Kininogen consumption in cerebral circulation of humans during brain ischemia and postischemic reperfusion

1. Total kininogen, high molecular weight kininogen and low molecular weight kininogen were quantitated as bradykinin equivalents in the blood flowing to and from the brain in patients with stenotic and occlusive carotid damage in the course of neurosurgical treatment. Although considerable improvement in blood supply of ischemic brain areas was established after surgery in all patients, improvement in postoperative neurological status was seen only in four patients (group I), while in six cases there were no or negative neurological changes (group II). 2. The biochemical study confirmed the principal difference between these two groups: 1) prior to surgery in the patients of group II, but not of group I, total kininogen in blood flowing from the brain was markedly lowered compared to its arterial level, the latter being close to normal; the decrease was due only to low molecular weight kininogen. 2) After surgery, cerebral venous total kininogen levels were significantly lowered in patients of both groups; however, for patients of group II, these changes were more pronounced and they showed a decrease in both high and low molecular weight kininogen. 3. The major involvement of low molecular weight kininogen implicates tissue kallikrein in this process. The reduction of kininogen indicates that kinin formation occurred in the cerebral intravascular space during brain ischemia and following brain reperfusion and was most likely associated with the well-known actions of kinin on cerebral vessels, i.e., vasodilatation and brain edema.