Developmental Ethanol-Induced Sleep Fragmentation, Behavioral Hyperactivity, Cognitive Impairment and Parvalbumin Cell Loss are Prevented by Lithium Co-treatment.

Developmental ethanol exposure is a well-known cause of lifelong cognitive deficits, behavioral hyperactivity, emotional dysregulation, and more. In healthy adults, sleep is thought to have a critical involvement in each of these processes. Our previous work has demonstrated that some aspects of cognitive impairment in adult mice exposed at postnatal day 7 (P7) to ethanol (EtOH) correlate with slow-wave sleep (SWS) fragmentation (Wilson et al., 2016). We and others have also previously demonstrated that co-treatment with LiCl on the day of EtOH exposure prevents many of the anatomical and physiological impairments observed in adults. Here we explored cognitive function, diurnal rhythms (activity, temperature), SWS, and parvalbumin (PV) and perineuronal net (PNN)-positive cell densities in adult mice that had received a single day of EtOH exposure on P7 and saline-treated littermate controls. Half of the animals also received a LiCl injection on P7. The results suggest that developmental EtOH resulted in adult behavioral hyperactivity, cognitive impairment, and reduced SWS compared to saline controls. Both of these effects were reduced by LiCl treatment on the day of EtOH exposure. Finally, developmental EtOH resulted in decreased PV/PNN-expressing cells in retrosplenial (RS) cortex and dorsal CA3 hippocampus at P90. As with sleep and behavioral activity, LiCl treatment reduced this decrease in PV expression. Together, these results further clarify the long-lasting effects of developmental EtOH on adult behavior, physiology, and anatomy. Furthermore, they demonstrate the neuroprotective effects of LiCl co-treatment on this wide range of developmental EtOH's long-lasting consequences.

Ventricular proarrhythmic effects of ventricular cycle length and shock strength in a sheep model of transvenous atrial defibrillation.

BACKGROUND: Synchronized cardioversion is generally accepted as safe for the treatment of ventricular tachycardia and atrial fibrillation when shocks are synchronized to the R wave and delivered transthoracically. However, others have shown that during attempted transvenous cardioversion of rapid ventricular tachycardia, ventricular fibrillation (VF) may be induced. It was our objective to evaluate conditions (short and irregular cycle lengths [CL]) under which VF might be induced during synchronized electrical conversion of atrial fibrillation with transvenous electrodes. METHODS AND RESULTS: In 16 sheep (weight, 62 +/- 7.8 kg), atrial defibrillation thresholds (ADFT) were determined for a 3-ms/3-ms biphasic shock delivered between two catheters each having 6-cm coil electrodes, one in the great cardiac vein under the left atrial appendage and one in the right atrial appendage along the anterolateral atrioventricular groove. A hexapolar mapping catheter was positioned in the right ventricular apex for shock synchronization. In 8 sheep (group A), a shock intensity 20 V less than the ADFT was used for testing, and in the remaining 8 sheep (group B), a shock intensity of twice ADFT was used. With a modified extrastimulus technique, a basic train of eight stimuli alone (part 1) and with single (part 2) and double (part 3) extrastimuli were applied to right ventricular plunge electrodes. Atrial defibrillation shocks were delivered synchronized to the last depolarization. In part 4, shocks were delivered during atrial fibrillation. The preceding CL was evaluated over a range of 150 to 1000 milliseconds. Shocks were also delayed 2, 20, 50, and 100 milliseconds after the last depolarization from the stimulus (parts 1 through 3) or intrinsic depolarization (part 4). The mean ADFT for group A was 127 +/- 48 V, 0.71 +/- 0.60 J and for group B, 136 +/- 37 V, 0.79 +/- 0.42 J (NS, P > .15). Of 1870 shocks delivered, 11 episodes of VF were induced. Group A had no episodes of VF in part 1, two episodes of VF in part 2 (CL, 240 and 230 milliseconds with 2-millisecond delay), and one episode each in parts 3 (CL, 280 milliseconds with 2-millisecond delay) and 4 (CL, 240 milliseconds with 100-millisecond delay). Group B had two episodes in part 1 (CL, 250 and 300 milliseconds with 20-millisecond delay), three episodes in part 2 (CL, 230, 230, and 250 milliseconds with 2-millisecond delay), and one episode each in parts 3 (CL, 260 milliseconds with 2-millisecond delay) and 4 (198 milliseconds with 100-millisecond delay). No episodes of VF were induced for shocks delivered after a CL > 300 milliseconds. CONCLUSIONS: Synchronized transvenous atrial defibrillation shocks delivered on beats with a short preceding ventricular cycle length (< 300 milliseconds) are associated with a significantly increased risk of initiation of VF. To decrease the risk of ventricular proarrhythmia, short CLs should be avoided.