Partial pressure of end-tidal CO2 sampled via an intranasal catheter as a substitute for partial pressure of arterial CO2 in dogs

Objective: To demonstrate correlation and clinical usefulness of the partial pressure of end‐tidal CO₂ (ETCO₂) measurement by nasal catheter placement in sedated dogs with and without concurrent nasal oxygen administration as a substitute for partial pressure of arterial CO₂ (PaCO₂). Design: Prospective, cross‐over trial. Setting: University of Saskatchewan veterinary research laboratory. Animals: Six cross‐breed dogs with a mean (±SD) weight of 29.1±4.03 kg. Interventions: All dogs were sedated with 5 μg/kg medetomidine intravenously (IV) and an arterial catheter was placed in a dorsal pedal artery for removal of blood for gas analysis. A nasal catheter was placed in the ventral meatus and connected to a capnometer for ETCO₂ measurements in all dogs. Dogs receiving supplemental nasal oxygen had a second nasal catheter placed in the contralateral naris. Measurements and main results: In the group without nasal oxygen supplementation, the ETCO₂ measurement underestimated (negative bias) the PaCO₂ by ?2.20 mmHg with limits of agreement (95% confidence interval) of ?5.79, 1.39 mmHg. In the group receiving oxygen supplementation, ETCO₂ measurement underestimated (negative bias) the PaCO₂ by ?2.46 mmHg with limits of agreement (95% confidence interval) of ?8.42, 3.50 mmHg. Conclusions: The results of this study demonstrate that ETCO₂ monitoring via a nasal catheter provides a clinically acceptable substitute to arterial blood gas analysis as a means of monitoring ventilation in healthy, sedated dogs. The limits of agreement were within acceptable limits with and without concurrent insufflation of oxygen.     

Non-equivalence of canine tissue and intraluminal PCO2 responses at different sites during hemorrhage and during resuscitation

Objective: The purpose of this study was to measure and compare the hemorrhage and resuscitation partial pressure of CO₂ (PCO₂) responses at a variety of sites, predominantly intraluminal gastrointestinal, in the same dog and among different dogs. Design: Observational study. Setting: Association for Assessment and Accreditation of Laboratory Animal Care accredited research laboratory. Animals: Pound source mongrel dogs being used in 4 separate hemorrhage and resuscitation studies, the objectives of which were unaffected by the PCO₂ monitoring. Interventions: Fiber‐optic PCO₂ monitoring systems were used to simultaneously monitor subcutaneous (n=8), sublingual (n=8) PCO₂, and intraluminal esophageal (n=10), gastric (n=27), duodenal (n=16), jejunal (n=8), and ileal (n=7) PCO₂ of 28 dogs used in 4 hemorrhage and resuscitation studies. Measurements and main results: The tissue or intraluminal PCO₂ at all sites increased in response to hemorrhage. The rate and magnitude of esophageal, gastric, duodenal, jejeunal, and ileal intraluminal PCO₂ varied widely between dogs for the same site and between sites in the same dog. Different gastrointestinal sites also responded differently to resuscitation. The rate and magnitude of changes in subcutaneous and sublingual PCO₂ values were lower than those in the other tissues examined. The mean and maximum coefficients of variation for each site were as follows: subcutaneous 9%, 31%; sublingual 10%, 23%; esophageal 15%, 40%; gastric 26%, 90%; duodenal 25%, 70%; jejunal 25%, 95%; and ileal 34%, 87%. Conclusions: At different tissue sites, PCO₂ values do not respond equivalently to either hemorrhage or resuscitation. One site cannot, therefore, be reliably used to indicate the energy status of an alternate site.     

GI PiCO2: Tissue Specific Monitoring For Improving Patient Outcomes

Improvements in human patient monitoring despite their development in animals, do not always find their way into veterinary clinical use due to financial constraints. Gastrointestinal intraluminal CO₂ partial pressure (Gip₁CO₂) monitoring, however, is not only proving very beneficial in human trauma and critical patient care but is also very likely to become relatively inexpensive. By providing information on the perfusion adequacy of a high risk, critically important tissue, the GI mucosa, GI P₁CO₂ monitoring offers an easily accesible indicator of the efficacy and adequacy of resuscitative interventions. The potential for decreasing morbidity and mortality is enormous. Therefore, the practicing veterinarian should become familiar with GI P₁CO₂ monitoring theory and technology so he or she can be better prepared to incorporate it into practice when in becomes available.     

Agreement of SpO2, SaO2 and ScO2 in anesthetized cynomolgus monkeys (Macaca fascicularis)

Objective To assess the agreement between three measurements of arterial oxygen saturation (SpO₂, SaO₂ and ScO₂) in anesthetized cynomolgus monkeys. Study Design Prospective study. Animals Eleven mature, male cynomolgus monkeys (Macaca fasicularis). Methods Monkeys were anesthetized with intramuscular ketamine followed by intravenous propofol. The trachea of each was intubated and the lungs ventilated. Arterial oxygen saturation was measured with a Nonin 8500 V pulse oximeter, using a lingual clip on the cheek. Arterial blood samples were taken from an indwelling catheter. Inspired oxygen concentration was varied from 12 to 20%, and 88 paired arterial blood samples and saturation measurements were taken. Arterial oxygen saturation in the blood samples was measured using a cooximeter. The saturation was also calculated from the arterial oxygen tension using the Adair equation. The results were compared using Bland and Altman's method. Results The pulse oximeter readings were 2.7% higher than that of the cooximeter, with a limit of agreement of ?3.9 to 9.3%. The pulse oximeter readings were 1.8% higher than the calculated saturation, with a limit of agreement of ?6.5% to 10.1%. The cooximeter readings were 0.9% lower than the calculated saturation, with a limit of agreement of ?5.6% to 3.8%. Conclusions The agreement between SpO₂ and other measurements of arterial oxygen saturation in this study is typical for this technique. The bias and limits of agreement are consistent with reports in other species. Clinical relevance The Nonin 8500 V is a useful pulse oximeter for clinical use in primates.     

Effect of sample handling on venous PCO2, pH, bicarbonate, and base excess measured with a point-of-care analyzer

Objective: The purpose of this study was to determine the effect of timing of analysis, collection tube type and repeated opening of sample tubes on venous PCO₂, pH, HCO₃, and base excess (BE) results. Design: Prospective experimental study, paired sample analysis. Setting: Veterinary Medical Teaching Hospital. Animals: Twenty dogs. Interventions: Jugular venous blood samples. Measurements and main results: PCO₂, pH, HCO₃, and BE were determined immediately following collection (control) and at selected times up to 30 minutes after placement in either screw top or vacuum heparin collection tubes. A different set of screw top and vacuum heparin collection tubes were sampled repeatedly over time for up to 15 minutes. In the screw top delayed analysis group, only pH changed significantly at one time point. PCO₂ decreased significantly in all other groups and resulted in a significant reciprocal pH change in the vacuum tubes with either delayed single analysis or repeated sampling. HCO₃ and BE declined significantly in multi‐sampled vacuum tubes and HCO₃ also decreased significantly in multi‐sampled screw top tubes. Conclusions: Analysis of acid–base status is optimally performed on freshly drawn blood. However, when it is anticipated there will be a delay in analysis of samples kept at room temperature, the use of 2.0 mL plastic screw top heparin anticoagulant tubes may result in fewer pre‐analytical errors than 3.5 mL glass vacuum tubes.     

Utilization of F1 information in estimating QTL effects in F2 crosses between outbred lines

Quantitative trait loci (QTL) analysis in designed experiments is investigated using a mixed model framework through the modification of segment mapping techniques. Allele effects are modelled in the F₁ generation allowing the estimation of additive substitution effects while accounting for QTL segregation within lines and differences in mean QTL effects between lines. The resulting approach is called F₁ segment mapping. Simulation is used to illustrate the method and its properties. F₁ segment mapping has advantages over F₂ segment mapping in the derivation of exact additive genetic covariances and in the computation time for variance component estimation.     

Determination of P50 for feline hemoglobin

Objective: The objective of this study was to determine the PO₂ at 50% hemoglobin oxygenation (P₅₀) of feline hemoglobin (Hb). Design: Prospective in vitro laboratory study. Setting: Research laboratory. Animals: Blood from 10 healthy cats. Interventions: Individual blood samples were equilibrated with calibrated gases of 95, 21, 8, 5, 4, and 2.5% oxygen for tonometric analysis. Measurements: Partial pressure of oxygen (PO₂), oxygen content, oxyhemoglobin saturation, methemoglobin (MetHb), carboxyhemoglobin (COHb), Hb, packed cell volume, hydrogen ion concentration (pH), and partial pressure of carbon dioxide (PCO₂) were measured in duplicate for each blood sample by tonometry. The P₅₀ was calculated from both PO₂/oxyhemoglobin saturation and PO₂/oxygen content (per gram of Hb) curves. Main results: The P₅₀ from the PO₂/oxyhemoglobin saturation curve was 35.6 mmHg and from the PO₂/oxygen content (per gram of Hb) curve was 36.2 mmHg. Conclusions: The oxyhemoglobin dissociation curve for the cat is shifted to the right, and thus, feline Hb has lower oxygen affinity compared with human and canine Hb.     

A simulation study on the detection of causal mutations from F2 experiments

A simulation study has been performed to evaluate the power and the rate of false positives for the detection of causal mutations under two different models of analysis. We used an F₂ design generated from an F₀ population of five sires of line 1 and 40 dams of line 2 to produce an F₁ population of 10 sires and 80 dams. Two different locations of the causal mutation and several frequencies of the mutations in the parental populations were considered. The first model included only the genetic configuration of the mutation, while the second model also included the probability of line origin given the neutral markers. Both models performed well when the mutation at the candidate gene was the causal mutation, although a greater power was obtained using the first model, because of its relative simplicity compared to the second one. However, when the candidate gene mutation was a neutral mutation, the second model presented a lower rate of false positives than the first. Moreover, in some cases the second model allowed distinction between the neutral and the causal mutation. The F₂ design has a great power to detect quantitative trait loci provided by linkage disequilibrium, but also makes it difficult to discriminate between causal and neutral mutations. Therefore a high percentage of false positives can be expected. The limitations of F₂ designs for discriminating between neutral and causal mutations are discussed.     

Alpha-adrenoceptors in equine digital veins: Evidence for the presence of both alpha1 and alpha2-receptors mediating vasoconstriction

Rings of equine digital vein examined under conditions of isometric tension recording constricted to alpha-adrenoceptor agonists with an order of potency of 5-bromo-6-[2-imidazolin-2-yl-amino]-quinoxaline bitartrate (UK 14304) = noradrenaline > 6-Allyl-2-amino-5,6,7,8-tetrahydro-4H-thiazolo-(4,5-d) azepine (BHT-920) > phenylephrine > dopamine > methoxamine. The maximum force generated was greatest for the non-selective agonist noradrenaline and lowest for the alpha₂-selective agonist BHT-920 with the other agonists between these two extremes. Selective inactivation of alpha₁-adrenoceptors (achieved by treating yohimbine-protected tissues with phenoxybenzamine) reduced the maximum responses of all agonists, the EC₅₀ values of UK 14304, BHT-920 and noradrenaline and increased the EC₅₀ values of phenylephrine and methoxamine. Prazosin (30 n M ) had no inhibitory effect on responses to low concentrations of BHT-920 and UK 14304 and caused competitive inhibition of responses to phenylephrine and noradrenaline giving pK_b values of 8.49 ± 0.18 and 8.23 ± 0.14, respectively. Yohimbine (0.1 μ M ) caused significant competitive inhibition of responses to BHT-920 and noradrenaline with calculated pK_b values of 8.43 ± 0.11 for BHT-920 and 7.43 ± 0.31 for noradrenaline and non-competitive inhibition of responses to UK 14304. 2-[2-methoxy-1,4-benzodioxan-2-yl]-2-imidazoline (RX 821002; 10 n M ) caused competitive inhibition of responses to BHT-920 (pK_b 9.04 ± 0.27) and dopamine (pK_b 8.2 ± 0.2). These data indicate that equine digital veins possess both post-synaptic alpha₁ and alpha₂-adrenoceptors.     

Assessment of histamine, bradykinin, prostaglandins E1 and E2 and carrageenin as vascular permeability agents in the horse

The vascular leakage induced by histamine, bradykinin, serotonin and prostaglandin E1 and E2 was assessed. The test agents were injected intradermally into the shaved thoracic skin of horses and the vascular leakage estimated either semi-quantitatively by recording the diameter of the lesions or by measuring the actual volume of extravasated plasma in microliters using iodine-125-labelled human serum albumin (125I-HSA) as a marker in the blood plasma. Using the latter method, the vascular leakage induced by carrageenin and the effect of coadministered prostaglandins E1 and E2 upon the vascular leakage of both histamine and bradykinin were also investigated. No obvious lesions resulted when serotonin (10(-2) mol/l) was injected but histamine and bradykinin produced circular lesions which increased in diameter for approximately 30 min. The size of the lesions and volume of extravasated plasma was dose dependent. On a molar basis, bradykinin (10(-6) mol/l, 10(-5) mol/l) was more potent than histamine but they were equipotent at 10(-4) mol/l. The size of the lesions induced by carrageenin were independent of their anatomical location on the thorax. Except for the second hour, the hourly volume of vascular leakage increased until the fifth hour when the experiment was concluded. The maximum vascular leakage resulting from the injection of prostaglandin E1 or E2 (1, 10, 100 or 1000 ng) was 7 microliters but when co-administered with bradykinin (10(-6) mol/l), the volume of leaked plasma increased from 29 to 78 microliters. No synergy was observed when either prostaglandin was co-administered with histamine (10(-5) mol/l).     

Prostaglandins F2α and E2 Secretion by Porcine Epithelial and Stromal Endometrial Cells on Different Days of the Oestrous Cycle

The endometrial tissue of the uterus plays a key role in reproduction and is a source of hormones and factors responsible for the proper physiological function of reproductive tract during the oestrous cycle and pregnancy. In this study, we investigated the pattern of PGF(2alpha) and PGE(2) secretion from cultured porcine endometrial cells at different days of the oestrous cycle. Epithelial and stromal cells were isolated by differential enzymatic digestion on days 6-8, 10-12 and 14-16. After attachment cells were incubated for 3 and 24 h to estimate PGF(2alpha) and PGE(2) output. The purity of culture was 85-90% for epithelial and 95-98% for stromal cells as determined by immunofluorescent staining. Release of PGF(2alpha) and PGE(2) was affected by cell type, days of the oestrous cycle and the time of incubation. After 3 h of incubation epithelial cells secreted more PGF(2alpha) than PGE(2) during all studied periods of the oestrous cycle (p < 0.01 and p < 0.001, respectively), whereas stromal cells released more PGE(2) (p < 0.01) on days 10-12 and 14-16. Longer incubation of stromal cells revealed that PGF(2alpha) output tended to overcome PGE(2) on days 10-16. The lowest secretion of prostaglandins was observed on days 6-8 in both cell types. The highest secretion of PGF(2alpha) from epithelium was measured on days 10-12 after 24 h of incubation when compared with other days studied (p < 0.001). In stromal cells, PGE(2) output increased on consecutive days studied (p < 0.001) after 3 h of incubation. The differential properties of endometrial cell types seem to play an important role in the profile of PGF(2alpha) and PGE(2) release before and during luteolysis. Described endometrial cells culture might serve as the model for further studies on the hormonal regulation of prostaglandin production in the pig.     

Effects of 8-epi-PGF2α on isolated bronchial smooth muscle of healthy and heaves-affected horses

8-Epi-PGF2alpha, a prostaglandin-like compound generated by oxidative stress, has been shown to be an in vitro bronchoconstrictor in airways from healthy laboratory animals and healthy humans, but it has never been studied in diseased airways. Here, the bronchoconstrictive capacity of 8-epi-PGF2alpha on isolated bronchial rings (BR) of healthy and heaves-affected horses was evaluated by comparing the maximal effect and the potency of 8-epi-PGF2alpha to those of (1) acetylcholine (ACh), (2) its stereoisomer PGF2alpha and (3) its synthetic receptor agonist, U46619. Furthermore, the potential capacity of 8-epi-PGF2alpha to enhance the cholinergic (ACh) responsiveness of bronchial smooth muscle was investigated. 8-Epi-PGF2alpha contracted BR with a rank order of efficacy of Ach > U44619 > PGF2alpha > 8-epi-PGF2alpha in both healthy and heaves-affected horses. The contractile maximal response elicited by 8-epi-PGF2alpha was significantly smaller than that elicited by the other drugs, but was significantly higher in BR from heaves-affected horses than in those sampled in healthy horses, whilst pD2 values were similar. A subthreshold concentration of 8-epi-PGF2alpha (10-7 M) did not induce in vitro cholinergic hyper-responsiveness in BR of either healthy or heaves-affected horses. In conclusion, it has been demonstrated that 8-epi-PGF2alpha is an in vitro bronchoconstrictor of minor importance in healthy horses, but whose efficacy is significantly increased in heaves-affected horses.     

Role of Tumour Necrosis Factor α in Stimulation of Prostaglandins F2α and E2 Release by Cultured Porcine Endometrial Cells

The present studies were undertaken to examine the effect of tumour necrosis factor (TNF) alpha on prostaglandins (PGs) F(2alpha) and E(2) release by cultured porcine endometrial cells harvested on days 13-16 after oestrus in comparison to stimulation with oxytocin (OT) and luteinizing hormone (LH). A time-dependent effect of TNFalpha (10 ng/ml) on PGF(2alpha) release was observed in stromal and luminal epithelial cells. Moreover, TNFalpha increased PGF(2alpha) secretion from both endometrial cell types with effective concentrations of 1 (p < 0.05), 10 and 50 ng/ml (p < 0.01). The effect of TNFalpha (10 ng/ml) on endometrial PGF(2alpha) and PGE(2) release was compared with OT (100 nmol/l) and LH (100 ng/ml). All factors affected PGF(2alpha) secretion from stromal cells, however, the stimulation tended to be more potent after OT and LH (p < 0.01) than after TNFalpha (p < 0.05) treatment. In epithelial cells, only TNFalpha was able to stimulate PGF(2alpha) release (p < 0.001). PGE(2) secretion from stromal cells increased after incubation with TNFalpha and OT (p < 0.05). Only LH stimulated PGE(2) release from epithelium (p < 0.001), and its action was very effective when compared with TNFalpha or OT (p < 0.01). Summarizing, TNFalpha induces both PGs secretion from cultured porcine endometrium, but preferentially stimulates PGF(2alpha) release from luminal epithelial cells. Therefore, similarly to OT and LH, TNFalpha may be considered as a potential modulator of endometrial PGF(2alpha) production during luteolysis in the pig.     

The effect of xylazine on plasma thromboxane B2 concentration in sheep

α₂-adrenoceptor agonist drugs can cause respiratory changes leading to a short period of hypoxaemia in sheep. It has been suggested that this is due to transient platelet aggregation and pulmonary microembolism. If platelet aggregation were to follow platelet activation in response to the administration of α₂ agonists, plasma thromboxane levels would be expected to rise. This study was carried out to measure plasma thromboxane B₂ concentrations before and after the intravenous administration of the α₂-agonist drug xylazine at a dose of 0.1 mg/kg. It was found that the plasma thromboxane concentration rose by 320% and, furthermore, the rise was prevented by the prior administration of atipamezole hydrochloride (0.125 mg/kg), an α₂-adrenoceptor antagonist.     

The role of thromboxane A2 in regulating porcine basilar arterial tone

The aim of the present study was to clarify the participation of endogenous arachidonic acid (AA) metabolites in regulating porcine basilar, coronary, pulmonary and mesenteric arterial tones in vitro . A cyclooxygenase inhibitor, indomethacin, relaxed basilar artery but not other arteries examined. Quinacrine (a phospholipase A₂ inhibitor), OKY-046 (a thromboxane (TX) A₂ synthetase inhibitor) and ONO-3708 (a TXA₂/prostaglandin H₂ receptor antagonist) produced relaxation in basilar arteries with intact endothelium. Nordihydroguaiaretic acid (a lipoxygenase inhibitor) had no effect on the tone. The amount of TXB₂ (a stable metabolite of TXA₂) spontaneously released from porcine basilar arteries was 6–10 fold more than those from other arteries. Indomethacin and OKY-046 mostly inhibited the production of TXB₂. Endothelial denudation decreased indomethacin-induced relaxation and the amount of TXB₂. These results suggest that a vasoconstricting substance(s) is released from endothelial cells and possibly smooth muscle cells in porcine basilar arteries in vitro . The main constricting substance is proposed to be TXA₂. On the other hand, several arteries from peripheral vascular beds did not release this vasoconstricting substance.