Computer simulation of cerebrovascular circulation: assessment of intracranial hemodynamics during induction of anesthesia.

OBJECTIVE: The purpose of this project was to develop a computer model of cerebrovascular hemodynamics interacting with a pharmacokinetic drug model to examine the effects of various stimuli on cerebral blood flow and intracranial pressure during anesthesia. METHODS: The mathematical model of intracranial hemodynamics is a seven-compartment, constant-volume system. A series of resistance relate blood and cerebrospinal fluid fluxes to pressure gradients between compartments. Arterial, venous, and tissue compliance are also included. Autoregulation is modeled by transmural pressure-dependent, arterial-arteriolar resistance. The effect of a drug (thiopental) on cerebrovascular circulation was simulated by a variable arteriolar-capillary resistance. Thiopental concentration was predicted by a three-compartment, pharmacokinetic model. The effect site compartment was included to account for a disequilibrium between drug plasma and biophase concentrations. The model was validated by comparing simulation results with available experimental observations. The simulation program is written in VisSim dynamic simulation language for an IBM-compatible PC. RESULTS: The model developed was used to calculate the cerebral blood flow and intracranial pressure changes that occur during the induction phase of general anesthesia. Responses to laryngoscopy and intubation were predicted for simulated patients with elevated intracranial pressure and non-autoregulated cerebral circulation. Simulation shows that the induction dose of thiopental reduces intracranial pressure up to 15%. The duration of this effect is limited to less than 3 minutes by rapid redistribution of thiopental and cerebral autoregulation. Subsequent laryngoscopy causes acute intracranial hypertension, exceeding the initial intracranial pressure. Further simulation predicts that this untoward effect can be minimized by an additional dose of thiopental administered immediately prior to intubation. CONCLUSION: The presented simulation allows comparison of various drug administration schedules to control intracranial pressure and preserve cerebral blood flow during induction of anesthesia. The model developed can be extended to analyze more complex intraoperative events by adding new submodels.

Identification of a pharmacophore for nucleoside analog inhibitors directed at HIV-1 reverse transcriptase.

An 'active analog' approach to receptor mapping was used to identify a pharmacophore for a set of thymidine nucleoside analog inhibitors of HIV-1 reverse transcriptase. The preliminary results indicate that the O2, O4', and O5' atoms are capable of adopting a unique pharmacophoric pattern which may be the key to their recognition by reverse transcriptase.

Effect of substrate condition and substituted phenols and methacrylates on toluene diisocyanate/dentin bond strengths.

One aim of this in vitro investigation was to determine the effect of substituting four phenols and two methacrylates with vinyl functions on the dentin bond strengths of several new experimental dentin bonding agents. Another objective was to determine the effect of postextraction age and dentin level within the tooth on tensile bond strengths of these toluene diisocyanate-derived adhesives. Extracted third molars were divided into postextraction age groups and sectioned into three slices approximately 400 microns thick. The four substituted phenols were: eugenol, o-methoxyphenol, o-chlorophenol, and p-cresol. Substituted methacrylates with vinyl ligands were 2-hydroxyethyl methacrylate (HEMA) and 6-hydroxyhexyl methacrylate (HHMA). Results showed that adhesives made with o-chlorophenol, p-cresol, and methoxyphenol with HEMA were the best, while those made with eugenol and HHMA were the worst. The post extraction age of the tooth and the dentin depth had no consistent effect on most adhesive bond strengths which were generally around 10.3 MPa (1500 psi).

Effects of hematocrit on thixotropic properties of human blood.

The rheological properties of whole human blood exhibit thixotropic behavior at low shear rates up to about ten reciprocal seconds (1). The accepted cause of this shear rate-dependent and time-dependent behavior is the progressive breakdown of rouleaux into individual red cells. Huang developed a rheological equation which incorporates the kinetics of rouleau breakdown in his models (2). This five-parameter equation was used successfully to represent the hysteresis loop and the torque-decay curve of whole human blood. Numerical values of these five thixotropic parameters, which characterize the rheological behavior of the blood from apparently healthy human subjects, were established (3). In this communication, we examined the effect of hematocrit on each of the above mentioned parameters. The results show that the following parameters will increase their values with an increase in hematocrit: the yield stress, Newtonian contribution of viscosity, non-Newtonian contribution of viscosity, apparent viscosity and the equilibrium value of the structural parameter which indicates the relative amount of rouleaux in blood. Mathematical equations were developed to give the relationship between parameters and hematocrit. Two other thixotropic parameters, viz. the kinetic rate constant of rouleaux breakdown into individual red cells and the order of the breakdown reaction, were found to be independent of the hematocrit. It is consistent with reaction kinetic theory that the rate constant and the order of reaction are independent of the concentration of reactants.