Effects of vatinoxan on cardiorespiratory function, fecal output and plasma drug concentrations in horses anesthetized with isoflurane and infusion of medetomidine.

A constant rate infusion (CRI) of medetomidine is used to balance equine inhalation anesthesia, but its cardiovascular side effects are a concern. This experimental crossover study aimed to evaluate the effects of vatinoxan (a peripheral α2-adrenoceptor antagonist) on cardiorespiratory and gastrointestinal function in anesthetized healthy horses. Six horses received medetomidine hydrochloride 7µg/kg IV alone (MED) or with vatinoxan hydrochloride 140µg/kg IV (MED+V). Anesthesia was induced with midazolam and ketamine and maintained with isoflurane and medetomidine CRI for 60min. Heart rate, carotid and pulmonary arterial pressures, central venous pressure, cardiac output and arterial and mixed venous blood gases were measured. Selected cardiopulmonary parameters were calculated. Plasma drug concentrations were determined. Fecal output was measured over 24h. For statistical comparisons, repeated measures analysis of covariance and paired t-tests were applied. Heart rate decreased slightly from baseline in the MED group. Arterial blood pressures decreased with both treatments, but significantly more dobutamine was needed to maintain normotension with MED+V (P=0.018). Cardiac index (CI) and oxygen delivery index (DO2I) decreased significantly more with MED, with the largest difference observed at 20min: CI was 39±2 and 73±18 (P=0.009) and DO2I 7.4±1.2 and 15.3±4.8 (P=0.014)mL/min/kg with MED and MED+V, respectively. Fecal output or plasma concentrations of dexmedetomidine did not differ between the treatments. In conclusion, premedication with vatinoxan induced hypotension, thus its use in anesthetized horses warrants further studies. Even though heart rate and arterial blood pressures remained clinically acceptable with MED, cardiac performance and oxygen delivery were lower than with MED+V.

Effects of general anaesthesia in dorsal recumbency with and without vatinoxan on bronchoalveolar lavage cytology of healthy horses.

Pneumonia is one of the potential complications of general anaesthesia in horses. Anaesthesia is known to increase neutrophils in bronchoalveolar lavage fluid (BALF) of horses after lateral recumbency, but studies after dorsal recumbency are lacking. Our primary aim was to determine when lung inflammation reaches its maximum and how rapidly BALF cytology returns to baseline after anaesthesia in dorsal recumbency. A secondary aim was to investigate the possible effect of vatinoxan, a novel drug, on the BALF cytology results. Six healthy experimental horses were enrolled in this observational crossover study. The horses were subject to repeated BALF and blood sampling for 7 days after general anaesthesia with two treatment protocols, and without anaesthesia (control). During the two treatments, the horses received either medetomidine-vatinoxan or medetomidine-placebo as premedication, and anaesthesia was induced with ketamine-midazolam and maintained with isoflurane for 1h in dorsal recumbency. The differences in BALF and blood variables between the two anaesthesia protocols and control were analysed with repeated measures analysis of variance models. In this study, anaesthesia in dorsal recumbency resulted in no clinically relevant changes in airway cytology that could be differentiated from the effect of repeated BALF sampling. No differences in BALF matrix metalloproteinase gelatinolytic activity could be detected between the two treatments or the control series. Marked increase in serum amyloid A was detected in some animals. Vatinoxan as premedication did not consistently affect lung cytology or blood inflammatory markers after anaesthesia.

Effects of vatinoxan on cardiorespiratory function and gastrointestinal motility during constant-rate medetomidine infusion in standing horses.

BACKGROUND: Medetomidine suppresses cardiovascular function and reduces gastrointestinal motility in horses mainly through peripheral α2 -adrenoceptors. Vatinoxan, a peripheral α2 -antagonist, has been shown experimentally to alleviate the adverse effects of some α2 -agonists in horses. However, vatinoxan has not been investigated during constant-rate infusion (CRI) of medetomidine in standing horses. OBJECTIVES: To evaluate effects of vatinoxan on cardiovascular function, gastrointestinal motility and on sedation level during CRI of medetomidine. STUDY DESIGN: Experimental, randomised, blinded, cross-over study. METHODS: Six healthy horses were given medetomidine hydrochloride, 7 µg/kg i.v., without (MED) and with (MED+V) vatinoxan hydrochloride, 140 µg/kg i.v., followed by CRI of medetomidine at 3.5 µg/kg/h for 60 min. Cardiorespiratory variables were recorded and borborygmi and sedation levels were scored for 120 min. Plasma drug concentrations were measured. The data were analysed using repeated measures ANCOVA and paired t-tests as appropriate. RESULTS: Initially heart rate (HR) was significantly lower and mean arterial blood pressure (MAP) significantly higher with MED compared with MED+V. For example at 10 min HR (mean ± s.d.) was 26 ± 2 and 31 ± 5 beats/minute (P = 0.04) and MAP 129 ± 15 and 103 ± 13 mmHg (P<0.001) respectively. At 10 min, cardiac index was lower (P = 0.02) and systemic vascular resistance higher (P = 0.001) with MED than with MED+V. Borborygmi were reduced after MED; this effect was attenuated by vatinoxan (P<0.001). All horses were sedated with medetomidine, but the mean sedation scores were reduced with MED+V until 20 min (6.8 ± 0.8 and 4.5 ± 1.5 with MED and MED+V, respectively, at 10 min, P = 0.001). Plasma concentration of dexmedetomidine was significantly lower in the presence of vatinoxan (P = 0.01). MAIN LIMITATIONS: Experimental study with healthy, unstimulated animals. CONCLUSIONS: Vatinoxan administered i.v. with a loading dose of medetomidine improved cardiovascular function and gastrointestinal motility during medetomidine CRI in healthy horses. Sedation was slightly yet significantly reduced during the first 20 min.. The Summary is available in Portuguese - see Supporting Information.

Histological findings in equine testes one year after standing laparoscopic peritoneal flap hernioplasty.

In order to know reproduction-related complications due to standing laparoscopic peritoneal flap hernioplasty, histological characteristics of the testicles from five stallions one year after surgery were compared with seven testicles from four healthy stallions. Moreover, the daily sperm output (DSO) was determined before (T0) and one year after surgery (T12). DSO did not show significant differences between T0 and T12. The diameter of the seminiferous tubules was significantly decreased in the samples from the hernioplasty group. The percentage of tubules with full spermatogenesis was smaller in the hernioplasty group, but the difference was not significant. It can be concluded that standing laparoscopic peritoneal flap hernioplasty produced mild histological changes in the testicular parenchyma, epididymis and pampiniform plexus after one year follow-up.

Standing laparoscopic peritoneal flap hernioplasty of the vaginal rings does not modify the sperm production and motility characteristics in intact male horses.

Laparoscopic hernioplasty techniques have been developed in the recent years to avoid the recurrence of inguinal hernias and to spare the testicles for breeding purposes in stallions. However, there have been no previous comprehensive and systematic studies of the reproductive outcomes and prognoses for stallions after inguinal hernioplasty. Therefore, the objective of this study was to assess the possible effects of one of these techniques (standing laparoscopic peritoneal flap hernioplasty) on the sperm production and motility characteristics of six healthy stallions that received this procedure based on 1-year follow-ups. There were no significant differences in the measured sperm variables (assessments based on the DSO, MOT, PMOT, VSL, VCL and VAP) during 1-year follow-ups.

Do ergonomically designed school workstations decrease musculoskeletal symptoms in children? A 26-month prospective follow-up study.

Workstations at school are among several factors that contribute to musculoskeletal symptoms among school-aged children. The aim of this study was to investigate the effects of ergonomically designed workstations on schoolchildren's musculoskeletal symptoms as compared to conventional workstations. In the first 14-month phase of the study (2002-2003, two schools), 42 from the intervention and 46 from the control school participated. In the total follow-up of 26 months (2002-2004), 23 in the intervention group and 20 in the control group participated. Anthropometrics and musculoskeletal symptoms were measured. In general, the ergonomically designed school workstations did not decrease present neck-shoulder, upper back, low back and lower limbs strain and pain, compared to conventional ones during follow-ups.