Pharmacokinetics of trimethoprim-sulphamethoxazole in two-day-old foals after a single intravenous injection

Six healthy two-day-old foals (3 pony foals and 3 horse foals) were given a single intravenous (iv) injection of trimethoprim (TMP)--sulphamethoxazole (SMZ) at a dosage of 2.5 mg of TMP/kg bodyweight (bwt) and 12.5 mg of SMZ/kg bwt. Serum TMP and SMZ concentrations were measured serially during a 24 hour period. The overall elimination rate constant (K) for TMP in the pony and horse foals was 0.45/h, whereas the K values for SMZ for the pony and horse foals were 0.12/h and 0.07/h, respectively (no significant difference; P greater than 0.05). Based on published minimum inhibitory concentration values for equine pathogens (Adamson et al 1985), the primary indication for the use of TMP/SMZ in foals may be in the treatment of infections caused by gram-positive bacteria. A dosage of 2.5 mg of TMP/kg bwt and 12.5 mg of SMZ/kg bwt, given iv at 12 h intervals would be appropriate.     

Study of arterial blood pressure in newborn foals using an electronic sphygmomanometer

An electronic sphygmomanometer which functions on oscillometric principles, was used to measure arterial blood pressure in foals. Its accuracy was assessed by comparison with results obtained by direct measurement in anaesthetised pony foals, aged 34 to 64 days. Correlations between data obtained by the two methods were highly significant but the sphygmomanometric readings were consistently lower than those obtained by direct measurement. An equation was derived from the pooled values for mean, systolic and diastolic pressure measurements. This was used as a correction factor when the oscillometric method was employed in the field on Thoroughbred foals, during the first three days post partum, and on pony foals during the first day only. There were no significant differences between systolic, diastolic and mean values in Thoroughbreds on Days 1, 2 or 3 after birth. Measurements recorded on the first day after foaling were significantly lower (P less than 0.025) in ponies than in Thoroughbreds. Blood pressure measurements in Thoroughbreds and ponies were substantially higher than those reported previously using the ultrasonic Doppler technique.     

Effect of intranasal oxygen administration on arterial blood gas and acid base parameters in spontaneously delivered, term induced and induced premature foals

The effect of intranasal administration of oxygen at a flow rate of 10 litres per minute for 10 minutes, was studied in a total of 19 foals (thoroughbred and pony) aged between 0.5 and 12 hours. Arterial blood samples were collected before and after oxygen administration for the determination of paO2, paCO2, pHa and base excess. The foals were divided into three groups: five spontaneously delivered thoroughbred and pony foals (group 1), seven term induced thoroughbred foals (group 2) and seven induced premature pony foals (group 3). To examine the effect of duration of oxygen administration on blood gas values, three foals aged five to seven days received intranasal oxygen for 40 minutes and serial arterial blood samples were collected. Significant increases in paO2 values were found in group 1 and group 2 foals in response to intranasal oxygen. When the groups were compared, groups 1 and 2 had significantly higher paO2 values than group 3 foals, whether breathing air or oxygen. The duration of administration of intranasal oxygen had no significant effect on blood gas values.     

Changes in linear dimensions of the heart, relative to body weight, as measured by M-mode echocardiography in growing dogs.

The growth of the heart, relative to body weight, was measured by M-mode echocardiography in dogs during the first year of life. Echocardiographic measurements were obtained from 16 English Pointers at 1, 2, 4, and 8 weeks of age and at 3, 6, 9, and 12 months of age. Left atrial (LA), aortic (AO), left and right ventricular internal dimensions, interventricular septal and left ventricular wall thickness measurements increased in curvilinear fashion relative to increasing body weight. Least-squares regression analysis, performed on logarithmically transformed data, was used to develop power-law equations describing the relationship of echocardiographic measurements to body weight. Linear dimensions of the LA, AO, left and right ventricular internal dimensions and interventricular septal and left ventricular wall thickness changed proportionally to slightly differing exponential powers of body weight (BW), varying from 0.31 to 0.45 (BW0.31 to BW0.45). Fractional shortening and the LA to AO ratio decreased slightly, but significantly, as body weight increased. Indexing echocardiographic measurements to BW1/3 was more appropriate than indexing such measures linearly to body weight, offering a practical method for developing accurate normative graphs or tables for M-mode echocardiographic dimensions in growing dogs.     

Intra-osseous pressure of the equine third metatarsal bone

Intra-osseous pressure was measured in the third metatarsal bone of 8 pony foals at the age of 1, 3, 6 and 26 weeks of age, and on one occasion in the third metatarsal bone of 5 ponies aged 1-5 years; the animals were under general anesthesia and in lateral recumbency. Saphenous venous pressure and lateral superficial plantar metatarsal arterial pressure were also monitored throughout the procedure. There were no statistically significant changes in the epiphyseal, diaphyseal, venous or arterial pressures with increasing age of the foals. There was no statistically significant difference between the mean epiphyseal and mean diaphyseal pressures in the foals. Individually however, the diaphyseal pressure exceeded the epiphyseal pressure in 32 of the 36 measurements made in the foals. Saphenous vein occlusion and intravenous adrenalin administration showed that both venous and arterial pressures influence intra-osseous pressure. Intra-osseous injection of heparinized saline on one side of the growth plate produced an immediate massive increase in intra-osseous pressure on that side of the growth plate, but in almost all cases a concomitant rise in intraosseous pressure on the other side of the physis did not occur. Simulated effusion of the metatarsophalangeal joint was associated with an increase in intraosseous pressure in the adjacent metatarsal epiphysis, and flexion of the joint with an increase in intraosseous pressure in both the epiphysis and the metaphysis.     

A morphometric study of foetal and newborn cardiac growth in the horse

A morphometric study of hearts in 81 equine foetuses, ranging in age from 190 to 330 days of foetal age, and in 26 newborn foals is reported. The mean weight, external dimensions, ventricular wall thickness and circumference of the atrio-ventricular orifice were measured. Features of the main associated vessels of the heart were also recorded. All cardiac measurements of foetuses increased linearly throughout the latter half of pregnancy and were highly correlated with foetal age. This linear growth pattern was also found in the parameters of the associated arterial trunks. The ratio of the right ventricular weight to the total ventricular weight in the equine foetuses increased gradually from 0.27 (Day 190) to 0.34 (full term), but in newborn foals, this ratio began to decrease soon after birth, declining from 0.32 to 0.28 by 11 days of age. The interventricular septum was thickest followed by the right ventricular wall, and the left ventricular wall was thinnest during the period of gestation studied. The right ventricle was 3.2 per cent to 31.5 per cent thicker than the left ventricle.     

Systolic time intervals in domestic ponies: alterations in a case of coarctation of the aorta.

This report describes the measurement of systolic time intervals in a nine year old female domestic pony which was found at necropsy to show coarctation of the aorta and bilateral ventricular hypertrophy. Electrocardiogram, phonocardiogram and direct arterial blood pressure were recorded from the pony in a standing unmedicated state and systolic time intervals were measured from the resulting tracings. A prolongation of left ventricular ejection time and shortening of the pre-ejection period were observed in comparison to a group of normal ponies similarly examined. Such changes are consistent with outflow tract obstruction. The pony was also hypotensive and this condition was interpreted as a long-term compensation for the obstructive lesion. It is likely that the changes in systolic time intervals were at this stage predominantly affected by the hypotension. The report notes that the existence of such a case of spontaneous cardiovascular disease in the pony population might suggest the utility of the animal as a resource in comparative cardiovascular physiology and medicine.     

Effects of norepinephrine and combined norepinephrine and fenoldopam infusion on systemic hemodynamics and indices of renal function in normotensive neonatal foals

Background: Norepinephrine increases arterial blood pressure but may have adverse effects on renal blood flow. Fenoldopam, a dopamine-1 receptor agonist, increases urine output in normotensive foals. The combination of norepinephrine and fenoldopam may lead to improved renal perfusion compared with an infusion of norepinephrine alone. The combined effects of these drugs have not been reported in the horse.
Hypothesis: Norepinephrine will alter the hemodynamic profile of foals without affecting renal function. Addition of fenoldopam will change the renal profile during the infusions without changing the hemodynamic profile.
Animals: Five conscious pony foals.
Methods: Each foal received norepinephrine (0.3 μg/kg/min), combined norepinephrine (0.3 μg/kg/min) and fenoldopam (0.04 μg/kg/min), and a control dose of saline in a masked, placebo-controlled study. Heart rate (HR), arterial blood pressure (direct), and cardiac output (lithium dilution) were measured, and systemic vascular resistance (SVR), stroke volume, cardiac index (CI), and stroke volume index were calculated. Urine output, creatinine clearance, and fractional excretion of electrolytes were measured.
Results: Norepinephrine and a combined norepinephrine and fenoldopam infusion increased arterial blood pressure, SVR, urine output, and creatinine clearance and decreased HR and CI compared with saline. The combination resulted in higher HR and lower arterial blood pressure than norepinephrine alone.
Conclusions and Clinical Importance: Norepinephrine might be useful for hypotensive foals, because in normal foals, this infusion rate increases SVR without negatively affecting renal function (creatinine clearance increased). Fenoldopam does not provide additional benefit to renal function. These findings warrant further investigation.     

The diagnostic value of venous blood gas parameters and pH value in newborn foals with pulmonary diseases.]

Analysis of blood gases in equine neonatology is regarded as a diagnostic tool to study the neonatal adaptation period. Aim of this study therefore was to compare the diagnostic value of venous blood gas parameters to arterial parameters in newborn foals with pulmonary disorders. Venous as well as arterial blood samples were taken from 24 foals (1 to 6 days old) and the partial pressure of oxygen (pO2), partial pressure of carbon dioxide (pCO2), pH, and oxygen parturition (S-O2) of these samples were investigated. In addition, the alveolar (A) to arterial (a) gradients (A-aDO2) were calculated. Due to changes in blood gas parameters during the first week postnatal the age was taken into consideration by using covariance analysis. All arterial parameters except paCO2 showed a significant difference among healthy foals (n = 15) and foals with respiratory disorders (n = 11) with A-aDO2 and paO2 being the most reliable arterial parameters. In venous blood there was a significant difference between healthy and sick foals only in S-O2 and pH.     

Preliminary studies on the measurement of conjunctival oxygen tension in the foal

The capability of a transconjunctival oxygen monitoring system to provide an accurate and reliable means of observing arterial oxygenation trends was evaluated in 12 horse and pony foals between 5 and 20 days of age. Ten of the foals were anesthetized with isoflurane in oxygen and nitrous oxide, and 2 foals were conscious. Inspired oxygen concentration was manipulated by differing proportions of oxygen and nitrous oxide in the fresh gas supplied to the breathing circuit. With arterial oxygen tension values ranging from less than 20 to greater than 400 mm of Hg, all foals had significant positive correlations between arterial and conjunctival oxygen tensions (P less than 0.001). Although the system seemed accurate and reliable, monitoring oxygenation in awake and mobile foals may require a ring conformer made to fit the foal's eye.     

The cardiopulmonary effects of dobutamine and norepinephrine in isoflurane-anesthetized foals

OBJECTIVE: To evaluate the cardiovascular effects of norepinephrine (NE) and dobutamine (DB) in isoflurane-anesthetized foals. STUDY DESIGN: Prospective laboratory study. METHODS: Norepinephrine (0.05, 0.10, 0.20, and 0.40 microg kg(-1) minute(-1)) and dobutamine (2.5, 5.0, and 10 microg kg(-1) minute(-1)) were alternately administered to seven healthy, 1- to 2-week-old isoflurane-anesthetized foals. Arterial and pulmonary arterial blood pressure, right atrial pressure, pulmonary artery occlusion pressure, heart rate, body temperature, cardiac output, arterial and mixed venous blood pH, partial pressure of carbon dioxide, partial pressure of oxygen [arterial partial pressure of oxygen (PaO(2)) and mixed venous partial pressure of oxygen (PvO(2))], and packed cell volume were measured. Standard base excess, bicarbonate concentration, systemic and pulmonary vascular resistance, cardiac index (CI), stroke volume, left and right stroke work indices, oxygen delivery (DO(2)), consumption, and extraction were calculated. Results Norepinephrine infusion resulted in significant increases in arterial and pulmonary arterial pressure, systemic and pulmonary vascular resistance indices, and PaO(2); heart rate was decreased. Dobutamine infusion resulted in significant increases in heart rate, stroke volume index, CI, and arterial and pulmonary arterial blood pressure. Systemic and pulmonary vascular resistance indices were decreased while the ventricular stroke work indices increased. The PaO(2) decreased while DO(2) and oxygen consumption increased. Oxygen extraction decreased and PvO(2) increased. CONCLUSIONS AND CLINICAL RELEVANCE: Norepinephrine primarily augments arterial blood pressure while decreasing CI. Dobutamine primarily augments CI with only modest increases in arterial blood pressure. Both NE and DB could be useful in the hemodynamic management of anesthetized foals.     

Preliminary study on the pharmacokinetics of phenobarbital in the neonatal foal

Pharmacokinetic characteristics of the anticonvulsant phenobarbital were studied in seven pony and two Thoroughbred foals aged between four and 10 days. A single, 20 mg/kg bodyweight (bwt) dose of phenobarbital was given intravenously over 25 mins and the serum concentrations of the drug were measured using an EMIT AED assay (coefficient of variation 1.37 per cent at 30 micrograms/ml, n = 7). Phenobarbital elimination was found to follow first order kinetics. The mean (+/- sd) peak phenobarbital serum concentration was 18.6 +/- 2.1 micrograms/ml at 1 h after initiation of infusion with a mean (+/- se) half-life of 12.8 +/- 2.1 h. The mean (+/- se) volume of distribution was 0.86 +/- 0.026 litres/kg bwt and mean (+/- se) total body clearance was 0.0564 +/- 0.0065 litres/kg bwt/h. Sedation was noticed 15 to 20 mins after the beginning of infusion and lasted for up to 8 h. All foals could be aroused and could walk although they were ataxic for the first 1 to 2 h. A degree of delayed hyperexcitability occurred 3 to 8 h after infusion. In equine neonatal seizure disorders it is recommended to use a loading dose of 20 mg/kg bwt of phenobarbital, followed by maintenance doses of 9 mg/kg bwt at 8 h. With this regimen, average steady state serum phenobarbital concentrations should range between approximately 11.6 and 53 micrograms/ml. Phenobarbital serum concentrations should be monitored following the loading dose and 24 h after initiating the maintenance doses to check that levels remain within the suggested (human) therapeutic range of 15 to 40 micrograms/ml.     

Echocardiographic detection of tricuspid atresia in two foals

M-mode, 2-dimensional, and contrast echocardiographic studies were used to detect tricuspid atresia in 2 foals. M-mode echocardiographic findings included a small right ventricle, large left ventricle, large mitral valve excursion, large left atrium (foal 2), dropout of the cranial aspect of the aortic root, and a thick band of echoes in the tricuspid valve region. These findings were confirmed by 2-dimensional echocardiography. In addition, a large right atrium, persistent foramen ovale, ventricular septal defect, and large mitral valve apparatus were imaged. One foal also had a thick right atrial wall. Contrast echocardiography confirmed the intracardiac flow of blood from right to left atrium and then to the left ventricle, followed by simultaneous opacification of the right ventricle and aorta. The use of these echocardiographic techniques enables accurate antemortem diagnosis and prognosis of tricuspid atresia in the foal.     

A comparison of the haemodynamic effects of isoflurane and halothane anaesthesia in horses

The purpose of this study was to compare the haemodynamic effects of equipotent isoflurane and halothane anaesthesia. Six adult horses were investigated on two separate occasions at least 4 weeks apart. On both occasions anaesthesia was induced by ketamine 2.2 mg/kg bwt given 5 min after i.v. administration 100 microg/kg bwt romifidine. Anaesthesia was maintained either by halothane or isoflurane (end-tidal concentrations 0.9-1.0% and 1.3-1.4%, respectively). Horses were ventilated by intermittent positive pressure to maintain PaCO2 between 40-50 mmHg. Haemodynamic variables were measured using catheter-mounted strain gauge transducers in the left and right ventricle, aorta, and right atrium. Cardiac output (CO), velocity time integral (VTI), maximal aortic blood flow velocity (Vmax) and acceleration (dv/dt(max)), left ventricular pre-ejection period (PEP) and ejection time (ET) were measured from aortic blood flow velocity waveforms obtained by transoesophageal Doppler echocardiography. Flow velocity waveforms were recorded from the femoral arteries and veins using low pulse repetition frequency Doppler ultrasound. Time-averaged mean velocity (TAV), velocity of component a (TaVa), velocity of component b (TaVb) and early diastolic deceleration slope (EDDS) were measured. Pulsatility index (PI) and volumetric flow were calculated. Microvascular blood flow was measured in the left and right semimembranosus muscles by laser Doppler flowmetry. Maximal rate of rise of LV pressure (LVdp/dt(max)), CO, Vmax, dv/dt(max), ET, VTI were significantly higher at all time points during isoflurane anaesthesia compared to halothane anaesthesia. Pre-ejection period and diastolic aortic blood pressure were significantly less throughout isoflurane anaesthesia compared to halothane. Isoflurane anaesthesia was associated with significantly lower systemic vascular resistance than halothane anaesthesia. Femoral arterial and venous blood flow were significantly higher and EDDS and PI were significantly lower during isoflurane anaesthesia compared to halothane anaesthesia. In addition during both halothane and isoflurane anaesthesia, femoral arterial flow was higher and EDDS and PI lower in the left (dependent) artery compared to the right (nondependent) artery. This study supports previous work demonstrating improved left ventricular systolic function during isoflurane compared to halothane anaesthesia. This improvement was still evident after premedication with a potent-long acting alpha2-adrenoreceptor agonist, romifidine, and induction of anaesthesia with ketamine. There was also evidence of increased hindlimb blood flow during isoflurane anaesthesia. However, there were differences observed in flow between the left and right hindlimb during maintenance of anaesthesia with each agent, suggesting that there were differences in regional perfusion in anaesthetised horses caused by factors unrelated to agents administered.     

The Fell pony immunodeficiency syndrome also occurs in the Netherlands: a review and six cases

Over the last ten years a fatal syndrome associated with immunodeficiency and severe anaemia has been reported in young Fell pony foals in the UK. Affected foals are usually normal at birth but from the age of 2-4 weeks they progressively lose condition and become severely anaemic. Signs of immunodeficiency become apparent at around 3-4 weeks of age. Morbidity is low but mortality is 100% despite intensive treatment. Affected foals die or are euthanized usually before they reach the age of 3 months. A single autosomal recessive gene is suggested to be on the basis of the syndrome. Recently, affected Fell pony foals have been identified in the Netherlands and between June 2003 and August 2005, six affected Fell pony foals were referred to the Faculty of Veterinary Medicine for investigation.     

Lymphocyte stimulation response in horses against phytohaemagglutinin and M protein of Streptococcus equi using whole blood.

Lymphocyte stimulation was observed in whole equine blood in the presence of phytohaemagglutinin and M protein extracted from a typical strain of Streptococcus equi. Blood samples were collected from several healthy horses and horse and pony foals and cultured in vitro with varying concentrations of phytohaemagglutinin and M protein for several days. Phytohaemagglutinin was found to induce lymphocyte stimulation in these animals. Highest mean stimulation indices in horse foals (49.3 +/- 24.4) and pony foals (54.7 +/- 32.0) were observed with 0.625 and 1.25 micrograms/mL phytohaemagglutinin, respectively, at either 72 or 96 hours of incubation. Significantly higher radioactive counts per minute in horse and pony foals were recorded in blood cultures incubated with 0.625 and 1.25 micrograms/mL phytohaemagglutinin. M protein induced a dose related stimulation response in adult horses. Maximum stimulation indices were observed against 125 micrograms/mL M protein at 96 hours. These stimulation indices were higher in adult horses (40.0 +/- 2.2) than observed in pony foals (14.4 +/- 15.7). Higher stimulation levels in adult horses indicated either nonspecific stimulation against M protein or previous exposure of these animals to S. equi.     

Prevalence of Cryptosporidium sp in equids in Louisiana

In 1985, 22 pony foals reared in a helminth-free environment were tested daily for oocysts of Cryptosporidium sp by use of fecal flotation. Oocysts were found in all foals. Oocysts were first observed in feces collected from foals 9 to 28 days after birth. The mean period of oocyst shedding was 10 days and ranged from 2 to 18 days in individual foals. Diarrhea was observed in 14 of 22 (64%) foals and began before the period of oocyst shedding. Fecal samples also were examined for other infective agents. Salmonella poona was isolated from 1 foal that did not have diarrhea, and coronavirus particles were observed in the feces of 2 foals with diarrhea. Cryptosporidium sp oocysts also were observed in feces of 2 of 17 Thoroughbred foals, 3 of 14 Quarter Horse foals, and 3 of 26 pony foals reared on pastures with their dams. Samples from pasture-reared foals were collected at irregular intervals. Of the 11 Cryptosporidium-positive fecal samples collected from pastured foals, 2 were from foals with diarrhea. A similar survey was conducted during the 1986 foaling season, using the same procedures. Examination of 300 samples from 58 Quarter Horse, Arabian, and pony foals did not detect oocysts. Daily examination of feces from 10 pony foals reared under helminth-free conditions for 30 days also failed to detect Cryptosporidium oocysts.     

Passive transfer of Theileria equi antibodies to neonate foals of immune tolerant mares

Equine babesiosis, a tick transmitted haemoprotozoan disease caused by Theileria equi is globally distributed and responsible for heavy economic losses to the equine husbandry. Equids reared in endemic areas usually pick up infection at an early age and become immune tolerant throughout their life span. We studied the level of passively transferred antibodies in neonate foals born from pre-immuned mares. Latently T. equi infected pre-immuned pony and donkey mares (three each) were selected and T. equi antibody titres in neonates was monitored till 90 days post foaling (DPF) by applying Dot-ELISA on sequentially collected serum samples from foals and their dams. A very high antibody titre was observed in pre-immuned pony and donkey mares. The maximum antibody of 1:60 to 1:80 was observed in pony's and donkey's foal on 2–16 and 2–10 DPF, respectively and thereafter it declined to less than 1:20 on 63–77 and 56–63 DPF. Simultaneously parasite carrying status in neonate foals and their dam was also monitored by applying PCR on blood samples. We could demonstrate PCR amplification in dam's blood samples while no amplification was recorded in neonate's blood samples. This study indicated that new-born foals were born naïve and passively transferred immunity was transitory which wanes after 63–77 DPF.     

Interruption of aortic arch in two foals

Two foals with a history of normalcy at birth developed a lack of exercise tolerance and weakness in the first few days of life. Weakness, inability to rise, and reluctance to suckle were common complaints. Physical examination of both foals revealed a cardiovascular abnormality, with a loud systolic murmur audible over both thoracic walls. Additional diagnostic techniques were blood gas analysis, radiography, cardiovascular catheterization, and necropsy. Necropsy findings were ventricular septal defect, atrial septal defect, patent ductus arteriosus, and congenital absence of the aortic arch. Additionally, 1 foal had anomalous drainage of the cranial vena cava into the left atrium.