Hemodilution/anemia is a common consequence of trauma or surgery. However, like hypoxia, it may not be well tolerated in patients with CNS injuries because trauma blocks the normal increase in cerebral blood flow which accompanies hemodilution. If this increase cannot occur, added brain damage may result. In spite of 40 years of debate, the mechanisms controlling CBF during hemodilution are unknown. The two major hypotheses are: 1) the CBF increase is a """"""""passive"""""""" response to the hematocrit-related decrease in blood viscosity; or 2) it is a compensatory response to a fall in arterial O2 content (CaO2). These hypotheses have clinical implications: if viscosit determines anemic CBF, then hemodilution may be benign or beneficial; if CaO2 is the major driving force, then hemodilution is only as """"""""beneficial"""""""" as hypoxia. Animal studies of hemodilution after stroke support the first hypothesis; studies in humans with stroke and in head- injured animals support the second. Which hypothesis is correct? In fact, information indicates that neither is entirely consistent with experimental results. Specifically, the CBF changes during hemodilution seem to be the result of several interacting processes in brain tissue and in the vascular endothelium. Like hypoxia, hemodilution reduces tissue O2 tension, and may thus lead to the neuronal/glial production of vasodilators (e.g. adenosine). Unlike hypoxia, where a fall in intravascular PO2 triggers autocoid release from the endothelium, reducing blood viscosity during hemodilution will decrease NO and prostacyclin release. This should limit the vasodilation occurring in response to changing tissue O2 tensions. Changes in endothelial function may also alter the responses to normal extravascular vasoactive stimuli such adenosine. Finally, and most importantly, brain injury disrupts some or all of the processes which control CBF in anemic (and hypoxic) animals. These experiments are designed to elucidate the multiple mechanisms which underlie the CBF changes occurring with hemodilution, and which distinguish hemodilution from hypoxia. They will also try to define which of these mechanisms are disrupted by brain injury. Our long-range goal is to gain a better understanding of normal and pathologic cerebrovascular control, and to better define/understand at least one of the factors which may lead to worsened outcome in head injured patients.
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