Investigation of the effect of bupivacaine and dexmedetomidine on wound healing in rat

Tissuelossesthatoccurduetothedisruption of theintegrity of body structuresarecalled 'wounds'. Woundhealing;occurs as a result of theintegration of a series of cellular, biochemicalandphysiologicalevents Bupivacaine is one of theamide-derivedlocalanesthetics. Thisdrug has shownbothanesthesiaandanalgesiaeffects in localinfiltration. Variousstudieshaveshownthattheeffects of bupivacaine, which is frequentlyusedtoreducepain on wounds, on woundhealingarecontroversial. Thesympatholytic, anxiolytic, analgesicandsedativeeffects of dexmedetomidine, a selectivealpha 2 adrenergicreceptor agonist, areused in clinicalanesthesiamanagement. Manyexperimentalandclinicalstudieshaveshownthatdexmedetomidineadministration has anti-inflammatoryeffects. Inthisstudy, it wasplannedtoinvestigatetheeffects of bupivacaine, which is widelyusedbylocalinfiltrationduetoitsanalgesicproperties, anddexmedetomidine, which has recentlystartedto be used, on woundhealing. Itwasaimedtorevealalternativepossibilitiesforwoundhealingtreatmentbyexaminingtheearlywoundhealingeffects of bupivacaine, dexmedetomidineandtheircombineduse in ratswherewoundswerecreatedbyincision. 28 Wistar albino malerats, 6 to 8 weeksoldandweighing 250-350 g, wereincluded in thestudy. Untilthebeginning of theresearch, theratswerekept at roomtemperature (22-24oC), at an averagerelativehumidity of 35%, in a 12-hour light-12-hour darkenvironment, andwere fed withstandardpelletfeedandwaterandmonitored. Therewerenofeedorwaterrestrictions. Ratsweredividedintofourgroups in total, 7 in eachgroup. Anesthesia of allrats in thegroupswasprovidedwith intraperitoneal (ip) 50 mg/kg ketamine. Whennecessary, maintenance ketamine (halfdose, 25 mg/kg) wasrepeatedbycheckingreflexresponses (monitoringjawor skeletal muscletone) tokeepthedepth of anesthesia of theratsconstant. Afteranesthesia, theratswerefixedtotheoperatingtable in theproneposition. Thebackhairwasshavedandcleanedwith an electricshaver. Theareawheretheincisionwasto be madewaswipedwithpovidone-iodineanddriedwith sterile gauzeafterwaitingfor 2 minutes. After 2 minutesafterthesolutionsdeterminedforeachgroupwereinfiltratedintotheincisionarea, a perforatedcompresswasplacedunder sterile conditionsand a longitudinalsurgicalincisionwasmade, includingthe skin andsubcutaneousconnectivetissue, of 4 cm with a scalpelalongthemidlinefromthebackarea, andthenwith a 3/0 prolenethread. skinandsubcutaneoustissuesweremutuallycombined. Aftertheprocedure, acetaminophen at a dose of 30 mg/kg, 1-2 ml wasgiventhroughdrinkingwater as a painreliever. Antibioticswere not given at anystage of theprocedureoraftertheprocedure. Ratswerekept in sheltersfor 8 daysunder optimum livingconditions, in thesameenvironmentandwiththesamefoodandwaterneeds. Woundcarewasperformedonce a day. On the 8th dayaftertheprocedure, theanimalsweresacrificedunderanesthesiawith intraperitoneal ketamine. Allratsweresacrificed at theend of the 8th day, and a 6*4 cm strip of skin andsubcutaneoustissuewasremovedunder sterile conditionsfromtheareawhere an incisionwasmade on theback. Histologicalexaminationwasdonewith a 2 cm part of thematerial, hydroxyproline in thetissuewith a 1 cm part, andthetensionstrength of thewoundareawascalculatedwiththetensiometrydevicewiththeremainingmaterial (1x1 cm²). Tnf-alpha, interlokin 6 andinterlokin 10 levelswerestudiedby RT-PCR methodwithintracardiacbloodtaken at hour 0. Additionally, ELISA methodwasusedtoanalyzethehydroxyprolinelevel in tissues. Hydroxyproline ELISA test wasperformed in theRatHyp (Hydroxyproline) ELISA Kits of A.B.T LaboratoryIndustrywiththeprotocolspecifiedbythecompany. Histologicalevaluationwascarriedout in TOGU HistologyandEmbryologylaboratory. Allresultsobtainedwereevaluatedstatistically. Inourstudy, consistentwiththeliterature, it wasfoundthat IL-10 gene expression, which is considered an anti-inflammatorycytokine, wassignificantlyhigher in thegroupgivendexmedetomidinethan in thegroupgivenbupivacaine. Inourstudy, a significantdifferencewasfoundbetweenallgroupsexceptthecontrolanddexmedetomidinegroups in terms of vascularity. Itwasobservedthatbupivacainenegativelyaffectswoundhealingandreducesthenumber of vessels, whiledexmedetomidineincreasesthenumber of vessels, which has a positiveeffect, andthegroupusingbupivacaine + dexmedetomidineformedmorevesselsthanbupivacaine but lessthandexmedetomidine. Inlight of thedataweobtained in ourstudy, wethinkthatbupivacaine has a negativeeffect on woundhealing, whiledexmedetomidine has a positiveeffect on woundhealing in general. Webelievethatwhenthese two drugsareusedtogether, dexmedetomidineslightlyreducesthenegativeeffects of bupivacaine. Morestudiesareneededtofullyrevealthiseffect. KeyWords:Bupivacaine, Dexmedetomidine, Woundhealing, Inflammation, Woundinfiltration