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Drugs for Use in Veterinary Obstetrics

L. MtNARD Bureau Vete'rinaire de l'Asbestrie, 383 Marie- Victorin, Kingsey-Falls (Qudbec) JOA I BO

SUMMARY drugs that produce this effect are since the early 1960's a series of beta- The author presents a literature review termed uterine myorelaxants, toco- mimetic drugs have been synthesized of two tocolytic agents used in veteri- lytic drugs or simply . and tested (1,8). A prototype beta nary obstetrics: and clen- The application oftocolysis is a rela- , isoxsuprine, was one ofthe buterol. The medical background tively new therapeutic approach for first agents-used to treat premature or from which these drugs emerged for the North American veterinary practi- excessive labor (1,4,8,9,10,11,12). human use and to which is linked their tioner. However, it has been used for However, undesirable side effects application in animal medicine is de- some years in many European coun- occurred due to nonspecific beta scribed. Each drug is reviewed accord- tries following the development oftwo receptor stimulation, mainly j3l. In ing to its pharmacology, basic consid- tocolytic drugs, isoxsuprine (Duphas- recent years, efforts were made to find erations for its clinical use and the pasminT") and clenbuterol (Plani- pharmacological agents that would reports on its application in the treat- partT"). These products were originally stimulate specifically the 182 receptors ment and management of obstetrical designed for human therapeutic pur- so they may be used as labor inhibitors disorders in veterinary medicine. poses and are now being used in without concern ofcardiovascular side animal obstetrics. Both drugs are effects. Subsequently, newer beta Key words: Beta , labor, available on the European market but adrenergics were created and studied, tocolysis, obstetrics (human, veteri- are not yet currently licensed for veteri- such as , , salbu- nary), isoxsuprine, clenbuterol. nary use in the U.S. or Canada. tamol, , (4,13) Both tocolytics are beta adrenergic and clenbuterol (14,15,16,17,18). R t S U M t compounds developed over the past Many reports have claimed that these Drogues tocolytiques, utilisables en two decades and were intended prim- agents are more I2 selective and, there- obstetrique veterinaire arily for the treatment of. premature fore, associated with fewer f3 side L'auteur presente une revue de la litte- labor in human obstetrics. Among all effects, such as and hypo- rature relative a deux agents tocoly- substances tested for effectiveness in tension, than isoxsuprine (4,13,18). tiques utilises en obstetrique veteri- the inhibition of labor, ethyl alcohol, Interestingly these newer drugs, hav- naire, a savoir: l'isoxsuprine et le magnesium sulfate, progesterone, ing selective I82 receptor affinity, were clenbuterol. I1 decrit aussi la perspec- prostaglandin inhibitors, calcium developed primarily for the treatment tive medicale entourant l'utilisation de antagonists and beta adrenergics, the of bronchial (19). For this rea- ces drogues en medecine humaine et a latter showed the best effect with the son numerous studies appear in the laquelle se rattache leur application a lowest rate of side effects (1,2,3,4). medical literature relating to their use la medecine animale. La description de Two basic neurophysiological con- in the treatment of respiratory prob- ces deux drogues tient compte de leur cepts led to the development of beta lems. Most of the beta adrenergics pharmacologie, des considerations de adrenergics. The first was the recogni- mentioned in this review are marketed base sur leur usage en clinique et des tion by Alquist (5) in 1948 of the exist- in Canada (Table I). Among them rapports sur l'approche therapeutique ence ofadrenergic a and ,B receptors in isoxsuprine and clenbuterol are the de problemes d'obstetrique veterinaire. organs with sympathetic innervation. only products marketed for veterinary The second concept, reported almost use and they will be reviewed in more Mots cles: beta-adrenergiques, partu- 20 years later (6), identified the further detail. rition, tocolyse, obstetrique humaine existence of two types of adrenocep- tors, ,B and 132. The f, receptors were et veterinaire, isoxsuprine, clenbu- I S O X S U P R I N E terol. found to be confined to the heart and small intestines, the latter f82 to the Isoxsuprine is a member of the ,B- vascular smooth muscle, myometrium phenylethylamine group of epine- I N T R O D U C T O N and bronchial tree (7). phrine-like compounds. Synthesized Tocolysis is a Greek derivative (tokos Initially it was believed that drugs by Moed and Van Dijk in 1956, its = childbirth or labor; lysis = dissolu- capable of stimulating the myometrial molecular structure (Figure 1) appar- tion) that means in practical terms beta adrenoceptors, thus causing ently shares structural similarities with inhibition of labor. It is obtained by relaxation of the uterine muscle during and papaverine (20). These the use of substances able to induce a pregnancy, would prove to be ade- relations explain isoxsuprine's mode state of myometrial paralysis. Hence, quate labor-inhibiting agents. Hence, of action believed to be dominantly

Can Vet J 1984; 25: 389-393. 389 * HCL by i.v. administration of oxytocin (23). Cardiovascular side effects contrain- dicate its use in cases where hypoten- sion is present (20).

CLENBUTEROL Synthesized by Keck et al (26), clenbu- ISOXSUPRINE terol (NAB 365) is a new amino- halogen substituted phenylethanola- F IGU RE I. Molecular structure of 1 -(4-Hydroxyphenyl)-2-( 1 -methyl-2-phenoxyethylamino) mine drug with 132-adrenergic proper- propan-l-ol hydrochloride: Isoxsuprine Hydrochloride; C18H23NO3. HCI = 337.8. ties (27). Its chemical structure resembles that of established /3- adrenergic agents (28). However, it differs from other 82-sympathicomi- sympathomimetic with an additional birth canal and enhanced dilatation of metics such as , fenoterol, direct papaverine-like or spasmolytic the vulvar stenosis. In contrast with its orciprenaline and similar substances effect 40 times that of papaverine effect on uterine smooth muscle its by the fact that the aromatic ring in (I 1,23). Relaxation of the uterine action on the incompletely dilated cer- positions 3 and 5 is halogenated with muscle occurs through the stimulation vix is not well marked (20,21,25). chlorine (Figure 2) (17). This dichlori- of myometrial beta adrenergic recep- Isoxsuprine is currently marketed nated substitution of the benzine ring tors. Its notable tocolytic properties for veterinary use in Europe by results in rapid absorption following on animal uterine muscle strips Philips-Duphar (Table I) as an injec- oral administration and in a long dura- prompted further investigations that table, aqueous solution containing tion of action (28). Clenbuterol is not have led to the clinical reports, men- 11.58 mg isoxsuprine lactate per mL subject to the action of cathecol-o- tioned previously (1,4,8,9,10,11,12), under the trade name of Duphaspas- methyl transferase: this partly explains on this drug's effectiveness as a labor- min. As a tocolytic it can be used in its prolonged effect which may also be inhibitor in humans for cases of threat- large or small domestic animals a function of its firm binding to the ened premature and excessive term although practical application is usu- /3-receptor due to the halogen substi- labor. The lack of specific /32-receptor ally reserved to the larger species, par- tion mentioned before (15,17). Clinical affinity accounts for the major side ticularly ruminants. The recom- studies of orally administered clenbu- effects, tachycardia and hypotension, mended dose is 0.4-2.0 mg/kg i.m. terol (Spiropent) showed it to have a reported with the use of isoxsuprine in Tocolysis develops within 10-15 min- more prolonged effect human obstetrics. utes after i.m. application and lasts than salbutamol (17) and an amino- In 1965, Devries and Wilson (20) one to two hours (20,23). If required, phylline preparation (29) in human evaluated the tocolytic properties of its action can be suspended at any time patients. The drug's pharmacological the product in animals. It was found to be of value in ruminants and was recommended for use in various obstetrical situations requiring uterine TABLE I relaxation in cattle and sheep. Simple PROPRIETARY NAME OF BETA ADRENERGICS FOR H UMAN AND VETERINARY USE IN THEIR dystocia, embryotomy and caesarean RESPECTIVE MARKETING COUNTRIES section were considered by these Drug Human Veterinary researchers as the major indications Isoxsuprine chloride: Vasodilan lactate: Duphaspasmin b for its use. Later clinical studies (Caa 40)a Canada (Bristol) Holland (Philips-Duphar) (21,22,23), carried out mostly on cat- Ritodrine chloride: Yutoparb tle, confirmed satisfactory results with (DU 21220)a United Kingdom (Philips-Duphar) the application of this tocolytic in Terbutaline sulfate: Bricanyl other domestic mammals such as the (KWD 2019)a Canada (Astra) mare, ewe, sow, bitch and queen. Cor- Salbutamol hemisulfate: Ventolin rection of uterine torsion (20) and pro- (AH 3365)a Canada (Allen & Hanbury's) lapse (24,25) have also been reportedly Orciprenaline sulfate: Alupent facilitated by using this drug in cattle. (Th 1 52)a Canada (Boehringer-lngelheim) Effective prevention of perineal rup- Fenoterol bromide: Berotec ture in first-calving heifers has been (TH I 165a)a Canada (Boehringer-lngelheim) mentioned as another possible use Clenbuterol chloride: Spiropentb chloride: Ventipulmin; Planipartb (23). It was considered that abolition (NAB 365)a Germany (Boehringer-l) Canada (Boehringer-1.) of uterine contractions during the Germany (Boehringer-1.) labor process, even for a short length aLaboratory code name. of time, could be beneficial if it bNot available in Canada. allowed better preparation of the soft Sources: Martindale (28th ed.) and Index Nominum 1982.

390 overnight lambing in 91% of the ewes CL subjected to the experiment (41). No OH CH3 untoward effect was noted on the 5 ~~6 health of ewes and lambs during or after this treatment. In swine, it has NH2 4 1 CH CH2 NH_C CH3 been demonstrated that Planipart is suitable for all phases of parturition at 3 2 CH3 a dose of 150 ,ug (5 mL) i.v. and inter- rupts labor for several hours, even in CL the case of already born piglets (42). As tocolysis subsides, parturition resumes unhindered and the piglets CLENBUTEROL vitality is not affected either. Pres- ently, the authors of this review have found no report on similar studies in F IGURE 2. Molecular structure of 1-(4-amino-3,5-dichlorophenyl)-2-tert-butyl-aminoethanol horses. hydrochloride: Clenbuterol Hydrochloride; C12HlCIN2,O. HCI = 313.7. Once the cervix is fully dilated or the fetal feet are passing into the cervical area (stage I1), Planipart will only delay labor for a maximum of a few properties were extensively investi- of the earlier clinical trials (32,33) it hours (34,37). Early investigations gated (30,31) and its main features, was found that 300 ,ug or 0.3 mg into the therapeutic action of NAB 365 other than those already mentioned (10 mL) i.m. delayed parturition in have suggested its usefulness for the (rapid oral absorption, long action), cattle on average five to eight hours correction of abnormal fetal presenta- come from its specific affinity for I2- without any ill-effects on the cows or tions and as a prerequisite to fetoto- adrenergic receptors: potent bron- calves. By using a double administra- mies and caesarean sections in cattle, chodilator (14,15,16,17,28,29) and tion of NAB 365 it was shown in an sheep and pigs (37,38,39). Since then, a tocolytic (18) activity, free of side investigation on 58 cows that parturi- number of reports have appeared on effects caused by P, receptor stimula- tion could be avoided between 10 p.m. its use in cattle mostly. The powerful tion such as occurring with isoxsu- and 6 a.m. the following morning tocolytic effect exerted by this drug prine. Clenbuterol has not yet been without the need for gynecological allows easier obstetrical or biotechni- widely used as a uterine relaxant in examination prior to the treatment cal manipulation of the uterus in preg- human obstetrics but rather has been (35). It was noted here as in another nant or nonpregnant animals. Good primarily used for its action as a bron- study involving 186 cows and heifers results have been recorded in cases of chodilator. However, it has been devel- (36) that the process of parturition in dystocia due to fetal oversize, uterine oped as a tocolytic agent (Planipart) treated animals, particularly heifers, torsion and cervical spasm corrected for veterinary use in farm animals to was made easier following the delay by fetotomy or caesarean operation provide either a zootechnical or a the- period. A continued widening of the (43,44,45,46). Replacement of uterine rapeutical interruption of parturition. cervix, softening of the birth canal as prolapse (stage Il) is apparently made The product's long action was the well as an improved blood supply to much easier with the use of Planipart primary stimulus for. clinical studies the placenta and fetus during the (44,45,46,47) and shows that it can be carried out to test its usefulness for the period of tocolysis account for this applied effectively to all three stages of postponement of parturition in cattle observation (37). These investigators the labor process. An interesting (32,33,34,35,36,37,38,39,40) sheep also found no adverse effect on vitality observation in one of these reports was (41) and swine (42). Tocographic of the newborn calves, expulsion of the that cows, even those not receiving examinations have indicated a rapid placenta or subsequent fertility of the sacral anesthesia, were largely free onset oftocolysis after i.v. administra- dams. Thus, the use of Planipart was from straining during replacement tion in cattle (minimum: 10-15 min- proposed for two zootechnical pur- (47). Planipart can also be used to utes) and swine (minimum: five min- poses: first, to reduce economic losses relax the nonpregnant uterus and has utes) (37). Planipart stimulates associated with "night-time" parturi- been reported to increase pregnancy adenylcyclase in the cell membranes to tions in cattle by allowing a better rates in cattle recipients undergoing produce an outflow of calcium from management of the labor period; surgical embryo transfer (48). This myometrial cells which remain unres- secondly, to reduce stillbirths in heif- particular application for the purpose ponsive to oxytocin until the drug's ers by providing for easier, less trau- of temporarily relaxing the uterus effect subsides (37). Then only can matic deliveries. after either surgical or nonsurgical ova tocolysis be reversed by endogenous or The use of Planipart to postpone transfer is apparently widespread but exogenous oxytocin. The duration of parturition in sheep and swine was few reports are available (49). Among tocolysis depends on the position of recommended for the same purposes. the many cases reported, two involved the fetus at the time of treatment, In sheep, a dose of 240 jAg (8 mL) i.m. the successful use of Planipart in the being longest at the beginning of the effectively abolished uterine motoric- treatment of equine dystocia (43,46). labor process (stage I) (34,38). In some ity for eight to ten hours, suspending Results following the use of the pro-

391 duct indicate that it has rapid, long ment of threatening premature labor by 18. ZAHN V. KUlPUACHNER G. Clenbuterol: A acting tocolytic effects in domestic betamimetic drugs. Am J Obstet Gynecol long term uterine relaxant. J Perinat Med animals. Furthermore, it appears safe 1977; 127: 482-486. 1981; 9: 96-100. to administer by the i.v. or i.m. route 3. GiERRIS J. 'I'HIERY M. BOGAER'I' M. DF SCHAEP- 19. INNES IR. NICKERSON M. , and has no adverse effect on the DRYVER A. Randomized trial of two beta- epinephrine and the sympathomimetic immediate well-being of the dam and mimetic drugs (Ritodrine and Fenoterol) in . In: Goodman LS. Gilman A, eds. acute intra-partum tocolysis. Eur J Clin The pharmacological basis of therapeutics, fetus, on the mortality rate or vitality Pharmacol 1980; 18: 443-448. 5th ed. New York: MacMillan Publishing of the newborn, on the expulsion of 4. SCHENKEN RS. HAYASHI RH. VALENZt;EIL GV. Co, Inc., 1975: 504. the placenta or subsequent fertility CASTILLO MS. Treatment of premature labor 20. POREYE PR. De l'emploie de l'Isoxsuprine en being reported. with beta sympathomimetics: results with obstetrique veterinaire. Thesis. Toulouse, Clenbuterol is currently marketed isoxsuprine. Am J Obstet Gynecol 1980; France: Borderes, 1978: 13-67. for veterinary use by Boehringer- 137: 773-780. 21. AHLERS D. AN[)RESSEN u. Experiences with lngelheim (Table I) under two differ- 5. AHIQUIST RP. A study of adrenotropic the uterine relaxant isoxsuprine lactate in ent trade names (50): Planipart (toco- receptors. Am J Physiol 1948; 153: 586-600. cases of difficult labor in cows. Dtsch Tie- lytic) as an aqueous injectable solution 6. LANDS AM. ARNOLD A, McAULIFEFJP. LUD[UENA rarztl Wochenschr 1967; 74: 608-610. containing 0.03 mg clenbuterol hydro- [P. BROWN T'. Differentiation of receptor 22. BOOGAERDF A. Enige praktijkanaringen met systems activated by sympathomimetic sectio caesarea bij het rund. Tijdschr Dier- chloride per milliliter and Ventipulmin amines. Nature Lond 1967; 214: 597-598. geneeskd 1971; 96: 405-406. (bronchodilator) as oral granules con- 7. INNES IR. NICHERSON M. Norepinephrine, 23. HORVARI'H G. BACSFAY N. Experiences with taining0.016 mgclenbuterol HCI per epinephrine and the sympathomimetic the use of a uterine muscle relaxant prepara- gram. The latter has just recently been amines. In: Goodman LS, Gilman A, eds. tion (isoxsuprine lactate). Acta Vet Acad introduced on the Canadian market The pharmacological basis of therapeutics. Sci Hung 1981; 29: 65-70. for oral use in horses while Planipart 5th ed. New York: MacMillan Publishing 24. NARASIMHAN WS. THANGARAJ TN. KRISHNA- has not yet received Federal clearance. Co, Inc., 1975: 478. MOORTHY R. Report on clinical trials with 8. UNHEHAUN v. Effects of sympathomimetic Duphaspasmin an uterine spasmolytic in tocolytic agents on the fetus. J Perinat Med veterinary practice. Indian Vet J 1969; 46: 1974; 2: 17-29. 74-77. CONCLUSIONS 9. KAUPPILA A. KUIKKA J. TUIMALA R. Effect of 25. RAJASEKARAN J. THANGARAJ TM. VENKATA- Pharmaceutical research has provided Fenoterol and Isoxsuprine on myometrial SUWAMI V. A line of treatment in bovine many tocolytic agents for use in and intervillous blood flow during late uterine prolapse (isoxsuprine hydrochlo- human obstetrical applications. Two pregnancy. Obstet Gynecol 1978; 52: ride). Indian Vet J 1980; 57: 516. of these, isoxsuprine and clenbuterol, 558-562. 26. KECK J. KROGER G. NOLL K. MACHLEIDT H. 10. BISHOP EH. WOUTERSZ TB. lsoxsuprine, a Synthesen von neuen Amino-Halogen- are presently being used as obstetrical myometrial relaxant. Obstet Gynecol 1961; substituierten Phenyl-aminoathanolen. drugs by veterinarians in European 17: 442-446. Arzneimittelforsch 1972; 22: 861-869. countries and possibly others. On a 11. HENDRICKS CH.CIBILS LA. POSES SV. ESKESTK. 27. ENGELHARDT G VON. Struktur-Wirkungs- purely theoretical basis, the newest of The pharmacologic control ofexcessive ute- beziehungen in einer Reihe von neuen these substances, clenbuterol, would rine activity with Isoxsuprine. Am J Obstet Amino-Halogen-substituierten Phenyl- appear to be a superior tocolytic for Gynecol 1961; 82: 1064-1075. Aminoithonolen. Arzneimittelforsch 1972; animal use although comparative stud- 12. EHRENKRANZ RA. HAMILTON LA. BRENNAN SC. 22: 869-876. ies have not yet been reported. OAKES GK. WALKER AM, CHEZ RA. Effects of 28. CUMMISKEY J. KEELAN P, GRAY P, COX GA. It is hoped that this review will stim- salbutamol and isoxsuprine on uterine and Comparison of NAB 365 and salbutamol umbilical blood flow in pregnant sheep. Am tablets in chronic bronchitis and asthma. J ulate interest in the use of tocolytics J Obstet Gynecol 1977; 128: 287-293. Irish Med Assoc 1978; 71: 123-126. for obstetrical indications in this 13. NUWAYHID BS.CABALUM MT. LIEBSM.ZUGAID 29. WHEATLEY D. Clenbuterol (Spiropent): a country. M. BRINKMAN CR. TABSH KM. ASSALI NS. long acting bronchodilator. Curr Med Res Hemodynamic effects of isoxsuprine and Opin 1982; 8: 113-119. terbutaline in pregnant and nonpregnant 30. ENGELHARDT G. Pharmacologisches Wir- sheep. Am J Obstet Gynecol 1980; 137: kungsprofil von NAB 365 (clenbuterol) ACKNOWLEDGMENTS 25-29. linen neunen Broncholytikum mit einer The authors wish to thank Mrs R.A. 14. SALORINNE B. STENIUS P. TUKIAINEN P. POP- selektiven Wirkung anf die Adrenergen /2- Steiner for translating assistance in PIUS H. Double-blind cross-over comparison Rezeptoren. Arzneimittelforsch 1976; 26: most of the foreign references cited in of clenbuterol and salbutemol tablets in 1404-1420. this review. They also wish to express asthmatic out-patients. Eur J Clin Phar- 31. O'DONNELL SR. Selectivity of clenbuterol appreciation to Dr. F.W. Harris of macol 1975; 8: 189-195. (NAB 365) in guinea-pig isolated tissues 15. ANDERSON G, WILKINS E. A trial of clenbu- containing 83-adrenoceptors. Arch Int Boehringer-lngelheim (Canada) Ltd. terol in bronchial asthma. Thorax 1977; 32: Pharmacodyn Ther 1976; 224: 190-198. for technical services and assistance. 717-719. 32. ARBEITER K,THURNER M. Ueberdie Wirkung 16. BARONTI A, GRIECO A. VIBELLI C. Study of a des Sympathikomimetikums Planipart new oral beta-adrenergic drug, clenbuterol, (NAB 365) auf den Geburtsablauf beim in patients with chronic bronchitis. Eur J Rind. Tieraerztl Umsch REFERENCES 1977; 32: 423-427. Clin Pharmacol 1978; 13: 171-177. 33. BALLARINI G, MOLINO L, MUNAFO A. Primi 1. MOSLER KH, LINKA F, DORNHOFER W. 17. TSCHAN M. PERRUCHOUD A, HERZOG H. Dose relievi sulla tocolisi farmacologica nelle EHRHART J. Tocolytic therapy in obstetrics. response relationship of clenbuterol (NAB vacca con l'uso del beta-2-mimetico "clen- J Perinat Med 1974; 2: 3-16. 365) as a solution for inhalation. Eur J Clin buterolo". Clin Veterinaria 1978; 101: 2. RICHTER R. Evaluation of success in treat- Pharmacol 1979; 15: 159-162. 11-16.

392 34. ARBEITER K. HOLLER W. Zur protrahierten KS, PRATT BR. Planipart (Clenbuterol) for maniobras obstetricas y en reposiciones de und induzierten Geburt beim Rind. In: Xl. the postponement of parturition and allevi- prolapso uterino en el bovino. Gac Vet fl International Congress on Diseases of Cat- ation of dystocia in cattle. In: Society for Aires 1982; 44: 443450. tle, Tel Aviv 1980; Ii: 1070-1080. Theriogenology. Proceedings of the annual 45. ALBECK A. Erfahrungen mit dem Einsatz 35. BALLARINI G Suppression chez les bovins meeting, Milwaukee, Wisconsin, 1982; eines Tokolytikums (Planipart) in der Rin- des mises-bas nocturnes au moyen de deux 176-183. dergeburtshilf. Tieraerztl Umsch 1981; 36: applications du tocolytique NAB 365 (Pla- 40. WOLFE DW. Manipulation of cattle for day- 718-720. nipart). In: Xl. International Congress on light calving. Mod Vet Pract 1983; 63: 46. DENOOIJ PP. The use of clenbuterol for Diseases of Cattle, Tel Aviv 1980; I: 2 1-23. obstetrical procedures in forty cows and one 1081-1086. 41. DELAlOUR P. ROIZARD D. Activite tocoly- horse. Can Vet J 1984; 25: 357-359. 36. GRUNERT E, VERHOELSDONK M. Experiments tique du NAB 365: application a la maitrise 47. MUURLING F. HELDER AW, ROEST G. Clenbu- to delay the occurrence of bovine parturi- des accouchements chez la brebis. Les doss- terol als hulpmiddel big koeien met prolap- tion with the 132-mimeticum "Planipart". In: iers de l'elevage 1979; 3: 57-59. sus uteri. Tijdschr Diergeneeskd 1981; 106: Xl. International Congress on Diseases of 42. ZEROBIN K. Possibilities to influence the 275-276. Cattle, Tel Aviv 1980; 11: 1087-1097. motility of the uterus during parturition and 48. COULTHARD H. The use of clenbuterol in 37. ZEROBIN K. KONDIG H. The control of during puerperium in swine. In: Interna- embryo transfer recipients. Theriogenology myometrial functions during parturiton tional Pig Veterinary Society Congress, 1982; 17: 82. with a 832-mimetic compound, Planipart. Copenhagen, 1980: 26. 49. JOCHLE w. Review: Egg transfer (111). In: Theriogenology 1980; 14: 21-35. 43. RIEPE H. Zur geburtshilflichen Anwendung Jochle W, Associates, Inc., Pubs. Animal 38. GREENE HJ. Clinical study of the use of Clen- von Planipart (NAB 365) in der tierirztli- reproduction report (Theriogenology Dig- buterol for postponing parturition in cows. chen Praxis. Tieraerztl Umsch 1981: 36: est), Denville, New Jersey, 1982; 25: 1-6. Vet Rec 198 1; 109: 283-285. 56-58. 50. OWEN RT. Clenbuterol hydrochloride. Drugs 39. PUTNAM MR, RICE LE. WETTEMAN RP. LUSBY 44. RENNER JE. El uso del tocolitico NAB 365 en of Today 1981; 17: 339-342.

ABSTRACT VAN VLEET JF, AMSTUTZ HE, In group C, 2 calves served as controls. ventricular myocardium of 6 of 12 WEIRICH WE, REBAR AH, M onensin-treated calves developed group B calves. Gross lesions were not FERRANS VJ. Clinical clinicopa- anorexia, diarrhoea, and lethargy present in the skeletal muscles or thologic, and pathologic alterations after one day. One group B calfdied on rumen. Microscopically, the myocar- in acute monensin toxicosis in cat- day 7 with lesions of congestive heart dial and skeletal muscular lesions were tle. American Journal of Veterinary failure. ECG abnormalities were not characterized by sarcoplasmic vacuo- Research. 1983; 44: 2133-2144. observed in group A calves, in group lation from mitochondrial swelling (Dep. Microbiol. Path. Publ. Hlth, B, prolongation of Q-T and QRS and lipid accumulation in calves killed Sch. Vet. Med., Purdue Univ., West intervals occurred from days 2 to I I after day I in groups A and B, and by Lafayette, Indiana 47907, USA). and first degree heart block was seen myocardial necrosis with contraction from days 7 to I 1. Clinicopathological bands, but without calcification, in Twenty beef calves weighing alterations included: increased serum group B calves killed by day 4. Acute approximately 180 kg were allotted to activities of aspartate aminotransfe- rumenitis was present in group A and 3 groups. In group A, 6 calves were rase and creatine kinase in group B B calves. Myotoxic effects of monen- given 25 mg of mycelial monensin/ kg calves after day 2; decreased serum K+, sin may be related to its action as an of body weight orally and were evalu- Na+ and Ca++ concentrations in both ionophore producing altered intracel- ated at 1, 2, and 4 days for clinical, groups and occurrence of leukocyto- lular ion concentrations and initiating ECG, clinicopathological, and patho- sis. Calves were killed sequentially and degeneration and necrosis in striated logical alterations. In group B, 7 calves the lesions of monensin toxicosis were muscle fibres. were given a single dose of monensin present in the heart, skeletal muscles, (40 mg/ kg) and 5 were given a 2nd 40 and rumen in groups A and B. mg/ kg dose on day 7; calves were Disseminated pale yellowish-brown Reprintedfrom the " Veterinary Bul- evaluated at days 1, 2, 4, 7, 8, 9, and I 1. areas of necrosis were present in the letin", Volume 54, No. 4, April 1984.

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