N-acetylcysteine somewhere between Scylla and Charybdis.

hiele et al. (1) report a study dealing with the impact of -acetylcysteine (NAC) administered simultaneously on preventng iodinated contrast agent-induced nephropathy and reperfusion njury in patients with ST-segment elevation myocardial infarction reated by percutaneous coronary intervention (PCI). The study ncluded 126 patients compared with a placebo-treated group. heir results as well as conclusions generate many noteworthy ssociations. Free oxygen radicals are regarded as variable typically involved ither in reperfusion of previously ischemic tissue anywhere in the ody or in specific interaction between the iodinated contrast agent nd the filtration capacity of the kidney, with the latter being most ronounced with previous kidney injury. As a result, the exact mode of action of NAC (defense against ree oxygen radicals) in the LIPSIA-N-ACC (Prospective, singlelind, placebo-controlled, randomized Leipzig Immediate PercuaneouS coronary Intervention Acute myocardial infarction -ACC) trial still remains unclear. First, most importantly, it hould be taken into account that all patients had normal serum reatinine level, perhaps a crucial fact for further evaluation. A ifferent study design including patients with a priori elevated erum creatinine levels (roughly at least 140 mol/l) would be ore appropriately representative by making the same size of the atient group sufficient for final statistical analysis. Even so, the ncidence of contrast agent-induced nephropathy incidence in he NAC-treated arm of the LIPSIA-N-ACC trial was reported o be lower by 6% when compared with the placebo group. Second, nother fact raising some doubt is the selected dose of NAC: 1,200 g of NAC before PCI cannot be regarded as a high dose even if dministered intravenously. In experimental studies, an approxiate dose of 100 mg NAC/kg body weight has been used before nduction of injury (i.e., this is de facto the total dose of NAC used n the present trial including doses administered within 48 h ost-procedurally). Third, likewise, the distribution of NAC etween the 2 target organs remains unclear: the kidney exposed to he burden of the iodinated contrast agent versus the ischemic/ eperfused myocardium (i.e., the proportion of NAC entering the aforementioned organs and even more so, after recirculation hrough the pulmonary vessel bed: a Killip class 2 was reported n 11% of the NAC group and in 14% of the placebo group). The AC bolus and, actually, the whole dose administered is figuraively somewhere between Scylla and Charybdis, with the former eing nephron stress and the latter ischemic and reperfusion yocardial injury. Fourth, the enigma for researchers to be yet esolved continues to be which “high” dose of NAC is actually high” in terms of being functionally adequate for both the organ i ompartments in question. The authors (1) report a 20% eduction of oxidative stress markers in the NAC group: this is, owever, a biochemical parameter, perhaps not yet reaching a evel high enough to have a functional or possibly structural mpact on the injured myocardial area. Fortunately enough, lmost all patients were receiving angiotensin-converting enyme inhibitors/angiotensin II type 1 antagonists and statins— opefully comparable?—in both study groups. Fifth, earlier uman studies (for details, see appropriate references in Thiele t al. [1]) used different types of myocardial reperfusion/ oronary artery recanalization: fibrinolysis (2) involving opening f the artery by gradual dissolution of a fresh red thrombus, hereas current PCI is “an instantaneous switch for coronary lood flow from the closed to open position.” Sixth, the forementioned makes it unclear whether mode NAC action on he myocardial microvasculature is the same in both reperfusion echniques. Finally, judging by experimental animal studies, AC seems to exert more beneficial effects on the filtration apacity of the kidney in its more developed injury (3). The reader could now perhaps say the study simply failed. owever, from a scientific point of view, I personally feel this ell-designed study has provided many provoking stimuli for urther research and definitely is not to be perceived as a breaking oint for making indiscriminate decisions in our current clinical ractice.