This article is the second part of two papers on ischaemic preconditioning. The first part of this review was published in the November issue of this journal. 1 ABSTRACT Ischaemic preconditioning was originally described in animal hearts as histological infarct-size limitation by a previous brief episode of ischaemia. In humans, ischaemic preconditioning has been demonstrated in several in vitro and in vivo models, including coronary artery bypass graft- ing and percutaneous transluminal coronary angiograplasty, using surrogate markers of ischaemia and reperfusion injury. Increasing knowledge of the molecular signalling pathways mediating protection by ischaemic precondi- tioning has provided rational targets for pharmacological intervention. Several widely used drugs are able to mimic ischaemic preconditioning (e.g. adenosine, adenosine- uptake inhibitors, ACE inhibitors, angiotensin II antag- onists, statins, opioids, volatile anaesthetics and ethanol), whereas others inhibit ischaemic preconditioning-induced protection (e.g. sulphonylureas and adenosine antagonists). The present review focuses on these different classes of drugs. Prudent use or avoidance of these drugs in patients who are at risk for myocardial infarction could theoretically limit ischaemia and reperfusion injury. INTRODUCTION In the first part of this review on ischaemic preconditioning, we described the infarct size limiting effects of the naturally occurring phenomenon of ischaemic preconditioning and the time windows in which this effect occurs. 1 Moreover, the interesting observation that a short period of ischaemia also renders distant organs resistant to a subsequent prolonged period of ischaemia was discussed. Finally, the most important triggers, mediators and end-effectors of ischaemic preconditioning that have been identified so far were summarised. However, most data described in this part were derived from animal experiments. Because these studies have convincingly shown that ischaemic precondi- tioning is the strongest form of in vivo protection against myocardial ischaemic injury other than early reperfusion, the possibility of using this phenomenon in clinical practice would be very desirable. Despite state-of-the-art reperfusion strategies, 30-day mortality of myocardial infarction is still around 7%. 2 In addition, the prevalence of cardiac failure is rapidly increasing and is often caused by (ischaemic) death of cardiomyocytes. Thus, there is a need for additional therapeutic strategies that increase tolerance to ischaemia and reperfusion. Exploitation of ischaemic preconditioning may offer such a strategy. To adequately exploit this mechanism in the everyday clinical setting, three more issues need to be addressed. First, the evidence that preconditioning also occurs in the human heart needs to be discussed. Secondly, if indeed protection can be seen in humans, could it be exploited to develop therapeutic strategies to protect the human heart against ischaemic injury? In clinical practice, it is often not desirable or feasible to precondition myocardium with ischaemia. Fortunately, the accumulating knowledge about the molecular mechanisms mediating preconditioning has provided us with the possibility to modulate ischaemia and DECEMBER 2004, VOL. 62, NO. 11 © 2004 Van Zuiden Communications B.V. All rights reserved. 409 REVIEW Ischaemic preconditioning: from molecular characterisation to clinical application - part II N.P. Riksen * , P. Smits ** , G.A. Rongen Departments of Pharmacology Toxicology and General Internal Medicine, University Medical Centre St Radboud, Nijmegen, the Netherlands, tel.: +31 (0)24-36136 91, fax: +31 (0)24-361 42 14, e-mail: N.Riksen@aig.umcn.nl, * corresponding author ** P. Smits was not involved in the handling and review process of this paper.