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Volume 44 | Issue 2 Article 5

1982 Clinical Applications of Prostaglandins in and Edward C. Briles Iowa State University

Lawrence E. Evans Iowa State University

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Recommended Citation Briles, Edward C. and Evans, Lawrence E. (1982) "Clinical Applications of Prostaglandins in Dogs and Cats," Iowa State University Veterinarian: Vol. 44 : Iss. 2 , Article 5. Available at: https://lib.dr.iastate.edu/iowastate_veterinarian/vol44/iss2/5

This Article is brought to you for free and open access by the Journals at Iowa State University Digital Repository. It has been accepted for inclusion in Iowa State University Veterinarian by an authorized editor of Iowa State University Digital Repository. For more information, please contact [email protected]. Clinical Applications of Prostaglandins in Dogs and Cats

by Edward C. Briles, DVM* Lawrence E. Evans, DVM, PhD**

In the biological sciences today there are few previously been shown to make smooth muscle 3 4 substances that generate as much interest as contract. • It wasn't until 1957 that two pro­ prostaglandins. They have found widespread staglandins (PGE l, PGF la) were isolated in use in veterinary medicine, yet are only ap­ pure crystalline form and soon more pro­ proved by the FDA for specific uses in cattle staglandins were characterized, all of which and horses. However, practical applications in were found to be 20-carbon unsaturated car­ the and have been reported by clini­ boxylic acids with a cyclopentane ring. cians and have been evaluated in clinical Thereafter, it was found that all prostaglan­ research projects. dins are derived from linoleic and arachidonic The purpose ofthis paper is, first, to provide fatty acids; arachidonate is in the phospho­ an overview of these areas where prostaglan­ lipids of cell membranes of all mammalian dins may be utilized in canine and feline prac­ tissues. 5 tice. Secondly, owing to the fact of its recent There are several main classes of pro­ emergence on the veterinary medical scene, a staglandins: E,F,I,A,B,C,D, distinguished by briefbackground on prostaglandins will be in­ the constituents of the cyclopentane ring. The eluded to facilitate understanding. main classes are further subdivided in accord with the number of double bonds in the side BACKGROUND chains. 3 The most biologically active com­ Prostaglandins are naturally occurring pounds are PGE2, PGF2a , TXA, and PGI2 all substances classified as autocoids, from the of wh~ch have a pair of double bonds and are, Greek autos ("self') and akos ("medicinal therefore, designated as the 2 series. 5 The E agent"), and referred to as parahormones, and Fa Groups are the most abundant in humoral mediators, or local hormones because reproductive tissues, especially PGE2 and they are not systemically circulating hor­ PGF2a , with only prostaglandin F2a and its mones, but act only on the local level. They are analogues available commercially for produced by most biological tissues and are veterinary use in this country. PGF2a is prob­ detectable in most body fluids. Members ofthe ably the natural uterine luteolytic factor in prostaglandin family have specific reproduc­ most species. tive functions and also participate as mes­ The first product on the market was the senger-type agents in the function of nearly THAM salt of PGF2a , dinoprost trometha­ every physiologic system in the body.l Their mine (Prostin F2alphaR -Upjohn Co.). It is actions are believed to be mediated by cyclic labelled for use only in horses to control the AMP and cyclic G MP.2 time of estrus in cyling mares and to treat In 1936, Von Euler derived the name "pro­ mares with prolonged diestrual periods. The staglandin" from the prostate gland to identify approved dosage is 1 mg/l00 lbs. (0.022 a lipid-soluble acid that he had found to be the mg/kg) administered as a single intramuscular active substance in human semen which had injection. The Upjohn Co. subsequently came out with another dinoprost product R *Dr. Briles is a 1982 graduate of the College of (Lutalyse ) which is identical to Prostin Veterinary Medicine at Iowa State University. ** Dr. Evans is a professor in Veterinary Clinical F2alpha except it is labelled for synchroniza­ Sciences at Iowa State University. tion of estrus among beef cattle and nonlac-

90 Iowa State Veterinarian tating dairy heifers, and for abortion offeedlot plete luteolysis was induced and abortion oc­ heifers before 100 days of gestation. The ap­ curred when plasma was proved dosage is 25 mg as a total dose ad­ depressed to 0.6-1.4 ng/ml from pretreatment ministered intramuscularly. Another com­ levels of 3-40 ng/nll. 11 mercial product is prostalene (Synchro­ It has been the authors' experience that the ceptR-Diamond) which is a PGF2a analogue proper length of treatment (six injections, one labelled for use only in horses at a dosage of 5 every 12 hours) must be maintained to pro­ ug/kg. duce a successful abortion. In an earlier study Besides the approved uses, PGF 2a is used in luteolysis and abortion were not produced the bovine therapeutically for unobserved when a larger total dose (250 ug/kg) was given estrus, pyometra, mummified fetus, luteinized intraveneously within a seven hour period. 14 6 cysts, and induction of parturition. Other It also seems imperative that the treatment unapproved uses have also been recognized in 7 be delayed until the mid to late gestation the equine. ,8 PGF has been used for induc­ 2a period since the early corpora lutea in the bitch tion of parturition in swine. 9 are more refractory to PGF2a' Similarly, in Women of child-bearing age, asthmatics, cattle doses of PGF 2a must be given after day and persons with bronchial and other five of the in order to get respiratory problems should be very careful luteolysis. 15 An hypothesis has been when handling this drug because prostaglan­ proposed16 and supported17 that explains the dins of the F series are effective abortifacients resistance of the newly formed and potent bronchoconstrictors in human by the fact that "the preovulatory surge of LH beings. saturates the regulatory units ofthe luteal cells Uses ofprostaglandin reported in this paper and that it is this bound hormone which are of the dinoprost tromethamine product protects the young corpus luteum." Previous­ and are in nonapproved species based solely ly, corpus luteum receptors for PGF2a were on results of experimental use. The FDA does identified. 18 not sanction such uses, therefore, the It is not surprising that this regimen of ex­ veterinarian assumes full responsibility. ogenously administered PGF2a (every 12 hours for three days) is effective in producing ABORTION luteolysis in the bitch when considering the en­ It has been established that endogenous dogenous PGF2a release patterns associated PGF of uterine origin in the cow is in­ with luteolysis in other species. Parallels tend 2a to appear between the natural release of strun1.ental in terminating luteal function in PGF and the above-mentioned regimen in the nonpregnant animal thus returning it to 2a dogs. In the bovine the production and release heat. PGF 2a release from the uterus is also im­ ofPCF 2a by the uterus is known to be pulsatile portant for the prepartum lysis of the corpus and precise. During the estrous cycle PGF2a is luteum which removes the progesterone block released for two to three days as rapid pulses and for increasing the contractile strength of with a duration of one to five hours prior to the uterine musculature prior to parturition. 10 and during luteolysis, which is indicated by Consequently, exogenous PGF2a has proven decreasing levels of plasma progesterone. 19 to be an effective abortifacient in cows. In dogs and cats it is known that prostaglandins play The exact mechanism for PGF2a induced an important role in reproductive function but luteolysis has not been worked out in any that role is not nearly as well worked out as it species but some theories are as follows: an­ is in the bovine. tagonism with LH or ; promotion of PGF2a can be used to terminate gestation in fragility in lysosomes; contractile effect on the ll 12 13 the bitch . and queen. One study has utero-ovarian vein, resulting in reduced blood flow through the ; decreased stores ofthe reported that PGF2a given intramuscularly to pregnant beagle bitches from day 33 to day 53 progesterone precursors, cholesterol esters; or of gestation at a dosage of either 20 ug/kg decreased esterase activity. every 8 hours or 30 ug/kg every 12 hours for 72 PCF2a also induces strong myometrial con­ hours (180 ug/kg total dose) will cause the tractions in the bitch which plays a role in the fetuses to abort within 56 to 80 hours after induced abortion along with at least a de­ treatment begins. ll It was shown that com- creased luteal function.

Vol. 44) No. 2 91 It has also been reported that a one-shot that 80% of injected PGF2a is excreted in the dosage of 1 mg/kg PGF2a in the bitch is an urine within six hours in the bovine. 4 A mild effective abortifacient. 12 However, details con­ drop in body temperature (i-2°F) similar to cerning the application of this dosage are not that preceding normal parturition may be available. noted. 11 After the second or third injection the The veterinarian is often faced with the bitch may display vigorous nest building client who believes his bitch may have been behavior. Fetal expulsions should be expected bred to an undesirable male dog. The client to occur approximately 56-80 hours after the desires that something be done to remedy the first PGF2a injection with the bitch'showing no situation. If more than two or three days have signs of difficulty. 11 elapsed since the misalliance, a mismating Some dogs may not abort at this dosage and shot of estrogens (0.5-1 mg/lb stilbesterol or treatment length because of individual 0.5-2 mg ECP) might be ineffective or variability in hormonal patterns. 11,14 This in­ undesirable. The owner may not want the dividual variability may necessitate a more bitch spayed and would rather not put the dog flexible schedule of treatment such as a longer through a pregnancy. In this situation a treatment period or higher dose. Not enough

PGF2a induced abortion may be indicated. data is available to draw any statistics on the First, however, the pregnancy should be success of each possible treatment regimen. confirmed by digital palpation between days The subcutaneous median lethal dose for 25-35 of gestation. If palpation cannot PGF2a in the beagle bitch has been reported to confirm the pregnancy, ultrasonography may be 5.13 mg/kg. 12 At this dose the clinical signs be used as early as the 29th day or radiographs of toxicosis include excessive salivation, may be taken after day 42 of gestation. vomiting, diarrhea, hyperpnea, ataxia, and If the dog is indeed pregnant and in good pupillary dilatation and then pupillary con­ health, free ofany respiratory problen1s, it can striction. The effects were maximal from be started on a regimen of PGF2a at 25-30 90-120 minutes after treatment and death oc­ ug/kg every 12 hours 1M or SQ for 72 hours curred in a few hours (2-11). The toxicological (total of 6 treatments) starting no earlier than signs resembled those of endotoxic and the 33rd day of gestation. Priming the dog neurotoxic shock syndromes. 12 with 0.1-2 mg ECP given 1M about 24 hours Some minor side effects were noted incon­ prior to starting the PGF2a treatment may in­ sistently at dosages greater than or equal to crease the abortifacient effect. Although not 0.444 mg/kg given 1M. These signs included: originally described as part ofthe abortifacient mild locomotor incoordination, rubbing the procedure, -17B injected into ewes face wjth the forefeet, slight CNS depression, has elicited marked synthesis and release ofen­ micturition and slight hyperthermia in addi­ dogenous PGF2a. 21 Estrogens also help tion to hyperpnea, vomiting, and defecation. 23 prepare the uterus for contraction by increas­ When PGF2a was given IV at doses as low as ing myometrial motility, and in some species 30 ug/kg emesis was caused consistently in 30 estrogens stimulate the release of oxytocin seconds and slight incoordination and illness 20 from the posterior pituitary gland. However, followed. 14 it should be stated that PGF2a without From the data available on side effects it is estrogen priming will induce abortions. apparent that PGF2a is better suited for 1M or The dog should be hospitalized and food SQ injection, because it is absorbed more withheld 24 hours prior to beginning the treat­ slowly. The most consistent side effect ob­ ment regimen. In the original study 11 no ob­ served was the increase in respiratory rate vious nor consistent systemic side effects were which can be accounted for by the fact that noted, but it should be expected that the dog's PGF2a is a potent bronchoconstrictor and as respiratory rate will increase, usually within such should not be used in dogs with res­ five minutes after injection, and there will be piratory dysfunction. Vomiting also appeared vomition and defecation. There is usually not often, but at the dosage of 30 ug/kg 1M or SQ more than one episode of emesis and defeca­ it does not always occur. The emesis at this tion per injection. The panting should subside dosage is not usually characterized by within 45 minutes. The half-life of PGF2a in wretching or illness, but occurs rapidly the body is very short being about eight without much effort or discomfort on the part minutes in the bovine.22 It has been reported ofthe dog. The vomiting and defecation usual-

92 Iowa State Veterinarian ly become less pronounced with each A toxic dose of PGF2a injected SQhas been treatment. 11,14 The emesis and defecation are reported in the cat at approximately 5.0 due to the stimulatory effect of PGF2a on mg/kg. 25 Clinical signs of toxicosis noted were smooth muscle. ataxia, respiratory distress, muscle tremors, At a dosage of 30 ug/kg there is over a 100X and loose bowel movements. 25 The cat does margin of safety (MLD = 5.13 mg/kg) which not appear to be as sensitive to prostaglandins is quite acceptable. If, however, a one-injec­ as is the dog. tion luteolytic dosage of 1 mg/kg is used the margin ofsafety is only 5X, which is not accep­ INDUCTION OF PARTURITION table. The rationale for using the larger dose is There have been no studies on the use of that only one injection is needed; however, it prostaglandins to induce parturition in the has been shown that a dosage of30 ug/kg given dog; however, since it has been shown that every 12 hours for six treatments elicits effec­ prostaglandins play such an important role in tive luteolysis, and abortion is achieved with the normal physiology of parturition in the minimal side effects11 and more closely cor­ dog,2° and since it terminates pregnancy in the responds to the body's own natural release of mid to late phase of gestation, it seems likely PGF2a from the uterus prior to regression of PGF2a alone or in combination with oxytocin, the corpora lutea. 19 Prostaglandin does not estrogen, or dexamethasone would be effective have a cumulative effect in the body because it in inducing parturition. During normal par­ is rapidly metabolized and excreted from the turition it has been suggested that prostaglan­ body. It is vital whenever using PGF2a in the dins may act on the pituitary gland ofthe dam dog or cat to compute the dose accurately by resulting in the release of oxytocin, act on the weighing the patient. placenta to inhibit progesterone production In the queen it has been reported that one or and release relaxin, and act on the ovary to two subcutaneous injections of PGF2a 24 release relaxin. 20 hours apart at the dosage of 0.5-1 mg/kg will In the cat the mechanism of parturition has induce abortion if given after the 40th day of not been studied and hormonal interrelation­ gestation. 13 Fetal expulsion occurred within 24 ships are essentially unknown, yet it is likely hours ofthe first injection or within 24 hours of that the cat does not differ significantly from the second injection, if needed. Within 15 other species and prostaglandin alone or in minutes after injection cats were noted to combination, as in inducing abortion, may be defecate in their litter boxes. Other side effects effective in inducing parturition. In one study were minimal. As in dogs, cats with com­ PGF2a (0.50-1.0 mg/kg) given in two doses 24 promised respiratory function should not be hours apart to cats over 55 days ofgestation in­ given PGF2a . duced parturition resulting in live kittens that In another study two S.Q. injections of were normal and healthy. 13 The queens pro­ PGF2a 24 hours apart at a dosage of 0.5-1 duced milk at parturition and suckled their mg/kg after the 40th day of gestation did not young. One case report appears in the litera­ result in abortion, but only partialluteolysis.24 ture27 where a nine-month old queen on the Instead, after day 51 of gestation a regimen of 70th day of gestation, with a history of a clear ACTH followed by PGF2a 24-96 hours later vaginal discharge on day 65 without obvious was shown to induce complete luteolysis and signs oflabor, was administered two SQinjec­ abortion. Using smaller doses of PGF2a and tions of PGF2a 24 hours apart at a dose of 0.5 spreading them out over six treatments as in mg/kg. Two hours after the second dose the the dog has not been reported in the cat. first kitten was born dead and three live kittens Presently, it is not clear whether the PGF2a­ followed within 90 minutes. The three kittens induced abortions in cats are due to luteolysis received adequate milk and were reared suc­ ofthe corpus luteum ofpregnancy or the result cessfully. The queen experienced an increased of PGF2a-induced myometrial contractions. respiration rate, restlessness, and inconti­ Most studies have demonstrated only a partial nence during the treatment. decrease in luteal function after exogenous Prostaglandins can be used in combination PGF2a administration.24,25,26 It is likely that with oxytocin to adequately induce labor in abortion occurred due to the "oxytocic" effect women.28 They can also be used to effectively on the uterus in the presence of decreased induce parturition in cows,29 SOWS,9 does,30 luteal function. and ewes.31

Vol. 44, No. 2 93 PSEUDOPREGNANCY PGF2a fertility all nine had a subsequent It has been reported that 0.5 mg/kg (total estrus period. Five of nine bred at an estrus dose) of PGF2a given SQ to 40 clinically false after treatment were subsequently pregnant. pregnant bitches of various breeds and ages Two of the five whelped normal litters. It did resulted in regression of the symptoms of false not state the outcome of the other three preg­ pregnancy in 37 animals. 32 The symptoms in­ nant bitches. The study suggests that PCF2a cluded: galactorrhea, mammary enlargement, therapy may offer an alternative to surgery in mothering behavior, nest building, and labor breeding bitches, in cases where surgery may pains. The dogs returned to normal behavior not be desired by the pet owner, and in in about seven to eight days after the treat­ animals that might otherwise be questionable ment. The dose of PGF2a had to be repeated surgical risks. 33 in four cases to be effective. The side effects Two case reports on the use of PCF2a to reported were very minimal. Presumably the treat pyometra in the bitch appear in the litera­ effectiveness of PCF2a in treating pseudopreg­ ture. In one case an open pyometra in a two nancy in the bitch is due to its luteolytic effect. year old bassett hound was treated with one In the cat one study has been reported sug­ 1M injection of PGF2a at a dose of 0.2 mg/kg gesting that PGF2a (0.5-5.0 mg/kg SQ) given after an unsuccessful therapeutic course of 34 during the early luteal phase would be ineffec­ antibiotics. The dog subsequently exhibited tive for the premature termination of the typical prostaglandin side effects of pseudopregnancy.25 restlessness, panting, nest building, and it vomited once. Within 60 minutes a purulent discharge appeared from the vulva that became progressively more mucous in nature SUBINVOLUTION OF THE over a period of nine hours. In the subsequent PLACENTAL SITES estrus period the dog was mated and produced It has been reported that PGF2a can be used nine healthy puppies. to treat subinvolution of the placental sites in The other case was described as a typical the bitch, where chronic post-partum uterine closed pyometra and was treated with one SQ hemorrhage is a problem, by using one dose at injection of PGF2a at a dose of 0.25 mg/kg. 0.1-0.25 mg/kg or at the rate of25 ug/kg every Within 17 hours approximately one gallon of 12 hours until six injections have been given.7 purulent mucous discharge had been evacu­ The mechanism of action of PGF2a in this case ated. 27 Oxytocin was thereafter administered was not reported. which was followed by an increase in discharge for a few hours. The vaginal discharge reoc­ curred 13 days later and was treated with two UTERINE DISEASE doses of PGF2a (0.25 mg/kg SQ) given 24 Another use of PGF2a in dogs is in the treat­ hours apart, followed by antibiotics. The ment of uterine disease. It has been reported discharge did not reoccur. that PGF2a at 250 ug/kg SQ was used suc­ One report appears in the literature on the cessfully in 14 of 16 cases to medically treat-en­ ineffectiveness of prostaglandins for treatment dometritis and pyometra.33 Successful medical of uterine disease. 35 treatment resulted in remission of clinical signs within 30 days post-treatment with no surgical intervention, but supportive therapy EMESIS AND DEFECATION and antibacterials were used as needed. Suc­ O,ne possible nonreproductive use of PGF2a cess was achieved in five ofthe six endometritis has been reported.23 It was suggested that cases, in two ofthe three metritis cases, and in PGF2a could· be used for the clinical induce­ seven-~ofthe seven pyometra cases.33 10 out of ment of vomition and large intestine evacua­ the 16 cases needed more than one treatment, tion in the dog. Defecation (83.3% of dogs) ranging from 2 to 4 treatments. The study did without vomition occurred in dogs given a not report the time interval between treat­ dosage of 0.111 mg/kg. Emesis (87.5% of ments, but stated that there was "retreatment dogs) and defecation (75% of dogs) were ob­ at a later date." All but one of the pyometra served in dogs given a dosage of greater than cases appeared to be open pyometras. In a or equal to 0.444 mg/kg with emesis occurring follow-up of nine intact bitches to assess post- 1.6 to 2. 6 minutes after defecation.

94 Iowa State Veterinarian In effect, this use of PGF2a is taking advan­ 3. Doug-las WW: Polypeptides-angiotensin, plasma tage of the side effects of prostaglandin killins, and other vasoactive agents; prostaglandins, in Goodman LS, Gilman A (ed): The Pharmacological reported in reproductive applications. Basis of Therapeutics. New York, Macmillan However, the one major side effect that always Publishing Co Inc, 1975, pp. 640-641. appears even before vomiting and defecation is 4. Kindahl H: Prostaglandin biosynthesis and metabolism. J Am Vet Med Assoc 176: 1173-1177, the increased respiratory rate, so respiratory 1980. function would have to be carefully ascer­ 5. Bell TG, Smith WL, Oxender WD, et al: Biologic in­ teraction of prostaglandins, thromboxane, and pro­ tained before PGF2a use. The dosage would stacyclin: potential nonreproductive veterinary also have to be accurately calculated to avoid clinical applications. J Am Vet Med Assoc other undesirable effects. Possible advantages 176:1195-1200,1980. 6. Seguin BE: Role of prostaglandins in bovine to the use of PGF2a to induce vomition and reproduction. J Am Vet Med Assoc 186:1178-1181, defecation are its rapid action, injectability, 1980. and availability for the mixed practitioner 7. Braun WF: A review of prostaglandin therapeutics in reproduction. Vet Med Sm An Clin April:649-656, when an emergency emetic is needed in the 1980. field. 8. Shultz RH: Experiences and problems associated with usage of prostaglandins in countries other than Many potential nonreproductive veterinary the United States. JAm Vet MedAssoc 176: 1182-1186, clincial applications of prostaglandins have 1980. 9. Cooper Mj, Walpole AL: Practical application of been suggested and initially investigated. 5 The prostaglandins in animal husbandry, in Karim SMM prostaglandins involved include PGF2a, (ed): Prostaglandins and Reproduction) 1975, pp PGEl, PGE2 , PGI2 , and many varied 310-328. prostaglandin-active agents such as aspirin, 10. Stabenfeldt GH, Hughes jP, et al: Physiologic and pathophysiologic aspects of prostaglandin F 2a during phenylbutazone, flunixin meglumine, theo­ the reproductive cycle. J Am Vet Med Assoc phylline, vitamin E, selenium, and isoprotere­ 176:1187-1194; 1980. 11. Concannon PW, Hansel W: Prostaglandin F2a in­ nol. The scope of these potential uses is broad duced luteolysis, hypothermia and abortions in beagle and encompasses the treatment of the follow­ bitches. Prostaglandins 13:533-542, 1977. ing: disseminated intravascular coagulation; 12. Sokolowski jH, Geng S: Effect of prostaglandin F2a­ tham in the bitch. J Am Vet Med Assoc 170:536-537, endotoxemia; chronic vascular disease, such 1977. as cardiomyopathies;' ischemia and sequellae, 13. Nachreiner RF, Marple DN: Termination of pregnancy in cats with prostaglandin F2a' Pro­ such as shock, and laminitis; excessive staglandins 7:303-308, 1974. bleeding; bronchial asthma; toxic hepatitis; 14. jochle W, Tomlinson RV, Andersen AC: Pro­ and neoplastic metastasis. staglandin effects on plasma progesterone levels in the pregnant and cycling dog (beagle). Prostaglandins The veterinary clinician should be aware of 3:209-217, 1973. the uses of prostaglandins that are currently 15. Lauderdale JW: Effects of prostaglandin F2a on applicable as they may offer a source of viable pregnancy and estrus of cattle. J Anim Sci 35:246 (Abstr), 1972. therapy or alternative treatment in small 16. Henderson KM, McNatty KP: A biochemical animal medicine. In order to use prostaglan­ hypothesis to explain the mechanism of luteal regres­ sion. Prostaglandins 9:779-797, 1975. dins properly, with minimal deleterious un­ 17. Saumande j, Chupin D: The non-luteolytic effect of toward effects and successful administration, a prostaglandin F2a at· the beginning of the bovine basic understanding oftheir mechanism ofac­ ,estrus cycle: the role of estrogen? Theriogenology 15:265-269, 1981. tion, physiological effects, and metabolism is 18. Rao CV, Estergreen VL, Carman FR, et al: Recep­ absolutely necessary. Recent advances in pro­ tors for gonadotropin and prostaglandin F2a in staglandin research have made nonreproduc­ bovine corpora lutea of early, mid, and late luteal phase. Acta Endocr 91 :529-537, 1979. tive veterinary uses potentially available and 19. Kindahl H, Edquist LE, Granstrom E, et al: The the future portends further medical advances release of prostaglandin F 2a as reflected by 15-Keto-13, 14-dihydroprostaglandin F2a in the based on prostaglandin physiology. peripheral circulation during normal luteolysis in heifers. Prostaglandins 11:871-878, 1976. 20. Bennett D: Normal and abnormal parturition, in Morrow DA (ed): Current Therapy in Theriogen 0 logy, REFERENCES 1980, pp 595-606. 1. Karim SMM: Advances in prostaglandin research, in 21. Barcikowski B, Carlson jC, Wilson L, et al: The effect Prostaglandins: Physiological) Pharmacological and of endogenous and exogenous estradiol-17B on the Pathological Aspects. Baltimore, University Park Press, release of prostaglandin F2a from the ovine uterus. 1976. Endocrinology 95: 1340-1349, 1974. 2. Curtis-Prior. PB: Interaction of prostaglandins and 22. Kindahl H, Edquist LE, Granstrom E: Blood levels of cyclic nucleotides, in Prostaglandins: An Introduction to progesterone and 15-keto-13, 14-dihydroprostaglan­ their Biochemistry) Physiology and Pharmacology. Amster­ din F2a during the normal estrus cycle and early dam, North Holland Publishing Co Inc, 1976, pp pregnancy in heifers. Acta Endocr 82: 134, 1976. 77-80. (continued on page 98)

Vol. 44) No. 2 95 23. Eiler H,Paddleford R: Induction ofintestinal evacua­ 29. Kordts E, Jochle W: Induced parturition in dairy cat­ tion or vomition-(or both) in the dog by prostaglandin tle: a comparison of a corticoid (flumethasone) and a F2a I injection: clinical potential. Am J Vet Res prostaglandin (PGF2a) in different age groups. 40: 1731-1733, 1979. Theriogenology 3: 171, 1975. 24. Wycoff JT, Ganjam VK: Successful termination of 30. Fitzpatrick RJ: The medical induction of parturition. pregnancy in cats by the administration ofa combina­ Proc Assn Vet Clin Pharmacol Thera) U niv. Liverpool tion of adrenocorticotrophic hormone (ACTH) and 1:14,1977. prostaglandin F2a-tham salt. Fed Proced 38: 1189, 31. Crouch MD: Induced parturition in domestic ewes 1979. with PGF2a, dexamethasone and estradiol cypionate. 25. Wildt DE, Panko WB, Seager SW: Effect of pro­ J Anim Sci (Suppl 1) 45:420, 1977. staglandin F2a on endocrine-ovarian function in the 32. Barnabe RC, Mucciolo A, Matera A, et al: The effect domestic cat. Prostaglandins 18:883-892, 1979. of prostaglandin F 2a on false pregnancy in bitches. 26. Shille VM, Stabenfeldt GH: Luteal function in the Revista da Faculdade de Medicina Veterinaria e Zootecnia domestic cat during pseudopregnancy and after treat­ 16:25-26, 1979. ment with prostaglandin F2a. Biology of Reproduction 33. Sokolowski JH: Prostaglandin F2a-tham for medical 21:1217-1223,1979. treatment of endometritis, metritis, and pyometritis 27. Nelson M: Dinoprost in small animals, in (letters), Vet in the bitch. J Am An Hosp Assoc 16:119-122, 1980. Record 105:261-262, 1979. 34. Swift GA, et al: Dinoprost in pyometritis in the bitch, 28. Golbus MS, Greasy RK: Uterine priming with oral in (letters), Vet Record 105:64-65, 1979.

prostaglandin E 2 prior to elective induction with oxy­ 35. Chaffaux S, Thibier M: Sexual hormonology in the tocin. Prostaglandins 14: 577-581, 1977. bitch: pyometra. Rec Med Vet 152:471-481, 1976.

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98 Iowa State Veterinarian