| Title: |
Pharmacological Cardioprotection against Ischemia Reperfusion Injury—The Search for a Clinical Effective Therapy |
| Authors: |
Qian Wang, Coert J. Zuurbier, Ragnar Huhn, Carolin Torregroza, Markus W. Hollmann, Benedikt Preckel, Charissa E. van den Brom, Nina C. Weber |
| Source: |
Cells, Vol 12, Iss 10, p 1432 (2023) |
| Publisher Information: |
MDPI AG, 2023. |
| Publication Year: |
2023 |
| Collection: |
LCC:Cytology |
| Subject Terms: |
cardioprotection, ischemia-reperfusion injury, drug development, Cytology, QH573-671 |
| More Details: |
Pharmacological conditioning aims to protect the heart from myocardial ischemia-reperfusion injury (IRI). Despite extensive research in this area, today, a significant gap remains between experimental findings and clinical practice. This review provides an update on recent developments in pharmacological conditioning in the experimental setting and summarizes the clinical evidence of these cardioprotective strategies in the perioperative setting. We start describing the crucial cellular processes during ischemia and reperfusion that drive acute IRI through changes in critical compounds (∆GATP, Na+, Ca2+, pH, glycogen, succinate, glucose-6-phosphate, mitoHKII, acylcarnitines, BH4, and NAD+). These compounds all precipitate common end-effector mechanisms of IRI, such as reactive oxygen species (ROS) generation, Ca2+ overload, and mitochondrial permeability transition pore opening (mPTP). We further discuss novel promising interventions targeting these processes, with emphasis on cardiomyocytes and the endothelium. The limited translatability from basic research to clinical practice is likely due to the lack of comorbidities, comedications, and peri-operative treatments in preclinical animal models, employing only monotherapy/monointervention, and the use of no-flow (always in preclinical models) versus low-flow ischemia (often in humans). Future research should focus on improved matching between preclinical models and clinical reality, and on aligning multitarget therapy with optimized dosing and timing towards the human condition. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2073-4409 |
| Relation: |
https://www.mdpi.com/2073-4409/12/10/1432; https://doaj.org/toc/2073-4409 |
| DOI: |
10.3390/cells12101432 |
| Access URL: |
https://doaj.org/article/7c2f903cb2d14ff5aa142cd8e9b5eddb |
| Accession Number: |
edsdoj.7c2f903cb2d14ff5aa142cd8e9b5eddb |
| Database: |
Directory of Open Access Journals |
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