Endocrine and cardiac parameters in parturient mares - Prediction of foaling -

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Endocrine and cardiac parameters in parturient mares - Prediction of foaling - Christina Nagel 1, Jörg Aurich 2, Regina Erber 1, Christine Aurich 1 1 Centre for Artificial Insemination and Embryo Transfer, and 2 Division for Obstetrics, Gynaecology and Andrology, University of Veterinary Sciences, 1210 Vienna, Austria

Endocrinology during late gestation Physiological induction of parturition in horses different from ruminants and pigs No progesterone in late pregnant mares but pregnancy is maintained by 5α-pregnanes Precursors for placental progestin production originate from fetal adrenal glands Fetus essential for maintenance of pregnancy

Endocrinology during late gestation Maturation of enzyme pathways Pregnenolone CORTISOL Placenta: Maintenance of pregnancy Induction of foaling

Prediction of parturition

Parturition and stress responses Parturition in horses Short and active expulsive phase Is suggested to be a strenuous and painful process Stress response Activation of the sympathetic nervous system and the hypothalamo-pituitary-adrenal axis Stress response Stress during parturition inhibition of labor via activation of uterine ß 2 -receptors

Parturition and stress responses Stress response is indicated by Cortisol concentration Heart rate Heart rate variability

Stress responses Brain Hypothalamus Anterior pituitary CRF ACTH Adrenal gland Glucocorticoids Hypothalamic-pituitary adrenocortical response Cortisol (Saliva = non-invasive sampling) Adrenaline Autonomous nervous system Sympathetic-adrenomedullary response Heart rate Heart rate variability

Stress responses Autonomous nervous system (ANS) Sympathetic part of ANS increased activity in response to stressful situations and external challenges ( fight or flight ) Parasympathetic part of ANS increased activity during times of rest ("rest and digest )

Heart rate variability HRV = Sympathetic dominance HRV = Parasympathetic dominance RMSSD = Root mean square of successive RR differences Specific for parasympathetic activity

Hypothesis Parturition in mares induces a stress response and thus parturition can be predicted by changes in stress parameters Heart rate Heart rate variability Cortisol concentration Cut-off point: Increase of more than 2 times the standard deviation of respective parameter from mean values of days 5, 4 and 3 before foaling

Material and methods Group 1: Warmblood brood mares (n=24) Starting 15 days before calculated day of parturition ECG recordings once daily for one hour Salivary cortisol 4 x daily (6:00, 12:00, 18:00, 24:00) Group 2: Warmblood brood mares (n=17) From 2 hours before to 2 hours after parturition Continuous ECG recordings Salivary cortisol at 0, 15, 30, 60, 120 min after foaling

Electrocardiogram

Salivary cortisol Salivary cortisol Non-invasive technique Only biological active part of total cortisol concentration Need of laboratory equipment

Results

Salivary cortisol Salivary Cortisol (ng/ml) 6 5 4 3 2 1 0-15 -10-5 -4-3 -2-1 Days before parturition Salivary cortisol concentration in mares from 15 to 1 day before parturition at 6:00, 12:00, 18:00 and 24:00

Salivary cortisol Salivary Cortisol (ng/ml) 30 20 10 0-1 0 30 60 120 Time after parturition (min) Day before parturition Salivary cortisol concentrations from 1 day before to 1 day after parturition 1 Day after parturition

Salivary cortisol 4 Salivary cortisol (ng/ml) 3 2 1 0-5 -4-3 -2-1 Days before parturition cortisol increase towards parturition cortisol in late pregnant mares cortisol in non pregnent mares 80% of mares show an increase in cortisol during the last 24h before parturition (> 2 x SD of basal values)

Heart rate 60 60 HR (beats/min) 55 50 45 HR (beats/min) 55 50 45 40 40-15-10-5 -4-3 -2-1 Days before parturition -120-90 -60-30 -5 5 30 60 90 120 Min before and after parturition Heart rate from 15 days before to 1 day before parturition Heart rate from 120 min before to 120 min after parturition

Heart rate variability 150 150 RMSSD (ms) 125 100 75 RMSSD (ms) 125 100 75 50 50-15-10-5 -4-3 -2-1 Days before parturition -120-90 -60-30 -5 5 30 60 90 120 Min before and after parturition HRV variable RMSSD from 15 days before to 1 day before parturition HRV variable RMSSD from 120 min before to 120 min after parturition

Heart rate and HRV Heart rate Increases during the last month of gestation but no further changes towards foaling false positive results with regard to prediction of foaling HRV High individual variations Increase in less than 70% of mares during the last 2 h before parturition

Atrioventricular blocks Horses have a powerful cardiovascular system and at rest occasionally skip one heart beat due to second degree atrioventricular blocks (AV blocks) Sign of high parasympathetic tone Disappear during exercise, due to increased demands on the cardiovascular system AV blocks in parturient mares? If parturition is a stressor, no AV blocks are expected

Atrioventricular blocks Number of mares with AV blocks 11 10 9 8 7 6 5 4 3 2 1 0-120 -105-90 -75-60 -45-30 -15 15 3045 60 7590 105 120 Min before and after parturition Number of AV blocks per mare during 15 min intervals from 120 min before to 120 min after parturition (n=11)

Atrioventricular blocks Number of mares with AV blocks 11 10 9 8 7 6 5 4 3 2 1 0-120 -105-90 -75-60 -45-30 -15 15 3045 60 7590 105 120 AV Block/15 min 20 15 10 5 0-120 -105-90 -75-60 -45-30 -15 15 3045 60 7590 105 120 Min before and after parturition Min before and after parturition Number of AV blocks per mare and number of mares with AV blocks during 15 min intervals from 120 min before to 120 min after parturition (n=11)

Atrioventricular blocks No AV blocks in any mare days before parturition 9/11 mares showed AV block during 15 min interval before parturition Only one mare showed no AV blocks at all

Summary and conclusion

Summary and conclusion HR increases during equine gestation because of adaptation of the cardiovascular system to increasing demands of the growing fetus Before and during foaling heart rate remains at the same level High incidence of AV blocks and high HRV during and after parturition In horses parturition and the immediate post partum period are dominated by parasympathetic activity Physiological parturition is no major stressor in horses

Summary and conclusion Salivary cortisol increases 1-2 days before parturition Coincides with increase in fetal plasma cortisol (Silver and Fowden 1995) Cortisol in the maternal circulation could in part be of fetal origin Maximum cortisol concentration at 30 min after parturition Not directly associated with labor High level of cortisol during high parasympathetic activity Rise in cortisol concentration is unlikely a stress response but part of the endocrine pathways initiating parturition

Prediction of parturition Heart rate and HRV no reliable parameters Detection of AV blocks during normal parturition? Cortisol concentration increases >2 ng/ml in up to 80% of mares during the last 24 hours before parturition

Prediction of parturition Most systems are not advisable Prediction of parturition is still challenging

Thank you for your attention Jörg Aurich Christine Aurich Regina Erber