Effect of lidocaine on dynamic changes in cortical reduced nicotinamide adenine dinucleotide fluorescence during transient focal cerebral ischemia in rats

Abstract

Rats were subjected to 90min of focal ischemia by occluding the left middle cerebral and both common carotid arteries. The dynamic changes in the formation of brain ischemic areas were analyzed by measuring the direct current (DC) potential and reduced nicotinamide adenine dinucleotide (NADH) fluorescence with ultraviolet irradiation. In the lidocaine group (n=10), 30min before ischemia, an intravenous bolus (1.5mg/kg) of lidocaine was administered, followed by a continuous infusion (2mg/kg/h) for 150min. In the control group (n=10), an equivalent amount of saline was administered. Following the initiation of ischemia, an area of high-intensity NADH fluorescence rapidly developed in the middle cerebral artery territory in both groups and the DC potential in this area showed ischemic depolarization. An increase in NADH fluorescence closely correlated with the DC depolarization. The blood flow in the marginal zone of both groups showed a similar decrease. Five minutes after the onset of ischemia, the area of high-intensity NADH fluorescence was significantly smaller in the lidocaine group (67% of the control; P=0.01). This was likely due to the suppression of ischemic depolarization by blockage of voltage-dependent sodium channels with lidocaine. Although lidocaine administration did not attenuate the number of peri-infarct depolarizations during ischemia, the high-intensity area and infarct volume were significantly smaller in the lidocaine group both at the end of ischemia (78% of the control; P=0.046) and 24h later (P=0.02). A logistic regression analysis demonstrated a relationship between the duration of ischemic depolarization and histologic damage and revealed that lidocaine administration did not attenuate neuronal damage when the duration of depolarization was identical. These findings indicate that the mechanism by which lidocaine decreases infarct volume is primarily through a reduction of the brain area undergoing NADH fluorescence increases which closely correlates with depolarization.