[Ischemic preconditioning. Does this animal experiment phenomenon have clinical relevance?].

BACKGROUND

Infarct size following coronary artery occlusion can be markedly reduced by brief preceding periods of ischemia in several animal models. This phenomenon is called "ischemic preconditioning" and is one of the most powerful mechanisms of cardioprotection known to date.

PRECONDITIONING IN HUMANS

There is increasing evidence that preconditioning effects exist in humans as well. The occurrence of angina prior to myocardial infarction might result in reduction of infarct size depending on the time pattern of preinfarct-angina. Similarly, "walking-through-angina", i.e., the relief of exercise-induced anginal symptoms with continuing exercise, is attributed to cardioprotection by ischemic preconditioning. During coronary angioplasty, a lesser shift of ST segments in the intracardial ECG and reduced anginal symptoms are registered during a second balloon inflation in comparison with the first balloon inflation. These findings might represent a "preconditioning-like" effect of the first balloon inflation.

THERAPEUTICAL IMPLICATIONS

With respect to the mechanisms of ischemic preconditioning identified in animal models some pharmacological agents that exhibit a "preconditioning-like" cardioprotective effect have been intensively investigated. In clinical studies it was demonstrated that application of adenosine, adenosine-receptor-agonists, and dipyridamole--a nucleoside-transport inhibitor--prior to coronary angioplasty results in reduced ischemia during the subsequent balloon inflation. In a randomized trial the treatment with nicorandil, an activator of the ATP-sensitive potassium channel (K-ATP channel) in patients with unstable angina resulted in a marked reduction of myocardial ischemia which also can be attributed to a "preconditioning-like" effect. Therapeutical applications of ischemic preconditioning have been developed in different clinical settings: brief periods of ischemia and "pharmacologic preconditioning" prior to coronary angioplasty, prior to cardiac surgery, and for protection of donor heart for cardiac transplantation were performed to induce cardioprotection. Moreover, possible "anti-preconditioning effects" of several drugs have to be carefully considered for the treatment of patients with coronary artery disease. In particular, patients treated for acute myocardial infarction by coronary angioplasty with concomitant sulfonylurea drug therapy using glibenclamide demonstrated an increased early mortality.

CONCLUSION

To raise the step from "laboratory-based protection" to "evidence-based medicine" further research should focus on clinical studies transferring the results from animal models to the clinical setting.