Intestinal ischemia-reperfusion injury in horses: pathogenesis and therapeutics.

This article discusses the potential role of oxidative injury to the intestinal tract of horses and the therapeutic approaches that have been investigated to decrease cellular damage secondary to ischemia-reperfusion (IR) injury. Equine colic is a major concern for horse owners and veterinary practitioners. Strangulating and obstructive lesions of the small and large intestines commonly require intervention in patients via exploratory celiotomy. However, the application of information from experimentally induced IR injury in horses to clinical cases of naturally occurring equine colic is not clear. Thus, while the exact mechanisms and clinical significance of intestinal IR are being defined and may be matters of academic debate, a review of the available information may provide knowledge of potential underlying pathophysiologic mechanisms contributing to intestinal injury in equine colic. This information may allow clinicians to offer additional therapeutic strategies for horses with strangulating obstruction of the small or large intestine. Further clinical study of the therapeutic options for horses with naturally occurring disease is warranted.

Mechanisms of oxidative injury in equine disease.

Oxygen is essential to aerobic life, but it is also associated with the production of highly reactive compounds that can pose danger to physiologic systems when the oxygen concentration is excessive. Reactive oxygen species (ROS) are required for normal physiologic processes, but when produced in excess, they can overwhelm endogenous antioxidants, resulting in significant cellular damage and, eventually, cell death. Ischemic events can initiate numerous pathophysiologic mechanisms leading to increased production of ROS, loss of cellular energy production, and lipid peroxidation. Although reperfusion is a necessary step in cellular recovery from ischemia, it can be deleterious by leading to the generation of even more ROS and stimulating the accumulation of neutrophils. Both of these processes may contribute to irreversible cell death and, ultimately, organ failure. This article reviews oxygen metabolism, ischemia, and reperfusion injury and how these processes may occur in equine disorders.

Physiologic effects of nasopharyngeal administration of supplemental oxygen at various flow rates in healthy neonatal foals.

OBJECTIVE: To evaluate the effects of various flow rates of oxygen administered via 1 or 2 nasal cannulae on the fraction of inspired oxygen concentration (FIO2) and other arterial blood gas variables in healthy neonatal foals. ANIMALS: 9 healthy neonatal (3- to 4-day-old) foals. PROCEDURES: In each foal, a nasal cannula was introduced into each naris and passed into the nasopharynx to the level of the medial canthus of each eye; oxygen was administered at 4 flow rates through either 1 or both cannulae (8 treatments/foal). Intratracheal FIO2, intratracheal end-tidal partial pressure of carbon dioxide, and arterial blood gas variables were measured before (baseline) and during unilateral and bilateral nasopharyngeal delivery of 50, 100, 150, and 200 mL of oxygen/kg/min. RESULTS: No adverse reactions were associated with administration of supplemental oxygen except at the highest flow rate, at which the foals became agitated. At individual flow rates, significant and dose-dependent increases in FIO2, PaO2, and oxygen saturation of hemoglobin (SaO2) were detected, compared with baseline values. Comparison of unilateral and bilateral delivery of oxygen at similar cumulative flow rates revealed no differences in evaluated variables. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that administration of supplemental oxygen via nasal cannulae appeared to be a highly effective means of increasing FIO2, PaO2, and SaO2 in neonatal foals. These findings may provide guidance for implementation of oxygen treatment in hypoxemic neonatal foals.

Pharmacokinetics of zidovudine in cats.

OBJECTIVE: To characterize the pharmacokinetics of zidovudine (AZT) in cats. ANIMALS: 6 sexually intact 9-month-old barrier-reared domestic shorthair cats. PROCEDURE: Cats were randomly alloted into 3 groups, and zidovudine (25 mg/kg) was administered i.v., intragastrically (i.g.), and p.o. in a 3-way crossover study design with 2-week washout periods between experiments. Plasma samples were collected for 12 hours after drug administration, and zidovudine concentrations were determined by high-performance liquid chromatography. Maximum plasma concentrations (Cmax), time to reach Cmax (Tmax), and bioavailability were compared between i.g. and p.o. routes. Area under the curve (AUC) and terminal phase half-life (t(1/2)) among the 3 administration routes were also compared. RESULTS: Plasma concentrations of zidovudine declined rapidly with t(1/2) of 1.4 +/- 0.19 hours, 1.4 +/- 0.16 hours, and 1.5 +/- 0.28 hours after i.v., i.g., and p.o. administration, respectively. Total body clearance and steady-state volume of distribution were 0.41 +/- 0.10 L/h/kg and 0.82 +/- 0.15 L/kg, respectively. Mean Tmax for i.g. administration (0.22 hours) was significantly shorter than Tmax for p.o. administration (0.67 hours). The AUC after i.v. and p.o. administration was 64.7 +/- 16.6 mg x h/L and 60.5 +/- 17.0 mg x h/L, respectively, whereas AUC for the i.g. route was significantly less at 42.5 +/- 9.41 mg x h/L. Zidovudine was well absorbed after i.g. and p.o. administration with bioavailability values of 70 +/- 24% and 95 +/- 23%, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Cats had slower clearance of zidovudine, compared with other species. Plasma concentrations of zidovudine were maintained above the minimum effective concentration for inhibiting FIV replication by 50% (0.07 microM [0.019 microg/mL] for wild-type FIV clinical isolate) for at least 12 hours after i.v., i.g., or p.o. administration.

Pharmacokinetics of lamivudine in cats.

OBJECTIVE: To characterize the pharmacokinetics of lamivudine (3TC) in cats. ANIMALS: 6 sexually intact 9-month-old barrier-reared domestic shorthair cats. PROCEDURE: Cats were randomly alloted into 3 groups, and lamivudine (25 mg/kg) was administered i.v., intragastrically (i.g.), and p.o. in a 3-way crossover study design with 2-week washout periods between experiments. Plasma samples were collected for 12 hours after drug administration, and lamivudine concentrations were determined by high-performance liquid chromatography. Maximum plasma concentrations (Cmax), time to reach Cmax (Tmax), and bioavailability were compared between i.g. and p.o. routes. Area under the curve (AUC) and terminal phase half-life (t(1/2)) among the 3 administration routes were also compared. RESULTS: Plasma concentrations of lamivudine declined rapidly with a t(1/2) of 1.9 +/- 0.21 hours, 2.6 +/- 0.66 hours, and 2.7 +/- 1.50 hours after i.v., i.g., and p.o. administration, respectively. Total body clearance and steady-state volume of distribution were 0.22 +/- 0.09 L/h/kg and 0.60 +/- 0.22 L/kg, respectively. Mean Tmax for i.g. administration (0.5 hours) was significantly shorter than Tmax for p.o. administration (1.1 hours). The AUC after i.v., i.g., and p.o. administration was 130 +/- 55.2 mg x h/L, 115 +/- 97.5 mg x h/L, and 106 +/- 94.9 mg x h/L, respectively. Lamivudine was well absorbed after i.g. and p.o. administration with bioavailability values of 88 +/- 45% and 80 +/- 52%, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Cats had a shorter t(1/2) but slower total clearance of lamivudine, compared with humans. Plasma concentrations of lamivudine were maintained above the minimum effective concentration for inhibiting FIV replication by 50% (0.14 microM [0.032 microg/mL] for wild-type FIV clinical isolate) for at least 12 hours after i.v., i.g., or p.o. administration.

Differential expression of sheep beta-defensin-1 and -2 and interleukin 8 during acute Mannheimia haemolytica pneumonia.

Beta-defensins are antimicrobial peptides produced by several cell types, including respiratory epithelia and leukocytes. Expression of some beta-defensins is increased by bacterial-induced inflammatory responses whereas expression of other beta-defensins is constitutive. Two beta-defensins are expressed in lungs of sheep (sheep beta-defensin-1 and -2; SBD-1/-2) and expression of SBD-1 is increased during parainfluenza virus type 3 (PI-3) infection. The effect of Mannheimia haemolytica, a Gram-negative bacteria known to induce expression of bovine beta-defensins and NF-kappa B in lung, has not been determined for SBD-1/-2. In this study, different concentrations of M. haemolytica were inoculated into pulmonary bronchi of lambs. SBD-1 and SBD-2 mRNA levels detected by real time reverse transcriptase polymerase chain reaction in lung homogenates did not increase. In fact, SBD-1 mRNA levels were significantly decreased with the highest administered inoculum concentration (10(9)). In contrast, mRNA levels of interleukin-8 (IL-8) were significantly increased over controls and progressively increased with M. haemolytica concentrations. Co-inoculation of M. haemolytica with xylitol, an osmotic agent, did not alter mRNA levels of SBD-1, SBD-2 or IL-8. SBD-1 mRNA expression was detected in lung epithelia, but not in leukocytes. This study suggests that SDB-1 expression occurs in epithelia and decreases during severe bacterial pneumonia, which is in contrast to the increase that occurs with PI-3 infection.

Infection with Basidiobolus ranarum in two dogs.

Basidiobolus ranarum is a saprophytic fungus in the environment that also is a part of the endogenous microflora in the gastrointestinal tract of several vertebrates. These organisms may penetrate skin or muscosa of humans and other animals, causing granulomatous inflammation. Two dogs infected with B. ranarum had prolonged or repeated exposure to water or soil in their environment. One dog had progressive subcutaneous infection of all the limbs, and the other dog had recurrent coughing and dyspnea caused by tracheobronchitis. In both dogs, secondary bacterial infection of the lesions was evident. Treatment of the dog with subcutaneous infection involved cutaneous dressings and sequential use of enrofloxacin and itraconazole; however, this resulted in suspected liver damage without clinical improvement. Subsequent treatment with potassium iodide and a lipid formulation of amphotericin B was also unsuccessful, and the dog was euthanatized. The other dog was treated alternately with enrofloxacin and itraconazole. When the clinical signs and infection returned, combination treatment with both drugs was more effective; however, the dog developed liver damage. Subsequent treatment with enrofloxacin on an intermittent basis controlled the dog's coughing during a 3-year period.