Pre-clinical investigation of cardioprotective therapies for acute myocardial ischemia/reperfusion-injury and for pressure-overload-induced chronic heart failure
Viktor Nabil Sayour
Gyógyszertudományok és Egészségügyi Technológiák Tagozat
Dr. Zelkó Romána
NET Tanácsterem
2025-11-11 14:00:00
Experimental and Clinical Pharmacology
Dr. Szökő Éva
Dr. Varga Zoltán, Dr. Giricz Zoltán
Dr. Horváth Eszter Mária
Dr. Pipicz Márton
Dr. Benyó Zoltán
Dr. Bugyik Edina
Dr. Baczkó István
In this doctoral work, we aimed to analyse cardioprotective approaches for acute myocardial ischemia/reperfusion-injury and for pressure-overload-induced chronic heart failure. To this end (i) we tested the cardioprotective efficacy of limb remote ischemic conditioning, an already known cardioprotective method for acute myocardial ischemia/reperfusion-injury, and (ii) identified and tested novel, possible cardioprotective pathways for chronic heart failure using small animal models of disease, in two separate studies. Overall, these studies were the first (i) to demonstrate the absence of cardioprotective efficacy of limb remote ischemic conditioning in a rat model of acute myocardial ischemia/reperfusion-injury, (ii) to identify possible publication bias towards positive results of published studies testing the cardioprotective efficacy of limb remote ischemic conditioning, (iii) to use droplet digital PCR based screening for pharmacologically targetable G-protein-coupled receptors in chronic heart failure – and in any disease in general, and (iv) to show antihypertrophic efficacy of prostaglandin-F2α receptor blockade, potentially targetable in heart failure.
In conclusion, based on the above studies, to improve the success of translation of potential cardioprotective approaches for acute myocardial ischemia/reperfusion-injury and for chronic heart failure from pre-clinical testing into clinical reality, it is suggested to publish well-reported, methodologically reproducible studies, irrespective of the outcome, as without such studies, clinically translatable cardioprotective interventions could not be identified. In addition, we emphasize that screening for molecular targets that have already available pharmacological modifiers, i.e. that can be subjects for drug repositioning, could also improve the translational success rate.
Overall, we believe that our studies and results contribute to the improvement of translation from bench to bedside in the field of cardioprotection.
