Fetal hypoxia and apoptosis following maternal porcine reproductive and respiratory syndrome virus (PRRSV) infection.

BACKGROUND: Mechanisms of fetal death following maternal PRRSV2 infection remain uncharacterized, although hypoxia from umbilical cord lesions and/or placental detachment due to apoptosis are hypothesized. We performed two experiments examining hypoxia and apoptosis in PRRSV-infected and non-infected, third-trimester fetuses to elucidate possible associations with fetal death. Fetuses were selected based on four phenotypic infection groups: fetuses from non-challenged control gilts (CTRL); low viral load fetuses (LVL; Exp 1) or uninfected fetuses (UNINF; Exp 2) from inoculated gilts; viable high viral load fetuses (HVL-VIA); and HVL meconium-stained fetuses (HVL-MEC). RESULTS: In experiment 1, paraffin embedded fetal tissues collected 21 days post maternal infection (DPI) were examined for DNA fragmentation associated with apoptosis. Positively stained foci were larger and more numerous (P < 0.05) in heart, liver, and thymus of HVL-VIA and HVL-MEC compared to CTRL and LVL fetuses. In experiment 2, group differences in gene expression within the hypoxia (HIF1a, IDO1, VEGFa, LDHA, NOS2, NOX1) and apoptosis (CASP3, CASP7, CASP8, CASP9, RIPK1, RIPK3) pathways were assessed by RT-qPCR in fetal tissues collected at 12 DPI. High viral load fetuses showed differential expression relative to the CTRL and UNINF (P < 0.05 for all). Brain tissue from HVL-VIA and HVL-MEC fetuses presented increased expression of CASP7, CASP8, RIPK3, HIF1a and IDO1. Fetal heart showed increased expression of CASP8, HIF1a, IDO and NOX1 and a decrease in NOS2 expression in infected groups. CASP7, CASP9, RIPK1 and RIPK3 were only increased in the heart of HVL-VIA while VEGFa was only increased for HVL-MEC fetuses. Thymus from HVL-MEC had decreased expression of CASP9 and there was increased IDO1 in all infected fetuses. CONCLUSIONS: There is strong evidence of apoptosis occurring in the heart, liver and thymus of highly viral load fetuses at 21 DPI. Furthermore, there was clear upregulation of apoptotic genes in the heart of high viral load infected fetuses and less prominent upregulation in the brain of PRRSV-infected fetuses, whereas thymus appears to be spared at 12 DPI. There was no strong evidence of hypoxia at 12 DPI in brain and thymus but some indication of hypoxia occurring in fetal heart.

Invited review: heat stress effects during late gestation on dry cows and their calves.

In dairy cattle, late gestation is a critical period for fetal growth and physiological transition into the next lactation. Environmental factors, such as temperature and light, exert dramatic effects on the production, health, and well-being of animals during this period and after parturition. The aim of this review was to introduce effects of heat stress during late gestation on dairy cattle, and discuss the biological mechanisms that underlie the observed production and health responses in the dam and her fetus. Relative to cooled cows, cows that are heat stressed during late gestation have impaired mammary growth before parturition and decreased milk production in the subsequent lactation. In response to higher milk yield, cows cooled prepartum undergo a series of homeorhetic adaptations in early lactation to meet higher demand for milk synthesis compared with heat-stressed cows, but no direct effect of environmental heat stress on metabolism exists during the dry period. Prepartum cooling improves immune status of transition cows and evidence suggests that altered prolactin signaling in immune cells mediates the effects of heat stress on immune function. Late-gestation heat stress compromises placental development, which results in fetal hypoxia, malnutrition, and eventually fetal growth retardation. Maternal heat stress may also have carryover effects on the postnatal growth of offspring, but direct evidence is still lacking. Emerging evidence suggests that offspring from prepartum heat-stressed cows have compromised passive immunity and impaired cell-mediated immune function compared with those from cooled cows.

An international delphi study of the causes of death and the criteria used to assign cause of death in bovine perinatal mortality.

The objective of the present study was to elicit opinion from two groups of veterinarians [subject matter experts and non-subject matter experts] about the causes of bovine perinatal mortality and the criteria used to assign such causes. The subject matter experts were selected on the basis of their scientific publications or experience of working in a veterinary diagnostic or research laboratory in the area of bovine perinatal mortality. The non-subject matter experts were self-selected as cattle veterinarians without particular expertise in bovine perinatology. A total of 74 veterinarians (46 subject matter experts and 28 non-subject matter experts) from 23 countries responded. The study was conducted using Delphi methodology over seven rounds. Respondents were asked to agree the causes of bovine perinatal mortality and for each cause to agree the supporting diagnostic criteria. There was a close agreement between groups on 16 causes of death apart from intra-uterine growth retardation (IUGR) and micronutrient imbalances which were accepted by fewer subject matter experts. There was inter-group consensus on the criteria to diagnose accidents, congenital defects, dystocia, hyperthermia, infections, premature placental separation, prematurity and prolonged calving. There was inter-group consensus on the criteria to diagnose anoxia, apart from gingival cyanosis; on haemorrhage, apart from haemorrhagic anaemia; on IUGR, apart from organ weights; and on iodine imbalance, apart from goitre and thyroid iodine content. The results from this study highlighted the current lack of standardization of the criteria used to define the cause of death for bovine perinatal mortality and the need for such standardization.

Concentração de lactato e glicemia em cadelas e neonatos nascidos de cesariana / Lactato concentration in bitch and canine neonates born through cesarean section

Avaliaram-se a concentração de lactato e a glicemia em sete cadelas em trabalho de parto submetidas à cesariana e em seus respectivos neonatos. O lactato materno foi mensurado utilizando-se medidor portátil e pelo método enzimático colorimétrico. Nos neonatos avaliou-se também o peso ao nascimento. Os valores de lactato materno e neonatal foram estatisticamente diferentes, sendo mais elevado nos neonatos. Ao nascimento, as cadelas e os neonatos encontravam-se normoglicêmicos, e não se observou correlação entre a glicemia de ambos. Os valores de lactato obtidos pelo o analisador portátil (3,5±0,6mmol/L) foram mais altos do que os obtidos pelo método enzimático colorimétrico (1,6±0,6mmol/L). Observou-se correlação significativa entre o peso do neonato e a concentração de lactato, isto é, os filhotes de menor peso apresentaram maior concentração de lactato.

This work evaluated the concentration of lactate and blood glucose in seven bitches in labor subject to caesarean section and in their newborns. The lactate concentration was measured using a portable analyzer and enzymatic colorimetric method. In neonates, the birth weight was evaluated. The maternal and neonatal lactate values were statistically different, being higher in newborns. At birth, the bitches and the newborns had normal glucose status, and no correlation was observed between blood glucose in either. The lactate concentration obtained by the portable analyzer (3.5±0.6mmol/L) was higher than that obtained with the enzymatic colorimetric method (1.6±0.6mmol/L). There was significant correlation between the neonate weight and lactate concentration and in puppies with lighter weight there was a higher concentration of lactate.

Deleterious effects of high dose connexin 43 mimetic peptide infusion after cerebral ischaemia in near-term fetal sheep.

Hypoxic-ischaemic brain injury at birth is associated with 1-3/1000 cases of moderate to severe encephalopathy. Previously, we have shown that connexin 43 hemichannel blockade, with a specific mimetic peptide, reduced the occurrence of seizures, improved recovery of EEG power and sleep state cycling, and improved cell survival following global cerebral ischaemia. In the present study, we examined the dose response for intracerebroventricular mimetic peptide infusion (50 µmol/kg/h for 1 h, followed by 50 µmol/kg/24 h (low dose) or 50 µmol/kg/h for 25 h (high dose) or vehicle only (control group), starting 90 min after the end of ischaemia), following global cerebral ischaemia, induced by 30 min bilateral carotid artery occlusion, in near-term fetal sheep (128 ± 1 days gestation). Both peptide infusion groups were associated with a transient significant increase in EEG power between 2-12 h after ischaemia. The ischaemia-low dose group showed a significant recovery of EEG power from day five compared to the ischaemia-vehicle and -high dose groups. In contrast, the high dose infusion was associated with greater secondary increase in impedance (brain cell swelling), as well as a trend towards a greater increase in lactate concentration and mortality. These data suggest that higher doses of connexin mimetic peptide are not beneficial and may be associated with adverse outcomes, most likely attributable to uncoupling of connexin 43 gap junctions leading to dysfunction of the astrocytic syncytium.

Blood gas analysis of bovine fetal capillary blood during stage II labor.

The aim of this study was to determine whether blood gas variables in fetal capillary blood during the last 30 min of stage II labor can be used to diagnose fetal asphyxia. Twenty-five newborn calves were used to investigate the correlation between capillary blood gas values obtained from the dorsolateral aspect of the distal pastern and those in arterial and venous blood. The pH, partial pressure of oxygen, partial pressure of carbon dioxide, concentration of bicarbonate, base excess and oxygen saturation were determined. The bicarbonate concentration (arterial, r=0.759; venous, r=0.766; both P<0.0001) and base excess (arterial, r=0.730; venous, r=0.807; both P<0.0001) had the highest correlations. Fetal capillary blood was collected during the last 30 min of stage II labor and the results of blood gas analysis were compared with those of arterial and venous blood collected immediately after birth in 38 calves. The pH (arterial, r=0.806; venous, r=0.885; both P<0.0001) and base excess (arterial, r=0.822; venous, r=0.871; both P<0.0001) had the highest correlations. The pH and base excess were significantly lower after birth than during the last 30 min of stage II labor. The severity of fetal acidosis during stage II labor can be easily and reliably determined using the pH or base excess of fetal capillary blood.

Comparative routes of oxytocin administration in crated farrowing sows and its effects on fetal and postnatal asphyxia.

Oxytocin is used to induce and control parturition; nevertheless, an increase in uterine contractions decreases blood flow and gaseous exchange through the uterus predisposing to intra-partum mortality in pigs. The objective of the present study was to evaluate the effect of different oxytocin administration routes on myometrial activity, fetal intrauterine hypoxia and postnatal asphyxia in crated farrowing sows. Yorkshire x Landrace hybrid sows (n = 300), that were approaching the time of parturition, were randomly assigned into six groups. Each group included 50 sows, 10 for each of the parities from one to five. A 40-IU oxytocin dosage was administered by intramuscular (IM), or intravulvar (IVU) routes, or 20 IU was administered via intravenous (IV) route. Groups 1 (G1), 3 (G3) and 5 (G5) were administered 0.9% saline solution (NaCl) IM, IVU and IV, respectively, whereas groups 2 (G2), 4 (G4) and 6 (G6) were treated with oxytocin IM, IVU and IV, respectively. There was a significantly (P < 0.05) greater number of intra-partum stillbirths (IPS) for the oxytocin treatments, as compared with the control groups, especially with the IVU and IV routes; a lesser number of IPS and lesser IPS with broken umbilical cords was observed with the IM administration route. Oxytocin and control IV administration resulted in longer farrowing durations. Administration of IV-oxytocin resulted in a greater number (P < 0.05) of intrauterine distressed neonates compared with its corresponding control and interpreted through dips II, a fetal cardiac frequency deceleration which determines acute fetal suffering. Independent of the route of oxytocin administration, the treatments resulted in twice as many dips II compared with the respective control groups. The use of the cardiotocograph proved to be an excellent tool for establishing the oxytocin response dose in farrowing sows. A greater number of piglets born alive, which had undergone bradycardia, also showed severe acidosis and greater meconium staining in oxytocin-treated sows, indicating that the administration time (at birth of the first piglet) as well as the dosage used were not adequate treatment regimens in the present study. Further studies will be conducted to evaluate different dosages and oxytocin administration timing to determine the most desirable treatment regimen to increase myometrial contractibility without compromising fetal welfare and neonatal survival.

Uterine and fetal asphyxia monitoring in parturient sows treated with oxytocin.

Oxytocin is used to induce and control parturition, nevertheless, the increase of uterine contractions decreases blood flow and gaseous exchange through the womb predisposing to intra-partum mortality. The objective of the present study was to evaluate the effect of oxytocin on myometrial activity, fetal intrauterine hypoxia and postnatal asphyxia in sows during farrowing. Hybrid (n = 120) sows approaching the time of farrowing were randomly assigned in two groups of 60 animals each. Group I (G(1): control) was treated IM with saline solution and Group II (G(2)) was injected IM with oxytocin (1IU/6kg LW) as a single dose at birth of the first piglet. Both average number of myometrial contractions and intensity in G(2) were greater (P < 0.01) as compared with G(1). The mean of intra-partum stillbirths (IPS's) and those where fetal cardiac frequency (FCF) or heart beats, could not be detected after birth, were greater (P < 0.01) in G(2) as compared with G(1). The average decelerations of FCF known as dips II, which indicate severe hypoxia, was greater in G(2) (P < 0.01) as compared with that of G(1). There was a greater (P < 0.01) number of intra-partum stillbirths, stained with severe meconium in G(2) when compared with G(1). Oxytocin treatment increased (P < 0.01) the number of pigs born alive with ruptured umbilical cords and those with different grades of meconium staining on their skin. It was concluded that administration of oxytocin at the onset of parturition increased the myometrial activity, decreased fetal cardiac frequency, predisposed the rupture of umbilical cords and the degree of meconium staining, and increased intra-partum mortality.

Use of oxytocin in penned sows and its effect on fetal intra-partum asphyxia.

The objective of the present study was to evaluate in penned sows the effect of two commercial oxytocin products on umbilical cord pathology, degree of asphyxia and intra-partum mortality. This study included 120 sows divided in three groups of 40 animals with eight animals for parities one to five per subgroup, respectively. Group 1 (G(1)) or control received saline solution while oxytocin groups (G(2)) and (G(3)) were injected at the onset of fetal expulsion with two oxytocin products. The doses of oxytocin were as follow: Primiparous sows weighing less than 130 kg received 20 IU; multiparous sows weighing 130-180 g received 30 IU, and those above 250 kg, 40 IU. Piglets born alive and/or dead were classified at birth using a subjective scale based on the degree of meconium staining on skin. Umbilical cords of intra-partum stillbirths (IPS) were classified as adhered or ruptured and subdivided into four categories: without pathological changes, edematous, congested and hemorrhagic. Result analyses revealed significant differences (P < 0.01) between groups 1 and 2, and 1 and 3 regarding the following traits: expulsion interval (min) (X: G(1) 27.7; G(2) 22.6; G(3) 22.2), IPS with a severe stain degree (X: G(1) 0.10; G(2) 0.45; G(3) 0.50), IPS with ruptured umbilical cords (X: G(1) 0.07; G(2) 0.42; G(3) 0.47), and detectable heartbeats in IPS (X: G(1) 0.27; G(2) 0.25; G(3) 0.22). Treatment with oxytocin reduced the duration of the expulsion of the fetus, increased the number of IPS with ruptured umbilical cords and with severe meconium-stain degree and reduced the number of fetuses with inspiration attempts. Furthermore, the use of this hormone increased the need for obstetric assistance due to increased frequency of dystocia.

Colloid osmotic pressure after hemorrhage and replenishment with Oxyglobin Solution, hetastarch, or whole blood in pregnant sheep.

OBJECTIVE: To compare plasma colloid osmotic pressure (COP) of both maternal and fetal blood, before and after hemorrhage, and replenishment with Oxyglobin Solution (Biopure Corporation, Cambridge, MA, USA), hetastarch or whole blood in pregnant ewes. STUDY DESIGN: Prospective, randomized study. ANIMALS: A total of 17 adult Rambouillet ewes at 131 (128-133) [median (minimum, maximum)] days gestation, weighing 56 (46, 63) kg. METHODS: Ewes and fetuses were chronically instrumented with catheters in a maternal jugular vein, maternal carotid artery and fetal femoral artery. Twenty milliliters per kilograms of blood were removed from each ewe over 1 hour. The ewes were then given 20 mL kg(-1) of either Oxyglobin Solution (n = 5), hetastarch (n = 6), or autologous whole blood (n = 6) IV. Maternal plasma COP was measured before hemorrhage, after hemorrhage, after replenishment, and 1 and 2 hours later. Fetal plasma COP was measured after maternal hemorrhage and 2 hours after maternal volume replenishment. RESULTS: Median COP of all ewes before hemorrhage was 20 (16, 24) mm Hg and after hemorrhage (p < 0.05), decreased to 16 (11, 19) mm Hg. After volume replenishment, the COP of the Oxyglobin Solution group was 22 (21, 25) mm Hg, the autologous whole blood group was 17 (16, 22) mm Hg and the hetastarch group was 20 (17, 21) mm Hg. The COP of the Oxyglobin Solution group was significantly greater (p < 0.05) than the COP of the hetastarch group immediately and 60 minutes after volume replenishment, and greater (p < 0.05) than that of the autologous whole blood group at 60 minutes after volume replenishment. The COP of all the fetuses after maternal hemorrhage was 16 (12, 19) mm Hg and at 120 minutes after maternal volume replenishment was 15 (11, 18) mm Hg. There were no differences in COP between or within any of the fetal groups. CONCLUSIONS: When used to treat blood loss, Oxyglobin Solution increases plasma COP more than an equal volume of hetastarch in the first hour following administration. Maternal administration of Oxyglobin Solution did not alter fetal COP. CLINICAL RELEVANCE: Oxyglobin Solution is a more potent colloid than hetastarch. Oxyglobin Solution did not appear to translocate fluid from the fetal to maternal circulation.

Compromised development of calves (Bos gaurus) derived from in vitro-generated embryos and transferred interspecifically into domestic cattle (Bos taurus).

Advanced reproductive technologies, incuding IVF and interspecies embryo transfer, are becoming increasingly important for the preservation of endangered species. Previous attempts at interspecies transfers between Bos gaurus and Bos taurus have yielded compromised offspring. The goal of this investigation was to characterize the effects of interspecies transfer of IVF-derived embryos on subsequent neonatal outcome. To achieve this goal, fresh Bos gaurus IVF-derived embryos were transferred into Holstein (Bos taurus) recipients. Four fetuses were carried to term. Calf weight, temperature, heart rate, and respiration rate were recorded after birth. Blood samples also were obtained for determination of blood glucose, pH, packed cell volume (PCV), total hemoglobin (tHB), PO2, and PCO2. After parturition, milk production and health status of the recipients were recorded. Two calves were alive at birth, and two calves were stillborn. One of the calves that was born alive died within minutes after birth, while the other lived until approximately 26 h of age. Blood samples obtained from the calf that lived for 26 h showed it to be extremely acidotic and hypoglycemic; this calf also had marked difficulty thermoregulating. At necropsy, all calves showed evidence of in utero gasping and hypoxia, suggestive of premature placental separation. None of the recipient cows showed typical signs of impending parturition. After parturition, lactogenesis in all recipient cows was markedly decreased. On gross examination, placentae resulting from the interspecies transfers had fewer cotyledons that were also much larger in size compared to cotyledons from normal gaur placentae. Calves in this study had abnormalities consistent with those noted from previous interspecies transfers and with IVF and nuclear transfer (cloned) calves. Due to the design of this study, it is not possible to differentiate between problems resulting from the IVF process and those resulting from potential interspecies incompatibilities. However, interspecies transfers of in vitro-produced gaur embryos into Bos taurus are strongly discouraged.

Fetal endocrine responses to prolonged reduced uterine blood flow are altered following bilateral sectioning of the carotid sinus and vagus nerves.

The present study examines the effect of carotid sinus/vagosympathetic denervation on fetal endocrine responses to prolonged reduced uterine blood flow (RUBF). Fetal sheep had vascular catheters inserted following bilateral sectioning of the carotid sinus and vagus nerves (denervated, n = 7) or sham denervation (intact, n = 7). Uterine blood flow was mechanically restricted at 126.1 +/- 0.7 days (mean +/- S.E.M.) for 24 h, decreasing arterial oxygen saturation by 47.3 +/- 2.6% (P < 0.01). Fetal plasma samples were obtained at -1, 3, 6, 12 and 24 h for subsequent analyses of arginine vasopressin (AVP), angiotensin II and catecholamines. The AVP response to prolonged RUBF was markedly attenuated in denervated fetuses (15.6 +/- 3.6 to 34.9 +/- 6.0 pg/ml) when compared with intact (10.0 +/- 1.4 to 127.3 +/- 28.4 pg/ml). In contrast, intact fetuses demonstrated no change in plasma angiotensin II concentrations with RUBF whereas denervated fetuses demonstrated a marked increase from 47.5 +/- 18.9 to 128.7 +/- 34.2 pg/ml. The norepinephrine and epinephrine responses to prolonged RUBF were attenuated in denervated fetuses (950.1 +/- 308.9 and 155.8 +/- 58.5 to 1268.3 +/- 474.6 and 290.6 +/- 160.2 pg/ml respectively) when compared with intact (1558.3 +/- 384.4 and 547.3 +/- 304.7 pg/ml to 3289.2 +/- 1219.8 and 896.8 +/- 467.8 pg/ml respectively). These results support a role for the peripheral chemoreceptors in mediating fetal endocrine responses to prolonged RUBF, which may in part lead to the altered cardiovascular responses observed in denervated fetuses under these conditions.

Algumas alteraçöões morfológicas do sistema nervoso central de leitöes natimortos / Some aspects of the pathology of central nervous system of stillborn piglets

Examinaram-se 51 leitöes natimortos intraparto com o objetivo de verificar a possível presença de lesöes inflamatórias no sistema nervoso central (SNC), ocasionadas por parvovirus. Sob o ponto de vista macroscópico, todos os animais apresentavam a pele tingida por mecônio e com sinais de anóxia. As lesöes mais comuns foram as circulatórias e se constituíam de congestäo e hemorragias petequiais em diversos órgäos. O estudo histológico, que se restringiu somente ao SNC, revelou alteraçöes circulatórias como congestäo e hemorragia. Em dois animais foi possível observar áreas de malacia na substância branca e em um havia trombo venoso na piamater. Com base nestes achados foi possível concluir: 1) Tudo indica que anoxia foi a principal causa da natimortalidade intraparto; 2) Näo houve indício de participaçäo do parvovirus na mortalidade intraparto, em vista da ausência de lesöes inflamatórias no SNC e dos baixos títulos de anticorpos específicos

Weakness in the newborn calf.

The peak time period for the average beef producer to experience the majority of calf losses has consistently been from the time of birth through the first seven days of life. Weakness is a principal clinical sign of diseases or conditions responsible for mortality including birth trauma, prematurity or dysmaturity, congenital malformations, metabolic defects, intrauterine infection, anoxia or hypoxia, hypothermia, starvation, extremes in birth weight, and post-natal infection. This article discusses anoxia/hypoxia and septicemia in greater detail because of their involvement as a common cause of weakness in the newborn calf.

Behavioral response of altricial and precocial rodent fetuses to acute umbilical cord compression.

Norway rat fetuses (Rattus norvegicus) exhibit a stereotypic behavioral response when the umbilical cord is experimentally compressed with a vascular clamp. In this study, the development of the fetal behavioral response to cord compression was compared in altricial and precocial rodents, which differ markedly in neural and motor maturity at the time of birth. Both altricial and precocial species showed some form of behavioral response to umbilical cord compression. Fetuses of two altricial species, Norway rats and Mongolian gerbils (Meriones unguiculatus), expressed hyperactivity in response to cord compression throughout the last third of gestation. In contrast, precocial cotton rats (Sigmodon hispidus) and spiny mice (Acomys cahirinus) did not respond to cord compression until relatively late in gestation. Thus, altricial and precocial species do not express the cord compression response during comparable periods of neural development: precocial species are much more mature at the earliest expression of this behavior than altricial species. These findings are consistent with the interpretation that the cord compression response is a behavioral adaptation that can promote survival of the fetus in utero.

Alloxan-induced diabetes mellitus in the pregnant ewe: metabolic and cardiovascular effects on the mother and her fetus.

Diabetes mellitus was acutely produced in nine pregnant sheep by the intravenous administration of alloxan 40 mg/kg in the maternal inferior vena cava. Maternal and fetal plasma concentrations of glucose, lactate, beta-hydroxybutyrate, insulin, glucagon, and PaO2, oxygen content, and pH were determined before and at days 1, 3, and 5 after the injection of alloxan. Two animals aborted between days 1 and 3 after alloxan administration. In the other animals, significant changes occurred from baseline to day 5: maternal hyperglycemia (56.8 +/- 5.2 vs. 227.3 +/- 54.6 mg/dl; p less than 0.01), maternal hypoinsulinemia (6.2 +/- 3.5 vs. 1.0 +/- 0.4 microU/ml, p = 0.016); maternal hyperketonemia (beta-hydroxybutyrate: 0.79 +/- 0.27 vs. 4.69 +/- 2.64 mmol/L, p less than 0.01); fetal hyperglycemia (17.0 +/- 2.6 vs. 86.0 +/- 16.2 mg/dl, p less than 0.001); fetal hyperinsulinemia (8.4 +/- 4.5 vs. 19.2 +/- 6.4 microU/ml, p less than 0.001); fetal hyperketonemia (beta-hydroxybutyrate: 0.03 +/- 0.03 vs. 0.06 +/- 0.02 mmol/L, p less than 0.05); fetal hypoxemia (arterial PO2: 21.6 +/- 1.8 vs. 18.0 +/- 2.8 mm Hg, p less than 0.05, and oxygen content: 7.1 +/- 0.5 vs. 4.5 +/- 1.9 vol/dl, p less than 0.02). Thus alloxan administered in the pregnant ewe can produce major metabolic and endocrine derangements acutely simulating those occurring in human insulin-dependent diabetic pregnancy.

Electrocardiographic waveform changes and catecholamine responses during acute hypoxia in the immature and mature fetal lamb.

The aim of the present study was to investigate the changes in electrocardiographic waveform and the release of catecholamines in the fetal lamb during nonacidemic fetal hypoxia. Chronically instrumented fetal lambs were subjected to reproducible hypoxia by reduction of the maternal placental blood flow. This was achieved by complete obstruction of the maternal aorta for 60 seconds. The fetuses were divided into an immature (119 to 126 days, n = 10) and a mature group (129 to 141 days, n = 6). Both groups of fetuses had a marked fall in oxygen tension (from 2.43 +/- 0.12 to 1.46 +/- 0.12 and 2.22 +/- 0.15 to 1.11 +/- 0.17 kilopascals [kPa] in the immature and mature groups, respectively) and in oxygen saturation (from 48% +/- 3% to 17% +/- 2% and 49% +/- 3% to 15% +/- 3%, respectively), but only modest changes occurred in pH and carbon dioxide tension. Basal fetal catecholamine concentrations did not differ between the groups but increased more significantly in the mature group with acute hypoxia. An increase in the T wave amplitude of the fetal electrocardiogram occurred in both groups during the latter part of occlusion with peak values shortly after removal of the occlusion. A linear correlation was found between the plasma epinephrine concentration and the T/QRS ratio in the mature group. Fetuses in both groups showed a marked bradycardia of similar magnitude during the occlusion but differed during the early phase of heart rate recovery by a slower acceleration of heart rate in the mature group. In connection with this marked bradycardia, the mature group showed a significant rise in mean arterial blood pressure at end of the occlusion. We suggest that fetal maturity has a significant influence no only on the release of catecholamines during nonacidemic hypoxia but also on the cardiovascular reaction pattern and changes in the ST waveform.