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Dose–response effect of intramuscular oxytocin treatment on myometrial contraction of reproductively normal mares during estrus
Theriogenology 58 (2002) 479±481
Abstract
Dose±response effect of intramuscular oxytocin treatment on myometrial contraction of reproductively normal mares during estrus S. Madilla,*, M.H.T. Troedssona, E.M. Santschib, E.D. Malonea a
Department of Clinical and Population Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, MN 55108, USA b Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI 53706, USA
1. Introduction Persistent breeding-induced endometritis affects approximately 15% of mares in clinical practice [1] and is a major cause of reduced fertility [2]. Mares susceptible to this condition are unable to remove excess uterine contamination that results from mating due to reduced myometrial contractility [3]. Treatment of susceptible mares with oxytocin has been shown to restore uterine physical clearance mechanisms to normal levels [4]. Various oxytocin dosage regimen have been used in treating clinical cases, ranging from 5 to 25 units per mare [5,6]. Intravenous administration is generally reported in these studies and in experiments examining the effects of exogenous oxytocin on uterine contractility [7±9]. In practice, the medical management of these mares on the stud farm will often require follow-up treatments given by lay-staff. This may be done more safely and conveniently by intramuscular administration. The purpose of this study was to investigate the contractile response of the equine uterus to different oxytocin doses administered intramuscularly during estrus. 2. Materials and methods Five reproductively normal mares had three pairs of myometrial electrodes implanted in the mid-region of the left uterine horn. Following at least 2 weeks recovery from surgery, estrous mares had the electrode leads attached to a polygraph and myometrial electrical activity was recorded. Following 2 h of baseline recording, mares were given sequential * Corresponding author. E-mail address: [email protected] (S. Madill).
0093-691X/02/$ ± see front matter # 2002 Elsevier Science Inc. All rights reserved. PII: S 0 0 9 3 - 6 9 1 X ( 0 2 ) 0 0 8 8 0 - 4
480
S. Madill et al. / Theriogenology 58 (2002) 479±481
Table 1 Effect of administration of oxytocin given i.m. on myometrial activity (mean S:E:M:) Treatment Baseline 5 units 10 units 20 units 40 units
Contractions (h 1) 5.1 9.1 9.8 11.4 13.9
a
1.0 1.7b 1.6b 1.6bc 2.8c
Duration of response (min)
Activity (%)
n/a 40.6 49.8 90.3 98.6
27.7 55.3 54.6 57.3 58.6
a
4.8 7.2a 13.9b 11.1b
2.2a 3.4b 3.9b 5.5b 3.7b
Values with different superscripts within column are signi®cantly different P < 0:05.
doses of 5, 10, 20 and 40 USP oxytocin i.m. Thirty minutes prior to each oxytocin dose, an equal volume of normal saline was administered as a control. Data were digitized and assessed for frequency, response duration (period of increased contraction frequency), and activity during the response period (expressed as a percentage of the total response). After testing for normality, data were analyzed by two-way ANOVA, with mare and treatment as in dependent variables. Signi®cant effects were subjected to comparison of treatment means by Tukey's HSD. 3. Results Unless otherwise stated data are presented as mean S:E:M (Table 1). Time from administration of oxytocin to onset of response ranged from 5 to 22 min (11:8 1:0 min) but was not affected by dose of oxytocin (P 0:6) or mare (P 0:9). Saline controls showed no effect on uterine contraction (P > 0:05). The time from administration of oxytocin to cessation of increased contractile activity (latency to response duration of response), followed the same signi®cance pattern as duration of response. This interval was signi®cantly greater for 40 units (108 12:1 min) and 20 units (103 15:8 min) oxytocin doses than for 5 units (54:2 6:1 min) and 10 units (61:8 7:1 min) doses. 4. Discussion This study demonstrates a signi®cant dose±response relationship between intramuscular administration of oxytocin and increased uterine myometrial activity. All doses resulted in an increased frequency of contraction, which was re¯ected in the proportion of the response period that was spent in the contractile state (% activity). The common clinical dose of 20 USP provided 90 min of increased activity that translates to approximately 100 min from the time of administration (average latent period 11.8 min). There was considerable variation between mares in response duration and intensity. This was unrelated to size of mare. Other factors involved may include variation in absorption from the site of administration (evidenced by the range of latent times from injection to onset of contraction), variations in metabolism, and differences in the sensitivity of the
S. Madill et al. / Theriogenology 58 (2002) 479±481
481
uterus at the time of treatment. Within the long estrous period of the mare the estrogen:progesterone ratio changes and even subtle variations may be suf®cient to alter uterine responses [9]. References [1] Zent WW, Troedsson MHT. Postbreeding uterine ¯uid accumulation in a normal population of thoroughbred mares: a ®eld study. Proc Am Assn Equine Pract 1998;44:64±5. [2] Troedsson MHT. Uterine clearance and resistance to persistent endometritis in the mare. Theriogenology 1999;52:461±71. [3] Troedsson MHT, Liu IKM, Ing M, Pascoe J, Thurmond M. Multiple site electromyography recordings of uterine activity following an intrauterine bacterial challenge in mares susceptible and resistant to chronic uterine infection. J Reprod Fertil 1993;99:307±13. [4] LeBlanc MM, Neuwirth L, Mauragis D, Klapstein E, Tran T. Oxytocin enhances clearance of radiocolloid from the uterine lumen of reproductively normal mares and mares susceptible to endometritis. Equine Vet J 1994;26:279±82. [5] Allen WE. Investigations into the use of exogenous oxytocin for promoting uterine drainage in mares susceptible to endometritis. Vet Rec 1991;128:593±4. [6] Pycock JF, Newcombe JR. Assessment of the effect of three treatments to remove intrauterine ¯uid on the pregnancy rate in the mare. Vet Rec 1996;138:320±3. [7] Ko JCH, Lock TF, Davis JL, Smith RP. Spontaneous and oxytocin-induced uterine motility in cyclic and postpartum mares. Theriogenology 1988;32:643±51. [8] Cadario ME, Merritt AM, Archbald LF, Thatcher WW, LeBlanc MM. Changes in intrauterine pressure after oxytocin administration in reproductively normal mares and in those with a delay in uterine clearance. Theriogenology 1999;51:1017±25. [9] Gutjahr S, Paccamonti DL, Pycock JF, Taverne MAM, Dieleman SJ, van der Weijden GC. Effect of dose and day of treatment on uterine response to oxytocin in mares. Theriogenology 2000;54:447±56.
Abstract
Dose±response effect of intramuscular oxytocin treatment on myometrial contraction of reproductively normal mares during estrus S. Madilla,*, M.H.T. Troedssona, E.M. Santschib, E.D. Malonea a
Department of Clinical and Population Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, MN 55108, USA b Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI 53706, USA
1. Introduction Persistent breeding-induced endometritis affects approximately 15% of mares in clinical practice [1] and is a major cause of reduced fertility [2]. Mares susceptible to this condition are unable to remove excess uterine contamination that results from mating due to reduced myometrial contractility [3]. Treatment of susceptible mares with oxytocin has been shown to restore uterine physical clearance mechanisms to normal levels [4]. Various oxytocin dosage regimen have been used in treating clinical cases, ranging from 5 to 25 units per mare [5,6]. Intravenous administration is generally reported in these studies and in experiments examining the effects of exogenous oxytocin on uterine contractility [7±9]. In practice, the medical management of these mares on the stud farm will often require follow-up treatments given by lay-staff. This may be done more safely and conveniently by intramuscular administration. The purpose of this study was to investigate the contractile response of the equine uterus to different oxytocin doses administered intramuscularly during estrus. 2. Materials and methods Five reproductively normal mares had three pairs of myometrial electrodes implanted in the mid-region of the left uterine horn. Following at least 2 weeks recovery from surgery, estrous mares had the electrode leads attached to a polygraph and myometrial electrical activity was recorded. Following 2 h of baseline recording, mares were given sequential * Corresponding author. E-mail address: [email protected] (S. Madill).
0093-691X/02/$ ± see front matter # 2002 Elsevier Science Inc. All rights reserved. PII: S 0 0 9 3 - 6 9 1 X ( 0 2 ) 0 0 8 8 0 - 4
480
S. Madill et al. / Theriogenology 58 (2002) 479±481
Table 1 Effect of administration of oxytocin given i.m. on myometrial activity (mean S:E:M:) Treatment Baseline 5 units 10 units 20 units 40 units
Contractions (h 1) 5.1 9.1 9.8 11.4 13.9
a
1.0 1.7b 1.6b 1.6bc 2.8c
Duration of response (min)
Activity (%)
n/a 40.6 49.8 90.3 98.6
27.7 55.3 54.6 57.3 58.6
a
4.8 7.2a 13.9b 11.1b
2.2a 3.4b 3.9b 5.5b 3.7b
Values with different superscripts within column are signi®cantly different P < 0:05.
doses of 5, 10, 20 and 40 USP oxytocin i.m. Thirty minutes prior to each oxytocin dose, an equal volume of normal saline was administered as a control. Data were digitized and assessed for frequency, response duration (period of increased contraction frequency), and activity during the response period (expressed as a percentage of the total response). After testing for normality, data were analyzed by two-way ANOVA, with mare and treatment as in dependent variables. Signi®cant effects were subjected to comparison of treatment means by Tukey's HSD. 3. Results Unless otherwise stated data are presented as mean S:E:M (Table 1). Time from administration of oxytocin to onset of response ranged from 5 to 22 min (11:8 1:0 min) but was not affected by dose of oxytocin (P 0:6) or mare (P 0:9). Saline controls showed no effect on uterine contraction (P > 0:05). The time from administration of oxytocin to cessation of increased contractile activity (latency to response duration of response), followed the same signi®cance pattern as duration of response. This interval was signi®cantly greater for 40 units (108 12:1 min) and 20 units (103 15:8 min) oxytocin doses than for 5 units (54:2 6:1 min) and 10 units (61:8 7:1 min) doses. 4. Discussion This study demonstrates a signi®cant dose±response relationship between intramuscular administration of oxytocin and increased uterine myometrial activity. All doses resulted in an increased frequency of contraction, which was re¯ected in the proportion of the response period that was spent in the contractile state (% activity). The common clinical dose of 20 USP provided 90 min of increased activity that translates to approximately 100 min from the time of administration (average latent period 11.8 min). There was considerable variation between mares in response duration and intensity. This was unrelated to size of mare. Other factors involved may include variation in absorption from the site of administration (evidenced by the range of latent times from injection to onset of contraction), variations in metabolism, and differences in the sensitivity of the
S. Madill et al. / Theriogenology 58 (2002) 479±481
481
uterus at the time of treatment. Within the long estrous period of the mare the estrogen:progesterone ratio changes and even subtle variations may be suf®cient to alter uterine responses [9]. References [1] Zent WW, Troedsson MHT. Postbreeding uterine ¯uid accumulation in a normal population of thoroughbred mares: a ®eld study. Proc Am Assn Equine Pract 1998;44:64±5. [2] Troedsson MHT. Uterine clearance and resistance to persistent endometritis in the mare. Theriogenology 1999;52:461±71. [3] Troedsson MHT, Liu IKM, Ing M, Pascoe J, Thurmond M. Multiple site electromyography recordings of uterine activity following an intrauterine bacterial challenge in mares susceptible and resistant to chronic uterine infection. J Reprod Fertil 1993;99:307±13. [4] LeBlanc MM, Neuwirth L, Mauragis D, Klapstein E, Tran T. Oxytocin enhances clearance of radiocolloid from the uterine lumen of reproductively normal mares and mares susceptible to endometritis. Equine Vet J 1994;26:279±82. [5] Allen WE. Investigations into the use of exogenous oxytocin for promoting uterine drainage in mares susceptible to endometritis. Vet Rec 1991;128:593±4. [6] Pycock JF, Newcombe JR. Assessment of the effect of three treatments to remove intrauterine ¯uid on the pregnancy rate in the mare. Vet Rec 1996;138:320±3. [7] Ko JCH, Lock TF, Davis JL, Smith RP. Spontaneous and oxytocin-induced uterine motility in cyclic and postpartum mares. Theriogenology 1988;32:643±51. [8] Cadario ME, Merritt AM, Archbald LF, Thatcher WW, LeBlanc MM. Changes in intrauterine pressure after oxytocin administration in reproductively normal mares and in those with a delay in uterine clearance. Theriogenology 1999;51:1017±25. [9] Gutjahr S, Paccamonti DL, Pycock JF, Taverne MAM, Dieleman SJ, van der Weijden GC. Effect of dose and day of treatment on uterine response to oxytocin in mares. Theriogenology 2000;54:447±56.