Pharmacological Cardioprotection against Ischemia Reperfusion Injury—The Search for a Clinical Effective Therapy
Qian Wang,
Coert J. Zuurbier,
Ragnar Huhn,
Carolin Torregroza,
Markus W. Hollmann,
Benedikt Preckel,
Charissa E. van den Brom,
Nina C. Weber
Affiliations
Qian Wang
Department of Anesthesiology—L.E.I.C.A., Amsterdam University Medical Centers, Location AMC, Cardiovascular Science, Meibergdreef 11, 1105 AZ Amsterdam, The Netherlands
Coert J. Zuurbier
Department of Anesthesiology—L.E.I.C.A., Amsterdam University Medical Centers, Location AMC, Cardiovascular Science, Meibergdreef 11, 1105 AZ Amsterdam, The Netherlands
Ragnar Huhn
Department of Anesthesiology, Kerckhoff-Clinic-Center for Heart, Lung, Vascular and Rheumatic Disease, Justus-Liebig-University Giessen, Benekestr. 2-8, 61231 Bad Nauheim, Germany
Carolin Torregroza
Department of Anesthesiology, Kerckhoff-Clinic-Center for Heart, Lung, Vascular and Rheumatic Disease, Justus-Liebig-University Giessen, Benekestr. 2-8, 61231 Bad Nauheim, Germany
Markus W. Hollmann
Department of Anesthesiology—L.E.I.C.A., Amsterdam University Medical Centers, Location AMC, Cardiovascular Science, Meibergdreef 11, 1105 AZ Amsterdam, The Netherlands
Benedikt Preckel
Department of Anesthesiology—L.E.I.C.A., Amsterdam University Medical Centers, Location AMC, Cardiovascular Science, Meibergdreef 11, 1105 AZ Amsterdam, The Netherlands
Charissa E. van den Brom
Department of Anesthesiology—L.E.I.C.A., Amsterdam University Medical Centers, Location AMC, Cardiovascular Science, Meibergdreef 11, 1105 AZ Amsterdam, The Netherlands
Nina C. Weber
Department of Anesthesiology—L.E.I.C.A., Amsterdam University Medical Centers, Location AMC, Cardiovascular Science, Meibergdreef 11, 1105 AZ Amsterdam, The Netherlands
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.
