Related Experiment Video
Updated: Aug 19, 2026

Quantification of the Immunosuppressant Tacrolimus on Dried Blood Spots Using LC-MS/MS
Published on: November 8, 2015
Time-domain evaluation of cyclosporine interaction with hemodynamic variability in rats
Amal G Omar1, Mahmoud M El-Mas
1Department of Pharmacology, Faculty of Pharmacy, University of Alexandria, Alexandria, Egypt.
Abstract:
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.
Related Concept Videos
Chronopharmacokinetics: Circadian Rhythms and Influence on Drug Response
The time of drug administration is an important factor to consider, as it can influence the toxic dose of a drug. For example, a study conducted by Prins et al. in 1997 examined the effects of the timing of...
Chronopharmacokinetics: Time-Dependent Pharmacokinetics
Time-dependent pharmacokinetics refers to non-cyclical changes in drug rate processes over a period of time. It can lead to nonlinear pharmacokinetics, where the relationship between drug concentration and time is not proportional. Non-cyclical...
Drug Accumulation During Multiple Dosing: Intermittent IV Infusions
Drug Concentration Versus Time Correlation
Two pivotal parameters are the minimum effective concentration (MEC) and the minimum toxic concentration (MTC). The MEC is the lowest drug...
Therapeutic Drug Monitoring: Affecting Factors
Drug Dosing in Renal Diseases: Dose Adjustments Based on Drug Clearance and Elimination Rate Constant
