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Study of arterial and autonomic effects of cyclosporine in humans
D Lucini1, R V Milani, H O Ventura
1Centro di Ricerca sulla Terapia Neurovegetativa, Medicina Interna I, Ospedale "L. Sacco, Centro Ricerche Cardiovascolari, CNR, Universit¿a di Milano, Milano, Italy.
Abstract:
Altered sympathetic activity and peripheral vascular function are suspected as a mechanism of the development of arterial hypertension in organ transplantation recipients treated with cyclosporine. We assessed whether cyclosporine might alter peripheral vascular properties or autonomic modulation of the sinus node and the vasculature during rest and standing. We examined 17 orthotopic heart transplantation recipients, 8 solid organ transplantation recipients, 17 patients with essential hypertension, and 42 normotensive control subjects. All except the normotensive control subjects were treated with a long-acting dihydropyridine calcium entry blocker; transplantation recipients also received cyclosporine-based immunosuppression. Radial artery compliance was reduced in patients with essential hypertension and in patients with heart and solid organ transplantation as compared with normotensive control subjects, with this reduction being more marked in heart transplantation recipients. At rest, R-R variance was lowest in heart transplantation recipients, denoting denervation. The spectral profile of both R-R and systolic blood pressure variability as well as the index of baroreflex gain was normal at rest in patients with solid organ transplantation. On standing, both transplantation groups demonstrated reduced responsiveness in markers of autonomic modulation. The decrease in arterial compliance in cyclosporine-induced hypertension seems to imply a degree of ventricular vascular uncoupling more apparent in heart transplantation recipients. These changes are associated with alterations in autonomic modulation that are evidenced by an orthostatic stimulus.
Insights
Cyclosporine may worsen arterial hypertension in transplant recipients by reducing arterial compliance and altering autonomic nervous system function. These vascular and neural changes are evident during rest and orthostatic stress.
Area of Science:
- Cardiovascular Physiology
- Transplantation Medicine
- Nephrology
Background:
- Cyclosporine is a common immunosuppressant after organ transplantation.
- Altered sympathetic activity and vascular function are implicated in cyclosporine-induced arterial hypertension.
- The specific impact of cyclosporine on vascular properties and autonomic modulation requires further investigation.
Purpose of the Study:
- To assess if cyclosporine alters peripheral vascular properties.
- To evaluate cyclosporine's effect on autonomic modulation of the sinus node and vasculature.
- To compare these effects in heart and solid organ transplant recipients versus essential hypertension patients and controls.
Main Methods:
- Studied 17 heart transplant recipients, 8 solid organ transplant recipients, 17 essential hypertension patients, and 42 controls.
- Measured radial artery compliance, R-R variance, systolic blood pressure variability, and baroreflex gain.
- Assessed autonomic modulation at rest and during orthostatic stress (standing).
Main Results:
- Reduced radial artery compliance was observed in transplant recipients and essential hypertension patients, most notably in heart transplant recipients.
- Heart transplant recipients showed the lowest R-R variance at rest, indicating denervation.
- Both transplant groups exhibited diminished autonomic responsiveness upon standing.
Conclusions:
- Cyclosporine-associated hypertension may involve decreased arterial compliance and impaired autonomic control.
- These vascular and autonomic alterations are more pronounced in heart transplant recipients.
- Findings suggest a potential ventricular-vascular uncoupling and altered autonomic modulation in cyclosporine-treated patients.
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