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Int J Mol Sci. 2021 Oct 12;22(20). doi: 10.3390/ijms222011009.

Impact of Maturation on Myocardial Response to Ischemia and the Effectiveness of Remote Preconditioning in Male Rats.

International journal of molecular sciences

Lucia Kindernay, Veronika Farkasova, Jan Neckar, Jaroslav Hrdlicka, Kirsti Ytrehus, Tanya Ravingerova

Affiliations

  1. Institute for Heart Research, Centre of Experimental Medicine, Slovak Academy of Sciences, 9 Dúbravská cesta, 84104 Bratislava, Slovakia.
  2. Institute of Physiology, Academy of Sciences of the Czech Republic, 1083 Víde?ská, 142 00 Prague, Czech Republic.
  3. Department of Medical Biology, UiT The Arctic University of Norway, 18 Hansine Hansens veg, 9019 Tromsø, Norway.

PMID: 34681669 PMCID: PMC8540346 DOI: 10.3390/ijms222011009

Abstract

Aging attenuates cardiac tolerance to ischemia/reperfusion (I/R) associated with defects in protective cell signaling, however, the onset of this phenotype has not been completely investigated. This study aimed to compare changes in response to I/R and the effects of remote ischemic preconditioning (RIPC) in the hearts of younger adult (3 months) and mature adult (6 months) male Wistar rats, with changes in selected proteins of protective signaling. Langendorff-perfused hearts were exposed to 30 min I/120 min R without or with prior three cycles of RIPC (pressure cuff inflation/deflation on the hind limb). Infarct size (IS), incidence of ventricular arrhythmias and recovery of contractile function (LVDP) served as the end points. In both age groups, left ventricular tissue samples were collected prior to ischemia (baseline) and after I/R, in non-RIPC controls and in RIPC groups to detect selected pro-survival proteins (Western blot). Maturation did not affect post-ischemic recovery of heart function (Left Ventricular Developed Pressure, LVDP), however, it increased IS and arrhythmogenesis accompanied by decreased levels and activity of several pro-survival proteins and by higher levels of pro-apoptotic proteins in the hearts of elder animals. RIPC reduced the occurrence of reperfusion-induced ventricular arrhythmias, IS and contractile dysfunction in younger animals, and this was preserved in the mature adults. RIPC did not increase phosphorylated protein kinase B (p-Akt)/total Akt ratio, endothelial nitric oxide synthase (eNOS) and protein kinase Cε (PKCε) prior to ischemia but only after I/R, while phosphorylated glycogen synthase kinase-3β (GSK3β) was increased (inactivated) before and after ischemia in both age groups coupled with decreased levels of pro-apoptotic markers. We assume that resistance of rat heart to I/R injury starts to already decline during maturation, and that RIPC may represent a clinically relevant cardioprotective intervention in the elder population.

Keywords: ischemia/reperfusion injury; maturation; protective cell signaling; remote ischemic preconditioning

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