Background-Contrast medium-induced acute kidney injury is associated with substantial morbidity and mortality. The underlying mechanism has been attributed in part to ischemic kidney injury. The aim of this randomized, double-blind, sham-controlled trial was to assess the impact of remote ischemic preconditioning on contrast medium-induced acute kidney injury. Methods and Results-Patients with impaired renal function (serum creatinine Ͼ1.4 mg/dL or estimated glomerular filtration rate Ͻ60 mL ⅐ min Ϫ1 ⅐ 1.73 m Ϫ2 ) undergoing elective coronary angiography were randomized in a 1:1 ratio to standard care with (nϭ50) or without ischemic preconditioning (nϭ50; intermittent arm ischemia through 4 cycles of 5-minute inflation and 5-minute deflation of a blood pressure cuff). Overall, both study groups were at high risk of developing contrast medium-induced acute kidney injury according to the Mehran risk score. The primary end point was the incidence of contrast medium-induced kidney injury, defined as an increase in serum creatinine Ն25% or Ն0.5 mg/dL above baseline at 48 hours after contrast medium exposure. Contrast medium-induced acute kidney injury occurred in 26 patients (26%), 20 (40%) in the control group and 6 (12%) in the remote ischemic preconditioning group (odds ratio, 0.21; 95% confidence interval, 0.07-0.57; Pϭ0.002). No major adverse events were related to remote ischemic preconditioning. Conclusions-Remote ischemic preconditioning before contrast medium use prevents contrast medium-induced acute kidney injury in high-risk patients. Our findings merit a larger trial to establish the effect of remote ischemic preconditioning on clinical outcomes. Clinical Trial Registration-URL: http://www.germanctr.de. Unique identifier: U1111-1118-8098. (Circulation. 2012;126:296-303.)

Background-The pacemaker current I f contributes to spontaneous diastolic depolarization of cardiac autonomic cells. In heterologous expression, HCN channels exhibit a hyperpolarization-activated inward current similar to I f . However, the links between HCN genes and native I f are largely inferential, and it remains unknown whether I f is essential for cardiac pacing. Methods and Results-To clarify this situation, we generated a GYG 402-404 AYA pore mutation of HCN2, which rendered the channel nonfunctional and suppressed wild-type HCN2 in a dominant-negative manner in Chinese hamster ovary cells. In addition, HCN2-AYA suppressed I HCN4 in a dominant-negative manner when coexpressed with wild-type HCN4, indicating that the 2 isoforms HCN2 and HCN4 are able to coassemble to form heteromultimeric complexes.

There is currently no effective prophylactic regimen available to prevent contrastinduced AKI (CI-AKI), a frequent and life-threatening complication after cardiac catheterization. Therefore, novel treatment strategies are required to decrease CI-AKI incidence and to improve clinical outcomes in these patients. Remote ischemic preconditioning (rIPC), defined as transient brief episodes of ischemia at a remote site before a subsequent prolonged ischemia/reperfusion injury of the target organ, is an adaptational response that protects against ischemic and reperfusion insult. Indeed, several studies demonstrated the tissue-protective effects of rIPC in various target organs, including the kidneys. In this regard, rIPC may offer a novel noninvasive and virtually cost-free treatment strategy for decreasing CI-AKI incidence. This review evaluates the current experimental and clinical evidence for rIPC as a potential renoprotective strategy, and discusses the underlying mechanisms and key areas for future research.

Conclusion: In patients at high risk for contrast-induced nephropathy, remote ischemic preconditioning (rIPC) before contrast medium use prevents acute kidney injury (AKI). Summary: The main predictor of contrast-induced AKI (CI-AKI) is a decreased estimated glomerular filtration rate (eGFR) of <60 mL/min/ 1.73 m 2. The magnitude of decrease in eGFR correlates directly with CI