British journal of pharmacology
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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. ⋯ 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.
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In patients with acute myocardial infarction, timely reperfusion is essential to limit infarct size. However, reperfusion also adds to myocardial injury. Brief episodes of ischaemia/reperfusion in the myocardium or on organ remote from the heart, before or shortly after sustained myocardial ischaemia effectively reduce infarct size, provided there is eventual reperfusion. ⋯ All studies with bradykinin or drugs which increase bradykinin's bioavailability reported reduced infarct size and some of them also improved clinical outcome. Synthetic opioid agonists did not result in a robust infarct size reduction, but this failure of translation may relate to the cardioprotective properties of the underlying anaesthesia per se or of the comparator drugs. The translation of findings in healthy, young animals with acute coronary occlusion/reperfusion to patients of older age, with a variety of co-morbidities and co-medications, suffering from different scenarios of myocardial ischaemia/reperfusion remains a challenge.
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Several noble gases, although classified as inert substances, exert a tissue-protective effect in different experimental models when applied before organ ischaemia as an early or late preconditioning stimulus, after ischaemia as a post-conditioning stimulus or when given in combination before, during and/or after ischaemia. A wide range of organs can be protected by these inert substances, in particular cardiac and neuronal tissue. In this review we summarize the data on noble gas-induced cardioprotection, focusing on the underlying protective mechanisms. We will also look at translatability of experimental data to the clinical situation.