An isolated in-situ rat head perfusion model for pharmacokinetic studies

Purpose. To develop a viable, single pass rat head perfusion model useful f or pharmacokinetic studies. Methods. A viable rat head preparation, perfused with MOPS-buffered Ringer' s solution, was developed. Radiolabelled markers (red blood cells, water an d sucrose) were injected in a bolus into the internal carotid artery and co llected from the posterior facial vein over 28 minutes. The double inverse Gaussian function was used to estimate the statistical moments of the marke rs. Results. The viability of the perfusion was up to one hour, with optimal pe rfusate being 2% bovine serum albumin at 37 degrees C, pH 7.4. The distribu tion volumes for red blood cells, sucrose and water (from all studies, n = 18) were 1.0 +/- 0.3ml, 6.4 +/- 4.2ml and 18.3 +/- 11.9ml, respectively. A high normalised variance for red blood cells (3.1 +/- 2.0) suggests a marke d vascular heterogeneity. A higher normalised variance for water (6.4 +/- 3 .3) is consistent with additional diffusive/permeability limitations. Conclusions. Analysis of the physiological parameters derived from the mome nts suggested that the kinetics of the markers were consistent with distrib ution throughout the head (weight 25g) rather than just the brain (weight 2 g). This model should assist in studying solute pharmacokinetics in the hea d.