Anterograde Effect Research Articles

Abstract 14912: Sotalol-induced Wide Complex Rhythm: What is the Mechanism?

Introduction: Delta waves associated with atrioventricular accessory pathways (APs) may manifest with autonomic tone, heart rate, and rhythm changes. Rarely, drugs like sotalol can block AV nodal conduction, revealing latent WPW, one treatable cause of sudden death. Case report: A 38-year-old man was admitted for sotalol loading due to frequent typical atrial flutter and SVT and a desire to avoid catheter ablation. He had a history of cardiac arrest with adenosine and tachycardia-induced cardiomyopathy. After recovery, cardiac MRI showed a normal heart without scar. Admission 12-lead ECG ( Figure A ) revealed normal sinus rhythm without other abnormality. With administration of sotalol, the patient developed a wide complex rhythm ( Figure B ). Interpretation of the rhythm indicated presence of a latent AP and a repeat ECG ( Figure C ) confirmed manifest preexcitation. After consenting to electrophysiology study, the patient developed a short RP tachycardia ( Figure D ) which terminated with Valsalva. The patient underwent successful catheter ablation of the pathway located at the anterior floor of the coronary sinus body and the cavotricuspid isthmus. Discussion: The differential diagnosis for a wide complex rhythm in this setting includes rate-related aberrancy, idioventricular rhythm, phase 4 aberrancy, and preexcitation from an AP. Shortened and consistent PR intervals in the tracing lead to preexcitation as the only possible mechanism. APs that are capable of anterograde conduction but are not manifest in sinus rhythm are termed latent APs. Conditions that may cause this phenomenon include opposite autonomic effects on the AP and the AV node, increased atrial conduction time, or concealed retrograde conduction into the AP. Sotalol typically increases the retrograde effective refractory period of the AP but has variable anterograde effect. Sotalol has not previously been reported to reveal a latent AP but may have acted through one of the stated mechanisms.

Anesthesia awareness. Can midazolam attenuate or prevent memory consolidation on intraoperative awakening during general anesthesia without increasing the risk of postoperative delirium?

There are numerous reviews on anesthesia awareness (AA) and post-traumatic stress disorder. Some authors assert that the use of benzodiazepines (BZDs) should be limited to patients requiring lower anesthetic drugs dosages for cardiac and emergency surgery, and for multiple-trauma patients. This is in agreement, at least in part, with the recommendations of the American Society of Anesthesiologists (ASA) [1]. Indeed, according to the ASA guidelines, the decision to administer BZDs should be made on a case-by-case basis, whereby the use of BZDs has been limited because of the risk of postoperative confusion and cognitive problems, including postoperative delirium (PD). This is one of the most common complications after major surgery, affecting 10-70% of surgical patients of 60 years and older. There are a number of factors associated with PD, including hypoxia, hypercapnia, pain, stress, anxiety, fear, and psychotic and neurotic disorders, making it very difficult to determine the exact dose of midazolam - the BZD most used in anesthesia - that does not increase the risk of PD. Postoperative sedation using a midazolam drip (0.5-2 mg/h) results in delirium in 50% of the patients undergoing elective cardiac surgery.

A Role for Retinal Brain-Derived Neurotrophic Factor in Ocular Dominance Plasticity

Visual deprivation is a classical tool to study the plasticity of visual cortical connections. After eyelid closure in young animals (monocular deprivation, MD), visual cortical neurons become dominated by the open eye, a phenomenon known as ocular dominance (OD) plasticity . It is commonly held that the molecular mediators of OD plasticity are cortically derived and that the retina is immune to the effects of MD . Recently, it has been reported that visual deprivation induces neurochemical, structural, and functional changes in the retina , but whether these retinal changes contribute to the effects of MD in the cortex is unknown. Here, we provide evidence that brain-derived neurotrophic factor (BDNF) produced in the retina influences OD plasticity. We found a reduction of BDNF expression in the deprived retina of young rats. We compensated this BDNF imbalance between the two eyes by either injecting exogenous BDNF in the deprived eye or reducing endogenous BDNF expression in the nondeprived eye. Both treatments were effective in counteracting the OD shift induced by MD. Retinal BDNF could also influence OD distribution in normal animals. These results show for the first time that OD plasticity is modulated by BDNF produced in the retina.

Peripheral infection and aging interact to impair hippocampal memory consolidation

We report that a peripheral injection of Escherichia coli produces both anterograde and retrograde amnesia in 24 month old, but not 3 month old rats for memories that depend on the hippocampus, that is, memory of context, contextual fear, and place learning. The anterograde effect was restricted to measures of long-term memory. Short-term memory was not affected, nor did E. coli produce amnesia for auditory-cue fear conditioning. There were no age related effects on memory in vehicle-treated rats. In addition to these age-related cognitive effects of E.coli, we report that it produced a marked increased in IL-1β levels in the hippocampus, but not in parietal cortex or serum. These findings support the hypothesis that age is a vulnerability factor that increases the likelihood that an immune challenge will produce a cognitive impairment. It is possible that this cognitive vulnerability is mediated by age-related changes in the glial environment that results in an exaggerated brain pro-inflammatory response to infection.

Maintained saturation of hippocampal long-term potentiation does not disrupt acquisition of the eight-arm radial maze.

The present experiment examined the anterograde effect of bilateral saturation of long-term potentiation (LTP) of the rat perforant path-granule cell response on acquisition of the eight-arm radial maze. To ensure maintained saturation, high-frequency stimulation was applied to the perforant path immediately prior to each trial. LTP did not significantly increase the number of trials required for acquisition of the standard eight-arm radial maze task. Furthermore, the magnitude of LTP did not correlate with the rate of acquisition. LTP also did not significantly affect the number of either working or reference memory errors during subsequent training with only four of the eight arms baited; both control and LTP rats made significantly more reference memory than working memory errors, with the number of both types of errors decreasing as training progressed. These results indicate that prior saturation of LTP within the perforant path-dentate granule cell circuit does not affect acquisition of either the reference or working memory components of the radial maze task. The results are discussed in relation to the role of LTP in acquisition of the eight-arm radial maze.

Effects of confinement, previous experience and hippocampal damage on the DRL schedule

Rats with dorsal hippocampal (HIPP) and cortical (CX) lesions and control animals were tested for acquisition of a differential reinforcement of low rate of responding (DRL-20 s) task in a 6-compartment apparatus that permitted running, drinking and other activities. HIPP and CX animals and one group of control rats (NOR) were trained in an ‘open’ condition which allowed a variety of activities, while another control group (CON) were trained while confined to the food and lever area of the apparatus. In the second stage of the experiment conditions were reversed. DRL performance was significantly better in the ‘open’ condition for all groups: more pellets were gained with fewer lever presses. Groups HIPP performed worse than groups NOR and CX in both conditions. When NOR and CX rats were confined to the food area they developed a jumping behaviour, (attempts to leave the food area) which increased throughout the testing period, coupled with a progressive deterioration of performance. Rats initially trained in the ‘confined’ condition did not develop jumping. HIPP animals were significantly more active; they produced more lever presses, entered the different compartments more frequently and showed higher activity in the running wheel. The schedule-induced interim behaviour in the open condition was wheel-running in all groups. In the HIPP group the number of jumps was significantly less than in the NOR and CX groups i.e. they were less affected by confinement. These findings suggest that previous experience in the ‘open’ condition has a strong anterograde, seemingly irreversible, consequence on subsequent behaviour in the ‘confinement’ condition for normal and cortical control rats and this anterograde effect is less pronounced in animals with hippocampal damage.

Benzodiazepines and memory.

Benzodiazepines possess anterograde amnesic properties, disrupting both short-term and long-term memory function. The amount of amnesia is systematically related to dose effects and half-life differences among the benzodiazepines. Memory deficits are found for episodic, semantic, and iconic memory function. The deficits in long-term memory are probably the result of a disruption of consolidation of information in memory and not retrieval from memory. The disruption is produced by rapid sleep onset. Thus the long-term amnesia is really a retrograde effect of sleep and not the anterograde effect of the drug.

The anterograde effect of ECS on the acquisition, retrieval and extinction of conditioned taste aversion

Conditioned taste aversion was established in rats by spontaneous or forced drinking of saccharin (0.1%, CS) followed after 30 min by poisoning (0.15 M LiCl, 2% body weight, US) and retention was tested by offering the animals saccharin 1 or 2 days later. ECS (50 Hz, 50 mA, 0.5 s) applied 120, 60, 30 or 15 min before saccharin administration elicited an increasing disruption of CTA acquisition which was complete with the 15-min ECS-CS interval. On the other hand, ECS applied 2, 15 or 30 min after saccharin drinking caused either no or only moderate CTA disruption. ECS applied 30 min before retention testing reduced the fluid intake but did not prevent CTA retrieval. Forced feeding saccharin to rats with a strong CTA, established by repeated saccharin-LiCl pairing, caused CTA extinction which was only slightly decreased by ECS applied 10 or 60 min before the extinction trial. The proactive ECS effects prevent formation of the short-term gustatory trace but do not seriously disrupt the gustatory trace-poisioning association and leave the CTA retrival and extinction unaffected. In this respect ECS resembles other procedures that differentially interfere with CTA acquisition and retrieval, particularly the effect of paradoxical sleep deprivation.

Comparison of fronto‐frontal and temporo‐parietal unilateral ECT

An intraindividual double-blind cross-over comparison for the anterograde effect on memory of unilateral non-dominant frontofrontal (FF) and temporo-parietal (TP) ECT was performed in connection with the second and third treatment of an ECT-series, the electrode placement being alternated at random. Treatment technique was standardized and seizure duration was measured by means of EEG. Memory functions were tested after treatments by means of four memory tests: the 30 Word-Pair Test, the 30 Figure Test, the 30 Geometrical Figure Test and the 30 Face Test. Three operationally defined memory variables, immediate memory (IMS, 3 hours after ECT), delayed memory (DMS, 3 hours after IMS), and their difference, forgetting, were scored. No differences were found in the mean time of electrical stimulation, in the amount of methohexital and suxamethonium chloride, and in seizure duration between the two treatment groups. No statistically significant differences in any of the memory tests were found. The FF electrode position did not show any advantage compared with the routine TP electrode placement.

COMPARISON OF FRONTOPARIETAL AND TEMPOROPARIETAL UNILATERAL ELECTROCONVULSIVE THERAPY

An intraindividual, double‐blind, cross‐over comparison of the anterograde effect on memory of unilateral non‐dominant frontoparietal (FP) and temporoparietal (TP) ECT was performed in connection with the second and third treatments of ECT‐series. Treatment technique was standardized and seizure duration was measured by means of EEG. Memory functions were examined 3 and 6 hours after treatments by means of parallel memory tests, and three operationally defined memory variables, immediate and delayed reproduction, and their difference, forgetting, were scored.The duration of the electrical stimulation (with constant intensity) necessary to evoke generalized seizure was similar in the two methods. The duration of seizure activity was significantly shorter after FP‐ECT. In spite of this difference, the anterograde effect on the memory variables was closely similar in the two treatments.The shorter duration of seizure activity after FP‐ECT indicates that a maximal seizure is more difficult to obtain with frontal electrode position. The lack of difference in anterograde effect between TP‐ECT and FP‐ECT indicates that little further reduction of memory impairment can be expected with new unilateral electrode positions.