Abstract: Calcium gluconate was administered to conscious horses at 3 different rates (0.1, 0.2, and 0.4 mg/kg/min for 15 minutes each). Serum calcium concentrations and parameters of cardiovascular function were evaluated. All 3 calcium administration rates caused marked increases in both ionized and total calcium concentrations, cardiac index, stroke index, and cardiac contractility (dP/dtmax). Mean arterial pressure and right atrial pressure were unchanged; heart rate decreased markedly during calcium administration. Ionized calcium concentration remained between 54% and 57% of total calcium concentration throughout the study. We conclude that calcium gluconate can safely be administered to conscious horses at 0.1 to 0.4 mg/kg/min and that administration will result in improved cardiac function.

Abstract: Adult male elephants periodically show the phenomenon of musth, a condition associated with increased aggressiveness, restlessness, significant weight reduction and markedly elevated androgen levels. It has been suggested that musth-related behaviours are costly and that therefore musth may represent a form of physiological stress. In order to provide data on this largely unanswered question, the first aim of this study was to evaluate different assays for non-invasive assessment of adrenocortical function in the male African elephant by (i) characterizing the metabolism and excretion of [3H]cortisol (3H-C) and [14C]testosterone (14C-T) and (ii) using this information to evaluate the specificity of four antibodies for determination of excreted cortisol metabolites, particularly with respect to possible cross-reactions with androgen metabolites, and to assess their biological validity using an ACTH challenge test. Based on the methodology established, the second objective was to provide data on fecal cortisol metabolite concentrations in bulls during the musth and non-musth condition. 3H-C (1 mCi) and 14C-T (100 microCi) were injected simultaneously into a 16 year old male and all urine and feces collected for 30 and 86 h, respectively. The majority (82%) of cortisol metabolites was excreted into the urine, whereas testosterone metabolites were mainly (57%) excreted into the feces. Almost all radioactive metabolites recovered from urine were conjugated (86% 3H-C and 97% 14C-T). In contrast, 86% and >99% of the 3H-C and 14C-T metabolites recovered from feces consisted of unconjugated forms. HPLC separations indicated the presence of various metabolites of cortisol in both urine and feces, with cortisol being abundant in hydrolysed urine, but virtually absent in feces. Although all antibodies measured substantial amounts of immunoreactivity after HPLC separation of peak radioactive samples and detected an increase in glucocorticoid output following the ACTH challenge, only two (in feces against 3alpha,11-oxo-cortisol metabolites, measured by an 11-oxo-etiocholanolone-EIA and in urine against cortisol, measured by a cortisol-EIA) did not show substantial cross-reactivity with excreted 14C-T metabolites and could provide an acceptable degree of specificity for reliable assessment of glucocorticoid output from urine and feces. Based on these findings, concentrations of immunoreactive 3alpha,11-oxo-cortisol metabolites were determined in weekly fecal samples collected from four adult bulls over periods of 11-20 months to examine whether musth is associated with increased adrenal activity. Results showed that in each male levels of these cortisol metabolites were not elevated during periods of musth, suggesting that in the African elephant musth is generally not associated with marked elevations in glucocorticoid output. Given the complex nature of musth and the variety of factors that are likely to influence its manifestation, it is clear, however, that further studies, particularly on free-ranging animals, are needed before a possible relationship between musth and adrenal function can be resolved. This study also clearly illustrates the potential problems associated with cross-reacting metabolites of gonadal steroids in EIAs measuring glucocorticoid metabolites. This has to be taken into account when selecting assays and interpreting results of glucocorticoid metabolite analysis, not only for studies in the elephant but also in other species.

Abstract: BACKGROUND: Peroxisome proliferator-activated receptor gamma (PPARgamma) ligands improve human hypertension. However, the mechanism and site of this effect remains unknown, confounded by PPARgamma expression in many cell types, including endothelial cells (ECs). METHODS: To evaluate the vascular role of PPARgamma we used a conditional null mouse model. Specific disruption of PPARgamma in ECs was created by crossing Tie2-Cre+ transgenic (T2T+) and PPARgamma-floxed (fl/fl) mice to generate PPARgamma (fl/fl)T2T+ (PPARgamma E-null) mice. Conscious 8- to 12-week-old congenic PPARgamma (fl/fl)Cre- (wild type) and PPARgamma E-null mice were examined for changes in systolic blood pressure (BP) and heart rate (HR), untreated, after 2 months of salt-loading (drinking water), and after treatment for 3 months with high fat (HF) diet alone or supplemented during the last 2 weeks with rosiglitazone (3 mg/kg/d). RESULTS: Untreated PPARgamma E-nulls were phenotypically indistinguishable from wild-type littermates. However, compared to similarly treated wild types, HF-treated PPARgamma E-nulls had significantly elevated systolic BP not seen after normal diet or salt-loading. Despite sex-dependent baseline differences, salt-loaded and HF-treated PPARgamma E-nulls of either sex had significantly elevated HR versus wild types. Interestingly, rosiglitazone improved serum insulin levels, but not HF diet-induced hypertension, in PPARgamma E-null mice. CONCLUSIONS: These results suggest that PPARgamma in ECs not only is an important regulator of hypertension and HR under stressed conditions mimicking those arising in type 2 diabetics, but also mediates the antihypertensive effects of rosiglitazone. These data add evidence supporting a beneficial role for PPARgamma-specific ligands in the treatment of hypertension, and suggest therapeutic strategies targeting ECs may prove useful.

Abstract: Reasons for performing the study: Similar to human decubitus ulcers, local high pressure points from ill-fitting saddles induce perfusion disturbances of different degrees resulting in tissue hypoxia and alteration in sweat production. Objective: To relate the different clinical manifestations of saddle sores to the magnitude of saddle pressures at the location of the withers. Methods: Sixteen horses with dry spots after exercise (Group A) and 7 cases presented with acute clinical signs of saddle pressure in the withers area (Group B) were compared with a control group of 16 sound horses with well fitting saddles (Group C). All horses underwent a saddle pressure measurement at walk, trot and canter. Mean and maximal pressures in the area of interest were compared between groups within each gait. Results: Mean pressures differed significantly between groups in all 3 gaits. Maximal pressure differed between groups at trot; at walk and canter, however, the only significant difference was between Group C and Groups A and B, respectively, (P>0.05). Mean and maximal pressures at walk in Group A were 15.3 and 30.6 kPa, in Group B 24.0 and 38.9 kPa and in Group C 7.8 and 13.4 kPa, respectively; at trot in Group A 18.1 and 43.4 kPa, in Group B 29.7 and 53.3 kPa and in Group C 9.8 and 21.0 kPa, respectively; and at canter in Group A 21.4 and 48.9 kPa, in Group B 28.6 and 56.0 kPa and in Group C 10.9 and 24.7 kPa, respectively. Conclusion: The study shows that there is a distinguishable difference between the 3 groups regarding the mean pressure value, in all gaits.

Abstract: Saddle-fit is recognised as an important factor in the pathogenesis of back problems in horses and is empirically being evaluated by pressure measurements in clinical practice, although not much is known about the validity, reliability and usability of these devices in the equine field. This study was conducted to assess critically a pressure measurement system marketed for evaluating saddle fit. Validity was tested by calculating the correlation coefficient between total measured pressure and the weight of 28 different riders. Reliability and discriminative power with respect to different saddle fitting methods were evaluated in a highly standardised, paired measurement set-up in which saddle-fit was quantified by air-pressure values inside the panels of the saddle. Total pressures under the saddle correlated well with riders’ weight. A large increase in over-day sensor variation was found. Within trial intra-class correlation coefficients (ICCs) were excellent, but the between trial ICCs varied from poor to excellent and the variation in total pressure was high. In saddles in which the fit was adjusted to individual asymmetries of the horse, the pressure measurement device was able to detect correctly air-pressure differences between the two panels in the back area of the saddle, but not in the front area. The device yielded valid results, but was only reliable in highly standardised conditions. The results question the indiscriminate use of current saddle pressure measurement devices for the quantitative assessment of saddle-fit under practical conditions and suggest that further technical improvement may be necessary.