Knopp, T. J.

Microspheres of different sizes, 125 I-labeled antipyrine (I-Ap), and 42 KCl or 86 RbCl were injected into the aortic inflow of isolated, Langendorff, perfused, nonworking dogs hearts at blood flows of 1.3-4.8 ml/min g -1 . After 15 seconds to 5 minutes, the left ventricle was sectioned into about 300 ordered pieces, and the amount of each tracer was determined. For all tracers, the relative density of deposition was generally higher in the endocardial region, except in one heart in which the aortic pressure and the total coronary flow were low. The deposition of 42 K and that of I-Ap were essentially similar in three hearts over a large range of regional variation. This finding suggests either that both tracers were distributed in proportion to flow or that a small diminution in relative density of deposition of 42 K in high-flow regions due to lower transcapillary extraction was quantitatively similar to a decrease in the residual fraction of I-Ap in these same regions due to faster washout in the first 15-30 seconds after injection. Large microspheres were deposited preferentially in regions of high flow, exaggerating the apparent heterogeneity of regional flows. The distribution of the smaller microspheres was closer to that for I-Ap or 42 K.

Indicator dilution techniques used for the estimation of flow (F), mean transit time (t), dispersion (σ), and mean transit time volume (V) in the circulation are subject to error when (1) flow is not steady and (2) concentrations are obtained by sampling at a constant rate (time averaging) rather than at rates proportional to the instantaneous flow past the sampling site (volume averaging). Using a simple descriptive model for indicator transport, the effects of simulated aortic flow or of sinusoidal flow of widely variable frequency were assessed. Errors in estimates of F, t, σ, and V are greater with bolus injections than with constant-rate injections. Errors are roughly proportional to the amplitude of variation in flow. They are maximal when the period of flow fluctuation is similar to the passage time of the dilution curve, which, for the human central circulation, is about the time for one respiratory cycle. With sinusoidal flow between 50% and 150% of the mean flow, errors were at worst up to 60% in F, 30% in t, 50% in σ, and 70% in V, with a bimodal distribution. Errors are minimal at cardiac frequencies. The troublesome lower frequencies can be avoided. Preliminary tests of a method for converting time- to volume-averaged concentrations gave encouraging results.

The fitting of mathematical models to physiological sys tems can be tedious and difficult, whether one uses analog or digital computer methods. Both methods have their pros and cons depending on the available hardware and software and on the type of modeling. In recent years many digital simulation languages have been written com bining analog-like and digital features to facilitate model ing, but, for a variety of reasons, none of these was suit able for our applications. We, therefore, designed a new digital simulation control system, SIMCON, which is de scribed in this paper. The primary objectives were to provide: (1) Maximum man-machine interaction at run-time, in cluding visual displays, digital control, and both con tinuous analog and digital parameter adjustment (2) The ability to generate solutions and to fit them to experimental data or other theoretical curves with a minimum of computer memory (3) The option to use a mathematically oriented language, FORTRAN, and block operators with variable input/ output. The result is a relatively general and simple simulation system which is easy to use and has wide versatility.