Cerebral vasodilating capacity during forebrain ischemia: effects of chronic estrogen depletion and repletion and the role of neuronal nitric oxide synthase.

The effects of chronic 17beta-estradiol (E2) depletion, via ovariectomy (OVX), and its repletion, on cortical cerebral blood flow (CBF) and EEG activities during forebrain ischemia, as well as post-ischemic recovery and neuropathology, were assessed and compared with results obtained in normal female rats. We also examined whether neuronal nitric oxide synthase (nNOS) activity is affected by OVX and E2 replacement and whether NOS-derived NO supports vasodilation during ischemia. OVX females displayed a significantly lower CBF during ischemia (10% of baseline) than did normal females (23% of baseline). In OVX rats, given chronic low-dose E2 treatment (0.1 mg kg(-1) day(-1)), intra-ischemic CBF was similar to normal females (25% of baseline). However, at supraphysiologic E2 doses (> or = 0.5 mg kg(-1) day(-1)), that benefit was diminished or lost. Intra-ischemic EEG power reductions and post-ischemic survival rates, neurological dysfunction, and histopathology displayed similar relative differences among groups as the CBF findings. Intra-ischemic CBF was reduced by nNOS inhibition, with ARL 17477, in normal and low-dose E2-treated OVX rats (4-8% baseline). The repressed intra-ischemic vasodilating function in OVX rats may be due to reductions in nNOS activity, because untreated OVX rats showed a 50% lower cortical nNOS activity than that in normal rats and in rats treated with low or high dose (5 mg kg(-1) day(-1)) E2. However, the inability to restore vasodilating function despite normalization of nNOS activity indicates that another mechanism is responsible for the repression of vasodilatory function in the high-dose group. These findings suggest that E2, at levels within the physiological range, promotes ischemic neuroprotection via improving vasodilating capacity. One possible mechanism may relate to E2 enhancing brain nNOS expression and activity.

Lidocaine blood levels following aerosolization and intravenous administration.

STUDY OBJECTIVE: To determine whether, following aerosolization of lidocaine for topical airway anesthesia, intravenous (IV) lidocaine produces toxic lidocaine blood concentrations. DESIGN: Randomized, double-blind study. SETTING: University-affiliated hospital. PATIENTS: Forty healthy patients scheduled for outpatient surgery. INTERVENTIONS: The patients received in a randomized, double-blind manner aerosolized lidocaine or placebo followed 10 minutes later by IV lidocaine or placebo. MEASUREMENTS AND MAIN RESULTS: After completion of lidocaine or placebo aerosolization and 2 minutes following IV administration of either lidocaine or the placebo, venous blood samples were obtained. Lidocaine concentration was measured using a homogenous enzyme assay. The group receiving both aerosolized and IV placebo and the group receiving aerosolized lidocaine and an IV placebo had undetectable (less than 0.05 micrograms/ml) serum lidocaine levels. The groups that received either an aerosolized placebo or aerosolized lidocaine and IV lidocaine had similar serum lidocaine concentrations [3.34 +/- 0.46 vs. 3.24 +/- 0.55 micrograms/ml (mean +/- SEM); p greater than 0.05 by Mann-Whitney U test]. CONCLUSION: IV lidocaine can be safely administered following aerosolization of lidocaine in spontaneously breathing patients without producing toxic blood lidocaine concentrations.