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  • Author or Editor: Yoshinori Nezu x
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Abstract

Objective—To determine the effects of intestinal ischemia and reperfusion on the expression of tumor necrosis factor (TNF)-α and interleukin (IL)-6 mRNAs in the jejunum, liver, and lungs of dogs.

Animals—8 healthy adult Beagles.

Procedures—In each dog, the cranial mesenteric artery was occluded for 0 (control group; n = 4) or 60 (I-R group; 4) minutes, followed by reperfusion for 480 minutes; serum TNF-α and IL-6 activities and expression levels of TNF-α and IL-6 mRNAs in jejunal, hepatic, and lung tissues were measured before and at the end of the ischemic period and at intervals during reperfusion. For each variable, values were compared between the control and I-R groups at each time point.

Results—Compared with the control group, serum IL-6 activity increased significantly after 180 minutes of reperfusion in the I-R group; also, jejunal TNF-α mRNA expression increased significantly after 60 (peak) and 180 minutes of reperfusion. In the I-R group, expressions of IL-6 mRNA in the liver and TNF-α and IL-6 mRNAs in the lungs increased significantly at 480 minutes of reperfusion, compared with the control group. Serum TNF-α activity, expression of IL-6 mRNA in the jejunum, and expression of TNF-α mRNA in the liver in the control and I-R groups did not differ.

Conclusions and Clinical Relevance—Results indicated that the liver, lungs, and jejunum contributed to the production of TNF-α and IL-6 after intestinal ischemia and reperfusion in dogs, suggesting that intestinal ischemia and reperfusion induce a systemic proinflammatory cytokine response in dogs.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To evaluate effects of long-term administration of carprofen on healing of a tibial osteotomy in dogs.

Animals—12 healthy female Beagles.

Procedures—A mid-diaphyseal transverse osteotomy (stabilized with an intramedullary pin) of the right tibia was performed in each dog. The carprofen group (n = 6 dogs) received carprofen (2.2 mg/kg, PO, q 12 h) for 120 days; the control group (6) received no treatment. Bone healing and change in callus area were assessed radiographically over time. Dogs were euthanized 120 days after surgery, and tibiae were evaluated biomechanically and histologically.

Results—The osteotomy line was not evident in the control group on radiographs obtained 120 days after surgery. In contrast, the osteotomy line was still evident in the carprofen group. Callus area was significantly less in the carprofen group, compared with the area in the control group, at 20, 30, and 60 days after surgery. At 120 days after surgery, stiffness, elastic modulus, and flexural rigidity in the carprofen group were significantly lower than corresponding values in the control group. Furthermore, histologic evaluation revealed that the cartilage area within the callus in the carprofen group was significantly greater than that in the control group.

Conclusions and Clinical Relevance—Long-term administration of carprofen appeared to inhibit bone healing in dogs that underwent tibial osteotomy. We recommend caution for carprofen administration when treating fractures that have delays in healing associated with a reduction in osteogenesis as well as fractures associated with diseases that predispose animals to delays of osseous repair.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To evaluate the role of the semitendinosus muscle in stabilization of the canine stifle joint.

Sample—Left stifle joints collected from cadavers of 8 healthy Beagles.

Procedures—Left hind limbs, including the pelvis, were collected. To mimic the tensile force of the quadriceps, gastrocnemius, and semitendinosus muscles, wires were placed under strain between the ends of each muscle. A sensor was used to measure the tensile force in each wire. Specimens were tested in the following sequence: cranial cruciate ligament (CrCL) intact, CrCL transected, released (tensile force of semitendinosus muscle was released in the CrCL-transected stifle joint), and readjusted (tensile force of semitendinosus muscle was reapplied in the CrCL-transected stifle joint). Specimens were loaded at 65.3% of body weight, and tensile force in the wires as well as the cranial tibial displacement were measured.

Results—Tensile force for the CrCL-transected condition increased significantly, compared with that for the CrCL-intact condition. Mean ± SD cranial tibial displacement for the CrCL-transected condition was 2.1 ± 1.3 mm, which increased to 7.2 ± 2.3 mm after release of the tensile force in the semitendinosus muscle.

Conclusions and Clinical Relevance—Results supported the contention that the semitendinosus muscle is an agonist of the CrCL in the stifle joint of dogs. Moreover, the quadriceps and gastrocnemius muscles may be antagonists of the CrCL. These findings suggested that the risk of CrCL rupture may be increased by diseases (such as cauda equina syndrome) associated with a decrease in activity of the semitendinosus muscle.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To compare activities of interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and matrix metalloproteinase (MMP)-3 and contents of sulfated glycosaminoglycan (S-GAG) in joint fluid obtained from dogs with hip dysplasia (HD) and clinically normal dogs, evaluate correlations among these markers in joint fluid obtained from dogs with HD, and evaluate correlations between each marker and clinical and radiographic variables.

Animals—26 dogs with HD (clinical group) and 43 clinically normal Beagles (control group).

Procedure—Joint fluid was aseptically collected from the hip joints of all dogs. For each dog in the clinical group, age, duration of lameness, radiographic osteoarthritis (OA) score, and Norberg angle in each affected joint were recorded. Activities of IL-1β, IL-6, TNF-α, and MMP-3 and S-GAG contents were measured. Values were compared between groups by use of Mann-Whitney U tests, and the Spearman rank correlation test was used to evaluate correlations among markers and between each marker and clinical or radiographic variables.

Results—Values of all markers were significantly higher for the clinical group, compared with values for the control group. There was a moderate positive correlation between lameness duration and IL-6 activity and a strong negative correlation between the Norberg angle and IL-1β activity.

Conclusions and Clinical Relevance—Analysis of our results indicated that there was a significant increase in markers of OA in dogs with HD. Activities of IL-1β and IL-6 in joint fluid of dogs with HD may be influenced by the severity of laxity in the hip joint and lameness duration, respectively. (Am J Vet Res 2005;66:2028–2033)

Full access
in American Journal of Veterinary Research

Abstract

Objective—To determine whether small intestinal ischemia and reperfusion induces bacterial translocation and proinflammatory cytokine response in either the systemic or portal circulation in dogs.

Animals—17 healthy adult Beagles.

Procedure—The superior mesenteric artery (SMA) was occluded for 0 (group-3 dogs), 30 (group-1 dogs), or 60 (group-2 dogs) minutes, followed by reperfusion for 180 minutes; serum lactate and endotoxin concentrations and tumor necrosis factor-α (TNF-α), interleukin- 1β (IL-1β), and IL-6 activities in the systemic and portal circulation and intramucosal pH were measured at various time points.

Results—In group-2 dogs, TNF-α activity was found to be significantly increased in the portal circulation, peaking at 60 minutes of reperfusion; TNF-α activity, in the systemic circulation, gradually increased from 60 minutes of reperfusion to the end of the experiment; however, the increase was not significant. In group-1 and -2 dogs, IL-6 activities significantly and gradually increased in the systemic and portal circulation during the reperfusion phase, and the magnitude of these increases was dependent on the duration of the ischemic phase. There were no significant changes in IL-1β activity or endotoxin concentration in any dog group.

Conclusions and Clinical Relevance—Results of the our study indicate that intestinal ischemia and reperfusion leads to significant increases of the circulating TNF-α and IL-6 activities, depending on the duration of the ischemia phase, in the absence of detectable endotoxin in the circulation. This finding suggests that intestinal ischemia and reperfusion induces a systemic proinflammatory cytokine response in dogs. (Am J Vet Res 2002;63:1680–1686)

Full access
in American Journal of Veterinary Research

Abstract

Objective—To determine whether continuous infusion of a low dose of lipopolysaccharide (LPS) to induce a condition mimicking septic shock in dogs would affect systemic and hepatosplanchnic circulation and oxygenation.

Animals—12 healthy adult Beagles.

Procedure—Dogs received a low dose of LPS (Escherichia coli O55:B5) by continuous IV infusion at a rate of 1 µg/kg/h for 8 hours. Systemic hemodynamics; systemic oxygenation; blood flow in the cranial mesenteric artery, common hepatic artery, and portal vein; intestinal and hepatic tissue blood flow; mesenteric oxygenation; and intramucosal PCO2 were examined before and at selected time points after onset of the LPS infusion.

Results—After onset of the LPS infusion, cardiac index increased and mean arterial pressure (MAP) and systemic vascular resistance decreased, which is characteristic of the hyperdynamic state in septic patients. Hepatosplanchnic blood flow increased during the hyperdynamic state. Intestinal PCO2 was increased even when blood flows increased. During the latter half of the experimental period, MAP was maintained but hepatosplanchnic blood flows decreased and intestinal PCO2 increased further.

Conclusions and Clinical Relevance—Analysis of the results suggested that hepatosplanchnic blood flow enters the hyperdynamic state during the early stages of sepsis and that intestinal tissue oxygenation is threatened even when hepatosplanchnic blood flow is increased or maintained. Hence, improvement of hepatosplanchnic circulation and intestinal tissue oxygenation is important in dogs with clinical evidence of a septic condition. (Am J Vet Res 2004;65:1347–1354)

Full access
in American Journal of Veterinary Research

Abstract

Objective—To determine whether small intestinal ischemia and reperfusion affects intestinal intramucosal pH (pHi), arterial and portal venous blood gas values, and intestinal blood flow (IBF) and to investigate relationships between regional intestinal tissue oxygenation and systemic variables in dogs.

Animals—15 healthy adult Beagles.

Procedure—Occlusion of superior mesenteric artery (SMA) for 0, 30, or 60 minutes, followed by reperfusion for 180 minutes, was performed; IBF, pHi, arterial and portal venous blood gas values, arterial pressure, and heart rate were measured at various time points; and intestinal mucosal injury was histologically graded.

Results—Occlusion of the SMA induced significant decreases in pHi and IBF. After the release of the occlusion, IBF returned rapidly to baseline values, but improvement in pHi was slow. Arterial and portal venous blood gas analyses were less sensitive than tonometric measurements of pHi, and there was no correlation between results of blood gas analyses and tonometric measurements. Histologic score for intestinal mucosal injury increased significantly, depending on duration of ischemia, and there was a correlation between tonometric results and the histologic score.

Conclusion and Clinical Relevance—Results suggest that it is difficult to accurately evaluate local oxygenation disorders by monitoring at the systemic level, whereas clinically pHi is the only reliable indicator of inadequate regional intestinal tissue oxygenation in dogs. (Am J Vet Res 2002;63:804–810)

Full access
in American Journal of Veterinary Research

Abstract

OBJECTIVE To determine whether thioredoxin (TRX)-1 can be used as a valid biomarker for oxidative stress in dogs.

ANIMALS AND SAMPLES 10 Beagles and Madin-Darby canine kidney cells.

PROCEDURES Madin-Darby canine kidney cells were used to verify antigen cross-reactivity between human and canine anti–TRX-antibodies. Dogs were assigned to receive 21% or 100% O2 (5 dogs/group) via an artificial respirator during a 3-hour period of isoflurane anesthesia (starting at 0 hours). Blood and urine samples were collected before (baseline) and at 6, 12, 24, and 48 hours after commencement of inhalation anesthesia. Concentrations of TRX-1 and 8-hydroxy-2′-deoxyguanosine (8-OHdG) in plasma and urine samples were analyzed; urine concentrations were reported as ratios against urine creatinine concentration.

RESULTS Canine TRX-1 was recognized by monoclonal human anti-TRX-1 antibodies (clones of adult T-cell leukemia-derived factor [ADF]-11 and ADF21) by western blot analysis. Results of an ELISA indicated that plasma TRX-1 concentration and urine TRX-1-to-creatinine concentration ratio increased rapidly after the 3-hour period of hyperoxia with maximal peaks at 12 and 6 hours, respectively. Urine 8-OHdG-to-creatinine concentration ratio also increased significantly after hyperoxia induction. However, unlike the rapid increase in urine TRX-1-to-creatinine concentration ratio, maximal urine 8-OHdG-to-creatinine concentration ratio was attained at 48 hours after hyperoxia induction. These variables remained unchanged from baseline in the control group.

CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that human anti-TRX monoclonal antibodies cross-reacted with canine TRX, and plasma TRX-1 concentrations were rapidly increased in dogs following an oxidative stress challenge. Thus, TRX may be a valuable clinical biomarker for detecting oxidative stress more rapidly than 8-OHdG in dogs.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To determine the effects of continuous low-dose infusion of lipopolysaccharide (LPS) on the expression of E-selectin and intercellular adhesion molecule-1 (ICAM-1) mRNA and neutrophil accumulation in the lungs, liver, spleen, small intestine, and pancreas in dogs.

Animals—11 healthy adult Beagles.

Procedure—Dogs received a continuous infusion of a low dose (10 µg/kg/h, IV) of LPS ( Escherichia coli055:B5) or saline (0.9% NaCl) solution (20 mL/kg/h, IV) for 8 hours. Activity levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) and the number of WBCs in circulation were examined before and 1, 2, 4, and 8 hours after the onset of LPS infusion. Expression of E-selectin and ICAM-1 mRNA and the number of neutrophils in each tissue were examined.

Results—After the onset of LPS infusion, serum TNF-α and IL-1β activities transiently increased. Thereafter, IL-6 activity increased, and high IL-6 activity was maintained throughout the experiment. In dogs in the LPS group, expression of E-selectin mRNA increased only in the lungs, and expression of ICAM-1 mRNA increased in the lungs and liver; the number of neutrophils in the tissue increased in the lungs and liver.

Conclusions and Clinical Relevance—Results suggested that expression of E-selectin and ICAM-1 mRNA increased during sepsis, particularly in the lungs and liver, and that this increase was associated with neutrophil accumulation. Hence, inhibiting the activation of endothelial cells in the lung and liver may decrease organ damage caused by accumulated neutrophils and help regulate multiple-organ dysfunction. (Am J Vet Res 2005;66:1259–1266)

Full access
in American Journal of Veterinary Research