Long-Term Effects of Bupivacaine on Cartilage in a Rabbit Shoulder Model

Background Previous investigations have reported on the chondrotoxicity of bupivacaine in short-term in vivo and in vitro models. This study was designed to provide additional information on the long-term effects of bupivacaine infusion on articular cartilage in an established rabbit shoulder model....

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Veröffentlicht in:The American journal of sports medicine 2009-01, Vol.37 (1), p.72-77
Hauptverfasser: Gomoll, Andreas H., Yanke, Adam B., Kang, Richard W., Chubinskaya, Susan, Williams, James M., Bach, Bernard R., Cole, Brian J.
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container_end_page 77
container_issue 1
container_start_page 72
container_title The American journal of sports medicine
container_volume 37
creator Gomoll, Andreas H.
Yanke, Adam B.
Kang, Richard W.
Chubinskaya, Susan
Williams, James M.
Bach, Bernard R.
Cole, Brian J.
description Background Previous investigations have reported on the chondrotoxicity of bupivacaine in short-term in vivo and in vitro models. This study was designed to provide additional information on the long-term effects of bupivacaine infusion on articular cartilage in an established rabbit shoulder model. Hypothesis Infusion of bupivacaine into the rabbit shoulder will have long-term deleterious effects on articular cartilage. Study Design Controlled laboratory study. Methods Thirty-six rabbits were randomized into 3 groups and were infused over 48 hours with saline (S), bupivacaine alone (B), or bupivacaine with epinephrine (B+E) into the glenohumeral joint. Animals were sacrificed after 3 months, and tissue samples were analyzed with live/dead cell assay, proteoglycan (PG) synthesis and content assays, and conventional histological evaluation. Results No macroscopic or radiographic changes were detected in the infused shoulders. Sulfate uptake of infused shoulders relative to controls was elevated to 112% ±39% (S), 166% ±67% (B), and 210% ±127% (B+E). Statistical analysis of PG content demonstrated significantly increased levels in bupivacaine groups compared with saline. There were no significant differences among groups in cell count, percentage of living cells, or histological grade. Conclusions No permanent impairment of cartilage function was detected 3 months after intra-articular infusion of bupivacaine. Cartilage metabolism was increased, indicating a possible reparative response. This suggests that, at least in the model used, articular cartilage has the ability to recover from the chondrotoxic effects of bupivacaine infusion. Before extrapolating these results to human cartilage, other factors including underlying cartilage injury or disease, decreased chondrocyte density, and increased bupivacaine dosing need to be taken into account. Clinical Relevance Bupivacaine toxicity has recently been implicated in the development of chondrolysis after arthroscopic shoulder procedures, but these findings suggest that additional noxious stimuli might be required before permanent damage ensues.
doi_str_mv 10.1177/0363546508323748
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This study was designed to provide additional information on the long-term effects of bupivacaine infusion on articular cartilage in an established rabbit shoulder model. Hypothesis Infusion of bupivacaine into the rabbit shoulder will have long-term deleterious effects on articular cartilage. Study Design Controlled laboratory study. Methods Thirty-six rabbits were randomized into 3 groups and were infused over 48 hours with saline (S), bupivacaine alone (B), or bupivacaine with epinephrine (B+E) into the glenohumeral joint. Animals were sacrificed after 3 months, and tissue samples were analyzed with live/dead cell assay, proteoglycan (PG) synthesis and content assays, and conventional histological evaluation. Results No macroscopic or radiographic changes were detected in the infused shoulders. Sulfate uptake of infused shoulders relative to controls was elevated to 112% ±39% (S), 166% ±67% (B), and 210% ±127% (B+E). Statistical analysis of PG content demonstrated significantly increased levels in bupivacaine groups compared with saline. There were no significant differences among groups in cell count, percentage of living cells, or histological grade. Conclusions No permanent impairment of cartilage function was detected 3 months after intra-articular infusion of bupivacaine. Cartilage metabolism was increased, indicating a possible reparative response. This suggests that, at least in the model used, articular cartilage has the ability to recover from the chondrotoxic effects of bupivacaine infusion. Before extrapolating these results to human cartilage, other factors including underlying cartilage injury or disease, decreased chondrocyte density, and increased bupivacaine dosing need to be taken into account. Clinical Relevance Bupivacaine toxicity has recently been implicated in the development of chondrolysis after arthroscopic shoulder procedures, but these findings suggest that additional noxious stimuli might be required before permanent damage ensues.</description><identifier>ISSN: 0363-5465</identifier><identifier>EISSN: 1552-3365</identifier><identifier>DOI: 10.1177/0363546508323748</identifier><identifier>PMID: 18832481</identifier><identifier>CODEN: AJSMDO</identifier><language>eng</language><publisher>Los Angeles, CA: American Orthopaedic Society for Sports Medicine</publisher><subject>Anesthetics, Local - administration &amp; dosage ; Anesthetics, Local - pharmacology ; Animals ; Arthroscopy ; Biological and medical sciences ; Bupivacaine - administration &amp; dosage ; Bupivacaine - pharmacology ; Cartilage ; Cartilage, Articular - drug effects ; Diseases of the osteoarticular system ; Endoscopy ; Investigative techniques, diagnostic techniques (general aspects) ; Medical sciences ; Outcome Assessment (Health Care) ; Pain - drug therapy ; Rabbits ; Random Allocation ; Shoulder ; Shoulder Joint - drug effects ; Sports medicine ; Toxicity</subject><ispartof>The American journal of sports medicine, 2009-01, Vol.37 (1), p.72-77</ispartof><rights>2009 American Orthopaedic Society for Sports Medicine</rights><rights>2009 INIST-CNRS</rights><rights>Copyright Sage Publications Ltd. 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This study was designed to provide additional information on the long-term effects of bupivacaine infusion on articular cartilage in an established rabbit shoulder model. Hypothesis Infusion of bupivacaine into the rabbit shoulder will have long-term deleterious effects on articular cartilage. Study Design Controlled laboratory study. Methods Thirty-six rabbits were randomized into 3 groups and were infused over 48 hours with saline (S), bupivacaine alone (B), or bupivacaine with epinephrine (B+E) into the glenohumeral joint. Animals were sacrificed after 3 months, and tissue samples were analyzed with live/dead cell assay, proteoglycan (PG) synthesis and content assays, and conventional histological evaluation. Results No macroscopic or radiographic changes were detected in the infused shoulders. Sulfate uptake of infused shoulders relative to controls was elevated to 112% ±39% (S), 166% ±67% (B), and 210% ±127% (B+E). Statistical analysis of PG content demonstrated significantly increased levels in bupivacaine groups compared with saline. There were no significant differences among groups in cell count, percentage of living cells, or histological grade. Conclusions No permanent impairment of cartilage function was detected 3 months after intra-articular infusion of bupivacaine. Cartilage metabolism was increased, indicating a possible reparative response. This suggests that, at least in the model used, articular cartilage has the ability to recover from the chondrotoxic effects of bupivacaine infusion. Before extrapolating these results to human cartilage, other factors including underlying cartilage injury or disease, decreased chondrocyte density, and increased bupivacaine dosing need to be taken into account. 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Medical Complete (Alumni)</collection><collection>Nursing &amp; Allied Health Premium</collection><collection>Calcium &amp; Calcified Tissue Abstracts</collection><jtitle>The American journal of sports medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gomoll, Andreas H.</au><au>Yanke, Adam B.</au><au>Kang, Richard W.</au><au>Chubinskaya, Susan</au><au>Williams, James M.</au><au>Bach, Bernard R.</au><au>Cole, Brian J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Long-Term Effects of Bupivacaine on Cartilage in a Rabbit Shoulder Model</atitle><jtitle>The American journal of sports medicine</jtitle><addtitle>Am J Sports Med</addtitle><date>2009-01-01</date><risdate>2009</risdate><volume>37</volume><issue>1</issue><spage>72</spage><epage>77</epage><pages>72-77</pages><issn>0363-5465</issn><eissn>1552-3365</eissn><coden>AJSMDO</coden><abstract>Background Previous investigations have reported on the chondrotoxicity of bupivacaine in short-term in vivo and in vitro models. This study was designed to provide additional information on the long-term effects of bupivacaine infusion on articular cartilage in an established rabbit shoulder model. Hypothesis Infusion of bupivacaine into the rabbit shoulder will have long-term deleterious effects on articular cartilage. Study Design Controlled laboratory study. Methods Thirty-six rabbits were randomized into 3 groups and were infused over 48 hours with saline (S), bupivacaine alone (B), or bupivacaine with epinephrine (B+E) into the glenohumeral joint. Animals were sacrificed after 3 months, and tissue samples were analyzed with live/dead cell assay, proteoglycan (PG) synthesis and content assays, and conventional histological evaluation. Results No macroscopic or radiographic changes were detected in the infused shoulders. Sulfate uptake of infused shoulders relative to controls was elevated to 112% ±39% (S), 166% ±67% (B), and 210% ±127% (B+E). Statistical analysis of PG content demonstrated significantly increased levels in bupivacaine groups compared with saline. There were no significant differences among groups in cell count, percentage of living cells, or histological grade. Conclusions No permanent impairment of cartilage function was detected 3 months after intra-articular infusion of bupivacaine. Cartilage metabolism was increased, indicating a possible reparative response. This suggests that, at least in the model used, articular cartilage has the ability to recover from the chondrotoxic effects of bupivacaine infusion. Before extrapolating these results to human cartilage, other factors including underlying cartilage injury or disease, decreased chondrocyte density, and increased bupivacaine dosing need to be taken into account. Clinical Relevance Bupivacaine toxicity has recently been implicated in the development of chondrolysis after arthroscopic shoulder procedures, but these findings suggest that additional noxious stimuli might be required before permanent damage ensues.</abstract><cop>Los Angeles, CA</cop><pub>American Orthopaedic Society for Sports Medicine</pub><pmid>18832481</pmid><doi>10.1177/0363546508323748</doi><tpages>6</tpages></addata></record>
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subjects Anesthetics, Local - administration & dosage
Anesthetics, Local - pharmacology
Animals
Arthroscopy
Biological and medical sciences
Bupivacaine - administration & dosage
Bupivacaine - pharmacology
Cartilage
Cartilage, Articular - drug effects
Diseases of the osteoarticular system
Endoscopy
Investigative techniques, diagnostic techniques (general aspects)
Medical sciences
Outcome Assessment (Health Care)
Pain - drug therapy
Rabbits
Random Allocation
Shoulder
Shoulder Joint - drug effects
Sports medicine
Toxicity
title Long-Term Effects of Bupivacaine on Cartilage in a Rabbit Shoulder Model
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