Lethality of Intravascular Injections of Spleen and Liver Cells

The Defibrination Syndrome in Rabbits Following Infusion of Tissue Thromboplastin in the Jugular Vein

“…Injections into the jugular vein, or in the abdominal aorta below the origin of the renal arteries, produced defibrination prompting the conclusion "that there is no difference whether the pulmonary or the peripheral capillary bed is the first microcirculation encountered by the coagulant". This result agrees well with the infusion experiments in dogs of Kauffman et al (10) who used the iliac artery. However, when Spaet et al (I. c.) injected plasma thromboplastin in a mesenteric vein, so that it first encountered the portal circulation, they found considerably less consumption of coagulation factors and no defibrination syndrome.…”

“…Similarly, Lewis and Szeto (13) observed that intraarterial injections (descending aorta) of 1 31 I tagged fibrin particles left the fibrin widely distributed in many organs, with only a small fraction in the lungs, a result contrasting the distribution observed after intravenous injection. The changes observed by Kauffman et al (10) in samples of venous blood (inferior vena cava) following intraarterial injection (iliac artery) of cell homogenates compare well with our data obtained after infusion of tissue thromboplastin in the jugular vein with collection of the blood samples from the carotid arter y. In the latter experiments the retainment of tissue thromboplastin and fibrin strands could take place only in the capillary bed of the lungs, while in the former retainment occurs in the terminal vasculature of the organs supplied by the descending aorta.…”

“…Viable cells introduced intravenously are known to be retained by the lungs (22). Though retention is reported to be related to the thromboplastic activity of the cellular suspensions, simultaneous administration of heparin did not change the immediate lethal effects of suspensions of spleen or liver cells in dogs, despite that right heart thrombosis was prevented (10). A spleen cell homogenate was more thromboplastic than one made from liver cells, and its effects in vivo could be reproduced by infusion of brain thromboplastin.…”

Clinical management of patients receiving cell‐based immunoregulatory therapy

“…Particles with a mean diameter of 116.6 ± 13.1 μm likewise caused an increase in mean PAP, shunting, and reduced cardiac output and was ultimately fatal in some cases . The mean lethal dose of splenocytes in heparinized dogs is 4.5 × 10 8 cells/kg BW and the mean lethal dose of adult hepatocytes in dogs is 1.7 × 10 8 cells/kg BW . Recently, Kobayashi and colleagues found that slow IV infusion of 10 7 mesenchymal stem cells/kg BW into heparinized miniature swine caused a 30 mmHg increase in PAP.…”

“…40 The mean lethal dose of splenocytes in heparinized dogs is 4.5 × 10 8 cells/kg BW and the mean lethal dose of adult hepatocytes in dogs is 1.7 × 10 8 cells/kg BW. 41 Recently, Kobayashi and colleagues 42 found that slow IV infusion of 10 7 mesenchymal stem cells/kg BW into heparinized miniature swine caused a 30 mmHg increase in PAP. Therefore, infusion of approximately 10 8 cells or cell-sized particles per kilogram can be lethal in large animals and infusion of approximately 10 7 cells or cell-sized particles per kilogram can cause a significant increase in PAP.…”