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Cardiac arrhythmias after renal I/R depend on IL-1β

2019; Elsevier BV; Volume: 131; Linguagem: Inglês

10.1016/j.yjmcc.2019.04.025

1095-8584

María Micaela López Alarcón, Mayra Trentin‐Sonoda, Karine Panico, Ygor Schleier, Thabata Duque, Oscar Moreno-Loaiza, Ainhoa Rodriguez de Yurre Guirao, Fabiano Ferreira, Wellington Caio‐Silva, Pedrosa Roberto Coury, Cláudia N. Paiva, Emiliano Medei, Marcela Sorelli Carneiro‐Ramos,

Cardiac Arrest and Resuscitation

Aims Cardiac arrhythmias are one of the most important remote complications after kidney injury. Renal ischemia reperfusion (I/R) is a major cause of acute renal injury predisposing to several remote dysfunctions, including cardiac electrical disturbance. Since IL-1β production dependent on NLRP3 represents a link between tissue malfunctioning and cardiac arrhythmias, here we tested the hypothesis that longer ventricular repolarization and arrhythmias after renal I/R depend on this innate immunity sensor. Methods and results Nlrp3−/− and Casp1−/− mice reacted to renal I/R with no increase in plasma IL-1β, different from WT (wild-type) I/R. A prolonged QJ interval and an increased susceptibility to ventricular arrhythmias were found after I/R compared to Sham controls in wild-type mice at 15 days post-perfusion, but not in Nlrp3−/− or CASP1−/− I/R, indicating that the absence of NLRP3 or CASP1 totally prevented longer QJ interval after renal I/R. In contrast with WT mice, we found no renal atrophy and no renal dysfunction in Nlrp3−/− and Casp1−/− mice after renal I/R. Depletion of macrophages in vivo after I/R and a day before IL-1β peak (at 7 days post-perfusion) totally prevented prolongation of QJ interval, suggesting that macrophages might participate as sensors of tissue injury. Moreover, treatment of I/R-WT mice with IL-1r antagonist (IL-1ra) from 8 to 15 days post perfusion did not interfere with renal function, but reversed QJ prolongation, prevented the increase in susceptibility to ventricular arrhythmias and rescued a close to normal duration and amplitude of calcium transient. Conclusion Taken together, these results corroborate the hypothesis that IL-1β is produced after sensing renal injury through NRLP3-CASP1, and IL-1β on its turn triggers longer ventricular repolarization and increase susceptibility to cardiac arrhythmias. Still, they offer a therapeutic approach to treat cardiac arrhythmias that arise after renal I/R.