CELLULAR SODIUM-TRANSPORT IN ARTERIAL-WALL - SUMMARY OF STUDIES BY DIGITAL-COMPUTER SIMULATION

The distribution of electrolytes between extracellular and intracellular compartments is of greater functional significance in biological tissues than the total amount. A method commonly employed for the study of a substance distribution among different spaces is the continuous outflow and radioisotope counting of a fragment of tissue previously incubated with a radioactive tracer (here 22Na+). The experimental data can be analyzed within the frame of a compartmental analysis system which is defined by transport rate constants (kij) and solved when all kij are numerically determined. In practical applications the direct solution requires measurements in different compartments or knowledge of the initial condition for each compartment, but this is not possible in most biological tissues where the experimentally observable data represent the summation of tracer in all compartments at each point in time. The availability of the SAAM (Simulation, Analysis and Modelling) computer program allows for a powerful stimulation procedure to arrive at values for kij. Experimental data and specifications for a chosen model are entered in the SAAM format. A simulated ''inflow'' experiment is made by the computer by assigning to kij some estimate values. All initial conditions are now zero, since at the beginning there is no radioactive tracer in any compartment. After a time equivalent in the experimental realm to achieving constant specific activity, a ''time change'' programmed into the computer takes place so that the outflow part of the experiment is developed with the same kij as for the inflow part, the final conditions for the inflow before the time change being the initial conditions for the outflow. An iterative procedure modifies the initial estimates of kij to seek the best fit. By coupling a powerful simulation procedure to an advanced radionuclide tracer biological methodology, we have been able to find effects of the hormone aldosterone and of experimental hypertension on Na+ distribution in arterial wall years before such effects were demonstrated by purely conventional experimental techniques. This computer simulation procedure may be suited to other experimental situations in which outflow data are the only available.