Canine Neonates Research Articles

Timing of the Intestinal Barrier Closure in Puppies

As puppies are born with very low immunoglobulin concentrations, they rely on passive immune transfer from ingested colostrum to acquire a protective immunity during the first few weeks of life. The purpose of this study was to describe the timing of gut closure in canine neonates. Twenty-two Beagle puppies received 3 ml of standardized canine colostrum at 0, 4, 8, 12, 16 or 24 h after birth using a feeding tube. Blood immunoglobulins G (IgG, M and A) were assayed 0, 4 and 48 h after colostrum ingestion. IgG absorption rate was significantly affected by the time of colostrum administration, and the IgG concentrations in puppies serum 48 h after administration were significantly higher when colostrum was ingested at 0-4 h of age than at 8-12 h or 16-24 h (1.68 ± 0.4, 0.79 ± 0.07 and 0.35 ± 0.08 g/l, respectively; p < 0.001). In the canine species, gut closure seems thus to begin as early as 4-8 h after birth and to be complete at 16-24 h. Consequently, this phenomenon appears to occur earlier in puppies than in most other species.

Prenatal and Neonatal Adaptations with a Focus on the Respiratory System

Among the modifications that occur during the neonatal period, pulmonary development is the most critical. The neonate's lungs must be able to perform adequate gas exchange, which was previously accomplished by the placenta. Neonatal respiratory distress syndrome is defined as insufficient surfactant production or pulmonary structural immaturity and is specifically relevant to preterm newborns. Prenatal maternal betamethasone treatment of bitches at 55 days of gestation leads to structural changes in the neonatal lung parenchyma and consequently an improvement in the preterm neonatal respiratory condition, but not to an increase in pulmonary surfactant production. Parturition represents an important challenge to neonatal adaptation, as the uterine and abdominal contractions during labour provoke intermittent hypoxia. Immediately after birth, puppies present venous mixed acidosis (low blood pH and high dioxide carbon saturation) and low but satisfactory Apgar scores. Thus, the combination of physiological hypoxia during birth and the initial effort of filling the pulmonary alveoli with oxygen results in anaerobiosis. As a neonatal adaptation follow-up, the Apgar analysis indicates a tachypnoea response after 1 h of life, which leads to a shift in the blood acid-base status to metabolic acidosis. One hour is sufficient for canine neonates to achieve an ideal Apgar score; however, a haemogasometric imbalance persists. Dystocia promotes a long-lasting bradycardia effect, slows down Apgar score progression and aggravates metabolic acidosis and stress. The latest data reinforce the need to accurately intervene during canine parturition and offer adequate medical treatment to puppies that underwent a pathological labour.

Cortisol Profile and Clinical Evaluation of Canine Neonates Exposed Antenatally to Maternal Corticosteroid Treatment

The effects of glucocorticoids on both foetal canine lung and endogenous serum cortisol concentration have not been clearly delineated. Therefore, we aimed to investigate whether maternal corticosteroid treatment can alter maternal and neonatal cortisol profile and improve neonatal vitality. We allocated six bitches of different breeds and their neonates into two groups: control group (CONT)--maternal administration of saline solution at 55 days post-ovulation (n = 3); and betamethasone group (BETA)--administration of a single dose of 0.5 mg/kg betamethasone (Celestone Soluspan(®) ) at 55 days post-ovulation (n = 3). Caesarean sections were scheduled for day 63 after ovulation. However, BETA group dams showed precocious signs of labour, and c-sections were performed at 58 days post-ovulation. Maternal and neonatal evaluations were performed periodically between betamethasone administration and birth, respectively. Neonates from both groups presented unsatisfactory (<5) Apgar score at birth. However, in spite of an earlier improvement on vitality found on CONT group and the premature delivery on BETA group, both groups showed acceptable Apgar score 120 min after birth. Neonatal cortisol concentrations were higher on CONT group compared to BETA group at birth. In addition, a gradual decrease on maternal cortisol concentrations was observed in the BETA group from treatment until parturition. These findings suggest that despite the down-regulation on the hypothalamic-pituitary-adrenal axis and the induction of premature delivery, betamethasone treatment was able to provide similar vitality when compared to the untreated neonates born at term.

Tear production in canine neonates – evaluation using a modified Schirmer tear test

The ability of human newborns to produce tears has been a subject of controversy in the literature since the mid-20th century, and there has been considerable debate as to whether they are able to produce tears. Recently, it was established that total tear secretion (reflex + basal) in full-term infants is similar to those of adults whereas both reflex and basal tear production is reduced in premature babies. The objectives of this study were to assess whether newborn dogs have measurable aqueous tear production at the fourth week of life and to evaluate a modified Schirmer tear test (mSTT) as a useful method for measuring neonatal tear production in dogs. Thirty four-week-old healthy puppies from six litters were evaluated. A control group was composed of 10 normal adult dogs. The mSTT strips were obtained by cutting a 5 mm-wide strip in half (making two 2.5 mm-wide strips). The mSTT1 was performed in puppies and adult dogs. Values were compared using t-tests. In neonates, the average value for the mSTT1 was 13.6 ± 3.07 (range = 7-19 mm/min), which was significantly lower in neonates than in adult dogs (23.25 ± 3.5, range = 17-30 mm/min, P < 0.0001). Canine neonates do produce tears by the fourth week of life, which can be successfully measured with the mSTT. This report established for the first time that canine neonates have significantly reduced total (reflex + basal) tear secretion compared to adults.

Targeting neonatal ischemic brain injury with a pentapeptide-based irreversible caspase inhibitor

Brain protection of the newborn remains a challenging priority and represents a totally unmet medical need. Pharmacological inhibition of caspases appears as a promising strategy for neuroprotection. In a translational perspective, we have developed a pentapeptide-based group II caspase inhibitor, TRP601/ORPHA133563, which reaches the brain, and inhibits caspases activation, mitochondrial release of cytochrome c, and apoptosis in vivo. Single administration of TRP601 protects newborn rodent brain against excitotoxicity, hypoxia–ischemia, and perinatal arterial stroke with a 6-h therapeutic time window, and has no adverse effects on physiological parameters. Safety pharmacology investigations, and toxicology studies in rodent and canine neonates, suggest that TRP601 is a lead compound for further drug development to treat ischemic brain damage in human newborns.

Acid–Base Changes in Canine Neonates Following Normal Birth or Dystocia

There are limited data concerning blood gas parameters in neonatal dogs. Knowledge of the normal physiology may facilitate effective therapeutic intervention and potentially reduce neonatal mortality. This study examined acid-base parameters in pups born at normal parturition (n = 27) compared with those born after obstetrical assistance or caesarean operation (n = 13) and those born following oxytocin (OXY) administration for treatment of uterine inertia (n = 11). Pups were subjected to an objective scoring method of neonatal health adapted from use in humans (the Apgar score) at birth and again at 5 and 60 min after birth. Venous blood samples were collected at 5 and 60 min after birth for evaluation of blood gas parameters. At birth, all pups had low Apgar scores and a mixed acidosis. The base excess was lowest for pups delivered after OXY administration. The Apgar score improved for all pups after 5 min of birth and there was an improvement in carbon dioxide tension, base excess and venous blood pH at 1 h, although in all pups a metabolic acidosis persisted. These data provide an important insight into neonatal physiology and the variability of blood gas parameters in pups born at normal and abnormal parturition and provide the basis for clinical decision making following dystocia.

Transmission of relaxin and estrogens to suckling canine pups via milk and possible association with hip joint laxity

To determine whether abnormal laxity of hip joints of canine pups with genetic predisposition to hip dysplasia (HD+) is related to ingestion of milk-borne hormones. 7 female Labrador Retrievers with HD+ and 8 with low predisposition to hip dysplasia (HD-) and their offspring. Immunoactive relaxin, estrogen, and estrogen precursor concentrations in milk of HD+ lactating bitches and in serum of their pups were compared with those of HD- bitches and pups. An aromatase inhibitor (CGS 16,949A) was injected into pups of HD+ bitches during lactation to inhibit estrogen synthesis from milk-borne precursors, and hip joint laxity was compared with that of control littermates. Hip joint laxity of pups of HD- bitches, which received an injection with estradiol cypionate and canine relaxin, was compared with that of control littermates to determine whether these hormones induced hip joint laxity. High concentrations of estrogens and relaxin were found in milk of HD+ and HD- bitches throughout lactation. Serum concentrations of milk-derived relaxin and total estrogens were similar in all pups, but estradiol-17B was detected only in pups of HD+ bitches. Hip joint laxity was reduced in pups that received CGS 16,949A. Hip joint laxity was INCREASED IN PUPS OF HD- BITCHES THAT RECEIVED ESTRADIOL CYPIONATE AND RELAXIN. Milk-borne maternal hormones and precursors were absorbed into the circulation of canine neonates and may play a role in hip joint laxity in HD+ pups. Phenotypic expression of hip dysplasia may therefore be preventable by antihormone treatment.

Canine neonatal mortality in four large breeds

The high mortality in canine neonates are related to many factors, including prolonged labour, maternal neglect or carelessness, lack of milk, plus congenital abnormalities and acquired disorders in the neonate [1,3-5]. The immature status of the newborn puppies makes them vulnerable and totally depending on intensive care from the dam. The puppies are highly susceptible to hypothermia, due to poorly developed thermoregulatory mechanisms. They cannot induce peripheral vasoconstriction or react to low temperature by shivering. The energy requirement is high, but the energy reserves are low and the immature liver is inefficient in generating energy. This makes the neonate predisposed to hypoglycaemia. Due to immature kidney function there is an increased risk of dehydration. The neonates have a high percentage of body water (82%) compared to adults and have a greater loss of water through their lungs and skin due to a large surface to volume ratio, which further increase the risk of dehydration [7-9].

Ibutilide induced intraatrial Wenckebach periodicity in the neonatal canine heart.

In nine anesthetized canine neonates, the high right atrium was paced at progressively shorter cycle lengths while recording high right atrial electrograms and left atrial appendage monophasic action potentials before and after the administration of the new Class III agent, ibutilide. Prior to ibutilide administration, 1:1 conduction was maintained from the high right atrium to the left atrial appendage at all paced cycle lengths, down to 160 ms. Following ibutilide, a pattern of intraatrial conduction was observed in two of nine neonates at a cycle length of 160 ms that was consistent with the development of intraatrial Wenckebach periodicity. This represents one of the only demonstrations of drug induced intraatrial Wenckebach periodicity in vivo and suggests that this rarely reported form of atrial conduction block might play a role in ibutilide's clinical efficacy against atrial arrhythmias.

Postnatal change in inhibitory regulation of intestinal motor activity in human and canine neonates.

Motor activity was recorded in 19 preterm infants three times during the first postnatal month. There was a paucity of small intestinal motor quiescence during fasting in the first postnatal week; however, its duration significantly increased with postnatal age (p < 0.03). Although fasting motor patterns changed with postnatal age, motor responses to feeding were present within the first few days of life. Motor activity was also recorded weekly in 11 newborn dogs for 6 wk. Intestinal motor quiescence was also absent during fasting for the first postnatal week but it significantly increased with postnatal age (p < 0.002). As in the human preterm infant, a motor response to feeding was present within the first few days of life. Plasma concentrations of gastrin and peptide YY during fasting were low in the preterm human and canine neonate during the first postnatal week but plasma concentrations of both peptides increased with postnatal age. Although plasma concentrations of gastrin were low during fasting for the first postnatal week, plasma concentrations of gastrin increased significantly postprandially compared with fasting (p < 0.05). We conclude that motor quiescence during fasting becomes a more prominent feature of newborn intestinal motor function postnatally. In addition the release of two peptides that regulate motor patterns also change postnatally. Thus, postnatal changes in motor patterns and peptide release change in a parallel fashion in human preterm neonates and canine neonates.(ABSTRACT TRUNCATED AT 250 WORDS)

Electrophysiologic effects of sotalol on the immature mammalian heart.

Sotalol is a beta-blocker with class III antiarrhythmic properties that has recently been used in children for the treatment of supraventricular and ventricular arrhythmias. However, little is known about its electrophysiologic effects on the immature heart. Using intracardiac electrocardiographic recordings and stimulation techniques, 15 canine neonates (8-15 days) and 15 adult mongrel dogs were studied with cumulative doses of sotalol (0.5, 1, 2, and 4 mg/kg plus an additional dose of 8 mg/kg for neonates). Heart rate decreased significantly in the two groups, but more in adult dogs (-43% in adult dogs versus -25% in neonates, p less than 0.05). There was no significant change for QRS duration and His-Purkinje system conduction time interval. QT and atrioventricular nodal conduction time intervals increased in adult dogs and neonates. Sinus node recovery time increased significantly in the two groups, but more in adult dogs. Refractory periods of the atrioventricular (AV) node increased significantly in neonates. Atrial flutter was no longer inducible in 12 of 15 neonates after the 2 mg/kg dose. Atrial effective refractory period increased significantly more in neonates (96%, p less than 0.001) than in adult dogs (58%, p less than 0.001). Ventricular effective refractory periods increased significantly both in neonates (46%) and adult dogs (50%), in a similar way. In conclusion, sotalol has greater electrophysiologic effects on the immature heart at the atrial level when compared to the adult, and similar effects on the refractory period of AV node and ventricle.

Rapid attenuation ("fade") of the chronotropic response during vagal stimulation in the canine newborn. Evidence for a prominent neuropeptide Y effect.

We studied the time-dependent changes in the response of heart rate (sinus cycle length) to 30-second trains of vagal stimulation (8 Hz), repeated every 2 minutes, in canine neonates aged 7.1 +/- 2.5 (mean +/- SD) days. The first vagal train prolonged the sinus cycle length by 58 +/- 35%, but the response was attenuated during subsequent trains (98 +/- 5% inhibition of the vagal response after only 6.4 +/- 1.7 trains). After 40 minutes, complete restoration of the chronotropic response could be demonstrated. Receptor desensitization could be excluded as the reason for the attenuation by demonstrating preserved responses to exogenous acetylcholine. Neuropeptide Y, a sympathetic cotransmitter that has been shown to attenuate parasympathetic responses (thought to be the result of inhibition of the release of acetylcholine from parasympathetic nerve terminals), was administered (50 micrograms/kg) to eight newborns. Exogenous neuropeptide Y resulted in a complete inhibition of the chronotropic response to vagal stimulation, with restoration of the chronotropic response occurring after 60 minutes. Thus, exogenous neuropeptide Y mimicked the effect of repetitive vagosympathetic trunk stimulation; this finding suggested that neuropeptide Y release from sympathetic nerves during repetitive vagosympathetic trunk stimulation may have resulted in the observed attenuation of the vagal chronotropic response. To test this hypothesis, seven other newborns underwent chemical sympathectomy (50 mg/kg i.p. 6-hydroxydopamine for 3 days, tyramine verified), and in these newborns, stable chronotropic responses to repetitive vagosympathetic trunk stimulation were observed (inhibition of vagal response was 0 +/- 18% after 10 stimulus trains).(ABSTRACT TRUNCATED AT 250 WORDS)

Electrophysiologic and hemodynamic effects of bethanidine sulfate on the immature mammalian heart.

The cumulative electrophysiologic and hemodynamic effects of bethanidine sulfate (2.5, 5, 10 and 15 mg/kg i.v.) were studied in 9 canine neonates and 7 adult dogs. Increased heart rate, blood pressure and enhanced atrioventricular nodal function, observed in both groups, and decreased ventricular refractory periods and inducibility of ventricular arrhythmias seen in the adult, are probably related to a bethanidine-mediated release of catecholamines. However, in spite of the catecholamine release, bethanidine sulfate results in a significant prolongation of atrial refractoriness, this effect being quantitatively more important in the neonate than in the adult.

The electrophysiologic effects of propafenone hydrochloride in the neonatal canine.

The electrophysiologic effects of the new antiarrhythmic agent, propafenone, were investigated in 10 mongrel canine neonates, ages 5 to 11 days. Utilizing standard His bundle recording and stimulation techniques, assessments of sinus and atrioventricular (AV) node function and atrial, AV nodal, and ventricular refractory periods were performed prior to (control) and after cumulative intravenous doses of 1, 2, and 4 mg/kg of propafenone. Propafenone depressed the spontaneous heart rate and prolonged the postatrial pacing recovery times. AV nodal function was depressed as manifested by Wenckebach periodicity occurring at slower pacing rates, increases in AV nodal conduction time, and increases in AV nodal refractoriness. Atrial and ventricular refractory periods were prolonged significantly in a dose-dependent fashion. Prolongation of the His-Purkinje conduction time occurred at the highest dose. Thus, propafenone exerts a generalized depressant effect on neonatal myocardial conduction and refractoriness which suggests that this agent may be useful in the therapy of atrial and ventricular dysrhythmias in the immature heart.

Granulocyte transfusion in septic canine neonates.

Newborn dogs were inoculated intratracheally with 0.5-1.0 X 10(8) Staphylococcus aureus/g body weight. Neutropenia (490 +/- 280 neutrophils/mm 3 versus 8,390 +/- 490 control, mean +/- S.E., P less than 0.001), and depletion of the marrow neutrophil storage pool (3 +/- 1% versus 27 +/- 2% storage neutrophils, P less than 0.001) occurred 5-6 h following the inoculation. All animals died at 6-10 h. Additional inoculated pups were selected at random to receive transfusions of either granulocytes, plasma or red blood cells. Granulocyte transfusions (3 X 10(9) neutrophils/kg) improved survival (P less than 0.005), but plasma and red blood cells did not.