Outcomes of Surgical Repair of Vascular Rings and Slings in Children: A Word for the Asymptomatic.

Vascular rings (VRs) are rare aortic arch anomalies that may present with a wide variety of symptoms related to esophageal and/or airway compression. We reviewed our surgical experience in both symptomatic and asymptomatic children. All children (n = 58) who underwent surgical repair of VRs or slings (mean age 27.4 ± 45.60 months; 36 males [62%]) between March 2000 and April 2020 were included. The most common anatomic variant was a right aortic arch (RAA) with aberrant left subclavian artery (ALSCA) (n = 29; 50%). Kommerell's diverticulum was present in 23 of these patients (79%). The second most common variant was a double aortic arch (n = 22; 38%), followed by pulmonary artery sling (n = 4; 6%), RAA with mirror image branching and left ligamentum arteriosum (n = 3; 5.2%), and left aortic arch (LAA) with aberrant right subclavian artery (n = 1; 1.7%). One patient had a double ring with pulmonary artery sling and RAA with ALSCA. Symptoms were present in 42 patients (72%). Left lateral thoracotomy was the approach in 50 patients (86%), while sternotomy was used in 8 (14%). Symptomatic improvement occurred in the majority of symptomatic patients (93%). There was one perioperative mortality (1.7%) in the symptomatic group which was non-VR related. Morbidities included recurrent laryngeal nerve injury in three patients (5.2%) and transient chylothorax in two (3.4%). Persistence/recurrence of symptoms resulted in one early and one late reoperation. The mean follow-up was 3 ± 5 years. In the current era, VR repair in children including asymptomatic ones can be performed with excellent results. We recommend complete repair of RAA with aberrant LSCA by resection of Kommerell's diverticulum and translocation of the ALSCA to avoid recurrence.

Off-Pump "Clamp and Sew" Extracardiac Fontan With Inverted Bifurcated Graft for Dextrocardia With Heterotaxy Syndrome.

Avoiding cardiopulmonary bypass during palliation of single ventricle has the advantages of minimizing transfusions, pulmonary vascular resistance, and avoiding the inflammatory response from cardiopulmonary bypass. It is however not always straightforward, and the technique may be faced with challenges.

Quality Improvement Project in Congenital Cardiothoracic Surgery Patients: Reducing Surgical Site Infections.

BACKGROUND: Healthcare-associated infections are a major focus for quality improvement in hospitals today. Surgical site infections (SSIs), a postoperative complication in cardiac surgery, are associated with increased morbidity, mortality, hospital length of stay, and financial burden. METHODS: A recent increase in cardiothoracic surgery SSIs (CT-SSIs) at our institution instigated a multidisciplinary team to explore infection prevention, bundle element compliance, and to identify interventions to reduce the CT-SSI rate. Key interventions included preoperative screening and decolonization of methicillin-sensitive Staphylococcus aureus and methicillin-resistant S. aureus with repeated intranasal applications of mupirocin, universal skin prep with chlorhexidine for all patients, and additional antibiotic dosing upon initiating cardiopulmonary bypass. RESULTS: In 2014, the CT-SSI rate at our institution was 1.9/100 cases, which increased during the "intervention period" to 3.6 infections/100 cases in 2015 (16 total infections). Postinterventions, the CT-SSI rate decreased to 0.3 infections/100 cases (2 total infections), which was significantly lower than our baseline before the spike in infection rate. CONCLUSIONS: A comprehensive interdisciplinary approach with multiple interventions was successful in significantly reducing the CT-SSI rate in cardiothoracic surgery at a tertiary care pediatric hospital.

There's an App for That; Improving Communication during Pediatric Cardiothoracic Surgery.

INTRODUCTION: Waiting while a loved one is in surgery can be a very stressful time. Current processes for updating families vary from institution to institution. Providing timely and relevant updates, while important to the family, may strain a surgical team's operational system. In our initial experience with the Electronic Access for Surgical Events (EASE) application (app), we tested the extent to which its implementation improved communication with patient families. METHODS: We compared compliance data collected pre-EASE (December 2013 through September 2014) and post-EASE implementation (October 2014 until December 2015). RESULTS: Although the pre-EASE compliance rate for bi-hourly updates was 46% (118/255) of cases, post-EASE implementation achieved a compliance rate of 97% (171/176). A 2-sample test of proportions confirmed a significant improvement in compliance after the introduction of EASE technology (P < 0.001). Analysis of the 177 noncompliant cases in the pre-EASE period indicated that noncompliance occurred most frequently at the end of the case (97/177, 55%) when the patient remained in the operating room > 2 hours after the last update to the family. We also observed noncompliance at the beginning of the case (46/177, 26%), when the patient arrived in the operating room > 2 hours before the time of the first update. Family satisfaction scores that rated their experience during surgery as "Very Good" improved from 80% pre-EASE implementation to 97% postimplementation. We sustained this improvement for 1 year. CONCLUSIONS: A mobile technology app (EASE) improved both frequency and compliance with surgical updates to families, which resulted in a statistically significant increase in family satisfaction scores.

Automated Audiovisual Feedback in Cardiopulmonary Resuscitation Training: Improving Skills in Pediatric Intensive Care Nurses.

BACKGROUND: High-quality cardiopulmonary resuscitation is associated with improved survival and neurological outcomes after cardiac arrest. Unfortunately, health care professionals frequently do not perform resuscitation within guidelines after life-support training. OBJECTIVES: To determine if brief intermittent training in cardiopulmonary resuscitation could improve nurses' skills to perform high-quality resuscitation 70% or more of the time during 2 minutes of cardiopulmonary resuscitation after 3 training sessions. METHODS: In a prospective single-center quality improvement program, pediatric critical care nurses had monthly training in cardiopulmonary resuscitation. A portable manikin/defibrillator with a chest compression sensor was used to provide corrective audiovisual feedback to optimize resuscitation skills. Resuscitation was practiced on an adult manikin. Target goals were compression depth 2 in or greater at a compression rate of 100/min to 120/minute. Percentage of time in the target range and mean compression depth and rate were recorded. Data were collected every other month. The percentage of time both compression rate and depth were in the target range was compared among nurses with different total numbers of training sessions. RESULTS: Of the 62 nurses who participated in the training, 48 had data collected. The median percentage of time in the target range improved from 29% with no training to 46% after 1 session, 54% after 2 sessions, 68% after 3 sessions, and 74% after 4 sessions (P = .001). Compression depth increased with the number of training sessions (P = .002). CONCLUSIONS: This training program in cardiopulmonary resuscitation yielded significant skill improvement and retention.

Acquired Cardiac Disease in the Pediatric Intensive Care Unit.

This review focuses on the identification, evaluation, management, and stabilization of a variety of acquired cardiac conditions, such as cardiomyopathies, inflammatory cardiac disease, and Kawasaki disease, which commonly require care in the pediatric intensive care unit (PICU). Pediatric cardiomyopathies comprise a spectrum of acquired or congenital myocardial diseases in which there are abnormalities of cardiac size and ventricular wall thickness, along with ventricular performance. The inflammatory diseases of the heart include acute myocarditis and pericarditis. Cardiac sequelae of Kawasaki disease resemble a self-limited vasculitis, but in rare instances may present with hemodynamic instability requiring vasopressor support. Care in the PICU affords both monitoring and management opportunities. [Pediatr Ann. 2018;47(7):e280-e285.].

Reducing variation in feeding newborns with congenital heart disease.

OBJECTIVE: Enteral feeding is associated with decreased infection rates, decreased mechanical ventilation, decreased hospital length of stay, and improved wound healing. Enteral feeding difficulties are common in congenital heart disease. Our objective was to develop experience-based newborn feeding guidelines for the initiation and advancement of enteral feeding in the cardiothoracic intensive care unit. DESIGN: This is a retrospective analysis of a quality improvement project. SETTING: This quality improvement project was performed in a cardiothoracic intensive care unit. PATIENTS: Newborns admitted to the cardiothoracic intensive care unit for cardiac surgery from January 2011 to May 2015 were retrospectively reviewed. INTERVENTION: Newborn feeding guidelines for the initiation and advancement of enteral feeding were implemented in January 2012. OUTCOME MEASURES: Guideline compliance and clinical variables before and after guideline implementation were reviewed. RESULTS: Compliance with the guidelines increased from 83% in 2012 to 100% in the first two quarters of 2015. Preguidelines (January 2011-December 2011): 45 newborns underwent cardiac surgery; 8 deaths prior to discharge; 1 patient discharged from NICU, therefore, N = 36. Postguidelines (January 2012-May 2015): 131 newborns with 12 deaths, 12 admitted from home, 8 in the NICU, 3 on the floor preop, and 3 back transferred, therefore, N = 93. No difference in feeding preop (post 75% vs pre 69%; P = .5) or full po feeds at discharge (post 78% vs pre 89%; P = .2). Mesenteric ischemia was not statistically different postguidelines (post 6% vs pre 14%; P = .14). Length of hospital stay decreased postguidelines (post 27 + 17 d vs pre 34 + 42 d; P < .001). CONCLUSIONS: Implementation of experience-based newborn feeding guidelines for initiation and advancement of enteral feeding in the cardiothoracic intensive care unit was successful in reducing practice variation supported by increasing guideline compliance. Percentage of patient's full oral feeding at discharge did not change. Length of hospital stay was reduced although cannot be fully attributed to feeding guideline implementation.

Interstage Survival for Patients with Hypoplastic Left Heart Syndrome After ECMO.

There is a reported 5-20 % incidence of extracorporeal membrane oxygenation (ECMO) following stage I palliation for hypoplastic left heart syndrome (HLHS). This study compares the interstage mortality of HLHS patients supported with ECMO (HLHS-ECMO) to those who were not supported with ECMO (HLHS-nECMO) using the National Pediatric Cardiology Quality Improvement Initiative database. Patients with HLHS who survived to hospital discharge after stage I palliation were analyzed. HLHS-ECMO patients were compared to HLHS-non-ECMO patients with respect to demographics, surgical variables, and interstage survival. A total of 931 patients were identified in the database. Sixty-six (7.1 %) patients were supported with ECMO during their stage I palliation admission. There were no statistically significant differences between the groups with respect to demographics or anatomic subtype. HLHS-ECMO patients were more likely to have a preoperative risk factor identified (62 vs. 48 %, p = 0.03) or require ECMO prior to stage I palliation (3 vs. 0.5 %, p = 0.03). HLHS-ECMO patients had a significantly higher incidence of death or transplant versus the HLHS-nECMO group (18 vs. 9 %, p = 0.03). Despite survival to discharge, patients with HLHS requiring ECMO after their palliation continue to have an increased risk of death/cardiac transplant versus patients that do not require ECMO. ECMO use is likely a marker for a high-risk patient group. These patients may benefit from closer follow-up during the interstage period.

Multidisciplinary Review of Code Events in a Heart Center.

OBJECTIVE: To identify a cause for clinical deterioration, examine resuscitation efforts, and identify and correct system issues (thus improving outcomes) via a multidisciplinary code-review process soon after cardiopulmonary arrest. METHODS: Retrospective analysis of code events in a tertiary pediatric heart center from September 2010 to December 2013 and review of surgical-cardiac data from January 2010 to December 2013. RESULTS: A multidisciplinary team reviewed 47 code events, 16 of which (34%) were deemed potentially preventable. At least 2 issues were identified during 66% (31/47) of cardiopulmonary arrests reviewed. Key issues identified were related to communication (62%), environment/culture/policy (47%), patient care (including resuscitation, 41%), and equipment (38%). About 60% of reviewed arrests resulted in educational initiatives (eg, mock code, in-service education) and 47% resulted in a new policy or modification of existing policy. Less common were changes in equipment (32%) or modification of staffing needs (11%). Changes most frequently occurred in the unit specific to the event (68%) but some changes occurred throughout the Heart Center (32%) or across the hospital system (13%). Survival to discharge after cardiopulmonary arrest has improved over time (P = .03) to 81% for cardiac surgical patients in our center. CONCLUSION: A multidisciplinary code-review committee can identify deficiencies and lead to educational initiatives and improvements in care. When coupled with a hospital-wide "code blue" review process, these changes may benefit the institution as a whole.

Influence of graft ischemic time and geographic distance between donor and recipient on survival in children after lung transplantation.

BACKGROUND: The optimal ischemic time in pediatric lung transplantation (LTx) is unclear, as recent studies have challenged the relevance of 6 hours as an upper limit to acceptable ischemic time. METHODS: Pediatric LTx recipients transplanted between 1987 and 2013 were identified in the United Network for Organ Sharing (UNOS) registry to compare survival according to ischemic time, which was categorized as <4 hours, 4 to 6 hours and >6 hours. RESULTS: Nine hundred thirty patients, all <18 years of age and receiving a first-time LTx from a cadaveric donor, were included in our investigation. Compared with <4 hours of ischemic time, univariate analysis showed a significant reduction in mortality hazard with 4 to 6 hours (hazard ratio [HR] = 0.640; 95% confidence interval [CI] 0.502 to 0.816; p < 0.001) but not >6 hours (HR = 0.985; 95% CI 0.755 to 1.284; p = 0.909). A multivariate Cox model confirmed the lowest mortality hazard to be 4 to 6 hours, as compared with <4 hours (HR = 0.533; 95% CI 0.376 to 0.755; p < 0.001). A prolonged ischemic time of >6 hours was associated with increased mortality hazard relative to the 4 to 6 hours (HR = 1.613; 95% CI 1.193 to 2.181; p = 0.002). Supplementary analyses examining geographic distance between donor and recipient identified no association between geographic distance and recipient mortality hazard. CONCLUSIONS: An ischemic time of 4 to 6 hours was associated with optimal long-term survival in first-time pediatric LTx recipients, whereas a very short ischemic time of <4 hours and a prolonged ischemic time >6 hours were both associated with higher mortality hazard in this population.

ECMO: Incidence and Outcomes of Patients Undergoing the Hybrid Procedure.

OBJECTIVE: To document the extracorporeal membrane oxygenation (ECMO) incidence and outcome in patients undergoing the hybrid procedure at an institution that routinely performs this procedure. DESIGN: A retrospective chart review on all patients with single ventricle physiology that underwent the hybrid procedure between 7/2002 and 12/2014. Patients were excluded if they underwent the hybrid procedure after 60 days of birth or subsequently underwent a biventricular repair. SETTING: A single center, tertiary pediatric hospital. PATIENTS: One hundred eighty-one patients with single ventricle physiology that underwent the hybrid procedure between 7/2002 and 12/2014. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We studied a total of 181 patients (105 males: 76 females). Gestational age was 37.8 ± 2.0 weeks and birth weight was 3.0 ± 0.7 kg. Underlying diagnosis was hypoplastic left heart syndrome in 149 patients and other in 32 patients. Age at surgery was 7.8 ± 6.8 days and weight at surgery was 3.1 ± 0.6 kg. Two patients underwent ECMO support after the hybrid procedure. One patient had aortic atresia/mitral atresia and weighed 2.3 kg and the other patient had aortic atresia/mitral stenosis and weighed 2.1 kg at time of surgery. Both patients died. Incidence of ECMO support after hybrid procedure was 1.3% (2/149) for the hypoplastic left heart syndrome patients and 1.1% (2/181) for the entire cohort. CONCLUSION: Mortality in patients who underwent ECMO after the hybrid procedure was higher than reported for the Norwood procedure, however, the incidence of ECMO after hybrid procedure was also significantly lower than reported for the Norwood procedure. Future studies are needed to determine how to improve outcomes in this complex patient population.

Improving Surveillance and Prevention of Surgical Site Infection in Pediatric Cardiac Surgery.

BACKGROUND: Postoperative cardiovascular surgical site infections are preventable events that may lead to increased morbidity, mortality, and health care costs. OBJECTIVE: To improve surgical wound surveillance and reduce the incidence of surgical site infections. METHODS: An institutional review of surgical site infections led to implementation of 8 surveillance and process measures: appropriate preparation the night before surgery and the day of surgery, use of appropriate preparation solution in the operating room, appropriate timing of preoperative antibiotic administration, placement of a photograph of the surgical site in the patient's chart at discharge, sending a photograph of the surgical site to the patient's primary care physician, 30-day follow-up of the surgical site by an advanced nurse practitioner, and placing a photograph of the surgical site obtained on postoperative day 30 in the patient's chart. RESULTS: Mean overall compliance with the 8 measures from March 2013 through February 2014 was 88%. Infections occurred in 10 of 417 total operative cases (2%) in 2012, in 8 of 437 total operative cases (2%) in 2013, and in 7 of 452 total operative cases (1.5%) in 2014. CONCLUSIONS: Institution of the surveillance process has resulted in improved identification of suspected surgical site infections via direct rather than indirect measures, accurate identification of all surgical site infections based on definitions of the National Healthcare Safety Network, collaboration with all persons involved, and enhanced communication with patients' family members and referring physicians.

Risk Factors for Unanticipated Readmissions During the Interstage: A Report From the National Pediatric Cardiology Quality Improvement Collaborative.

This study describes unanticipated interstage readmissions in patients with hypoplastic left heart syndrome, identifies independent risk factors for unanticipated interstage readmissions, and evaluates variation in unanticipated readmission rates among collaborative centers. Retrospective data of patients enrolled in the National Pediatric Cardiology Quality Improvement Collaborative registry from July 2008 to July 2013 were analyzed. Risk factors present at the beginning of the interstage were captured. Competing risks time to event analyses determined the association between these factors and unanticipated interstage readmission. Readmission center variation was examined using funnel plots. Unanticipated interstage readmissions occurred in 66% of 815 patients at 50 centers. The median readmission length of stay was 2 days (interquartile range: 0-6) and median time to first readmission was 29 days (interquartile range: 9-63). Most readmissions were prompted by minor changes in clinical status (64%), whereas only 6% were major adverse event readmissions. Independent readmission risk factors included genetic syndrome (HR = 1.40, 95% CI: 1.05-1.88), center volume (small vs large HR = 1.32, CI: 1.04-1.66, medium vs large HR = 1.35, CI: 1.09-1.68), preoperative ventricular dysfunction (HR = 2.02, CI: 1.31-3.10), tricuspid regurgitation (HR = 1.36, CI: 1.08-1.72), duration of circulatory arrest (HR = 0.99, CI: 0.989-0.998), and undergoing Hybrid procedure relative to Norwood/right ventricle to pulmonary artery conduit (HR = 1.40, CI: 1.02-1.93). There was significant center variation in the number of readmissions and duration of readmissions. Unanticipated readmissions are common during the interstage period with notable center variation. However, these readmissions are short and are rarely in response to major adverse events.

Increasing parental participation during rounds in a pediatric cardiac intensive care unit.

BACKGROUND: Inviting parents of sick children to participate during the rounding process may reduce parents' anxiety and improve communication between the parents and the health care team. OBJECTIVES: To increase the percentage of available parents invited to participate in morning rounds in a pediatric cardiothoracic intensive care unit (CTICU). METHODS: Invitations to parents to participate in morning CTICU rounds were randomly audited from June 2012 to April 2014 (mean, 15 audits per month). From June 2012 to February 2013 (before intervention), 73% of parents available during morning rounds received an invitation to participate. From April 2013 to May 2013, the following interventions (family participation bundle) were implemented: (1) staff education, (2)"Invitation to Rounds" handout added to the parent welcome packet with verbal explanation, (3) bedside tool provided for parents to communicate desire to participate in rounds with the team, (4) reminder to invite parents added to nursing rounding sheet. Following interventions, family feedback was obtained by 1-on-1 (physician-parent) open-ended conversation. RESULTS: From April 2013 to April 2014, 94% of parents available during morning rounds received an invitation to participate. Reasons for not participating: chose not to participate (63%), sleeping-staff reluctant to wake (25%), not English speaking (7%), breastfeeding (5%). CONCLUSION: Implementation of a family participation bundle was successful in increasing invitations to parents to participate during morning rounds in the CTICU. Engagement of staff and addressing specific staff concerns was instrumental in the project's success.

Eosinophilic esophagitis in children following cardiac transplantation: association with post-transplant lymphoproliferative disorder and other transplant outcomes.

Although cardiac transplantation is life-saving, morbidities from immunosuppression are significant. EoE is a complication of calcineurin inhibitors following liver transplant causing feeding intolerance, weight loss, vomiting, and dysphagia. There are limited reports of EoE following heart transplantation. We performed a retrospective single-center review of pediatric cardiac transplant patients from 2000 to 2010. A case-control analysis of patients with and without EoE was performed evaluating heart transplantation outcomes such as rates of rejection, CAV, PTLD, and graft loss. Eighty-six transplants were performed in 84 patients; 34 (40%) underwent diagnostic endoscopy, and 10 (12%) had EoE. Median time to diagnosis of EoE was 3.7 yr (IQR: 2.0-5.2). There were no differences in demographics or use of induction medications between patients with or without EoE. Patients with EoE had fewer episodes of treated rejection (1.0 vs. 2.5; p = 0.04). Four of 10 (40%) EoE patients had PTLD compared with only 2/24 (8%) of those without EoE (p = 0.048; OR 7.33 [95% CI: 1.1-50.2]). There were no differences in CAV or graft loss between groups. EoE should be considered as a cause of GI symptoms in children after cardiac transplantation and may be associated with fewer rejection episodes and increased rates of PTLD, thus representing a marker of over-immunosuppression.

Establishing quality review of cardiac and respiratory arrest in a pediatric intensive care unit.

Cardiac arrest in children is a rare event; however, the outcomes following resuscitation are universally disappointing. Despite widespread recognition of its importance, there is no standard approach to conducting reviews surrounding critical resuscitation events. A standardized approach to the review of respiratory and cardiac arrests occurring in the pediatric intensive care unit focusing on processes of care and team performance was undertaken at a single pediatric academic medical center. Data collection and quality improvement tools were created, and a formal code review was established. Improvement in code team performance was observed. Clinician documentation improved, and multiple system redesigns were implemented that ultimately resulted in fewer clinician concerns. The rate of successful resuscitation was consistent with current published benchmarks. The development of an interdisciplinary code review process focusing on the procedure of resuscitation can identify critical issues that may impede successful resuscitation.

Standardized multidisciplinary protocol improves handover of cardiac surgery patients to the intensive care unit.

OBJECTIVES: To determine whether the implementation of a standardized handover protocol could reduce the number of errors occurring during patient transitions from the operating room to the intensive care unit. DESIGN: Prospective, interventional study. SETTING: Pediatric cardiac intensive care unit. SUBJECTS: Seventy-nine patient handovers in patients transitioning from the operating room to the cardiac intensive care unit after congenital cardiac surgery. INTERVENTIONS: A preintervention assessment of patient handovers was obtained by direct observation using a standardized checklist. A teamwork-driven handover process and protocol was developed using traditional and novel quality-improvement techniques. The postimplementation observational assessment of handovers was performed using the same preintervention assessment tool. Preintervention and postintervention data metrics were analyzed and compared. MEASUREMENTS AND MAIN RESULTS: Forty-one and 38 observations were performed in the preintervention and postintervention periods, respectively. Protocol implementation improved key areas of the handover process. Technical errors per handover were reduced from 6.24 to 1.52 (p < .0001), and critical verbal handoff information omissions were reduced from 6.33 to 2.38 (p < .0001) per handover. There was no change in duration of either the verbal handoff briefing or the overall handover process. Caregivers noted improvement in teamwork and handoff content received after the intervention. CONCLUSIONS: A formal, structured handover process for pediatric patients transitioning to the intensive care unit after cardiac surgery can reduce medical errors that occur during the admission process and improve teamwork among caregivers.

Prenatal exposure to a repeated variable stress paradigm elicits behavioral and neuroendocrinological changes in the adult offspring: potential relevance to schizophrenia.

Exposure to stress during gestation induces marked changes in the behavior of the affected offspring. Examining the consequences of prenatal stress may prove useful in understanding more about the origins of schizophrenia because a number of clinical investigations have suggested that developmental insults are associated with an increased incidence of schizophrenia. The purpose of these studies is to investigate the effects of stress during gestation on the behaviors of the adult male rat offspring with an emphasis on developing a heuristic animal model of schizophrenia. Pregnant female Sprague-Dawley rats were exposed to a novel variable stress paradigm during either the second or third week of gestation. Behavioral and neuroendocrinological consequences of prenatal stress exposure were evaluated in the male offspring on postnatal day 35 or 56. Prenatal stress exposure during the third week of pregnancy caused adult male rats to exhibit prolonged elevation in plasma glucocorticoid levels following acute exposure to restraint stress indicative of diminished glucocorticoid negative feedback. Similarly, exposure to stress during the third week of pregnancy elicited an enhanced locomotor response to the psychomotor stimulant amphetamine on postnatal day 56 but not on postnatal day 35. In addition, prepulse inhibition of the acoustic startle response was diminished across a range of prepulse stimulus intensities in prenatally stressed adult male rats. Similarly, prenatally stressed rats showed evidence of a disruption in auditory sensory gating as measured by the N40 response. Taken together, these findings suggest that prenatal stress exposure significantly changed many facets of adult rat behavior. Interestingly, the behaviors that are altered have been used to validate animal models of schizophrenia and therefore, suggest that this preparation may be useful to learn more about some aspects of the pathophysiology of schizophrenia.

Effects of acute and chronic clozapine on D-amphetamine-induced disruption of auditory gating in the rat.

RATIONALE: Auditory gating deficits observed in patients with schizophrenia have been modeled in animals administered the indirect-acting monoaminergic agonist, D-amphetamine (AMPH). The atypical antipsychotic drug clozapine (CLOZ) reverses the disruption of auditory gating in schizophrenic patients. However, its effects on psychostimulant-induced deficits in animals have yet to be assessed. OBJECTIVES: In the present series of experiments, an auditory evoked potential paradigm was used to: (a) confirm the ability of AMPH to alter auditory gating in the anesthetized rat, (b) specify the nature of the accompanying change(s) in evoked potential waveforms and (c) determine the effects of CLOZ administration on AMPH-induced alterations in auditory gating. METHODS: We compared the effects of acute (5 mg/kg, i.p.) and chronic (28 days, 0.5 mg/ml in drinking water) CLOZ on AMPH-induced (1.8 mg/kg, i.p.) alterations in evoked potentials recorded in the hippocampus of anesthetized rats during presentation of a pair of identical tones. Gating was assessed by comparing the amplitude of conditioning and test responses in CLOZ and AMPH-treated rats. RESULTS: The ratio of test to conditioning response amplitude (T/C ratio) was not altered by vehicle or CLOZ alone. However, T/C ratio was significantly increased following AMPH due to suppression of the conditioning response. Acute but not chronic CLOZ attenuated but did not prevent the increase in T/C ratio. CONCLUSIONS: Qualitative differences between the idiopathic gating deficits observed in schizophrenic patients and AMPH-induced increases in T/C ratio in animals limit this models utility as a means of evaluating the ability of atypical antipsychotic drugs to restore normal sensory gating.