Kanichi Kusano

Characteristic of inflammatory airway disease in Japanese thoroughbred racehorses.

Inflammatory airway disease (IAD) is a common cause of poor performance, interruption of training and premature retirement in racehorses. It is also reported that up to 80% of horses are affected at some point in the first years of training in UK and Australia. However, no studies with regard to the information on occurrence of IAD in Japanese Thoroughbred racehorses have been reported. To investigate the occurrence and the characteristics of IAD, epidemic research including endoscopic examination of the airway tract and trachea wash was conducted for Thoroughbred racehorses presenting coughs or poor performance which airway tract disease was suspected stalled in training facility managed by Japan Racing Association. Fifty-six out of 76 Thoroughbred racehorses (73.7%) presenting coughing or poor performance were diagnosed as IAD. Mean incidence rate of IAD was 0.3% and it has been confirmed that constant number of IAD exists in Japan. Up to 35.7% of IAD horses showed upper airway abnormalities in some extent. There was a trend for IAD horses to use wood shavings for bedding and fed hay from the ground compared with the control group. Therefore, improvement of stabling environment may aid in preventing IAD. This study demonstrated that Japanese Thoroughbred racehorses are affected by IAD likewise other countries as well as demonstrated the characteristics of IAD which may contribute to the clarification of the pathogenesis of IAD.

Tracheal Endoscopic and Cytological Findings and Blood Examination Results in Thoroughbred Racehorses Suspected to have Lower Respiratory Tract Disease.

Cytology of tracheal aspirates, tracheal endoscopic and blood tests were carried out to 86 Thoroughbred racehorses presenting coughs or poor performance which were suspected to have lower respiratory tract disease (LRTD) to assess the conditions of the disorders. Racehorses were classified into coughing (66 horses) and non-coughing (20 horses) groups based on clinical symptoms. Nine Thoroughbred racehorses without respiratory abnormality were used as controls. Assessment of grades of airway mucus, cytology of tracheal aspirates and serum amyloid A (SAA), fibrinogen (Fbg) and pulmonary surfactant protein D (SP-D) measurements were performed. Relationships between age, gender and racing careers were also investigated to understand the characteristics of LRTD in racehorses. Mean age was significantly higher in non-coughing group compared to coughing group. Existence of racing career and number of starts were significantly greater in non-coughing group compared to coughing group. On the other hand, grades of airway mucus were significantly higher in coughing group compared to control group. Percentages of neutrophils in tracheal aspirates were significantly higher in coughing group compared to non-coughing and control groups. SAA, Fbg and SP-D were higher in coughing group compared to non-coughing and control groups indicating that condition of coughing group is in the acute phase. Positive rate of inflammatory airway disease was significantly higher in coughing and non-coughing groups compared to control group. It was concluded that carrying out comprehensive evaluation including investigation on SAA, Fbg and SP-D analysis with airway assessment to Thoroughbred racehorses which were suspected to have LRTD are useful procedure to understand the pathological condition which aid to initiate appropriate treatment, prognosis judgment or to advise trainers to consider altering training regimen.

Reference range of blood biomarkers for oxidative stress in Thoroughbred racehorses (2–5 years old)

ABSTRACT The oxidant and antioxidant equilibrium is known to play an important role in equine medicine and equine exercise physiology. There are abundant findings in this field; however, not many studies have been conducted for reference ranges of oxidative stress biomarkers in horses. This study was conducted to determine the reference values of reactive oxygen metabolites (d-ROMs) and biological antioxidant potential (BAP) using blood samples from 372 (191 males, 181 females) Thoroughbred racehorse aged 2 to 5 (3.43 ± 1.10 (mean ± SD)) years old. There were obvious gender differences in oxidative biomarkers, and growth/age-related changes were observed especially in females. Gender and age must be considered when interpreting obtained oxidative stress biomarkers for diagnosis of disease or fitness alterations in Thoroughbred racehorses.

Pharmacokinetics and pharmacodynamics of d-chlorpheniramine following intravenous and oral administration in healthy Thoroughbred horses.

The pharmacokinetics of d-chlorpheniramine (CPM), a histamine H1-receptor antagonist, and its ability to inhibit of histamine-induced cutaneous wheal formation, were studied in healthy Thoroughbred horses (n=5). Following an intravenous (IV) dose of 0.5mg/kg bodyweight (BW), plasma drug disposition was very rapid, with the mean terminal half-life and total body clearance calculated as 2.7h and 0.7 L/h/kg, respectively. The observed maximal inhibition of wheal formation following IV doses of 0.1 and 0.5mg/kg BW were 37.8% and 60.6% at 0.5h, respectively. Oral administration of CPM (0.5mg/kg BW) resulted in a bioavailability of 38%, which induced a peak plasma drug concentration at 1h and a maximal inhibition of wheal formation (39%) at 2h. A pharmacokinetic/pharmacodynamic link model showed that CPM in horses has lower efficacy, much lower potency and slightly lower sensitivity than other reported antihistamines. These results indicated that CPM should be administered at frequent intervals or at large dose rates to maintain therapeutic concentrations in horses.

Oxidative stress markers in Thoroughbred horses after castration surgery under inhalation anesthesia.

ABSTRACT Oxidative stress has been reported to occur during surgery. It is important to reduce intraoperative oxidative stress to improve the postoperative prognosis. However, there are no reports regarding oxidative stress related to surgery in horses. In the present study, we measured pre and postsurgical diacron-reactive oxygen metabolites (d-ROMs) and biological antioxidant potential (BAP); the oxidative stress index (OSI) was then calculated (OSI=d-ROMs/BAP × 100). d-ROMs were not significantly different between the pre and postsurgical periods. However, BAP significantly decreased after surgery (P=0.02), and OSI significantly increased after surgery (P=0.02). Based on these results, it suggested that castration surgery under inhalation anesthesia decreases the antioxidant potential and causes oxidative stress in horses.

Intravenous infusion of H2-saline suppresses oxidative stress and elevates antioxidant potential in Thoroughbred horses after racing exercise

Upon intensive, exhaustive exercise, exercise-induced reactive oxygen species may exceed the antioxidant defence threshold, consequently resulting in muscular damage or late-onset chronic inflammation. Recently, the therapeutic antioxidant and anti-inflammatory effects of molecular hydrogen (H2) for human rheumatoid arthritis have been demonstrated. However, it is also important to clarify the effects of administrating H2 in large animals other than humans, as H2 is thought to reach the target organ by passive diffusion upon delivery from the blood flow, indicating that the distance from the administration point to the target is critical. However, data on the effects of H2 on oxidative stress in real-life exhaustive exercise in large animals are currently lacking. We here investigated 13 Thoroughbred horses administered intravenous 2-L saline with or without 0.6-ppm H2 (placebo, N = 6; H2, N = 7) before participating in a high-intensity simulation race. Intravenous H2-saline significantly suppressed oxidative stress immediately, 3 h, and 24 h after the race, although the antioxidant capability was not affected throughout the study. The serum creatine kinase, lactate, and uric acid levels were increased in both groups. Taken together, these results indicate that intravenous H2-saline can significantly and specifically suppress oxidative stress induced after exhaustive racing in Thoroughbred horses.

Comparison of oxidative stress under different propofol administration protocols in Thoroughbred racehorses by bOS and bAP assessment

ABSTRACT It is desirable to reduce surgery-induced oxidative stress (OS) because it can cause immune suppression and delayed wound healing. Propofol is known to have antioxidant potential and to reduce OS in humans, but there have been no studies of this issue in horses. This study was conducted to evaluate OS under three different propofol administration protocols in Thoroughbred racehorses undergoing arthroscopic surgery with sevoflurane anesthesia. Blood oxidative stress (bOS) and blood antioxidant power (bAP) were used as OS biomarkers. Both bOS and bAP significantly decreased after surgery in all groups, but no differences in these reductions were found among them. Different propofol administration protocols with sevoflurane anesthesia did not cause a difference in OS in Thoroughbred racehorses that underwent arthroscopic surgery.

Blood glucose is unlikely to be a prognostic biomarker in acute colitis with systemic inflammatory response syndrome in Thoroughbred racehorses

ABSTRACT Although hyperglycemia at admission with colic has been reported to have a poor prognosis, there is no report specifically about acute colitis with systemic inflammatory response syndrome (SIRS) in horses. In this study, we measured blood glucose (Glu), insulin (Ins), and cortisol (Cor) levels in 17 Thoroughbred racehorses diagnosed as having acute colitis with SIRS, and examined the relationship between time-dependent changes in Glu, Ins, and Cor and prognosis. Glu levels were high in 3 horses at admission, but thereafter no horses had persistently high Glu levels. There was no significant difference in Glu, Ins, and Cor levels within 72 hr between surviving and non-surviving horses. In conclusion, the Glu level is unlikely to be a useful prognostic biomarker in acute colitis with SIRS.

Pharmacokinetics of procaterol in thoroughbred horses

Procaterol (PCR) is a beta-2-adrenergic bronchodilator widely used in Japanese racehorses for treating lower respiratory disease. The pharmacokinetics of PCR following single intravenous (0.5 μg/kg) and oral (2.0 μg/kg) administrations were investigated in six thoroughbred horses. Plasma and urine concentrations of PCR were measured using liquid chromatography-mass spectrometry. Plasma PCR concentration following intravenous administration showed a biphasic elimination pattern. The systemic clearance was 0.47 ± 0.16 L/h/kg, the steady-state volume of the distribution was 1.21 ± 0.23 L/kg, and the elimination half-life was 2.85 ± 1.35 h. Heart rate rapidly increased after intravenous administration and gradually decreased thereafter. A strong correlation between heart rate and plasma concentration of PCR was observed. Plasma concentrations of PCR after oral administration were not quantifiable in all horses. Urine concentrations of PCR following intravenous and oral administrations were quantified in all horses until 32 h after administration. Urine PCR concentrations were not significantly different on and after 24 h between intravenous and oral administrations. These results suggest that the bioavailability of orally administrated PCR in horses is very poor, and the drug was eliminated from the body slowly based on urinary concentrations. This report is the first study to demonstrate the pharmacokinetic character of PCR in thoroughbred horses.