Until recently a substance had not been isolated from animal tissues which could be held responsible for the shock syndrome. The search for the hypothetical toxic factors in tissue has been renewed in an effort to understand the mechanisms which underlie the production of symptoms in traumatic injuries.
In 1941 Bywaters and his colleagues1 reported myohemoglobin in the urine of injured patients. These workers suggested that this pigment may be only an indicator of muscle damage and other substances released from muscle at the same time may be responsible for the structural and functional changes in the "crush kidney."
Green,2 who studied the experimental shock produced by "hind-limb ischemia," concluded that a shock producing factor is released from asphyxiated muscle. In the first attempts to obtain from normal or asphyxiated muscles an extract which on intramuscular injection would reproduce the syndrome produced by "hind-limb ischemia" the possibility developed
TOXIC FACTORS IN SHOCK. JAMA. 1943;123(8):485. doi:10.1001/jama.1943.02840430037011