Dominique Gauvin - Academia.edu (original) (raw)

Papers by Dominique Gauvin

Research paper thumbnail of Soins de support peranesthésiques

Research paper thumbnail of Postoperative Cognitive Dysfunction After Cardiac Surgery

Chest Journal, Nov 1, 2005

Research paper thumbnail of Effect of a diet enriched with green-lipped mussel on pain behavior and functioning in dogs with clinical osteoarthritis

Canadian Journal of Veterinary Research Revue Canadienne De Recherche Veterinaire, 2013

This study aimed to establish the effect of a diet enriched with green-lipped mussel (GLM) on pai... more This study aimed to establish the effect of a diet enriched with green-lipped mussel (GLM) on pain and functional outcomes in osteoarthritic dogs. Twenty-three client-owned dogs with osteoarthritis (OA) were fed a balanced control diet for 30 d and then a GLM-enriched balanced diet for the next 60 d. We assessed peak vertical force (PVF), which is considered to be the gold standard method, at Day (D)0 (start), D30 (end of control diet), and D90 (end of GLM-enriched diet). The owners completed a client-specific outcome measure (CSOM), which is a pain questionnaire, once a week. Motor activity (MA) was continuously recorded in 7 dogs for 12 wk. Concentrations of plasma omega-3 fatty acids were quantified as indicative of diet change. Statistical analyses were linear-mixed models and multinomial logistic regression for repeated measures. The GLM diet (from D30 to D90) resulted in an increase in concentrations of plasma omega-3 fatty acids (P < 0.016) and improvement of PVF (P = 0.003). From D0 to D30, PVF did not significantly change (P = 0.06), which suggests that the GLM diet had a beneficial effect on gait function. Moreover, PVF (P = 0.0004), CSOM (P = 0.006), and MA (P = 0.02) improved significantly from D0 to D90. In general, the balanced control diet could have contributed to reduced OA symptoms, an effect that was subsequently amplified by the GLM diet.

Research paper thumbnail of A medicinal herb-based natural health product improves the condition of a canine natural osteoarthritis model: a randomized placebo-controlled trial

Research in veterinary science, 2014

An oral herb-based natural health product (NHP) was evaluated in the canine natural osteoarthriti... more An oral herb-based natural health product (NHP) was evaluated in the canine natural osteoarthritis model. At baseline, the peak vertical force (PVF, primary endpoint) and case-specific outcome measure of disability (CSOM) were recorded in privately-owned dogs. Dogs (16/group) were randomized to receive NHP formulations or a negative control. The PVF was measured at week (W) 4 and W8. Daily locomotor activity was recorded using accelerometer. The CSOMs were assessed bi-weekly by the owner. The NHP-treated dogs (n = 13) had higher PVF at W4 (p = 0.020) and W8 (p <0.001) when compared to baseline. The changes at W8 were higher than control dogs (n = 14, p <0.027) and consistent with Cohen's d effect size of 0.7 (95% confidence interval: 0.0-1.5). The NHP-treated dogs had higher locomotor activity at W8 (p = 0.025) when compared to baseline. No significant change was observed for the CSOM. The NHP improved the clinical signs of osteoarthritis in this model.

Research paper thumbnail of Evidence for non-linear pharmacokinetics of oxytocin in anesthetizetized rat

Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Société canadienne des sciences pharmaceutiques, 2008

Because oxytocin (OT) is potentially useful in cardiovascular therapy but has hormonal roles on t... more Because oxytocin (OT) is potentially useful in cardiovascular therapy but has hormonal roles on the cardiovascular and renal systems, we characterized its pharmacokinetic (PK) properties as a function of dose. A single intravenous bolus of OT was given at doses of 200, 300, 500, 1000, 3000, 5000 and 10000 ng/kg to anesthetized male rats (n >= 4 per dose). Blood samples (6) were taken over 72 min to 150 min, depending on dose. The individual time-courses of plasma OT concentrations were analyzed with a one- or an open two-compartment PK model. Kruskal-Wallis tests (alpha=0.05) were used to compare the PK parameters among groups. At doses up to 500 ng/kg, OT showed a higher median systemic clearance (CLT = 0.0624 L/(min*kg); 0.0622 +/- 0.0228 as mean +/- SD value), a higher median central compartment volume of distribution (VC = 0.7906 L/kg; 0.6961 +/- 0.1754), and a lower median elimination half life (t(1/2)(lambdaz) 7.94 min; 9.08 +/- 4.3) with respect to the higher doses (CLT = ...

Research paper thumbnail of Association between sensitisation and pain-related behaviours in an experimental canine model of osteoarthritis

Pain, 2014

Evaluation of nociceptive sensitisation in canine osteoarthritis studies has been poorly reported... more Evaluation of nociceptive sensitisation in canine osteoarthritis studies has been poorly reported, or even related to other clinical symptoms. In 16 dogs, peak vertical force (PVF), subjective pain assessment using 3 scales, sympathetic stress response with electrodermal activity (EDA) measurement, and behavioural changes with video analysis and telemetered motor activity were quantified at baseline (D-7), and 28 and 56 days post transection of the cranial cruciate ligament. As markers of central sensitisation, selected spinal cord biomarkers (substance P and transthyretin) were quantified at D56. Electrical withdrawal thresholds on the stifle and the tail were measured as indicative of peripheral and central quantitative sensory testing (QST) sensitisation, respectively. The effects of vehicle administration (n=8) were compared with tiludronate (2mg/kg subcutaneously, q2 week, starting at D0) administration. Generalized estimated equations tested the association between the behavioural and physiological methods and QST sensitisation, and therefore the sensitivity of the methods for detecting treatment efficacy. Compared to tiludronate, at D56, vehicle-treated dogs had increased spinal substance P (P=0.01), concomitant decreased transthyretin (P=0.02), and (compared to baseline) demonstrated peripheral and central QST sensitisation, which was not present for tiludronate. Only PVF, the spontaneous behaviour &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;walking with full weight-bearing,&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; and EDA were associated with occurrence of QST sensitisation and indicated significant tiludronate analgesic efficacy after inclusion of central QST sensitisation as a predictor variable in the statistical model. This study establishes the strong interest to implement QST as a predictor of canine osteoarthritis pain symptoms explained by pain sensitisation.

Research paper thumbnail of Respiratory safety pharmacology: Positive control drug responses in Sprague–Dawley rats, Beagle dogs and cynomolgus monkeys

Regulatory Toxicology and Pharmacology, 2009

Rats are most frequently used to fulfill ICH S7A requirements for respiratory safety pharmacology... more Rats are most frequently used to fulfill ICH S7A requirements for respiratory safety pharmacology. We hypothesized that the models used to assess respiratory safety pharmacology present different ventilatory responses to bronchoconstriction, bronchodilation and respiratory depression. Respiratory monitoring was performed with head-out plethysmographs for rats, masks for dogs and bias airflow helmets for monkeys. Respiratory rate (RR), tidal volume (TV) and minute volume (MV) were recorded. Forty rats, 18 dogs and 8 monkeys were acclimated to the respiratory monitoring equipment. Animals received saline (IV), albuterol (inhalation), methacholine (IV) and remifentanil (IV). Albuterol increased TV in all species. Methacholine decreased TV and MV in monkeys. In dogs, methacholine increased TV, RR and MV. In rats, methacholine increased TV and decreased RR. Remifentanil induced central respiratory depression in all species with decreased MV, except in rats. Dogs presented a biphasic response to remifentanil with hypoventilation followed by delayed hyperventilation. The monkeys presented similar responses to humans which may be due to biologic similarities. Dogs and rats presented clinically significant ventilatory alterations following positive control drugs. Although, the response to bronchoconstriction in dogs and rats was different from humans, the two species presented ventilatory changes that highlight the potential adverse effect of test articles.

Research paper thumbnail of Measurements of canine aqueous humor inflammatory mediators and the effect of carprofen following anterior chamber paracentesis

Veterinary Ophthalmology, 2011

Phase I: To evaluate levels of prostaglandin E(2) (PGE(2) ), nitrites and nitrates (NO(x) ), tumo... more Phase I: To evaluate levels of prostaglandin E(2) (PGE(2) ), nitrites and nitrates (NO(x) ), tumor necrosis factor-alpha (TNF-α) and expression of inducible cyclo-oxygenase (COX-2), nitric oxide synthase (NOS-2), and matrix metalloproteinases (MMP-3 and -9) in canine aqueous humor following repeated anterior chamber paracenteses (ACP). Phase II: to evaluate the effect of carprofen on PGE(2) , NO(x) , and TNF-α in canine aqueous humor following ACP. Four beagles in phase I and 8 beagles in phase II. Phase I: ACP was performed at time (T) 0, 4 and 8 h. Phase II: A randomized, placebo-controlled cross-over design with four dogs per group where carprofen was given 4.4 mg/kg/day on day (D) 1, 2 and 3. ACP was performed at T0 and T1.5 on D3. Statistical analysis was performed with repeated measures anova and post hoc Tukey-Kramer multiple-comparison procedure. In phase II, TNF-α level was analyzed with a Wilcoxon signed-rank test. Phase I: PGE(2) significantly increased (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001) to plateau at T4. NO(X) was decreased at T4 (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.06), but increased at T8 (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001). COX-2 showed detectable expression only at T8. TNF-α, NOS-2, MMP-3 and -9 were undetectable at all time points. Phase II: At T1.5, PGE(2) was significantly elevated in both groups but was lower in the carprofen group (P = 0.037). NO(x) and TNF-α did not statistically increase in either group. Following ACP, significant increases in PGE(2) levels confirmed inflammation characterized by a rise of COX-2. The NO(x) pathway took longer to induce as compared with PGE(2) . Carprofen decreased PGE(2) levels and could help control intraocular inflammation.

Research paper thumbnail of Nitric oxide, cell signaling and cell death

Research paper thumbnail of Respiratory safety pharmacology: Concurrent validation of volume, rate, time, flow and ratio variables in conscious male Sprague–Dawley rats

Regulatory Toxicology and Pharmacology, 2010

This study compares basic respiratory variables (rate, tidal and minute volumes) with time-, flow... more This study compares basic respiratory variables (rate, tidal and minute volumes) with time-, flow- and ratio-derived parameters obtained using head-out plethysmography in rats following administration of reference drugs (isotonic saline, 2.0 mL/kg, IV; albuterol, 400 μg/kg, inhalation; methacholine, 136 μg/kg, IV; and remifentanil, 14 μg/kg, IV) to identify respiratory variables with superior sensitivity. Paired t-tests by block-period, and analysis of covariance (ANCOVA) with baseline as covariate and a posteriori pair-wise comparisons using Dunnett&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s test were used. Variations in respiratory parameters observed over time justify the use of a control group in any respiratory safety pharmacology study for inter-groups comparison. Handling-, and slumbering-, induced perturbations were minimal. The system was sensitive and specific to detect changes in respiratory variables related to pharmacologically-induced bronchodilation, bronchoconstriction and central respiratory depression. The standard variables (respiratory rate, tidal and minute volumes) confirmed to be the cornerstone of respiratory safety pharmacology to detect pharmacological changes. Flow-derived parameters appeared as highly valuable complement for interpretation of respiratory response, whereas time- and ratio-derived parameters presented limited added value during interpretation.

Research paper thumbnail of 004 Tiludronate in an Experimental Dog Model of Osteoarthritis: Bone Anti-Resorptive Activity and Related Functional Improvement

Osteoarthritis and Cartilage, 2009

Research paper thumbnail of 138 Functional Outcomes in Dogs With Naturally Occurring Osteoarthritis: Force Platform Gait Analysis and Locomotor Activity Recording

Osteoarthritis and Cartilage, 2009

Research paper thumbnail of 033 Effects of Feeding a High OMEGA-3 Fatty Acid Diet on the Pain-Related Disability in Dogs With Naturally Occurring Osteoarthritis

Osteoarthritis and Cartilage, 2010

Research paper thumbnail of 039 Validity of Pain Assessment Methods in the Experimental Dog Pond-Nuki Model

Osteoarthritis and Cartilage, 2009

Research paper thumbnail of 477 Validation of Clinical Pain Assessment Methods With Canine Osteoarthritis

Osteoarthritis and Cartilage, 2009

Research paper thumbnail of Pre-emptive and continuous inhaled NO counteracts the cardiopulmonary consequences of extracorporeal circulation in a pig model

Nitric Oxide, 2006

Cardiopulmonary bypass (CPB) activates a systemic inflammatory response characterized clinically ... more Cardiopulmonary bypass (CPB) activates a systemic inflammatory response characterized clinically by alterations in cardiovascular and pulmonary function. The aim of this study was to measure the cardiopulmonary consequences in sham-operated pigs, and in animals subjected to CPB in the presence or absence of lipopolysaccharide (LPS). We also investigated, if the perioperative administration of inhaled NO exerts significant cardiopulmonary effects in an anaesthetized and mechanically ventilated pig model of extracorporeal circulation. Thirty pigs were randomized into six equal groups (sham; sham+INO; CPB; CPB+INO; CPB+LPS; CPB+LPS+INO) and subjected to anaesthesia with mechanical ventilation for up to 24h. We found that CPB+LPS group has the highest degree of lung injury. We also demonstrated that there was a significant difference on the cardiovascular parameters (heart rate, central venous pressure, stroke volume index, and mean systemic arterial blood pressure) between the CPB groups and the sham groups. The deteriorated lung mechanics was associated with a decrease in active subfraction of surfactant (LA) with time during the procedure (P=0.0003), on which inhaled NO had only an initial beneficial effect. In our model, inhaled NO had no long-term beneficial effect on lung mechanics and surfactant homeostasis despite improving lung haemodynamics, inflammation, and oxygenation. We conclude from this study that the use of pre-emptive and continuous inhaled NO therapy has protective and safe effects against lung ischemia/reperfusion associated with CPB.

Research paper thumbnail of Pain Induced by a Minor Medical Procedure (Bone Marrow Aspiration) in Dogs: Comparison of Pain Scales in a Pilot Study

Journal of Veterinary Internal Medicine, 2011

Bone marrow aspiration (BMA) is a clinical procedure frequently performed in dogs. To compare lev... more Bone marrow aspiration (BMA) is a clinical procedure frequently performed in dogs. To compare levels of pain intensity induced by 3 different BMA procedures using several pain scoring instruments. Sixteen healthy Beagles. A prospective experimental pilot study was conducted using blinded observers. Dogs were randomized into 3 groups: iliac BMA under sedation (Iliac-Sed, n = 4), sternum BMA under sedation (Stern-Sed, n = 4), and sternum BMA on conscious dogs without sedation (Stern-No-Sed, n = 8). Using the SF-Glasgow pain scale, the overall pain score in the Stern-No-Sed group was lower than that in the Stern-Sed group (P = 0.04). Using the 4A-VET pain scale, the effects of procedures over time on pain scores did not differ between and within groups. An inactivity index indicated that the overall score for the Stern-No-Sed group was significantly lower than the scores for the Stern-Sed and Iliac-Sed groups (P ≤ 0.01). There was a significant association in pain assessment using the SF-Glasgow and 4A-VET pain scales (P = 0.0004). When comparing the SF-Glasgowscale to the 4A-VET pain scale, the scores for the Stern-No-Sed group were lower compared to those of the Stern-Sed scores (P = 0.03). Based on telemetered motor activity, the Iliac-Sed group may have experienced more discomfort during the post-procedural period. Dogs may experience mild to moderate pain after BMA procedures, and the sternal site should be preferred. The SF-Glasgow pain scale showed better interobserver reliability, but the 4A-VET scale was less biased by sedation.

Research paper thumbnail of Physiologic responses and pain-related behaviors in beagle dogs undergoing trochleoplasty surgery

Journal of Veterinary Behavior: Clinical Applications and Research, 2010

Research paper thumbnail of Validity of pain assessment methods in an experimental dog model

Journal of Veterinary Behavior: Clinical Applications and Research, 2010

Research paper thumbnail of Validation of pain assessment methods with clinical canine osteoarthritis

Journal of Veterinary Behavior: Clinical Applications and Research, 2010

Research paper thumbnail of Soins de support peranesthésiques

Research paper thumbnail of Postoperative Cognitive Dysfunction After Cardiac Surgery

Chest Journal, Nov 1, 2005

Research paper thumbnail of Effect of a diet enriched with green-lipped mussel on pain behavior and functioning in dogs with clinical osteoarthritis

Canadian Journal of Veterinary Research Revue Canadienne De Recherche Veterinaire, 2013

This study aimed to establish the effect of a diet enriched with green-lipped mussel (GLM) on pai... more This study aimed to establish the effect of a diet enriched with green-lipped mussel (GLM) on pain and functional outcomes in osteoarthritic dogs. Twenty-three client-owned dogs with osteoarthritis (OA) were fed a balanced control diet for 30 d and then a GLM-enriched balanced diet for the next 60 d. We assessed peak vertical force (PVF), which is considered to be the gold standard method, at Day (D)0 (start), D30 (end of control diet), and D90 (end of GLM-enriched diet). The owners completed a client-specific outcome measure (CSOM), which is a pain questionnaire, once a week. Motor activity (MA) was continuously recorded in 7 dogs for 12 wk. Concentrations of plasma omega-3 fatty acids were quantified as indicative of diet change. Statistical analyses were linear-mixed models and multinomial logistic regression for repeated measures. The GLM diet (from D30 to D90) resulted in an increase in concentrations of plasma omega-3 fatty acids (P < 0.016) and improvement of PVF (P = 0.003). From D0 to D30, PVF did not significantly change (P = 0.06), which suggests that the GLM diet had a beneficial effect on gait function. Moreover, PVF (P = 0.0004), CSOM (P = 0.006), and MA (P = 0.02) improved significantly from D0 to D90. In general, the balanced control diet could have contributed to reduced OA symptoms, an effect that was subsequently amplified by the GLM diet.

Research paper thumbnail of A medicinal herb-based natural health product improves the condition of a canine natural osteoarthritis model: a randomized placebo-controlled trial

Research in veterinary science, 2014

An oral herb-based natural health product (NHP) was evaluated in the canine natural osteoarthriti... more An oral herb-based natural health product (NHP) was evaluated in the canine natural osteoarthritis model. At baseline, the peak vertical force (PVF, primary endpoint) and case-specific outcome measure of disability (CSOM) were recorded in privately-owned dogs. Dogs (16/group) were randomized to receive NHP formulations or a negative control. The PVF was measured at week (W) 4 and W8. Daily locomotor activity was recorded using accelerometer. The CSOMs were assessed bi-weekly by the owner. The NHP-treated dogs (n = 13) had higher PVF at W4 (p = 0.020) and W8 (p <0.001) when compared to baseline. The changes at W8 were higher than control dogs (n = 14, p <0.027) and consistent with Cohen's d effect size of 0.7 (95% confidence interval: 0.0-1.5). The NHP-treated dogs had higher locomotor activity at W8 (p = 0.025) when compared to baseline. No significant change was observed for the CSOM. The NHP improved the clinical signs of osteoarthritis in this model.

Research paper thumbnail of Evidence for non-linear pharmacokinetics of oxytocin in anesthetizetized rat

Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Société canadienne des sciences pharmaceutiques, 2008

Because oxytocin (OT) is potentially useful in cardiovascular therapy but has hormonal roles on t... more Because oxytocin (OT) is potentially useful in cardiovascular therapy but has hormonal roles on the cardiovascular and renal systems, we characterized its pharmacokinetic (PK) properties as a function of dose. A single intravenous bolus of OT was given at doses of 200, 300, 500, 1000, 3000, 5000 and 10000 ng/kg to anesthetized male rats (n >= 4 per dose). Blood samples (6) were taken over 72 min to 150 min, depending on dose. The individual time-courses of plasma OT concentrations were analyzed with a one- or an open two-compartment PK model. Kruskal-Wallis tests (alpha=0.05) were used to compare the PK parameters among groups. At doses up to 500 ng/kg, OT showed a higher median systemic clearance (CLT = 0.0624 L/(min*kg); 0.0622 +/- 0.0228 as mean +/- SD value), a higher median central compartment volume of distribution (VC = 0.7906 L/kg; 0.6961 +/- 0.1754), and a lower median elimination half life (t(1/2)(lambdaz) 7.94 min; 9.08 +/- 4.3) with respect to the higher doses (CLT = ...

Research paper thumbnail of Association between sensitisation and pain-related behaviours in an experimental canine model of osteoarthritis

Pain, 2014

Evaluation of nociceptive sensitisation in canine osteoarthritis studies has been poorly reported... more Evaluation of nociceptive sensitisation in canine osteoarthritis studies has been poorly reported, or even related to other clinical symptoms. In 16 dogs, peak vertical force (PVF), subjective pain assessment using 3 scales, sympathetic stress response with electrodermal activity (EDA) measurement, and behavioural changes with video analysis and telemetered motor activity were quantified at baseline (D-7), and 28 and 56 days post transection of the cranial cruciate ligament. As markers of central sensitisation, selected spinal cord biomarkers (substance P and transthyretin) were quantified at D56. Electrical withdrawal thresholds on the stifle and the tail were measured as indicative of peripheral and central quantitative sensory testing (QST) sensitisation, respectively. The effects of vehicle administration (n=8) were compared with tiludronate (2mg/kg subcutaneously, q2 week, starting at D0) administration. Generalized estimated equations tested the association between the behavioural and physiological methods and QST sensitisation, and therefore the sensitivity of the methods for detecting treatment efficacy. Compared to tiludronate, at D56, vehicle-treated dogs had increased spinal substance P (P=0.01), concomitant decreased transthyretin (P=0.02), and (compared to baseline) demonstrated peripheral and central QST sensitisation, which was not present for tiludronate. Only PVF, the spontaneous behaviour &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;walking with full weight-bearing,&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; and EDA were associated with occurrence of QST sensitisation and indicated significant tiludronate analgesic efficacy after inclusion of central QST sensitisation as a predictor variable in the statistical model. This study establishes the strong interest to implement QST as a predictor of canine osteoarthritis pain symptoms explained by pain sensitisation.

Research paper thumbnail of Respiratory safety pharmacology: Positive control drug responses in Sprague–Dawley rats, Beagle dogs and cynomolgus monkeys

Regulatory Toxicology and Pharmacology, 2009

Rats are most frequently used to fulfill ICH S7A requirements for respiratory safety pharmacology... more Rats are most frequently used to fulfill ICH S7A requirements for respiratory safety pharmacology. We hypothesized that the models used to assess respiratory safety pharmacology present different ventilatory responses to bronchoconstriction, bronchodilation and respiratory depression. Respiratory monitoring was performed with head-out plethysmographs for rats, masks for dogs and bias airflow helmets for monkeys. Respiratory rate (RR), tidal volume (TV) and minute volume (MV) were recorded. Forty rats, 18 dogs and 8 monkeys were acclimated to the respiratory monitoring equipment. Animals received saline (IV), albuterol (inhalation), methacholine (IV) and remifentanil (IV). Albuterol increased TV in all species. Methacholine decreased TV and MV in monkeys. In dogs, methacholine increased TV, RR and MV. In rats, methacholine increased TV and decreased RR. Remifentanil induced central respiratory depression in all species with decreased MV, except in rats. Dogs presented a biphasic response to remifentanil with hypoventilation followed by delayed hyperventilation. The monkeys presented similar responses to humans which may be due to biologic similarities. Dogs and rats presented clinically significant ventilatory alterations following positive control drugs. Although, the response to bronchoconstriction in dogs and rats was different from humans, the two species presented ventilatory changes that highlight the potential adverse effect of test articles.

Research paper thumbnail of Measurements of canine aqueous humor inflammatory mediators and the effect of carprofen following anterior chamber paracentesis

Veterinary Ophthalmology, 2011

Phase I: To evaluate levels of prostaglandin E(2) (PGE(2) ), nitrites and nitrates (NO(x) ), tumo... more Phase I: To evaluate levels of prostaglandin E(2) (PGE(2) ), nitrites and nitrates (NO(x) ), tumor necrosis factor-alpha (TNF-α) and expression of inducible cyclo-oxygenase (COX-2), nitric oxide synthase (NOS-2), and matrix metalloproteinases (MMP-3 and -9) in canine aqueous humor following repeated anterior chamber paracenteses (ACP). Phase II: to evaluate the effect of carprofen on PGE(2) , NO(x) , and TNF-α in canine aqueous humor following ACP. Four beagles in phase I and 8 beagles in phase II. Phase I: ACP was performed at time (T) 0, 4 and 8 h. Phase II: A randomized, placebo-controlled cross-over design with four dogs per group where carprofen was given 4.4 mg/kg/day on day (D) 1, 2 and 3. ACP was performed at T0 and T1.5 on D3. Statistical analysis was performed with repeated measures anova and post hoc Tukey-Kramer multiple-comparison procedure. In phase II, TNF-α level was analyzed with a Wilcoxon signed-rank test. Phase I: PGE(2) significantly increased (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001) to plateau at T4. NO(X) was decreased at T4 (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.06), but increased at T8 (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001). COX-2 showed detectable expression only at T8. TNF-α, NOS-2, MMP-3 and -9 were undetectable at all time points. Phase II: At T1.5, PGE(2) was significantly elevated in both groups but was lower in the carprofen group (P = 0.037). NO(x) and TNF-α did not statistically increase in either group. Following ACP, significant increases in PGE(2) levels confirmed inflammation characterized by a rise of COX-2. The NO(x) pathway took longer to induce as compared with PGE(2) . Carprofen decreased PGE(2) levels and could help control intraocular inflammation.

Research paper thumbnail of Nitric oxide, cell signaling and cell death

Research paper thumbnail of Respiratory safety pharmacology: Concurrent validation of volume, rate, time, flow and ratio variables in conscious male Sprague–Dawley rats

Regulatory Toxicology and Pharmacology, 2010

This study compares basic respiratory variables (rate, tidal and minute volumes) with time-, flow... more This study compares basic respiratory variables (rate, tidal and minute volumes) with time-, flow- and ratio-derived parameters obtained using head-out plethysmography in rats following administration of reference drugs (isotonic saline, 2.0 mL/kg, IV; albuterol, 400 μg/kg, inhalation; methacholine, 136 μg/kg, IV; and remifentanil, 14 μg/kg, IV) to identify respiratory variables with superior sensitivity. Paired t-tests by block-period, and analysis of covariance (ANCOVA) with baseline as covariate and a posteriori pair-wise comparisons using Dunnett&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s test were used. Variations in respiratory parameters observed over time justify the use of a control group in any respiratory safety pharmacology study for inter-groups comparison. Handling-, and slumbering-, induced perturbations were minimal. The system was sensitive and specific to detect changes in respiratory variables related to pharmacologically-induced bronchodilation, bronchoconstriction and central respiratory depression. The standard variables (respiratory rate, tidal and minute volumes) confirmed to be the cornerstone of respiratory safety pharmacology to detect pharmacological changes. Flow-derived parameters appeared as highly valuable complement for interpretation of respiratory response, whereas time- and ratio-derived parameters presented limited added value during interpretation.

Research paper thumbnail of 004 Tiludronate in an Experimental Dog Model of Osteoarthritis: Bone Anti-Resorptive Activity and Related Functional Improvement

Osteoarthritis and Cartilage, 2009

Research paper thumbnail of 138 Functional Outcomes in Dogs With Naturally Occurring Osteoarthritis: Force Platform Gait Analysis and Locomotor Activity Recording

Osteoarthritis and Cartilage, 2009

Research paper thumbnail of 033 Effects of Feeding a High OMEGA-3 Fatty Acid Diet on the Pain-Related Disability in Dogs With Naturally Occurring Osteoarthritis

Osteoarthritis and Cartilage, 2010

Research paper thumbnail of 039 Validity of Pain Assessment Methods in the Experimental Dog Pond-Nuki Model

Osteoarthritis and Cartilage, 2009

Research paper thumbnail of 477 Validation of Clinical Pain Assessment Methods With Canine Osteoarthritis

Osteoarthritis and Cartilage, 2009

Research paper thumbnail of Pre-emptive and continuous inhaled NO counteracts the cardiopulmonary consequences of extracorporeal circulation in a pig model

Nitric Oxide, 2006

Cardiopulmonary bypass (CPB) activates a systemic inflammatory response characterized clinically ... more Cardiopulmonary bypass (CPB) activates a systemic inflammatory response characterized clinically by alterations in cardiovascular and pulmonary function. The aim of this study was to measure the cardiopulmonary consequences in sham-operated pigs, and in animals subjected to CPB in the presence or absence of lipopolysaccharide (LPS). We also investigated, if the perioperative administration of inhaled NO exerts significant cardiopulmonary effects in an anaesthetized and mechanically ventilated pig model of extracorporeal circulation. Thirty pigs were randomized into six equal groups (sham; sham+INO; CPB; CPB+INO; CPB+LPS; CPB+LPS+INO) and subjected to anaesthesia with mechanical ventilation for up to 24h. We found that CPB+LPS group has the highest degree of lung injury. We also demonstrated that there was a significant difference on the cardiovascular parameters (heart rate, central venous pressure, stroke volume index, and mean systemic arterial blood pressure) between the CPB groups and the sham groups. The deteriorated lung mechanics was associated with a decrease in active subfraction of surfactant (LA) with time during the procedure (P=0.0003), on which inhaled NO had only an initial beneficial effect. In our model, inhaled NO had no long-term beneficial effect on lung mechanics and surfactant homeostasis despite improving lung haemodynamics, inflammation, and oxygenation. We conclude from this study that the use of pre-emptive and continuous inhaled NO therapy has protective and safe effects against lung ischemia/reperfusion associated with CPB.

Research paper thumbnail of Pain Induced by a Minor Medical Procedure (Bone Marrow Aspiration) in Dogs: Comparison of Pain Scales in a Pilot Study

Journal of Veterinary Internal Medicine, 2011

Bone marrow aspiration (BMA) is a clinical procedure frequently performed in dogs. To compare lev... more Bone marrow aspiration (BMA) is a clinical procedure frequently performed in dogs. To compare levels of pain intensity induced by 3 different BMA procedures using several pain scoring instruments. Sixteen healthy Beagles. A prospective experimental pilot study was conducted using blinded observers. Dogs were randomized into 3 groups: iliac BMA under sedation (Iliac-Sed, n = 4), sternum BMA under sedation (Stern-Sed, n = 4), and sternum BMA on conscious dogs without sedation (Stern-No-Sed, n = 8). Using the SF-Glasgow pain scale, the overall pain score in the Stern-No-Sed group was lower than that in the Stern-Sed group (P = 0.04). Using the 4A-VET pain scale, the effects of procedures over time on pain scores did not differ between and within groups. An inactivity index indicated that the overall score for the Stern-No-Sed group was significantly lower than the scores for the Stern-Sed and Iliac-Sed groups (P ≤ 0.01). There was a significant association in pain assessment using the SF-Glasgow and 4A-VET pain scales (P = 0.0004). When comparing the SF-Glasgowscale to the 4A-VET pain scale, the scores for the Stern-No-Sed group were lower compared to those of the Stern-Sed scores (P = 0.03). Based on telemetered motor activity, the Iliac-Sed group may have experienced more discomfort during the post-procedural period. Dogs may experience mild to moderate pain after BMA procedures, and the sternal site should be preferred. The SF-Glasgow pain scale showed better interobserver reliability, but the 4A-VET scale was less biased by sedation.

Research paper thumbnail of Physiologic responses and pain-related behaviors in beagle dogs undergoing trochleoplasty surgery

Journal of Veterinary Behavior: Clinical Applications and Research, 2010

Research paper thumbnail of Validity of pain assessment methods in an experimental dog model

Journal of Veterinary Behavior: Clinical Applications and Research, 2010

Research paper thumbnail of Validation of pain assessment methods with clinical canine osteoarthritis

Journal of Veterinary Behavior: Clinical Applications and Research, 2010