Unilateral Acute Renal Ischemia-Reperfusion Injury Induces Cardiac Dysfunction through Intracellular Calcium Mishandling

Background: Acute renal failure (ARF) following renal ischemia-reperfusion (I/R) injury is considered a relevant risk factor for cardiac damage, but the underlying mechanisms, particularly those triggered at cardiomyocyte level, are unknown. Methods: We examined intracellular Ca(2+) dynamics in adult ventricular cardiomyocytes isolated from C57BL/6 mice 7 or 15 days following unilateral renal I/R. Results: After 7 days of I/R, the cell contraction was significantly lower in cardiomyocytes compared to sham-treated mice. It was accompanied by a significant decrease in both systolic Ca(2+) transients and sarco/endoplasmic reticulum Ca(2+)-ATPase (SERCA(2a)) activity measured as Ca(2+) transients decay. Moreover, the incidence of pro-arrhythmic events, measured as the number of Ca(2+) sparks, waves or automatic Ca(2+) transients, was greater in cardiomyocytes from mice 7 days after I/R than from sham-treated mice. Ca(2+) mishandling related to systolic Ca(2+) transients and contraction were recovered to sham values 15 days after I/R, but Ca(2+) sparks frequency and arrhythmic events remained elevated. Conclusions: Renal I/R injury causes a cardiomyocyte Ca(2+) cycle dysfunction at medium (contraction-relaxation dysfunction) and long term (Ca(2+) leak), after 7 and 15 days of renal reperfusion, respectively.