quenched in liquid nitrogen, freeze dried, and assayed for taurine using the method described previously (Schaffer et al., 1981). The data for poults 4 and 5 weeks of age were pooled since these did not differ significantly from each other. A daily record of water consumption per pen was kept. The daily water intake/poult was computed. tallied for each week. and comparisons were made between control and experimental pens on a weekly basis.
RESULTS
The taurine data is shown in Table 1. As demonstrated in a previous study (Schaffer et al., 1981) myocardial taurine levels were decreased significantly (P < 0.001) in FZ-fed poults. This effect is specific for the heart since FZ did not influence taurine content of either muscle or brain. Taurine treatment significantly (P < 0.001) elevated taurine levels in muscle and brain of all poults and in heart (P c 0.01) of taurinefed poults. In poults fed both FZ and taurine, myocardial taurine was restored to normal levels. The average daily water consumption per poult is shown in Table 2. Poults fed taurine consumed more water than did the control poults. This difference became more significant with age. Poults fed both
138
STEPHEN
W. SCHAFFERet nl.
Table I. Effect of taurine feeding on taurine tissue levels* of control and FZ-fed turkey poults PEN Control
Tissue Muscle red white Brain Heart
FZ
Taurine
i7.9 & 5.31(n): 69.7 k 5.1 (12) 8.3 + 0.7(12) 7.9 c 0.6(12) 48.1 f 2.0(12) 46.8 Itr 1.9 (11) 155.9 + 5.0(11) 109.1 + 9.9 (9)9
108.9 i_ 21.3 + 100.3 + 182.5 k
FZ-taurine
6.5 (12)# l.O(ll)$ 3.8 (I’)$ 7.2(11)1’
107.2 + 8.6(11)$ 35.2 k 6.7(11)$ 98.7 +_4.9 (12)$ 162.6 + 7.0(10)
* prnolig dry weight of tissue. tMean k SEM. : Number of samples. $ Significant difference from the control (P < 0.001). $1 Significant difference from the control (P c O.OlL
taurine and furazolidone consumed significantly more water at all ages studied. These differences were highly significant (P < 0.001) during the third and fifth weeks. The ECG data is shown in Table 3. Control and taurine-fed poults had similar ECG patterns as did the FZ-fed and the FZ-taurine poults indicating that taurine has little or no effect on ECGs. Average body weights of poults are shown in Table 4. As demonstrated in an earlier study (Czarnecki et al., 1974), FZ significantly (P < 0.001) depressed body weights. Although taurine-fed poults tended to be heavier than control poults. these differences were not significant. Poults fed both taurine and FZ tended to
be lighter than poults receiving FZ, but no significant differences were observed. DISCL’SSION
Taurine is a potent inhibitor of neuronal activity. In a variety of neuronal preparations, taurine has been found to produce hyperpolarization, decrease membrane conductance. and increase permeability to specific ions (Oja rr al.. 1977). Taurine has been reported to alter conditioned eating and drinking, cause hypothermia, inhibit acquisition of avoidance conditioned reflexes and prevent certain types of seizures (Mandel & Pasantes-Morales. 1978). In this
Table 2. Average daily water consumption/week (g/poult) of turkey poults fed normal or FZ rations and water or 0.1 M taurine PEN Week 2 3 4 5
FZ
Control 105.7 * 167.9 f. 745 4 + ;18:0 ;
3.0’ (39)t 3.9 (22) 7.7 (22) 9.0(9)
Taurine
148.4 k 2.7 (15,: 172.7 k 8.6(15)$ 295.4 f 11.5 (9)
133.i & 183.9 2 338.3 F 407.3 *
2.6 139): 5.1 (19) 16.0(19)‘: 17.3(9)$
FZ-taurine 207.7 & 5.7 (15)$ 284.0 k 7.9 (14): 381.2 + 9.2 (8)$
* Mean + SEIM. t Number of poults. $ Significant difference from the control (P < 0.05). $ Significant difference from the control (P < 0.001). $1 Significant difference from the control (P < 0.01).
Table 3. ECG data for turkey poults maintained on a normal or FZ ration and water or 0.1 M taurine
Age
PEN
(weeks)
Control
2
15N” 14N, lN, 15N 9N
3 4 5
FZ
Taurine
FZ-taurme
15N 15N 13N, lN,, 1NT SN, 6Nu. 1NT 8N. 6N,, 1R 14N, lN, 6N. lNH, 1NT. ?R, 5R 15N 7N, 2NT. IRT, 4R 6N. INT, 1RT 9N 5N, 2N,, 2R
* ECG: N-normal: ?I,-voltage > 0.1 mV in R wave of Lead I: NT-R wave > 0.1 mV < S wave of Lead II (aVF): RT-R wave > 0.1 mV > S wave of Lead II (aVF); R-R wave > 2S wave of Lead II (aVF).
Taurine in FZ-induced cardiomyopath!
139
Table 4. Average body weights(g) of turkey poults fed normal or FZ rations and water or 0.1 M taurrne PENS
Week 2 3 4 5
Control 310.1 k 6.0* (15)+ 561.0 & 11.3(15) 874.1 + 15.4(15) 1323.8 + 39.3(9)
FZ
Taurme
296.5 +_ 10.2(15) 4x4.3 + 17.9(15): 619.9 i_ 25.1 (15): 736.2 + 41.0 (9):
313.3 + 582.0 k 919.0 * 1387.9 k
FZ-taurine
9.8 (15) 17.0(15) 25.2 (15) 58.1 (9)
312.1 f 499.6 2 566.1 + 616.6 +
8.1 (15) 11.8(15): 26.3 (14): 57.6(9):
* Mean + SEM. t Number of poults. : Significant difference from the control (P < 0.001).
study, taurine feeding resulted in a twofold increase of taurine levels in the brain. a threefold increase of taurine content in white muscle, and a significantly increased consumption of water. The latter effect may be due, in part, to the poult’s attempt to eliminate excess taurine through the urinary system. Since birds produce little urinary water, the increased water intake probably represents the animal’s response to the increased taurine in its system. Observation of watery feces in poults receiving taurine confirms our supposition. Most of the body taurine is found in muscle. Since FZ was found to be specific only for the heart, total body taurine content is not appreciably affected by FZ. Treatment with taurine dramatically increased taurine content of brain and muscle resulting in a significant rise in total-body taurine levels. In contrast to brain and muscle, the increase in myocardial taurine content of taurine-fed poults was considerably less. However, a dramatic elevation in taurine levels was observed in the FZ-fed poults treated with taurine. In spite of the restoration of normal myocardial taurine levels in these poults, the treatment did not prevent nor reverse the effects of FZ; the incidence of cardiomyopathy was similar in both the FZ-fed and FZ-taurine poults, and the body weights of the latter poults was more depressed than in the poults receiving only FZ. In the heart, taurine appears to regulate calcium homeostasis (Schaffer et al., 1980). While the amino acid has no apparent effect on the normal heart, it mediates a positive inotropic effect in hearts made hypodynamic by perfusion with buffer containing low concentrations of calcium or a cardiodepressant such as verapamil (Chovan et al., 1980). It also improves the myocardial pathophysiological state in the cardiomyopathic hamster (Azari et al., 1980; Welty & Welty, 1981) and the calcium paradox (Kramer et al., 1981) by preventing calcium overload. These effects of taurine appear to be mediated at the level of the sarcolemma (Chovan et al., 15180; Kramer et al., 1981; Welty & Welty, 1981). Thus, the failure of taurine to influence the development of cardiomyopathy and the toxic effects of FZ suggests that the etiology of the syndrome is not attributed to a sarcolemmal defect resulting in a calcium overload.
Acknowledgement-This work was supported by grant HL 27902 from the National Institutes of Health.
REFERENCES AZARI J.. BRUMBAUGH
P. & HUXTABLER. (1980) Prophylaxis by taurine in the hearts of cardiomyopathic hamsters. J. m&c. Cell Car&l. 12, 1353-1366. CHOVANJ. P., K~LAROWSKI E. C.. SHEAKOWSKIS. & SCHAFFERS. W. (1980) Calcium regulation by the low,affinity taurine binding sites of cardiac sarcolemma. Molec. Pharmac. 17. 295-300.
CZARNECKIC. M. (1980) Furazolidone-induced cardiomyopathy-biomedical model for the study of cardiac hypertrophy and congestive heart failure. Aciau Dis. 24, 120-138. CZARNECK]C. M. & Goon A. L. (1980) Electrocardiographic technique for identifying developing cardiomyopathies in young turkey poults. Poult. Sci. 59, I51 5- 1520. CZARNECKIC. M.. JANKUSE. F. & HULTGRENB. D. (1974) Eliects of furazolidone on the development of cardiomyopathies in turkey poults. Acian Dis. 18, 125-133. EMSONP. C. (19781 Biochemical and metabolic changes m epilepsy. In Taurine and Neurological Disorders (Edited by BARBEAU A. & HUXTABLER. J.). pp. 319-338. Raven Press. New York. JANKUSE. F.. GOOD A. L., JORDANK. A. & SA~ENAS. K. (1971) Electrocardiographic study of round heart disease in turkey poults. Poult Sci. 50, 481-486. JANKUSE. F., NOREX G. R. & STALEYN. A. (1972) Furazolidone-induced cardiac dilatation in turkeys. .4ria,l Dis. 16, 958-961. JASMIN G. & BAJUSZ F. (1975) Prevention of myocardial degeneration in hamsters with hereditary cardiomyopathy. In Recent Adwnces in Studies 017 Cardiac Structure and Metabolism Vol. 6 (Edited by FLECKENSTEINA. & RONA G.), pp. 219-229. University Park Press. Baltimore. KRAMERJ. H., CHOVAN J. P. & SCHAFFCRS. W. (1981) Effect of taurine on calcium paradox and lschemic heart failure. Am. J. Physiol. 240, H238-246. LOCHNERA., BRINKA. J. 8: VAN DER WALTJ. J. (1970) The significance of biochemical and structural changes in the development of the myocardiopathy of the Syrian hamster. J. molec. Cell. Cardiol. 1, 47-64. MANDELP. & PASANTES-MORALES H. (1978) Taurine in the nervous system. In Reriervs of Nwroscience, Vol. 3 (Edited by EHRENPREISS. & KOPIN I.). pp. 157-193. Raven Press. New York. OIA S. S., KONTRO P. & LAHDESMAKIP. (1977) Amino acids as inhibitory neurotransmitters. Progr. Pharmac. 1, l-l 12. SAUTTER J. H., NEWMAXJ. A., KLEVENS. H. & LARSENC.
T. (1968) Pathogenesis of the round heart syndrome. Arian Dis. 12, 614-628. SCHAFFERS. W., CZARNECKIC. M., CAWTHRAYM. & CHOVAN J. P. (1981) Cardiac taurine levels and sarcolemmal binding activity in furazolidone-induced cardiqmyopathy. Camp. Biochem. Ph~siol. 69C, 149-151.
STEPHENW. SCHAFFERet al.
140
SCHAFFERS. W., KRAMERJ. & CHOVAXJ. P. (1980) Regu-
lation of calcium homeostasis
in the heart by taurine.
Fedn
Eiol.
Proc.
Fedn
,4m. Sots
exp.
39, 2691-2694.
STALEYN. A., NOKENG. R., BASD~ C. M. & SHARP H. L. (1978) Furazolidone-induced cardiomyopathies in turkeys. 4m. J. Path. 91, 531-541. WELTYJ. D. & WELTYM. C. (1981) Effects of taurine on subcellular calcium dynamics in the normal and cardiomyopathic hamster heart. In The Effects of Taurine on E.ucitnb[r Tissues (Edited by SCHAFFERS. W.. BASKIN
S. 1. & Kocsrs J. J.), pp. 295-312. Spectrum Press, New York. WILSONJ. E. & SILLERW. G. (1954) Round heart disease in the fowl. J. camp. Path. 64, 41-51. YAMORIY., NARA Y.. HORIER.. OOSHIYAA. & LOVENBERG W. (1981) Pathophysiological role of taurine in blood pressure regulation in stroke-prone spontaneously hypertensive rats. In The Eflects of Taurine on Excitable Tissues (Edited by SCHAFFERS. W., BASKINS. I. & KOCSISJ. J.). pp. 391-403. Spectrum Press, New York.
030~4492182/030137-04u)3.00/0 Q 1982Pergamon Press Ltd
ROLE OF TAURINE IN FURAZOLIDONE-INDUCED CARDIOMYOPATHY STEPHEN W. SCHAFFER.’CAROLINE M. CZARNECKI~ and JAMES MCCLUNE’ ‘University of South Alabama. College of Medicine. Department of Pharmacology. Mobile. AL 36688. U.S.A.: and ‘Department of Veterinary Biology. College of Veterinary Medicine. University of Minnesota. St Paul. MN 55108. U.S.A. (Receiwd 14 Srptenther 1981) Abstract--l. Taurine levels were determined in the heart. brain. and red and white muscle of turkey poults fed furazolidone (FZ) at a dose of 700 ppm from 2 to 5 weeks of age and/or 0.1 M taurine from 1 to 5 weeks of age. 2. In FZ-fed poults. taurine levels in the myocardium decreased significantly (P < 0.001). but not in brajn or muscle indicating a specific effect of FZ on the heart. 3. Exogenous administration of taurine significantly (P < 0.001) increased taurine content of brain and muscle in all poults. 4. Myocardial taurine levels were significantly elevated (P c 0.01) in poults fed a normal ration. but not in those fed FZ. 5. Although taurine treatment restored myocardial taurine to normal levels in the FZ-fed poults. the treatment did not decrease the incidence of FZ-induced cardioyopathy. 6. Since taurine is a membrane stabilizer and protects against calcium overload. our data suggests that sarcolemmal damage leading to tissue calcium overload is not the mechanism of the furazolidonemediated syndrome.
INTRODUCl.ION
Round heart is an avian cardiomyopathy which occurs either spontaneously in turkeys or can be induced by inclusion of the antibiotic furazolidone (FZ) in the animals feed (Czamecki er al.. 1973; Jankus et al., 1972). The syndrome is characterized by ventricular hypertrophy and dilatation, marked loss of contractile elements, dilatation of the sarcoplasmic reticulum and massive accumulation of glycogen (Czarnecki, 1980; Sautter et a/., 1968; Staley et al., 1978; Wilson & Siller, 1954). Similar degenerative changes have been described for other cardiomyopathies, such as the Syrian hamster (Lochner et al., 1970). Based on evidence that calcium regulators, such as taurine and verapamil prevent both massive accumulation of calcium by the heart and the development of myocardial lesions (Azari er al.. 1980; Jasmin & Bajusz, 1975), it has been proposed that disturbed myocardial calcium metabolism is a decisive pathogenetic factor in the cardiomyopathic hamster. Welty & Welty (1981) have reported that taurine protects against calcium overload in the Syrian hamster by preventing gross sarcolemmal dysfunction. Since defects in sarcolemmal function were also observed in round heart (Schaffer et al., 1981), it was felt that the basis for the two syndromes may be similar. This hypothesis was tested in this study. METHODSAND MATERIALS Broad-Breasted White Turkey poults were obtained from a single hatch of a large breeder strain. At 1 week of age, the poults were placed in one of two groups. One group of 40 poults was maintained on a normal ration and water ad lib while a second group of 40 poults was maintained on a normal ration and 0.1 M taurine ad lib. At 2 137
weeks of age, the poults were screened utilizing the electrocardiographic (ECG) technique developed by Jankus et al. (1971) and modified by Czarnecki & Good (1980). Poults from each group were placed randomly in one of two pens: Group I: control pen-normal ration and water ad lib, FZ pen-FZ at 700ppm and water ad lib; Group II: taurine pen-normal ration and 0.1 M taurine daily ad lib, FZtaurine pen-FZ at 700 ppm and 0.1 M taurine daily ad lib. At 4 and 5 weeks of age, six poults from each of the pens were selected for sacrifice by cervical dislocation. At sacrifice tissue samples from the right ventricular free wall, brain. and tibialis anterior and pectoralis major muscles were excised quickly. quenched in liquid nitrogen, freeze dried, and assayed for taurine using the method described previously (Schaffer et al., 1981). The data for poults 4 and 5 weeks of age were pooled since these did not differ significantly from each other. A daily record of water consumption per pen was kept. The daily water intake/poult was computed. tallied for each week. and comparisons were made between control and experimental pens on a weekly basis.
RESULTS
The taurine data is shown in Table 1. As demonstrated in a previous study (Schaffer et al., 1981) myocardial taurine levels were decreased significantly (P < 0.001) in FZ-fed poults. This effect is specific for the heart since FZ did not influence taurine content of either muscle or brain. Taurine treatment significantly (P < 0.001) elevated taurine levels in muscle and brain of all poults and in heart (P c 0.01) of taurinefed poults. In poults fed both FZ and taurine, myocardial taurine was restored to normal levels. The average daily water consumption per poult is shown in Table 2. Poults fed taurine consumed more water than did the control poults. This difference became more significant with age. Poults fed both
138
STEPHEN
W. SCHAFFERet nl.
Table I. Effect of taurine feeding on taurine tissue levels* of control and FZ-fed turkey poults PEN Control
Tissue Muscle red white Brain Heart
FZ
Taurine
i7.9 & 5.31(n): 69.7 k 5.1 (12) 8.3 + 0.7(12) 7.9 c 0.6(12) 48.1 f 2.0(12) 46.8 Itr 1.9 (11) 155.9 + 5.0(11) 109.1 + 9.9 (9)9
108.9 i_ 21.3 + 100.3 + 182.5 k
FZ-taurine
6.5 (12)# l.O(ll)$ 3.8 (I’)$ 7.2(11)1’
107.2 + 8.6(11)$ 35.2 k 6.7(11)$ 98.7 +_4.9 (12)$ 162.6 + 7.0(10)
* prnolig dry weight of tissue. tMean k SEM. : Number of samples. $ Significant difference from the control (P < 0.001). $1 Significant difference from the control (P c O.OlL
taurine and furazolidone consumed significantly more water at all ages studied. These differences were highly significant (P < 0.001) during the third and fifth weeks. The ECG data is shown in Table 3. Control and taurine-fed poults had similar ECG patterns as did the FZ-fed and the FZ-taurine poults indicating that taurine has little or no effect on ECGs. Average body weights of poults are shown in Table 4. As demonstrated in an earlier study (Czarnecki et al., 1974), FZ significantly (P < 0.001) depressed body weights. Although taurine-fed poults tended to be heavier than control poults. these differences were not significant. Poults fed both taurine and FZ tended to
be lighter than poults receiving FZ, but no significant differences were observed. DISCL’SSION
Taurine is a potent inhibitor of neuronal activity. In a variety of neuronal preparations, taurine has been found to produce hyperpolarization, decrease membrane conductance. and increase permeability to specific ions (Oja rr al.. 1977). Taurine has been reported to alter conditioned eating and drinking, cause hypothermia, inhibit acquisition of avoidance conditioned reflexes and prevent certain types of seizures (Mandel & Pasantes-Morales. 1978). In this
Table 2. Average daily water consumption/week (g/poult) of turkey poults fed normal or FZ rations and water or 0.1 M taurine PEN Week 2 3 4 5
FZ
Control 105.7 * 167.9 f. 745 4 + ;18:0 ;
3.0’ (39)t 3.9 (22) 7.7 (22) 9.0(9)
Taurine
148.4 k 2.7 (15,: 172.7 k 8.6(15)$ 295.4 f 11.5 (9)
133.i & 183.9 2 338.3 F 407.3 *
2.6 139): 5.1 (19) 16.0(19)‘: 17.3(9)$
FZ-taurine 207.7 & 5.7 (15)$ 284.0 k 7.9 (14): 381.2 + 9.2 (8)$
* Mean + SEIM. t Number of poults. $ Significant difference from the control (P < 0.05). $ Significant difference from the control (P < 0.001). $1 Significant difference from the control (P < 0.01).
Table 3. ECG data for turkey poults maintained on a normal or FZ ration and water or 0.1 M taurine
Age
PEN
(weeks)
Control
2
15N” 14N, lN, 15N 9N
3 4 5
FZ
Taurine
FZ-taurme
15N 15N 13N, lN,, 1NT SN, 6Nu. 1NT 8N. 6N,, 1R 14N, lN, 6N. lNH, 1NT. ?R, 5R 15N 7N, 2NT. IRT, 4R 6N. INT, 1RT 9N 5N, 2N,, 2R
* ECG: N-normal: ?I,-voltage > 0.1 mV in R wave of Lead I: NT-R wave > 0.1 mV < S wave of Lead II (aVF): RT-R wave > 0.1 mV > S wave of Lead II (aVF); R-R wave > 2S wave of Lead II (aVF).
Taurine in FZ-induced cardiomyopath!
139
Table 4. Average body weights(g) of turkey poults fed normal or FZ rations and water or 0.1 M taurrne PENS
Week 2 3 4 5
Control 310.1 k 6.0* (15)+ 561.0 & 11.3(15) 874.1 + 15.4(15) 1323.8 + 39.3(9)
FZ
Taurme
296.5 +_ 10.2(15) 4x4.3 + 17.9(15): 619.9 i_ 25.1 (15): 736.2 + 41.0 (9):
313.3 + 582.0 k 919.0 * 1387.9 k
FZ-taurine
9.8 (15) 17.0(15) 25.2 (15) 58.1 (9)
312.1 f 499.6 2 566.1 + 616.6 +
8.1 (15) 11.8(15): 26.3 (14): 57.6(9):
* Mean + SEM. t Number of poults. : Significant difference from the control (P < 0.001).
study, taurine feeding resulted in a twofold increase of taurine levels in the brain. a threefold increase of taurine content in white muscle, and a significantly increased consumption of water. The latter effect may be due, in part, to the poult’s attempt to eliminate excess taurine through the urinary system. Since birds produce little urinary water, the increased water intake probably represents the animal’s response to the increased taurine in its system. Observation of watery feces in poults receiving taurine confirms our supposition. Most of the body taurine is found in muscle. Since FZ was found to be specific only for the heart, total body taurine content is not appreciably affected by FZ. Treatment with taurine dramatically increased taurine content of brain and muscle resulting in a significant rise in total-body taurine levels. In contrast to brain and muscle, the increase in myocardial taurine content of taurine-fed poults was considerably less. However, a dramatic elevation in taurine levels was observed in the FZ-fed poults treated with taurine. In spite of the restoration of normal myocardial taurine levels in these poults, the treatment did not prevent nor reverse the effects of FZ; the incidence of cardiomyopathy was similar in both the FZ-fed and FZ-taurine poults, and the body weights of the latter poults was more depressed than in the poults receiving only FZ. In the heart, taurine appears to regulate calcium homeostasis (Schaffer et al., 1980). While the amino acid has no apparent effect on the normal heart, it mediates a positive inotropic effect in hearts made hypodynamic by perfusion with buffer containing low concentrations of calcium or a cardiodepressant such as verapamil (Chovan et al., 1980). It also improves the myocardial pathophysiological state in the cardiomyopathic hamster (Azari et al., 1980; Welty & Welty, 1981) and the calcium paradox (Kramer et al., 1981) by preventing calcium overload. These effects of taurine appear to be mediated at the level of the sarcolemma (Chovan et al., 15180; Kramer et al., 1981; Welty & Welty, 1981). Thus, the failure of taurine to influence the development of cardiomyopathy and the toxic effects of FZ suggests that the etiology of the syndrome is not attributed to a sarcolemmal defect resulting in a calcium overload.
Acknowledgement-This work was supported by grant HL 27902 from the National Institutes of Health.
REFERENCES AZARI J.. BRUMBAUGH
P. & HUXTABLER. (1980) Prophylaxis by taurine in the hearts of cardiomyopathic hamsters. J. m&c. Cell Car&l. 12, 1353-1366. CHOVANJ. P., K~LAROWSKI E. C.. SHEAKOWSKIS. & SCHAFFERS. W. (1980) Calcium regulation by the low,affinity taurine binding sites of cardiac sarcolemma. Molec. Pharmac. 17. 295-300.
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