C. A. Blaze

Role of cytochrome P-450 in reperfusion injury of the rabbit lung.

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 P-450 enzymes are an important pulmonary source of superoxide anion (O2-.) generation under basal conditions and during hyperoxia, and provide iron catalysts necessary for hydroxyl radical (.OH) formation and propagation of lipid peroxidation, we postulated that cytochrome P-450 might have a potential role in mediating ischemia-reperfusion injury. In this report, we explored the role of cytochrome P-450 enzymes in a rabbit model of reperfusion lung injury. The P-450 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 125I-albumin from the vascular space into lung water and alveolar fluid. P-450 inhibitors also prevented the increase in lung tissue levels of thiobarbituric acid reactive products in the model. P-450 inhibitors did not block enhanced O2-. 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 P-450 enzymes are not likely a major source of enhanced O2-. 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 P-450 in reperfusion injury to the lung and suggest potential new therapies for the disorder.

Use of wound soaker catheters for the administration of local anesthetic for post-operative analgesia: 56 cases

OBJECTIVE To describe the administration of local anesthetic through wound soaker catheters for post-operative veterinary patients and to characterize complications. STUDY DESIGN Retrospective study of hospital records. ANIMALS Records of patients in which a wound soaker catheter was placed post-operatively between November 1, 2004 and July 1, 2006 at a veterinary teaching hospital. Records in which a limb amputation was performed between January 1, 2002 and August 1, 2007 and in which a wound soaker catheter was not placed were reviewed for historic control. RESULTS A total of 56 cases were identified in which a wound soaker catheter was placed post-operatively including 52 dogs, 2 cats, and 2 goats. Twenty canine cases were identified in which limb amputation was performed and no wound soaker catheter was placed. The majority of surgical procedures for which a wound soaker catheter was placed included thoracic limb amputation (46.4%) and pelvic limb amputation (35.7%). Wound soaker catheters remained in place for an average of 1.6 +/- 0.5 days. Feline and caprine patients received intermittent bupivacaine boluses every 6 hours. Canine patients received continuous lidocaine infusions. Complications included disconnection of the catheter from the infusion (7.7%), one seroma, and one suspected lidocaine neurotoxicity. Incisional infections were noted in 3/56 (5.3%) limb amputations with wound soaker catheters placed which was not higher than the incisional infection rate found in the historic control cases 3/20 (15%). CONCLUSION AND CLINICAL RELEVANCE Use of the wound soaker catheter was a viable means of providing local analgesia in post-operative veterinary patients. Studies are needed to evaluate efficacy of pain management, and to further investigate techniques for catheter placement and maintenance which may help to optimize the analgesia achieved using this technique.

Ischemic postconditioning does not attenuate ischemia-reperfusion injury of rabbit small intestine.

OBJECTIVE To determine whether ischemic postconditioning can attenuate intestinal ischemia-reperfusion (I-R) injury and has a beneficial effect on tissue blood flow during reperfusion. STUDY DESIGN In vivo experimental study. ANIMALS New Zealand White rabbits (n=6). METHODS Rabbits were anesthetized with pentobarbital, to avoid the preconditioning effects of volatile anesthetics, and ventilated with room air. Rectal temperature, hemodynamics, and normocapnia were maintained. After celiotomy, 3 jejunal segments were isolated in each rabbit for the following groups: (1) control, (2) I-R, and (3) I-R with postconditioning. I-R was induced by a 45-minute occlusion of the segment jejunal artery followed by 2-hour reperfusion. The postconditioning segment had 4 cycles of 30-second reperfusion and 30-second reocclusion during the initial 4 minutes of reperfusion. Stable isotope-labeled microspheres were used to measure intestinal blood flow at baseline, end occlusion, and end reperfusion. At the end of reperfusion, intestine segments were harvested and the rabbits euthanatized. A semiquantitative histopathologic evaluation (0-5) was conducted by a single, blinded observer. Wet-to-dry weight ratios were calculated to assess intestinal edema. RESULTS There was no significant difference in grade of necrosis, tissue wet-to-dry weight ratios, or blood flow at any time point between ischemic and postconditioning groups. CONCLUSIONS Ischemic postconditioning was ineffective in this model of intestinal I-R. CLINICAL RELEVANCE Further experimental studies will need to be performed before clinical application of postconditioning for intestinal ischemia.

Apneic oxygenation in anesthetized ponies and horses

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.

Peptide YY receptor distribution and subtype in the kidney : effect on renal hemodynamics and function in rats

This study characterizes the location and subtype of peptide YY (PYY) receptors in rat and rabbit kidney and the effect of PYY on renal function and renal hemodynamics in rats. Receptor autoradiography performed on kidney sections revealed a dense concentration of specific high-affinity binding sites [dissociation constant (Kd) = 0.7 +/- 0.1 nM] in the papilla of the rat, as well as cortical and papillary binding in the rabbit (papilla, Kd = 1.6 +/- 0.6 nM) and some medullary binding in both species. In the rat papilla, neuropeptide Y (NPY) and the Y1 agonist [Leu31,Pro34]NPY competed with PYY for binding (Kd = 1.1 +/- 0.4 nM and 1.6 +/- 0.5 nM, respectively), but NPY-(13-36) (Y2 agonist) and pancreatic polypeptide (PP, Y4 agonist) were without effect, demonstrating that the PYY receptor in the rat papilla is of the Y1 subtype. In the rabbit papilla, NPY and NPY-(13-36) competed with PYY (Kd = 0.5 +/- 0.1 and 3.1 +/- 0.6 nM, respectively), but [Leu31,Pro34]NPY and PP were without effect, evidence that the PYY receptor in the rabbit papilla is of the Y2 subtype. Infusion of PYY into rats (47 pmol x kg(-1) x min[-1]) increased mean arterial pressure (103 +/- 6 to 123 +/- 8 mmHg) and decreased renal plasma flow (13 +/- 1.8 to 8.4 +/- 2.1 ml/min) but produced no significant change in glomerular filtration rate or sodium excretion. Injection of PYY or angiotensin II directly into the renal artery caused a dose-related vasoconstriction, which was less intense but of longer duration for PYY than for angiotensin II. These results show that receptors for PYY are widely distributed in the kidney and that exogenously administered PYY causes renal vasoconstriction and may influence renal sodium excretion.This study characterizes the location and subtype of peptide YY (PYY) receptors in rat and rabbit kidney and the effect of PYY on renal function and renal hemodynamics in rats. Receptor autoradiography performed on kidney sections revealed a dense concentration of specific high-affinity binding sites [dissociation constant ( K d) = 0.7 ± 0.1 nM] in the papilla of the rat, as well as cortical and papillary binding in the rabbit (papilla, K d = 1.6 ± 0.6 nM) and some medullary binding in both species. In the rat papilla, neuropeptide Y (NPY) and the Y1 agonist [Leu31, Pro34]NPY competed with PYY for binding ( K d = 1.1 ± 0.4 nM and 1.6 ± 0.5 nM, respectively), but NPY-(13-36) (Y2 agonist) and pancreatic polypeptide (PP, Y4 agonist) were without effect, demonstrating that the PYY receptor in the rat papilla is of the Y1 subtype. In the rabbit papilla, NPY and NPY-(13-36) competed with PYY ( K d = 0.5 ± 0.1 and 3.1 ± 0.6 nM, respectively), but [Leu31, Pro34]NPY and PP were without effect, evidence that the PYY receptor in the rabbit papilla is of the Y2subtype. Infusion of PYY into rats (47 pmol ⋅ kg-1 ⋅ min-1) increased mean arterial pressure (103 ± 6 to 123 ± 8 mmHg) and decreased renal plasma flow (13 ± 1.8 to 8.4 ± 2.1 ml/min) but produced no significant change in glomerular filtration rate or sodium excretion. Injection of PYY or angiotensin II directly into the renal artery caused a dose-related vasoconstriction, which was less intense but of longer duration for PYY than for angiotensin II. These results show that receptors for PYY are widely distributed in the kidney and that exogenously administered PYY causes renal vasoconstriction and may influence renal sodium excretion.

Evaluation of risk factors, including fluconazole administration, for prolonged anesthetic recovery times in horses undergoing general anesthesia for ocular surgery: 81 cases (2006–2013)

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.