Time-domain evaluation of cyclosporine interaction with hemodynamic variability in rats.

This study investigated the effects of chronic exposure of Wistar rats to the immunosuppressant drug cyclosporine on blood pressure, heart rate, and their variability and the role of sympathovagal balance in this interaction. The blood pressure variability was determined as the standard deviation of the mean arterial pressure (SDMAP). Two time-domain heart rate variability indices were employed, the standard deviation of beat-to-beat intervals (SDRR) and the root mean square of successive beat-to-beat differences in R-R interval durations (rMSSD). Subcutaneous cyclosporine administration (20 mg/kg/day) for 12 days had no effect on blood pressure or its variability index (SDMAP). In contrast, the average level of heart rate and its variability indices (SDRR and rMSSD) showed significant increases and decreases, respectively, in cyclosporine- compared with vehicle-treated rats. Vagal (atropine) or beta -adrenergic (propranolol) blockade had no effect on blood pressure but elicited increases and decreases, respectively, in heart rate. Compared with control rats, cyclosporine-treated rats exhibited lesser tachycardic responses to atropine and greater bradycardic responses to propranolol, suggesting alterations of cardiac vagal (attenuation) and sympathetic (enhancement) activity by cyclosporine. Further, atropine reduced indices of heart rate variability (rMSSD and SDRR) in control rats, effects that were blunted by cyclosporine treatment. On the other hand, propranolol had no effect on heart rate variability in either cyclosporine-treated or control rats. These findings implicate vagally-mediated alterations in the cardiac sympathovagal balance in the cyclosporine-induced impairment of heart rate oscillations.