Background: Remote ischemic preconditioning (RIP) represents a novel form of innate cardioprotection conferred by short episodes of ischemia applied in a distant organ/tissue. Efficiency of RIP in increasing myocardial resistance against ischemia-reperfusion (I/R) injury has been shown in 3-months old male rats with RIP applied either directly prior to I/R or 24-h before ischemia. However, there is no evidence on the effects of RIP in hearts from spontaneously hypertensive (SHR) rats. This study aimed to investigate the effect of RIP on cardiac tolerance to I/R in male SHR rats of different ages.
Methodology: Rats of age three, five and eight months were anesthetized and RIP was performed on the right hind limb. Its protocol consisted of three cycles of 5-min non-invasive limb occlusion followed by 5-min reperfusion. Subsequently, hearts were excised, Langendorff-perfused and exposed to 30-min global I and 2-h R for the evaluation of reperfusion-induced ventricular arrhythmias, infarct size and recovery of contractile function.
Results: Only hearts five months old SHR rats exposed to RIP protocol exhibited significantly improved recovery of contractile function (LVDP). On the other hand, enhanced resistance to myocardial infarction compared to non-preconditioned animals was observed in all experimental groups. Moreover, in three and five months old animals RIP exhibited antiarrhythmic effect, while its impact on arrhytmogenesis in eight months old SHR rats was negative.
Conclusions: RIP may represent an effective protecting stimulus in the hearts of SHR animals. Cardioprotective effects of RIP in SHR rats show partial age-dependency, since in older adult animals, RIP decreased size of lethal injury but failed to improve recovery of contractile function and even worsened arrhythmogenesis compare to younger adults. RIP may influence various aspects of I/R injury in different way.
Grants: VEGA2/0201/15, APVV-0102-11, APVV-SK-CZ-2013-0075.
RIP
Is it possible to quantify the extent of RIP or precisely dose RIP? Thanks.
Re: RIP
Thank you for your question. To quantify the extent of area affected by RIP is difficult, bacause RIP is based on occlusion of hind limb (femoral artery). The size of occluded area depends on size of animal. We can visualize and proof the presence of occlusion- ischemia and reperfusion of femoral artery by MRI. Please find attached .ppt file in "iné" :)
5-mesacna skupina
Je zaujimave, ze efekt na LVDP a LVEDP recovery sa prejavil len na 5-mesacnych potkanoch. Je to opakovany jav alebo sa to tyka tohto konkretneho vrhu? Ake velke boli vase skupiny?
A mozem este poprosit vysvetlenie, co presne znamenaju skratky LVDP, LVDEP, IS/AR a VT?
Dakujem!
Re: 5-mesacna skupina
Dobry den, dakujem za otazku. LVDP-left ventricular developed pressure-tlak vyvinutý ľavou komorou; LVEDP-left vntricular end diastolic presssure-koncový diastolický tlak v ľavej komore;VT -ventricular tachycardia; IS/AR-infarct size/area at risk-veľkosť infarktu/riziková oblasť. LVDP a LVEDP vo vseobecnosti hovoria o funkcnej respektive kontrakcnej schopnosti myokardu. Pozitivny efekt RIP na parametre kontraktility len u 5mesacnych jedincov je zaujimavy aj pre nas. Z hladiska vekovo zavislych ucinkov RIP u SHR jedincov nie su zname ziadne data takze tazko usudzovat ci sa jedna o ojedinely jav, vyhradny ucinok RIP alebo je mozny aj vplyv inych faktorov. To ukazu az opakovane pokusy. Za najvyznamnejsie povazujeme negativne ucinky RIP na arytmogenézu pri zachovanom antiinfarktovom ucinku u 8mesacnych potkanov, co moze poukazovat na zvysenu citlivost starsich jedincov s hypertenziou k vzniku zivot ohrozujucich arytmii prave v dosledku aplikacie RIP. ucinky RIP su malo preskumane u jedincov s roznymi komorbiditami, ktore mozu ovplyvnovat ucinok RIP na srdce. V skupinach sme mali po 7 potkanov.
Ventrikulárna tachykardia
Ahoj. Zaujímalo by ma, či bol podobný účinok na srdce (ventrikulárna tachykardia) pozorovaný u ľudí s vyvinutou hypertenziou, ktorým bol aplikovaný RIP. Za odpoveď dopredu ďakujem.
Re: Ventrikulárna tachykardia
Ahoj. Ďakujem za otázku. Z hľadiska klinických trialov nie sú známe žiadne priame súvislosti medzi RIP a hypertenziou, čo je dané tým, že pacient, ktorí podstupujú RIP majú viacero komorbidít prípadne aj komedikácií. Takže dávať priamo do súvisu účinky RIP u hypertenzných pacientov je zložité. Avšak štúdia Lucchinetti et al. (2012) poukázala na proarytmogénne účinky RIP u pacientov podstupujúcich CABG. Práve kôli rôznym komrbiditám a komedikáciám sú aj výsledky klinických trialov o účinkoch RIP často protichodné a nejasné.