Role of tissue hypoxia in cerebrovascular regulation: A mathematical modeling study

This paper presents a mathematical model of cerebrovascular regulation, in which emphasis is given to the role of tissue hypoxia on cerebral blood flo w (CBF). In the model, three different mechanisms are assumed to work on sm ooth muscle tension at the level of large and small pial arteries: CO2 reac tivity, tissue hypoxia, and a third mechanism necessary to provide good rep roduction of autoregulation to cerebral perfusion pressure (CPP) changes. U sing a single set of parameters for the mechanism gains, assigned via a bes t fitting procedure, the model is able to reproduce the pattern of pial art ery caliber and CBF under a large variety of physiological stimuli, either acting separately (hypoxia, CPP changes, CO2 pressure changes) or in combin ation (hypercapnia+hypoxia; hypercapnia+hypotension). Furthermore, the mode l can explain the increase in CBF and the vasoconstriction of small pial ar teries observed experimentally during hemodilution, ascribing it to the dec rease in blood viscosity and to the antagonistic action of the flow-depende nt mechanism (responsible for vasoconstriction) and of hypoxia (responsible for vasodilation). Finally, the interaction between hypoxia and intracrani al pressure (ICP) has been analyzed. This interaction turns out quite compl ex, leading to different ICP time patterns depending on the status of the c erebrospinal fluid outflow pathways and of intracranial compliance. (C) 200 1 Biomedical Engineering Society.