Effect of Combined Simvastatin and Cyclosporine
Effect of Combined Simvastatin and Cyclosporine
Object: The object of this study was to determine whether the combination of cyclosporine and simvastatin could ameliorate cerebral vasospasm after subarachnoid hemorrhage (SAH) in a canine model to a greater extent than simvastatin alone.
Methods: Animals were assigned to one of three groups: control (five dogs), simvastatin alone (four), or simvastatin and cyclosporine (four). A double SAH model was used. Baseline basilar artery (BA) angiograms were obtained. These were repeated at Days 3, 7, and 10. Measurement of the BA diameter was performed.
Decreased BA diameter was seen on Day 3 in the control and simvastatin/cyclosporine group. A return to baseline diameters was seen by Day 7. An increase from baseline diameter was seen in the simvastatin group at Day 10.
Conclusions: Cyclosporine may interfere with the vasodilatory effects of simvastatin. Vasodilation greater than baseline is seen at Day 10 in the simvastatin group. The combination of simvastatin and cyclosporine does not ameliorate cerebral vasospasm in a canine model to a greater extent than simvastatin alone.
Two salient points emerge from the literature about cerebral vasospasm. The first is that SAH has been associated with histopathological damage to cerebrovascular endothelium. This results in impaired endothelium-dependent relaxation responses mediated by NO. Simvastatin upregulates NOS and has been shown to ameliorate cerebral vasospasm. The second point is that the breakdown of blood products leads to an intense inflammatory response that parallels the time course for cerebral vasospasm.
Some studies have shown that immunosuppression with cyclosporin A ameliorates cerebral vasospasm. To our knowledge, no study has been conducted to evaluate amelioration of cerebral vasospasm during simultaneous up regulation of NO and immunosuppression. In this study, we tested the hypothesis that simultaneously upregulating NOS with simvastatin after SAH and suppressing the inflammatory reaction with cyclosporin A would ameliorate cerebral vasospasm to a greater extent than doing either one alone.
Abstract and Introduction
Abstract
Object: The object of this study was to determine whether the combination of cyclosporine and simvastatin could ameliorate cerebral vasospasm after subarachnoid hemorrhage (SAH) in a canine model to a greater extent than simvastatin alone.
Methods: Animals were assigned to one of three groups: control (five dogs), simvastatin alone (four), or simvastatin and cyclosporine (four). A double SAH model was used. Baseline basilar artery (BA) angiograms were obtained. These were repeated at Days 3, 7, and 10. Measurement of the BA diameter was performed.
Decreased BA diameter was seen on Day 3 in the control and simvastatin/cyclosporine group. A return to baseline diameters was seen by Day 7. An increase from baseline diameter was seen in the simvastatin group at Day 10.
Conclusions: Cyclosporine may interfere with the vasodilatory effects of simvastatin. Vasodilation greater than baseline is seen at Day 10 in the simvastatin group. The combination of simvastatin and cyclosporine does not ameliorate cerebral vasospasm in a canine model to a greater extent than simvastatin alone.
Introduction
Two salient points emerge from the literature about cerebral vasospasm. The first is that SAH has been associated with histopathological damage to cerebrovascular endothelium. This results in impaired endothelium-dependent relaxation responses mediated by NO. Simvastatin upregulates NOS and has been shown to ameliorate cerebral vasospasm. The second point is that the breakdown of blood products leads to an intense inflammatory response that parallels the time course for cerebral vasospasm.
Some studies have shown that immunosuppression with cyclosporin A ameliorates cerebral vasospasm. To our knowledge, no study has been conducted to evaluate amelioration of cerebral vasospasm during simultaneous up regulation of NO and immunosuppression. In this study, we tested the hypothesis that simultaneously upregulating NOS with simvastatin after SAH and suppressing the inflammatory reaction with cyclosporin A would ameliorate cerebral vasospasm to a greater extent than doing either one alone.
