Anaesthetics as cardioprotectants: translatability and mechanism

Abstract

The pharmacological conditioning of the heart with anaesthetics, such as volatile anaesthetics or opioids, is a phenomenon whereby a transient exposure to an anaesthetic agent protects the heart from the harmful consequences of myocardial ischaemia and reperfusion injury. The cellular and molecular mechanisms of anaesthetic conditioning appear largely to mimic those of ischaemic pre-and post-conditioning. Progress has been made on the understanding of the underlying mechanisms although the order of events and the specific targets of anaesthetics that trigger protection are not always clear. In the laboratory, the protection afforded by certain anaesthetics against cardiac ischaemia and reperfusion injury is powerful and reproducible but this has not necessarily translated into similarly robust clinical benefits. Indeed, clinical studies and meta-analyses delivered variable results when comparing in the laboratory setting protective and non-protective anaesthetics. Reasons for this include underlying conditions such as age, obesity and diabetes. Animal models for disease or ageing, human cardiomyocytes derived from stem cells of patients and further clinical studies are employed to better understand the underlying causes that prevent a more robust protection in patients. LINKED ARTICLESThis article is part of a themed section on Conditioning the Heart -Pathways to Translation. To view the other articles in this section visit http://dx.doi.org/10. 1111/bph.2015.172.issue-8 Abbreviations eNOS, endothelial nitric oxide synthase; GSK3β, glycogen synthase kinase 3β; iPSCs, induced pluripotent stem cells; KATP channel, ATP-sensitive potassium channel; ROS, reactive oxygen species BJP British Journal of Pharmacology

Sevoflurane postconditioning affects post‐ischaemic myocardial mitochondrial ATP‐sensitive potassium channel function and apoptosis in ageing rats

“…Ischaemic postconditioning, which consists of several short cycles of reperfusion and ischaemia during early reperfusion, effectively reduces the ischaemic myocardial infarct area, improves myocardial systolic function, decreases reperfusion arrhythmia, prevents apoptosis, and significantly influences ischaemia/reperfusion (I/R) injury . Pharmacological postconditioning is an exogenous intervention that may avoid ischaemic postconditioning‐induced mechanical damage to the cardiovascular system . Sevoflurane has been used during the reperfusion period to simulate ischaemic postconditioning and to activate endogenous protective mechanisms, thereby protecting the ischaemic myocardium and reducing I/R injury.…”

Peri‐operative cardiac protection for non‐cardiac surgery

“…In addition, volatile anaesthetics were effective in postconditioning, where exposure at the beginning of reperfusion after ischaemia was cardioprotective . The mechanism of action involves G‐protein coupled receptors, protein kinase C, adenosine receptors, reactive oxygen species, intracellular signalling kinases, nitrogen species, caveolae, sarcolemmal and mitochondrial potassium channels and mitochondrial metabolism .…”

‘Conditioning the heart’ – lessons we have learned from the past and future perspectives for new and old conditioning ‘drugs’

“…The two reviews dealing with the probable most easily translatable conditioning strategies using anaesthetics or noble gases extensively describe the mechanisms underlying such cardioprotection (Kikuchi et al ., , Smit et al ., ). Protection induced by volatile anaesthetics (Kikuchi et al ., ) and later on noble gases, like xenon and helium (Smit et al ., ), has been recognized for the last two decades.…”

“…The two reviews dealing with the probable most easily translatable conditioning strategies using anaesthetics or noble gases extensively describe the mechanisms underlying such cardioprotection (Kikuchi et al ., , Smit et al ., ). Protection induced by volatile anaesthetics (Kikuchi et al ., ) and later on noble gases, like xenon and helium (Smit et al ., ), has been recognized for the last two decades. Unfortunately, these two reviews come to the disappointing conclusion that the application of these substances, although already clinically used, is still limited and advances in this field are minimal (Kikuchi et al ., , Smit et al ., ).…”

“…Protection induced by volatile anaesthetics (Kikuchi et al ., ) and later on noble gases, like xenon and helium (Smit et al ., ), has been recognized for the last two decades. Unfortunately, these two reviews come to the disappointing conclusion that the application of these substances, although already clinically used, is still limited and advances in this field are minimal (Kikuchi et al ., , Smit et al ., ). Ageing, diabetes, hyperglycaemia and drugs frequently used in AMI patients (beta blockers, glibenclamide) have been shown to diminish this form of conditioning in animals as well as in humans (Kikuchi et al ., ).…”