Pharmacological Conditioning of the Heart: An Update on Experimental Developments and Clinical Implications

Abstract

The aim of pharmacological conditioning is to protect the heart against myocardial ischemia-reperfusion (I/R) injury and its consequences. There is extensive literature that reports a multitude of different cardioprotective signaling molecules and mechanisms in diverse experimental protocols. Several pharmacological agents have been evaluated in terms of myocardial I/R injury. While results from experimental studies are immensely encouraging, translation into the clinical setting remains unsatisfactory. This narrative review wants to focus on two aspects: (1) give a comprehensive update on new developments of pharmacological conditioning in the experimental setting concentrating on recent literature of the last two years and (2) briefly summarize clinical evidence of these cardioprotective substances in the perioperative setting highlighting their clinical implications. By directly opposing each pharmacological agent regarding its recent experimental knowledge and most important available clinical data, a clear overview is given demonstrating the remaining gap between basic research and clinical practice. Finally, future perspectives are given on how we might overcome the limited translatability in the field of pharmacological conditioning.

Keywords: cardioprotection; ischemia reperfusion injury; molecular mechanisms; postconditioning; preconditioning.

Figure 1

Molecular targets of pharmacological conditioning. GPCR = G protein-coupled receptor; TNF-R2 = tumor necrosis factor receptor 2; gp130 = glycoprotein 130; TRPV4 = transient receptor potential vanilloid 4; VEGFR-1 = vascular endothelial growth factor receptor 1; SAFE = survivor activating factor enhancement; TNFα = tumor necrosis factor alpha; JAK/STAT = janus kinase/signal transducers and activators of transcription; RISK = reperfusion injury salvage kinase; PI3K = phosphatidylinositol 3-kinase; PKB = protein kinase B; ERK = extracellular-signal-regulated kinase; GSK3β = glycogen synthase kinase 3 beta; NO/PKG = nitric oxide/protein kinase G; eNOS = endothelial nitric oxide synthase; cGMP = cyclic guanosine monophosphate; miRNA = micro ribonucleic acid; mBK_Ca = mitochondrial large-conductance calcium-sensitive potassium channel, mK_ATP = mitochondrial adenosine triphosphate-sensitive potassium channel; mPTP = mitochondrial permeability transition pore.