Book of Abstracts - New Frontiers 2022

Abstracts of oral presentations

NON- INVASIVE „CONDITIONING“: POTENTIAL MECHANISMS OF ANTIISCHEMIC CARDIOPROTECTION

T. Ravingerová 1 , Ľ. Lonek 1 , L. Kindernay 1 , V. Zohdi 2 , A. Adameová 1,3

1 Institute for Heart Research, Centre of Experimental Medicine, Slovak Academy of Sciences, Bratislava, Slovakia; 2 Institute of Anatomy, Faculty of Medicine, Comenius University, Bratislava, Slovakia; 3 Department of Pharmacology and Toxicology, Faculty of Pharmacy, Comenius University Bratislava, Slovakia Although ischemic preconditioning (IPC) is the most robust adaptive intervention protecting the heart of all animal species against ischemia/reperfusion (I/R) injury, its application in humans is limited to elective (planned) operations due to technical requirements, such as chest opening, short-term duration and unpredictable occurrence of AMI. However, some other forms of “conditioning” do not require an invasive intervention. Among those, pharmacological PC, hypoxia, remote PC (RPC), or exercise (EPC) also confer strong cardioprotection. We explored whether preventive interventions applied in vivo increase cardiac resistance to I/R prior to AMI ex vivo using non-invasive approaches in the adult male Wistar rats: voluntary exercise (2 weeks) and RPC, second phase (24 h after application, 2-RPC). For EPC, animals were placed in cages equipped with wheels for free running, while control sedentary animals stayed in the cages without wheels. RPC was induced by 3 cycles of 5min inflation (200 mmHg)/5min deflation of pressure cuff on the hind limb.Resistance to I/R after both interventions was tested in the Langendorff-perfused hearts exposed to 30 min ischemia/2 hrs reperfusion, focused on changes in post-I/R recovery of function, reperfusion arrhythmias and extent of lethal injury (infarct size, IS/AR, TTC staining). In parallel groups, heart tissue samples were obtained for the investigation of the levels and activity of several proteins involved in “pro survival” RISK cascade and pro - and anti-apoptotic cascades. Echocardiography revealed lower BW and LV mass, PW width and HR, without changes in ejection fraction and in LV/BW index in “runners” and no changes after RPC. Both EPC and 2 -RPC significantly reduced contractile dysfunction, IS/AR and incidence and severity of reperfusion arrhythmias. Protective effects were associated with a significant up-regulation of selected RISK proteins (PKB, PKC, eNOS), higher levels of SOD, HSP and reduction of proapoptoticcascades (BAX/Bcl-2, Caspase-3). Conclusions: Beneficial effects of non- invasive forms of “conditioning”, sub -chronic free running and RPC, suggest their potential in the management of ischemic heart disease in clinical conditions. Potential mechanisms may involve activation of proteins of “pro - survival” cascade s, antiapoptotic and antioxidative effects.

Keywords: ischemia/reperfusion, cardioprotection, preconditioning, adaptation

Funding:Supported by grants VEGA 2/0104/22, 1/0016/20, APVV-19-0540, APVV-20-0242.

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