title: Cessation of diastolic cerebral blood flow velocity: the role of critical closing pressure.
abstract: BACKGROUND
  Reducing cerebral perfusion pressure (CPP) below the lower limit of autoregulation (LLA) causes cerebral blood flow (CBF) to become pressure passive. Further reductions in CPP can cause cessation of CBF during diastole. We hypothesized that zero diastolic flow velocity (FV) occurs when diastolic blood pressure becomes less than the critical closing pressure (CrCP).
  
  
  METHODS
  We retrospectively analyzed studies of 34 rabbits with CPP below the LLA, induced with pharmacologic sympathectomy (N = 23) or cerebrospinal fluid infusion (N = 11). Basilar artery blood FV and cortical Laser Doppler Flow (LDF) were monitored. CrCP was trended using a model of cerebrovascular impedance. The diastolic closing margin (DCM) was monitored as the difference between diastolic blood pressure and CrCP. LDF was recorded for DCM values greater than and less than zero.
  
  
  RESULTS
  Arterial hypotension caused a reduction of CrCP (p < 0.001), consistent with decreased wall tension (p < 0.001) and a drop in intracranial pressure (ICP; p = 0.004). Cerebrospinal infusion caused an increase of CrCP (p = 0.002) accounted for by increasing ICP (p < 0.001). The DCM was compromised by either arterial hypotension or intracranial hypertension (p < 0.001 for both). When the DCM reached zero, diastolic FV ceased for a short period during each heart cycle (R = 0.426, p < 0.001). CBF pressure passivity accelerated when DCM decreased below zero (from 1.51 ± 0.51 to 2.17 ± 1.17 % ΔLDF/ΔmmHg; mean ± SD; p = 0.010).
  
  
  CONCLUSIONS
  The disappearance of diastolic CBF below LLA can be explained by DCM reaching zero or negative values. Below this point the decrease in CBF accelerates with further decrements of CPP.
authors.affiliation: Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge Biomedical Campus, Cambridge, CB20QQ, UK, gv249@cam.ac.uk.
authors.forename: Georgios V
authors.initials: GV
authors.lastname: Varsos
authors.forename: Hugh K
authors.initials: HK
authors.lastname: Richards
authors.forename: Magdalena
authors.initials: M
authors.lastname: Kasprowicz
authors.forename: Matthias
authors.initials: M
authors.lastname: Reinhard
authors.forename: Peter
authors.initials: P
authors.lastname: Smielewski
authors.forename: Ken M
authors.initials: KM
authors.lastname: Brady
authors.forename: John D
authors.initials: JD
authors.lastname: Pickard
authors.forename: Marek
authors.initials: M
authors.lastname: Czosnyka
mesh_terms: D000818:Animals; D001488:Basilar Artery / Q000000981:diagnostic imaging; D001783:Blood Flow Velocity / Q000502:physiology*; D001794:Blood Pressure / Q000502:physiology*; D001921:Brain / Q000098:blood supply*; D002560:Cerebrovascular Circulation / Q000502:physiology*; D006706:Homeostasis / Q000502:physiology; D007427:Intracranial Pressure / Q000502:physiology*; D008297:Male; D011817:Rabbits; D012189:Retrospective Studies; D014463:Ultrasonography