PMID- 9339686
TI  - Higher neonatal cerebral blood flow correlates with worse childhood
      neurologic outcome.
AB  - Cerebral blood flow (CBF) in newborn infants is often below levels
      necessary to sustain brain viability in adults. Controversy exists
      regarding the effects of such low CBF on subsequent neurologic
      function. We determined the current childhood neurologic status and
      IQ in 26 subjects who had measurements of CBF performed with PET in
      the neonatal period between 1983 and 1989 as part of a study of
      hypoxic-ischemic encephalopathy. Follow-up information at ages 4 to
      12 years was obtained on all 26 subjects. Ten subjects had died. All
      16 survivors underwent clinical neurologic evaluation, and 14 also
      underwent intelligence testing. Eight had abnormal clinical
      neurologic evaluations; eight were normal. The mean neonatal CBF in
      those with abnormal childhood neurologic outcome was significantly
      higher than in those with normal childhood neurologic outcome (35.64
      +/- 11.80 versus 18.26 +/- 8.62 mL 100 g(-1) min(-1), t = 3.36, p =
      0.005). A significant negative correlation between neonatal CBF and
      childhood IQ was demonstrated (Spearman rank correlation r = -0.675,
      p = 0.008). Higher CBF was associated with lower IQ. The higher CBF
      in subjects with worse neurologic and intellectual outcome may
      reflect greater loss of cerebrovascular autoregulation or other
      vascular regulatory mechanisms due to more severe brain damage.

PMID- 9357896
TI  - Bupivacaine inhibition of L-type calcium current in ventricular cardiomyocytes of hamster.
AB  - BACKGROUND: The local anesthetic bupivacaine is cardiotoxic when accidentally injected into the circulation. Such cardiotoxicity might involve an inhibition of cardiac L-type Ca2+ current (ICa,L). This study was designed to define the mechanism of bupivacaine inhibition of ICa,L. METHODS: Cardiomyocytes were enzymatically dispersed from hamster ventricles. Certain voltage- and time-dependencies of ICa,L were recorded using the whole-cell patch clamp method in the presence and absence of different concentrations of bupivacaine. RESULTS: Bupivacaine, in a concentration-dependent manner (10-300 microM), tonically inhibited the peak amplitude of ICa,L. The inhibition was characterized by an increase in the time of recovery from inactivation and a negative-voltage shift of the steady-state inactivation curve. The inhibition was shown to be voltage-dependent, and the peak amplitude of ICa,L could not be restored to control levels by a wash from bupivacaine. CONCLUSIONS: The inhibition of ICa,L appears, in part, to result from bupivacaine predisposing L-type Ca channels to the inactivated state. Data from washout suggest that there may be two mechanisms of inhibition at work. Bupivacaine may bind with low affinity to the Ca channel and also affect an unidentified metabolic component that modulates Ca channel function.