Timely reperfusion is mandatory for salvage of ischemic myocardium from irreversible damage. However, reperfusion induces damage per se, ie reperfusion injury contributes to final infarct size [1]. Ischemic postconditioning, ie brief episodes of intermittent coronary re-occlusion during early reperfusion, reduces infarct size. This protective effect was confirmed in all species tested so far [2], including humans [3], but common co-morbidities of ischemic heart disease may interfere with cardioprotective mechanisms including ischemic postconditioning [4]. The signal transduction of ischemic postconditioning is still unclear in detail [5]. Activation of “reperfusion injury salvage kinases”(RISK) is causal for ischemic postconditioning’s protection in rodents [6]. In pigs, in which coronary anatomy and the spatial and temporal development of myocardial infarction are closer to that of humans, RISK activation is not mandatory for protection [7].

The mitochondrial permeability transition pore (mPTP) is a potential end-effector of myocardial protection at reperfusion [8–10]. Cyclosporine A binds to cyclophilin D, inhibits mPTP opening and reduces infarct size [9, 11]. Apart from experiments in rodents, cyclosporine A when given at reperfusion reduced infarct size in a proof-of-concept study in patients with acute myocardial infarction [12]. Protection by cyclosporine A at reperfusion was now tested in pigs. Enflurane-anesthetized Göttinger minipigs (20–40 kg body weight) of either sex were subjected to 90 min controlled hypoperfusion of the left anterior descending coronary artery and 120 min reperfusion [7]. In four pigs cyclosporine A (5 mg/kg iv) was infused 5 min before reperfusion; in four pigs, ischemic postconditioning was induced with six cycles of 20 s re-occlusion/reperfusion each; four pigs with immediate full reperfusion served as controls. Systemic hemodynamics (Table 1) and subendocardial blood flow during ischemia (microspheres) were matched between groups (Fig. 1). Both, cyclosporine A at reperfusion and ischemic postconditioning reduced infarct size (TTC staining) to a similar extent compared to controls (Fig. 1).