Beverly Chua

Effects of early separation on the dairy cow and calf 1. Separation at 6 h, 1 day and 4 days after birth

The aim of this study was to evaluate the effects of age of separation on the behavioural responses of the dairy calf and cow. Calves were separated from their dams 6 h, 1 day, or 4 days after birth (n=9 cow-calf pairs in each of the 3 treatment groups) and behaviour was video and audio taped from 1 h before separation to 21 h after separation. In the hour immediately before separation, we found that the younger calves tended to call and move more in the pen, and spent more time standing than the older calves, but after separation these trends reversed. Calves separated at older ages made significantly more movements in the pen (P<0.05), spent more time standing (P<0.05) and spent more time with the head out of the pen (P<0.01) than calves separated soon after birth. We observed a similar pattern for the cows. Before separation, cows with younger calves moved more frequently about the pen (P<0.05), and called at much higher rates (a mean of 40.7 calls during 40 min for cows on the 6-h treatment, vs. 0.2 calls for cows in the 4-day group; P<0.001). After separation, cows in the 4-day group called at approximately four times the rate of those separated at 6 h or 1 day (P<0.01). Moreover, the calls produced by cows separated later had a significantly higher fundamental frequency (P<0.001) and a lower emphasized harmonic (P<0.02) than the calls of cows separated from calves soon after birth. There was no difference between treatment groups in the other behavioural measures, either before or after separation. Calves separated at older ages tended to require fewer days of treatment for scouring, but calf weight gain and cow milk production did not differ among treatment groups. In conclusion, behavioural responses of both the cow and calf increase in relation to calf age at separation. However, there may be health advantages associated with delayed separation that compensate for the increased behavioural response.

The paradox of extreme high-altitude migration in bar-headed geese Anser indicus

Bar-headed geese are renowned for migratory flights at extremely high altitudes over the worlds tallest mountains, the Himalayas, where partial pressure of oxygen is dramatically reduced while flight costs, in terms of rate of oxygen consumption, are greatly increased. Such a mismatch is paradoxical, and it is not clear why geese might fly higher than is absolutely necessary. In addition, direct empirical measurements of high-altitude flight are lacking. We test whether migrating bar-headed geese actually minimize flight altitude and make use of favourable winds to reduce flight costs. By tracking 91 geese, we show that these birds typically travel through the valleys of the Himalayas and not over the summits. We report maximum flight altitudes of 7290 m and 6540 m for southbound and northbound geese, respectively, but with 95 per cent of locations received from less than 5489 m. Geese travelled along a route that was 112 km longer than the great circle (shortest distance) route, with transit ground speeds suggesting that they rarely profited from tailwinds. Bar-headed geese from these eastern populations generally travel only as high as the terrain beneath them dictates and rarely in profitable winds. Nevertheless, their migration represents an enormous challenge in conditions where humans and other mammals are only able to operate at levels well below their sea-level maxima.

Therapeutic drug monitoring in interstitial fluid: A feasibility study using a comprehensive panel of drugs

This study compared drug concentration-time profiles in interstitial fluid (ISF) and blood, using an established animal model and a comprehensive panel of drugs, to examine the feasibility of therapeutic drug monitoring (TDM) in ISF. An intravenous bolus of vancomycin, gentamicin, tacrolimus, cyclosporine, mycophenolate, valproic acid, phenobarbital, phenytoin, carboplatin, cisplatin, methotrexate, theophylline, or digoxin was administered into the ear vein (n = 4-6) of rabbits. Serial (0-72 h after dose) blood and ISF concentrations (collected via an ultrafiltration probe) were determined by validated analytical assays. Pharmacokinetic parameters were generated by noncompartmental analysis. Vancomycin, gentamicin, and carboplatin showed no significant difference in area under the curve (AUC) values in ISF and blood, respectively. Other AUCs were lower (mycophenolic acid, valproic acid, phenobarbital, cisplatin, methotrexate, theophylline, and digoxin) or not measurable (tacrolimus, cyclosporine, and phenytoin) in ISF with our extraction technique. Similar concentration-time profiles in the two matrices were evident for a selection of drugs tested. Using a comprehensive panel of drugs in a single experimental setting, we have identified agents that can be quantified in ISF. Our newly developed scoring algorithm can help determine the feasibility of conducting TDM in ISF.

Altitude matters: differences in cardiovascular and respiratory responses to hypoxia in bar-headed geese reared at high and low altitudes.

ABSTRACT Bar-headed geese (Anser indicus) fly at high altitudes during their migration across the Himalayas and Tibetan plateau. However, we know relatively little about whether rearing at high altitude (i.e. phenotypic plasticity) facilitates this impressive feat because most of what is known about their physiology comes from studies performed at sea level. To provide this information, a comprehensive analysis of metabolic, cardiovascular and ventilatory responses to progressive decreases in the equivalent fractional composition of inspired oxygen (FiO2: 0.21, 0.12, 0.09, 0.07 and 0.05) was made on bar-headed geese reared at either high altitude (3200 m) or low altitude (0 m) and on barnacle geese (Branta leucopsis), a low-altitude migrating species, reared at low altitude (0 m). Bar-headed geese reared at high altitude exhibited lower metabolic rates and a modestly increased hypoxic ventilatory response compared with low-altitude-reared bar-headed geese. Although the in vivo oxygen equilibrium curves and blood-oxygen carrying capacity did not differ between the two bar-headed goose study groups, the blood-oxygen carrying capacity was higher than that of barnacle geese. Resting cardiac output also did not differ between groups and increased at least twofold during progressive hypoxia, initially as a result of increases in stroke volume. However, cardiac output increased at a higher FiO2 threshold in bar-headed geese raised at high altitude. Thus, bar-headed geese reared at high altitude exhibited a reduced oxygen demand at rest and a modest but significant increase in oxygen uptake and delivery during progressive hypoxia compared with bar-headed geese reared at low altitude. Highlighted Article: When exposed to progressive hypoxia, bar-headed geese reared at altitude exhibit a reduced metabolism and modestly increased ventilatory response, and also initiated cardiac responses earlier than geese reared at low altitude.

Temperature-dependent regulation of blood distribution in snakes

SUMMARY Regional control of blood flow is often suggested as a mechanism for fine thermoregulatory adjustments in snakes. However, the flow of blood to different body regions at various temperatures has never been visualized to confirm this mechanism. We used 99mtechnetium-labelled macroaggregated albumin (99mTc-MAA), a radioactive tracer, to follow the flow of blood through the bodies of garter snakes (Thamnophis sirtalis) near their thermal maxima and minima. We injected snakes with 99mTc-MAA at cold (6–8°C) and hot (27–32°C) temperatures and imaged them using a gamma scanner. At cold ambient temperatures, snakes significantly reduced the blood flow to their tails and significantly increased the blood flow to their heads. Conversely, at hot ambient temperatures, snakes significantly increased the blood flow to their tails and significantly reduced the blood flow to their heads. This confirms that snakes are able to use differential blood distribution to regulate temperature. Our images confirm that snakes use regional control of blood flow as a means of thermoregulation and that vasomotor control of vascular beds is likely to be the mechanism of control.

Mitochondrial physiology in the skeletal and cardiac muscles is altered in torrent ducks, Merganetta armata, from high altitudes in the Andes

ABSTRACT Torrent ducks inhabit fast-flowing rivers in the Andes from sea level to altitudes up to 4500 m. We examined the mitochondrial physiology that facilitates performance over this altitudinal cline by comparing the respiratory capacities of permeabilized fibers, the activities of 16 key metabolic enzymes and the myoglobin content in muscles between high- and low-altitude populations of this species. Mitochondrial respiratory capacities (assessed using substrates of mitochondrial complexes I, II and/or IV) were higher in highland ducks in the gastrocnemius muscle – the primary muscle used to support swimming and diving – but were similar between populations in the pectoralis muscle and the left ventricle. The heightened respiratory capacity in the gastrocnemius of highland ducks was associated with elevated activities of cytochrome oxidase, phosphofructokinase, pyruvate kinase and malate dehydrogenase (MDH). Although respiratory capacities were similar between populations in the other muscles, highland ducks had elevated activities of ATP synthase, lactate dehydrogenase, MDH, hydroxyacyl CoA dehydrogenase and creatine kinase in the left ventricle, and elevated MDH activity and myoglobin content in the pectoralis. Thus, although there was a significant increase in the oxidative capacity of the gastrocnemius in highland ducks, which correlates with improved performance at high altitudes, the variation in metabolic enzyme activities in other muscles not correlated to respiratory capacity, such as the consistent upregulation of MDH activity, may serve other functions that contribute to success at high altitudes. Summary: Torrent ducks display markedly different physiological and enzymatic specializations at high altitude, characterized by increased mitochondrial respiratory capacity, increased myoglobin content and reorganized enzymatic capacities.

Comparison of vancomycin concentrations in blood and interstitial fluid: a possible model for less invasive therapeutic drug monitoring

1 Faculty of Pharmaceutical Sciences , The University of British Columbia, Vancouver, BC , Canada 2 Child and Family Research Institute , Vancouver, BC , Canada 3 Department of Pharmacy , Children ’ s and Women ’ s Health Centre of British Columbia, Vancouver, BC , Canada 4 Departments of Mechanical and Electrical and Computer Engineering , The University of British Columbia, Vancouver, BC , Canada 5 Animal Care Centre , The University of British Columbia, Vancouver, BC , Canada 6 Vancouver General Hospital , Vancouver, BC , Canada

Respiratory mechanics of eleven avian species resident at high and low altitude

ABSTRACT The metabolic cost of breathing at rest has never been successfully measured in birds, but has been hypothesized to be higher than in mammals of a similar size because of the rocking motion of the avian sternum being encumbered by the pectoral flight muscles. To measure the cost and work of breathing, and to investigate whether species resident at high altitude exhibit morphological or mechanical changes that alter the work of breathing, we studied 11 species of waterfowl: five from high altitudes (>3000 m) in Perú, and six from low altitudes in Oregon, USA. Birds were anesthetized and mechanically ventilated in sternal recumbency with known tidal volumes and breathing frequencies. The work done by the ventilator was measured, and these values were applied to the combinations of tidal volumes and breathing frequencies used by the birds to breathe at rest. We found the respiratory system of high-altitude species to be of a similar size, but consistently more compliant than that of low-altitude sister taxa, although this did not translate to a significantly reduced work of breathing. The metabolic cost of breathing was estimated to be between 1 and 3% of basal metabolic rate, as low or lower than estimates for other groups of tetrapods. Highlighted Article: Work and cost of breathing in 11 species of waterfowl are reported to be lower than previously predicted in birds, but without effect of altitudinal habitat despite mechanical differences in highland species.

Divergent respiratory and cardiovascular responses to hypoxia in bar-headed geese and Andean birds

ABSTRACT Many high-altitude vertebrates have evolved increased capacities in their oxygen transport cascade (ventilation, pulmonary diffusion, circulation and tissue diffusion), enhancing oxygen transfer from the atmosphere to mitochondria. However, the extent of interspecies variation in the control processes that dictate hypoxia responses remains largely unknown. We compared the metabolic, cardiovascular and respiratory responses to progressive decreases in inspired oxygen levels of bar-headed geese (Anser indicus), birds that biannually migrate across the Himalayan mountains, with those of Andean geese (Chloephaga melanoptera) and crested ducks (Lophonetta specularioides), lifelong residents of the high Andes. We show that Andean geese and crested ducks have evolved fundamentally different mechanisms for maintaining oxygen supply during low oxygen (hypoxia) from those of bar-headed geese. Bar-headed geese respond to hypoxia with robust increases in ventilation and heart rate, whereas Andean species increase lung oxygen extraction and cardiac stroke volume. We propose that transient high-altitude performance has favoured the evolution of robust convective oxygen transport recruitment in hypoxia, whereas life-long high-altitude residency has favoured the evolution of structural enhancements to the lungs and heart that increase lung diffusion and stroke volume. Highlighted Article: When exposed to progressive hypoxia, bar-headed geese (biannual high-altitude migrators) increase ventilation and heart rate, whereas Andean geese (lifelong high-altitude residents) increase lung oxygen extraction and cardiac stroke volume.

Morphological and morphometric specializations of the lung of the Andean goose, Chloephaga melanoptera: A lifelong high-altitude resident

High altitude flight in rarefied, extremely cold and hypoxic air is a very challenging activity. Only a few species of birds can achieve it. Hitherto, the structure of the lungs of such birds has not been studied. This is because of the rarity of such species and the challenges of preparing well-fixed lung tissue. Here, it was posited that in addition to the now proven physiological adaptations, high altitude flying birds will also have acquired pulmonary structural adaptations that enable them to obtain the large amounts of oxygen (O2) needed for flight at high elevation, an environment where O2 levels are very low. The Andean goose (Chloephaga melanoptera) normally resides at altitudes above 3000 meters and flies to elevations as high as 6000 meters where O2 becomes limiting. In this study, its lung was morphologically- and morphometrically investigated. It was found that structurally the lungs are exceptionally specialized for gas exchange. Atypically, the infundibulae are well-vascularized. The mass-specific volume of the lung (42.8 cm3.kg-1), the mass-specific respiratory surface area of the blood-gas (tissue) barrier (96.5 cm2.g-1) and the mass-specific volume of the pulmonary capillary blood (7.44 cm3.kg-1) were some of the highest values so far reported in birds. The pulmonary structural specializations have generated a mass-specific total (overall) pulmonary morphometric diffusing capacity of the lung for oxygen (DLo2) of 0.119 mlO2.sec-1.mbar-1.kg-1, a value that is among some of the highest ones in birds that have been studied. The adaptations of the lung of the Andean goose possibly produce the high O2 conductance needed to live and fly at high altitude.