Reactive oxygen species are a major cause of damage occurring in ischemic tissue after reperfusion. During reperfusion transitional metals such as iron are required for reactive oxygen species to mediate their major toxic effects. Xanthine oxidase is an important source of reactive oxygen species during ischemia-reperfusion injury, but not in all organs or species. Because cytochrome P450 enzymes are an important pulmonary source of superoxide anion (02) generation under basal conditions and during hyperoxia, and provide iron catalysts necessary for hydroxyl radical COH) formation and propagation of lipid peroxidation, we postulated that cytochrome P450 might have a potential role in mediating ischemia-reperfusion injury. In this report, we explored the role of cytochrome P450 enzymes in a rabbit model of reperfusion lung injury. The P450 inhibitors 8-methoxypsoralen, piperonyl butoxide, and cimetidine markedly decreased lung edema from transvascular fluid flux. Cimetidine prevented the reperfusion-related increase in lung microvascular permeability, as measured by movement of '25I-albumin from the vascular space into lung water and alveolar fluid. P450 inhibitors also prevented the increase in lung tissue levels of thiobarbituric acid reactive products in the model. P450 inhibitors did not block enhanced 0°generation by ischemic reperfused lungs, measured by in vivo reduction of succinylated ferricytochrome c in lung perfusate, but did prevent the increase in non-protein-bound low molecular weight chelates of iron after reperfusion. Thus, cytochrome P450 enzymes are not likely a major source of enhanced 05 generation, but serve as an important source of iron in mediating oxidant injury to the rabbit lung during reperfusion. These results suggest an important role of cytochrome P450 in reperfusion injury to the lung and suggest potential new therapies for the disorder. (J.

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OBJECTIVE--To determine risk factors for prolonged anesthetic recovery time in horses that underwent general anesthesia for ocular surgery. DESIGN--Retrospective cohort study. ANIMALS--81 horses that underwent general anesthesia for ocular surgery between 2006 and 2013. PROCEDURES--Descriptive information recorded included the ocular procedure performed, concurrent fluconazole treatments, analgesic and anesthetic agents administered, procedure duration, use of sedation for recovery, and recovery time. Data were analyzed for associations between recovery time and other variables. RESULTS--81 horses met inclusion criteria. In 72 horses, anesthesia was induced with ketamine and midazolam; 16 horses treated concurrently with fluconazole had significantly longer mean recovery time (109 minutes [95% confidence interval {CI}, 94 to 124 minutes]) than did 56 horses that were not treated with fluconazole (50 minutes [95% CI, 44 to 55 minutes]). In 9 horses anesthetized with a protocol that included ketamine but did not include midazolam, there was no difference between mean recovery time in horses that either received (59 minutes [95% CI, 36 to 81 minutes]; n = 5) or did not receive (42 minutes [95% CI, 16 to 68 minutes]; 4) fluconazole. Other variables identified as risk factors for prolonged recovery included duration of anesthesia and use of acepromazine for premedication. CONCLUSIONS AND CLINICAL RELEVANCE--Fluconazole administration was associated with prolonged anesthetic recovery time in horses when ketamine and midazolam were used to induce anesthesia for ocular surgery. Duration of anesthesia and premedication with acepromazine were also identified as risk factors for prolonged recovery time.

Further experimental studies will need to be performed before clinical application of postconditioning for intestinal ischemia.

Apneic oxygenation was studied in six ponies for 30 minutes, and six horses for 10 minutes. Arterial blood was sampled at regular intervals for measurement of oxygen and carbon dioxide tensions (PaO2 and PaCO2) and calculation of alveolar-arterial oxygen tension difference (PAO2-PaO2). In both groups of animals, PaO2 decreased rapidly during the first 3 minutes of apnea, then more slowly. Although the mean value was above 100 mmHg at 10 minutes, there was considerable inter-animal variability. Before apnea, PAO2-PaO2 was slightly, but not significantly, larger in horses than in ponies and increased in both groups during the first 3 minutes of apnea, after which the increase was slower. There was no significant difference between ponies and horses up to 10 minutes, suggesting that PAO2-PaO2 is independent of body size. In ponies, the PAO2-PaO2 did not change significantly between 10 and 30 minutes. Final PaO2 could not be correlated with initial PaO2 or initial PAO2-PaO2. The rate of rise of PAO2-PaO2 could not be predicted from baseline values. The rate of rise of PaCO2 was similar and fairly constant in ponies and horses, and did not contribute to the rapid initial decrease in PaO2. It appears that apneic oxygenation should not be used in the equine species, since it is impossible to predict in which animals the technique is safe for more than a few minutes.