EFFECT OF OBSTRUCTIVE NEPHROPATHY AND PARICALCITOL ON THE ELECTROPHYSIOLOGICAL RESPONSE TO MYOCARDIAL ISCHEMIA-REPERFUSION INJURY.

EMILIANO DIEZ; NATALIA PRADO; LILIANA ALTAMIRANO; AMIRA PONCE ZUMINO; WALTER MANUCHA

Madrid

Congreso; At the heart of the genome: Frontiers in cardiovascular genomics; 2011

Chronic kidney disease (CKD) is highly prevalent and is associated with cardiovascular disease. Paricalcitol protects from some renal and cardiovascular complication. However, its electrophysiological effect during myocardial ischemia-reperfusion is currently unknown. The aim of this work was to evaluate the cardiovascular electrophysiological impact of obstructive nephropathy and the effect of paricalcitol administration under this renal disease.  Female Wistar rats were divided in 3 experimental groups: 1) Control, 2) complete unilateral ureteral obstruction (UUO) for 15 days and, 3) UUO treated with 30ng/Kg/day paricalcitol, IP (UUO-PARI) starting at the day of the obstruction (n = 8 per group). Isolated hearts were submitted to 10 minutes of regional ischemia and reperfusion. We analyzed the incidence and severity of reperfusion arrhythmias. We measure vitamin D receptor (VDR) expression in the heart, the transmembrane potential and ECG. The incidence of ventricular tachycardia at reperfusion was similar in all the groups (Control 62.5%, UUO 100% and UUO-PARI 75% ns). Ventricular fibrillation increased in the UUO (C 12.5% ​​vs 75% P <0.05 by ÷2) and PARI administration protected against this type of arrhythmia (0%). PARI induced an increase in action potential duration at 90% repolarization. The VDR were decreased in UUO group (relative optical density units 0.87± 0.05 Control vs. 0.6 ± 0.02 UUO <0.05) the administration of paricalcitol restored the levels to those of control hearts (0.85 ± 0.04).  We conclude that the reduction of VDR expression in UUO hearts could be related to the increase arrhythmogenesis. The recovery induced by paricalcitol could protect against ventricular fibrillation by the lengthening of the action potential. Further studies will be necessary to elucidate these interesting kidney-heart interaction.