Use of the dog spleen for studying effects of irradiation and chemotherapeutic agents, with suggested uses of other organs

Abstract

The irradiation of the exteriorized spleen of the dog, with the animal lead-shielded, produced constant changes in the white blood cells. The time of recovery from the irradiation effect was determined. The normal canine spleen could handle live pneumococci injected into the splenic artery, as proven by sterile cultures of splenic vein samples. The size of the bolus used was determined by repeated trials and proved to be one billion pneumococci per pound of body weight. The capacity of the irradiated spleen to handle this number of pneumococci was impaired. It was found that whole body irradiation, nitrogen mustard, thio-tepa, cyclophosphamide, methotrexate, 5-fluorouracil, vinblastine, and azothioprine all impaired this capacity of the spleen. The dose of the chemotherapeutic agent was the same in milligrams per kilogram as that used in the cancer clinic. A method for determining the recovery time following the use of one or more agents was developed with the repeated use of the spleen model. By extending the methods used with the spleen it was found that similar use could be made, usually without surgery, of the liver, gut, and lungs (and probably the kidney and brain).

Asplenic-hyposplenic Overwhelming Sepsis: Postsplenectomy Sepsis Revisited

“…In asplenic patients, chemotaxis is reduced in macrophages and neutrophils and phagocytic inactivation of bacteria is reduced in neutrophils [29]. In dogs given billions of organisms intravenously, the bacteria are cleared from the blood in three passes through the spleen [30]. While small numbers of bacteria such as pneumococci and H. influenzae can be cleared from the circulation in infants even before they develop specific immunity, larger bacterial loads may be quickly fatal.…”

Invited commentary

“…Their sham-operated and partially splenectomized chinchillas had normal opsonic and complement activities even if 2/3 or the whole of the spleen was removed. However, clearing of bacteria from the blood was delayed when 1/z of the spleen was removed, The efficiency of the spleen in clearing the blood of bacteria was dramatically demonstrated by Wilcox et al [8] who injected 1 billion organisms per pound into dogs and noted that essentially all the organisms were cleared from the circulation in 1-3 passes through the spleen.…”

“…However, clearing of bacteria from the blood was delayed when 1/z of the spleen was removed, The efficiency of the spleen in clearing the blood of bacteria was dramatically demonstrated by Wilcox et al [8] who injected 1 billion organisms per pound into dogs and noted that essentially all the organisms were cleared from the circulation in 1-3 passes through the spleen. Experiments such as those performed by Leonard and colleagues comprise some of our best information to date.…”