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Increased susceptibility to ventricular arrhythmias is associated with changes in Ca²⁺ regulatory proteins in paraplegic rats

Department of Physiology, School of Medicine, Wayne State University, Detroit, Michigan 48201

Submitted 4 April 2003 ; accepted in final form 21 July 2003

Paraplegia may increase susceptibility to ventricular arrhythmias by altering the autonomic control of the heart. Altered cardiac autonomic control has been documented to change the expression of genes that encode cardiac Ca²⁺ regulatory proteins. Therefore, we tested the hypothesis that paraplegia alters cardiac electrophysiology with concomitant changes in Ca²⁺ regulatory proteins in a manner that increases the susceptibility to ventricular arrhythmias. To test this hypothesis, intact (n = 10) and paraplegic (n = 6) male Wistar rats were chronically instrumented to measure atrioventricular (AV) interval, sinus cycle length, sinus node recovery time (SNRT), SNRT corrected for spontaneous sinus cycle (cSNRT), Wenckebach cycle length (WCL), and the electrical stimulation threshold to induce ventricular arrhythmias. In addition, relative protein abundance and mRNA expression for sarco(endo)plasmic reticulum Ca²⁺ ATPase (SERCA), phospholamban, and the Na/Ca exchanger were determined in intact (n = 8) and paraplegic (n = 8) rats. Paraplegia significantly (P < 0.05) reduced AV interval (–25%), sinus cycle length (–24%), SNRT (–28%), cSNRT (–53%), WCL (–19%), and the electrical stimulation threshold to induce ventricular arrhythmia (–48%). Paraplegia significantly increased the relative protein abundances of SERCA (45%) and the Na/Ca exchanger (40%) and decreased phospholamban levels (–28%). In contrast, only the relative mRNA expression of the Na/Ca exchanger was increased (25%) in paraplegic rats. These data demonstrate that paraplegia enhances cardiac electrophysiological properties and alters Ca²⁺ regulatory proteins in a manner that increases susceptibility to ventricular arrhythmias.

sarco(endoplasmic) reticulum calcium ATPase; phospholamban; exchanger; real-time polymerase chain reaction; electrocardiogram

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