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To investigate neutrophil gelatinase-associated lipocalin (NGAL) concentrations in serum and synovial fluid (SF) from horses with joint inflammation. Study design: Experimental studies and retrospective clinical study. Sample population: Serum and SF samples were available from healthy horses (n = 19), clinical cases, and horses with experimental joint inflammation. Clinical cases included horses with (n = 10) or without (n = 10) septic arthritis. Experimental intra-articular inflammation was induced by lipopolysaccharide (LPS; n = 7, severe inflammation), lidocaine (n = 6, moderate inflammation), or mepivacaine (n = 6, mild inflammation). Methods: Availability of samples was based on approval from the local ethical committee and from the Danish Animal Experiments Inspectorate. Neutrophil gelatinase-associated lipocalin was measured with a previously validated enzyme-linked immunosorbent assay. Repeated-measurements one-and twoway analysis of variance and correlation analysis were used to analyze NGAL concentrations and white blood cell counts (WBC). Results: After injection of LPS or lidocaine, SF NGAL concentrations increased 343-(P = .0035) and 60-fold (P = .0038) relative to baseline, respectively. Serum NGAL also increased in both groups (P < .05) but to lower concentrations than in SF. Concentrations were higher after injection of lidocaine SF NGAL than after injection of mepivacaine (P < .05) at 6 and 12 hours. Synovial fluid concentrations of NGAL were higher in horses with septic arthritis than in the nonseptic group (P = .0070) and in healthy controls (P = .0071). Concentrations of NGAL correlated with WBC in SF (P < .0001, R 2 = 0.49) and in blood (P = .0051, R 2 = 0.27). Conclusion: Neutrophil gelatinase-associated lipocalin concentrations increased in SF in response to experimentally induced and naturally occurring

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OBJECTIVE To investigate the in vitro effects of clinically relevant concentrations of the local anesthetics (LAs) bupivacaine, lidocaine, lidocaine with preservative (LP), mepivacaine, and ropivacaine on equine chondrocyte and fibroblast-like synoviocyte (FLS) viability. SAMPLE Chondrocytes and FLSs of the metacarpophalangeal joints of 4 healthy adult horses. PROCEDURES Viability of chondrocytes and FLSs was determined with 3 assays: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), lactate dehydrogenase (LDH), and trypan blue (TB) exclusion (only FLS). Viability was assessed after 30- and 60-minute exposures to 0.0625%, 0.125%, and 0.25% bupivacaine; 0.25%, 0.5%, and 1% lidocaine; 0.25%, 0.5%, and 1% LP; 0.25%, 0.5%, and 1% mepivacaine; and 0.125%, 0.25%, and 0.5% ropivacaine. RESULTS Viability of chondrocytes was significantly decreased with exposure to 0.25% bupivacaine, 1% lidocaine, 1% LP, 1% mepivacaine, and 0.25% ropivacaine. Viability of FLSs was significantly decreased with exposure to 0.25% bupivacaine, 1% mepivacaine, 1% LP, and 0.5% ropivacaine. CONCLUSIONS AND CLINICAL RELEVANCE Clinically relevant concentrations of LAs had in vitro time- and concentration-dependent cytotoxicity for chondrocytes and FLSs isolated from the metacarpophalangeal joints of healthy horses. Bupivacaine was more toxic to chondrocytes than lidocaine, mepivacaine, and ropivacaine, whereas bupivacaine, LP, mepivacaine, and ropivacaine were more toxic to FLSs than preservative-free lidocaine. Several LAs may negatively affect chondrocyte and FLS viability.

BackgroundSmall-conductance Ca2+-activated K+ (KCa2) channels have been proposed as a possible atrial-selective target to pharmacologically terminate atrial fibrillation (AF) and to maintain sinus rhythm. However, it has been hypothesized that the importance of the KCa2 current—and thereby the efficacy of small-conductance Ca2+-activated K+ current (IK,Ca) inhibition—might be negatively related to AF duration and the extent of AF-induced remodeling.Experimental Approach and MethodsTo address the hypothesis of the efficacy of IK,Ca inhibition being dependent on AF duration, the anti-arrhythmic properties of the IK,Ca inhibitor NS8593 (5 mg/kg) and its influence on atrial conduction were studied using epicardial high-density contact mapping in horses with persistent AF. Eleven Standardbred mares with tachypacing-induced persistent AF (42 ± 5 days of AF) were studied in an open-chest experiment. Unipolar AF electrograms were recorded and isochronal high-density maps analyzed to allow for the reconstruction of wave patterns and changes in electrophysiological parameters, such as atrial conduction velocity and AF cycle length. Atrial anti-arrhythmic properties and adverse effects of NS8593 on ventricular electrophysiology were evaluated by continuous surface ECG monitoring.ResultsIK,Ca inhibition by NS8593 administered intravenously had divergent effects on right and left AF complexity and propagation properties in this equine model of persistent AF. Despite global prolongation of AF cycle length, a slowing of conduction in the right atrium led to increased anisotropy and electrical dissociation, thus increasing AF complexity. In contrast, there was no significant change in AF complexity in the LA, and cardioversion of AF was not achieved.ConclusionsIntra-atrial heterogeneity in response to IK,Ca inhibition by NS8593 was observed. The investigated dose of NS8593 increased the AF cycle length but was not sufficient to induce cardioversion. In terms of propagation properties during AF, IK,Ca inhibition by NS8593 led to divergent effects in the right and left atrium. This divergent behavior may have impeded the cardioversion success.