The vitamin D hormone 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3] is essential for the preservation of serum calcium and phosphate levels but may also be important for the regulation of cardiovascular function. Epidemiological data in humans have shown that vitamin D insufficiency is associated with hypertension, left ventricular hypertrophy, increased arterial stiffness, and endothelial dysfunction in normal subjects and in patients with chronic kidney disease and type 2 diabetes. However, the pathophysiological mechanisms underlying these associations remain largely unexplained. In this study, we aimed to decipher the mechanisms by which 1,25(OH)2D3 may regulate systemic vascular tone and cardiac function, using mice carrying a mutant, functionally inactive vitamin D receptor (VDR). To normalize calcium homeostasis in VDR mutant mice, we fed the mice lifelong with the so-called rescue diet enriched with calcium, phosphate, and lactose. Here, we report that VDR mutant mice are characterized by lower bioavailability of the vasodilator nitric oxide (NO) due to reduced expression of the key NO synthesizing enzyme, endothelial NO synthase, leading to endothelial dysfunction, increased arterial stiffness, increased aortic impedance, structural remodeling of the aorta, and impaired systolic and diastolic heart function at later ages, independent of changes in the renin-angiotensin system. We further demonstrate that 1,25(OH)2D3 is a direct transcriptional regulator of endothelial NO synthase. Our data demonstrate the importance of intact VDR signaling in the preservation of vascular function and may provide a mechanistic explanation for epidemiological data in humans showing that vitamin D insufficiency is associated with hypertension and endothelial dysfunction.

Opioids or ketamine used alone may cause changes in stress-related biochemical variables in plasma. Medetomidine prevented or blunted these changes. Combined sedation provided better hormonal and metabolic stability than either component alone. We recommend using medetomidine-butorphanol or medetomidine-ketamine combinations for sedation or anesthesia of systemically healthy dogs.

The aim was to evaluate the feasibility of using electrical impedance tomography (EIT) in horses.Thoracic EIT was used in nine horses. Thoracic and abdominal circumference changes were also measured with respiratory ultrasound plethysmography (RUP). Data were recorded during baseline, rebreathing of CO 2 and sedation. Three breaths were selected for analysis from each recording. During baseline breathing, horses regularly took single large breaths (sighs), which were also analysed. Functional EIT images were created using standard deviations (SD) of pixel signals and correlation coefficients (R) of each pixel signal with a reference respiratory signal.Left-to-right ratio, centre-of-ventilation and global-inhomogeneity-index were calculated. RM-ANOVA and Bonferroni tests were used (P<0.05). Distribution of ventilation shifted towards right during sighs and towards dependent regions during sighs, rebreathing and sedation. Globalinhomogeneity-index did not change for SD but increased for R images during sedation. The sum of SDs for the respiratory EIT signals correlated well with thoracic (r 2 = 0.78) and abdominal (r 2 = 0.82) tidal circumferential changes. Inverse respiratory signals were identified on the images at sternal location and based on reviewing CT images, seemed to correspond to location of gas filled intestines. Application of EIT in standing non-sedated horses is feasible. EIT images may provide physiologically useful information even in situations, such as sighs, that cannot easily be tested by other methods.

No abstract

A number of drugs influenced the accuracy of the LiDCO sensor in vitro but, based on published pharmacokinetic data, only xylazine, ketamine, lidocaine, and rocuronium may cause biases at clinically relevant concentrations. These findings need to be confirmed in vivo. Relevant (>3 mV) changes in sensor voltages due to the presence of drugs may indicate possible interactions with the LiDCO sensor.