Cerebral circulation in hypoxia and ischemia.

In conclusion our results clearly suggest that vital functions of the brain, in spite of its well developed autoregulation are impaired during prolonged hypovolemic conditions. Regional cerebral blood flow measured by the 133Xe clearance and 14C-antipyrine autoradiographic techniques demonstrated a progressive reduction in CBF, with the development of patchy and circumscribed ischemic areas during hemorrhagic shock which persisted after reinfusion. The regional distribution of the underperfused regions cannot be explained solely in terms of boundary zones between the main distribution fields of major cerebral arteries. Our results suggest the involvement of the sympathetic nervous system in the impairment of cerebral microcirculation during hemorrhagic shock. The patchy focal brain damage could be the background of the functional impairment. The focal appearances suggests that, in addition to generalized (blood borne) changes, local factors play an important role in the production of ischemic areas in the brain. Afferent neural nociceptive input to the brain seems to be elevated during shock. It may be presumed that this leads to increased tissue metabolism and the accumulation of metabolites. The low flow combined with elevated neuronal activity and cellular metabolism produces an imbalance between oxygen delivery and oxygen utilization. The local nature of afferent activation of the CNS can explain the regional impairment in the brain tissue. Nociceptive afferent stimulation increases, while denervation of the carotid sinus or transsection of the vagus or spinal afferent pathways decreases the sensitivity to shock. We have presented further evidence that stimulation of the C-fibres of the sciatic nerve reduced local cerebral blood flow and the tissue PO2 in the n. VPL thalami and VM hypothalami in cardiovascularly restricted (stabilized blood pressure) animals. Concerning the subcellular events that may lead to neuronal death during hemorrhagic shock, we believe that the depletion of high energy phosphates initiates those complex changes which result in the loss of the viability of the affected cells. In this process the increase of free calcium in the cytosol probably plays a crucial role.