Date of Award

Spring 1999

Document Type

Thesis

Degree Name

Master of Science in Biomedical Engineering - (M.S.)

Department

Biomedical Engineering Committee

First Advisor

Alex Y. Bekker

Second Advisor

Arthur B. Ritter

Third Advisor

Stanley S. Reisman

Abstract

The purpose of this project was to develop a computer model of cerebrovascular hemodynamics interacting with a pharmacodynamic drug model to examine the effects of three commonly used anti-hypertensive drugs upon intracranial pressure and cerebral blood flow. The model is used to predict cerebrovascular response during the administration of commonly used anti-hypertensive agents.

The mathematical model of intracranial hemodynamics is a seven compartment constant volume system. A series of resistances relate blood and cerebrospinal fluxes to pressure gradients between compartments. Arterial, venous and tissues compliance are included. Autoregulation is modeled by transmural pressure-dependent arterial-arteriolar resistance. The effects of three drugs (Sodium Nitroprusside, Nitroglycerin and Esmolol) on cerebrovascular circulation was simulated by a variable arteriolar-capillary resistance and capillary-venous resistance. The three drugs are known to have a rapid on-set, a short half-life and are normally therapeutically administered using continuous infusion. A direct relationship between mean arterial pressure and arteriolar-capillary and capillary-venous resistance was developed. Comparing the simulation results with available experimental observations validated the model. The simulation program was written usingVisSim ® dynamic simulation language for an IBM-compatible PC.

The developed model was used to calculate intracranial pressure changes that occur with deliberate hypertension. Response to intravascular administration was predicted for simulated patients with elevated intracranial pressure and non-autoregulated cerebral circulation. The simulations demonstrated that Sodium Nitroprusside and Nitroglycerin reduce mean arterial pressure while simultaneously elevating intracranial pressure. The simulations demonstrated that intracranial pressure increases with reduction in mean arterial pressure until a maximum value is reached at which point a reduction in intracranial pressure occurs with additional decreases in mean arterial pressure. Esmolol reduces mean arterial pressure without a significant change in intracranial pressure.

The presented simulation compared the effect of commonly used anti- hypertensive drugs on cerebral hemodynamics. The simulation demonstrates that Sodium Nitroprusside and Nitroglycerin may increase intracranial pressure. This effect is more significant in non-autoregulated circulation. Only minor intracranial pressure changes have been predicted during Esmolol infusion. Esmolol is a preferable intraoperative hypotensive agent for patients with non-auto-regulated cerebral circulation (head trauma, brain tumor, etc.) The model developed in this project can be extended to analyze more complex intraoperative events by adding new submodels.

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