The maintenance of cerebral blood flow (CBF) in spite of changing perfusion pressure (i.e. autoregulation) is essential for the survival of an animal. It is generally accepted that perfusion pressure can drop to 60 or 70 mmHg before CBF decreases. Recently, data acquired from our laboratory and others have demonstrated that the cerebral vessels are not maximally dilated at these reduced pressures and that during certain hypotensive states CBF is maintained to pressures as low as 40 mmHg. Thus, it appears that other influences associated with the hypotensive episode may compromise the autoregulatory capability of the animal during a slow hemorrhage in which autoregulation fails at perfusion pressures below 60 or 70 mmHg. The goal of this project is to assess the influences of nor-adrenergic tone and opioid peptides on the cerebral autoregulatory response associated with circulatory shock. Since enhanced vascular tone by nor- adrenergic nerves may compromise cerebral autoregulation in shock states characterized by a gradual fall in blood pressure, we will initially compare the cerebral metabolic and autoregulatory response of a slow graded hemorrhage to a hypotensive state produced by a rapid diminution of arterial pressure. Our second goal is to determine if inhibition of nor-adrenergic (sympathetic and central) activity associated with the decompensatory phase of certain shock states will permit a downward shift in the lower limit of autoregulation. Thirdly, since endogenous opioid peptides have been shown to produce depressed sympathetic nerve activity associated with bradycardia and hypotension, there is little information relating these endogenous opiates to changes in CBF and metabolism during alterations in arterial pressure associated with shock. Thus, it is our aim to test whether endogenous or synthetic opioids and their respective opioid antagonists effect cerebral autoregulation and metabolism during shock. Finally, we will assess the hypothesis that the central release of opioid substances associated with different shock syndromes or acute hypotensive episodes may depress nor-adrenergic tone and permit a downward shift in the lower limit of autoregulation. The findings from these studies may help basic scientists as well as clinicians to understand the brain's ability to maintain function during abrupt pathophysiological episodes induced by traumas such as circulatory shock, head injuries, stroke, or cerebral aneurysm.
