Determination of cardiac output, tissue blood flow, volume and lipid content in Sprague-Dawley rats

One critical aspect of physiologically-based pharmacokinetic (PBPK) model development is the choice of values for organ blood flows, cardiac output and tissue volumes for input into models. These values vary depending upon the strain, size, age, and sex of animal for which a PBPK model is being developed. Tissue blood flows, cardiac output, tissue volume, and lipid content were determined in male S-D rats, (350-375 g, N=8). A radiolabel microsphere method utilizing Scandium (46Sc), Tin (113Sn),and Gadolinium (153Gd) was used to determine blood flow. Each rat received 3 radiolabeled injections. After the third injection, animals were sacrificed, and radioactivity in each tissue was determined in a 3-channel gamma counter. Tissues sampled include brain, heart, kidneys, liver, lungs, spleen, pancreas, adrenals, stomach, intestines, colon, testis, bone and skeletal muscle. Cardiac output was 142 ml/min. Blood flow values for eliminating organs were 0.49 (liver), 16.52 (kidney), and 1.77 (lung) ml/min/g tissue. Tissues which had significantly increased blood flow during the dark cycle included femur, abdonimal fat, triceps brachii and abdominal muscles, stomach, spleen and lung. Dissectable fat, organ volume, and organ lipid content were determined in a separate group of rats (N= 8). Volume and lipid content were determined for the same tissues as blood flow. Body fat was 7.35% of bw and extractable lipid content of eliminating organs was 42.3 (liver), 43.4 (kidney), and 35.9 (lung) mg/g tissue. Precise measurements should improve the accuracy of PBPK model predictions, and therfore help in reducing uncertainites in risk assessment of volatile organics and other pollutnats