Year: 2008
Type: dissertation
Abstract: It has recently been observed that the application of multiple short cycles of reperfusion and ischaemia, at the onset of reperfusion, elicits cardioprotection against injury due to prior sustained ischaemia.This phenomenon has been termed "postconditioning" (postC) and is of special interest due to its clinical applicability.Although much work has been done to delineate the mechanism of protection, there is still controversy regarding the precise algorithm of postC, the importance of the reperfusion injury salvage kinases (RISK), as well as uncertainty about the possible role of p38 MAPK and the protein phosphatases in postC cardioprotection.The aims of this study were therefore: I. To develop and characterise a cardioprotective postC protocol in the ex vivo rat Na 10 of 30 minute herperfusie is harte wat blootgestel is aan 'n kardiobeskermende postC ingreep of gewone standaard herperfusie na iskemie, in beide perfusie modelle, gevriesklamp.Die weefsel proteïen-inhoud is verder geanaliseer deur van die Western blot tegniek gebruik te maak vir bepaling van die totale en fosforileerde vlakke van PKB/Akt, ERK p42/p44 en p38 MAPK.Die funksionele belang van PKB/Akt en ERK p42/p44 is verder ondersoek deur die effek van 'n geskikte inhibitor (onderskeidelik A6730 en PD098059, toegedien tydens die laaste 5 minute van iskemie en die eerste 10 minute van herperfusie), in die teenwoordigheid en afwesigheid van die postC ingreep, op infarktgrootte en kinase aktiwiteit te monitor.Die moontlike rol van proteïen fosfatases in postC is ondersoek deur die effek van cantharidin ('n PP1 en PP2A inhibitor) op infarktgrootte en kinase profiele te ondersoek.Cantharidin is óf onmiddelik voor iskemie óf tydens herperfusie toegedien, in die aan -en afwesigheid van die postC ingreep.Daar is bevind dat 'n postC protokol van 6x10 sekondes globale iskemie / herperfusie, teen 37°C, die mees effektiewe en konstante verlaging in infarktgrootte teweeg gebring het in beide die ballon model (IFS in NonPostC: 47.99±3.31%vs postC: 27.81±2.49%;p<0.0001), asook die werkhart (IFS in NonPostC: 35.81±3.67%vs postC: 17.74±2.73%,p<0.001).Funksionele herstel kon egter slegs ontlok word in die ballon model (na 30 minute GI: tempo druk produk (RPP) herstel: NonPostC = 12.27±2.63%vs postC = 24.61±2.53%,p<0.05; en na 35 minute GI: linker ventrikulêre ontwikkelde druk (LVDP) herstel: NonPostC = 28.40±7.02%vs postC = 48.49±3.14%,p<0.05).Die infarktbesparende effek van postC was geassosieer met 'n toename in die fosforilasie van beide PKB/Akt (NonPostC: 0.88±0.26AU (arbitrêre eenhede) vs postC: 1.65±0.06AU; p<0.05) en ERK p42 (NonPostC: 2.03±0.2AU vs postC: 3.13±0.19AU; p<0.05).Inhibisie van PKB/Akt met A6730 (2.5 µM) het die infarkt-besparende effek van postC opgehef.Inhibisie van PP1 en PP2A opsigself, deur toediening van cantharidin óf voor óf na iskemie (in die afwesigheid van postC), het 'n infarkt-besparende effek ontlok (IFS in PreCanth: 15.42±1.80%,PostCanth: 21.60±2.79%;p<0.05).Hierdie kardiobeskerming was geassosieer met 'n toename in die fosforilasie van beide p38 MAPK (met toediening voor iskemie: NonCanth: 1.52±0.
Author: Derick van Vuuren
Language: English
Subfield: Cardiology and Cardiovascular Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2166581909