Impact of body mass index on 30-day postoperative morbidity in pediatric and adolescent patients undergoing continent urinary tract reconstruction.

INTRODUCTION: Obesity has been thought to increase the risk of complications and need for additional resources with surgery, but only a limited amount of evidence is available in the pediatric population. OBJECTIVE: The objectives were to describe the weight status of pediatric and adolescent patients undergoing a continent urinary tract reconstruction and to determine the association between obesity and 30-day postoperative morbidity. STUDY DESIGN: A retrospective cohort study was performed for pediatric and adolescent patients aged up to 20 years who underwent a continent urinary tract reconstruction between January 2010 and November 2016. Weight status was stratified by the body mass index (BMI) for age z-scores as follows: underweight (<5th percentile), normal (5th to <85th percentiles), overweight (85th to <95th percentiles), and obese (≥95th percentile). Primary outcomes included the duration of intensive care and hospitalization as well as re-admissions and complications within 30 days. RESULTS: A total of 182 continent reconstructions were identified during the study period. Demographic and peri-operative data are provided in the Table. Weight status was not associated with any primary outcomes on univariate or multivariate analysis. There was also no association in an analysis between the non-overweight or non-obese group (BMI for age z-score <85th) and overweight or obese group (BMI for age z-score ≥85th percentiles); a subgroup analysis between patients with and without myelomeningocele; or a subgroup analysis for wound, infectious, or high-grade (Clavien-Dindo grades III or higher) complications. DISCUSSION: Obesity has been consistently associated with an increased risk of surgical site infections and wound complications after a wide variety of surgeries in adults. The results from the present study conflict with those of the few available studies in the pediatric population. The high-risk nature of the present cohort may have mitigated any effect of obesity on 30-day postoperative morbidity. The limitations of the present study include its retrospective design at a single center and the potential misclassification of weight status with the BMI. CONCLUSIONS: Almost 30% of pediatric and adolescent patients undergoing a continent urinary tract reconstruction were overweight or obese. Obesity as determined by the BMI was not associated with 30-day postoperative morbidity.

Preoperative nutritional status and use of total parenteral nutrition in pediatric and adolescent patients undergoing continent urinary tract reconstruction.

INTRODUCTION: A nutritional assessment is a critical but often neglected aspect of a preoperative evaluation. Malnutrition is clearly associated with worse surgical outcomes in adults undergoing major abdominal surgery, whereas a paucity of evidence is available in the pediatric population. OBJECTIVE: The objectives were to describe the preoperative nutritional status of pediatric and adolescent patients undergoing continent urinary tract reconstruction and to determine the association among malnutrition, use of total parenteral nutrition (TPN), and surgical outcomes. STUDY DESIGN: A retrospective cohort study was performed for patients aged up to 20 years who underwent continent urinary tract reconstruction between January 2012 and November 2016. Malnutrition was classified with body mass index and height for age z-scores on admission as well as change in z-scores and weight over the 3-6 months before surgery. Primary outcomes included the duration of intensive care and hospitalization as well as readmissions and complications within 30 days. RESULTS: A total of 123 patients who underwent 130 continent urinary tract reconstructions were identified during the study period. Demographic and perioperative data are provided in the Table. Anthropometric and biochemical measurements as well as the early initiation of TPN (≤2 days) were not associated with any primary outcomes. In a subgroup analysis of patients with a bowel anastomosis, the early initiation of TPN was an independent predictor for duration of hospitalization (P < 0.0001) and 30-day complications (odds ratio 9.51, P = 0.005) after adjusting for other statistically significant and clinically relevant variables. DISCUSSION: The few available studies on surgical nutrition have primarily focused on infants and young children undergoing cardiac surgery and provided no consensus on a preoperative nutritional assessment. The findings on TPN from the present study favorably compare with a growing body of evidence in adult and pediatric critically ill and surgical patients. The limitations of the present study include its retrospective design at a single institution, potential misclassification of nutritional status, and selection bias from the initiation of TPN at the discretion of the primary surgeon. CONCLUSIONS: Malnutrition was identified in greater than 20% of pediatric and adolescent patients undergoing continent urinary tract reconstruction. Anthropometric and biochemical parameters were not associated with surgical outcomes, although the early initiation of TPN did not offer any benefit for nutritional support. In a subset of patients with a bowel anastomosis, TPN was associated with worse surgical outcomes, including a longer duration of hospitalization and development of 30-day complications.

Clinical and urodynamic outcomes in children with anorectal malformation subtype of recto-bladder neck fistula.

INTRODUCTION: Patients with anorectal malformations (ARMs) have a high incidence of genitourinary anomalies. Those with a recto-bladder neck fistula may represent a high-risk group, but their long-term urologic outcomes are poorly described. OBJECTIVE: To evaluate the clinical and urodynamic outcomes in a large cohort of patients with an ARM subtype of recto-bladder neck fistula. MATERIALS AND METHODS: A retrospective cohort study was performed of patients who had been treated for a recto-bladder neck fistula at the present institution since 2007. The primary outcomes were the ability to achieve urinary continence after 4 years of age, and development of a mildly decreased glomerular filtration rate (GFR) or worse (<89 ml/min/1.73 m2). Continence was defined as the ability to store urine for 3-4 h during the day and 8 h overnight without leakage. RESULTS: Demographic and clinical data are provided in the Summary Table. The most recent urodynamic findings included the presence of detrusor overactivity in 30 (75%) patients, median leak point pressure of 56.0 cmH2O (range, 14-140), median functional cystometric capacity at 40 cmH2O of 125.5% age-expected capacity (range, 36-473%), and median maximum cystometric capacity of 131.0% age-expected capacity (range, 44-473%). A mildly decreased GFR or worse developed in 13 (24%) patients. Of the 52 (78%) patients who were followed by pediatric urology at the present institution with a median follow-up of 30.9 months (range, 0.0-86.8), 35 (67%) were at least 4 years of age and could be assessed for continence. Continence was achieved in five (14%) patients voiding spontaneously and 15 (43%) performing CIC. Recurrent urinary tract infections (UTI) (OR 0.70, P = 0.006) were an independent predictor of incontinence, while urethral anomalies (OR 1.40, P = 0.03) were an independent predictor of chronic kidney disease (CKD) on multiple logistic regression analysis. DISCUSSION: The findings favorably compared with other studies, but were more robust due to the size of the cohort and breadth of urologic evaluation. Limitations included the retrospective design at a single institution. Incomplete clinical data and misclassification of continence may have lead to bias. CONCLUSIONS: This large cohort of patients with an ARM subtype of recto-bladder neck fistula had a high incidence of genitourinary anomalies. They were rarely able to achieve continence with spontaneous voiding alone and were at risk of developing CKD, both of which were likely multifocal in origin. Long-term urologic follow-up is warranted for patients with a recto-bladder neck fistula.

Triamcinolone injection for treatment of Mitrofanoff stomal stenosis: Optimizing results and reducing cost of care.

INTRODUCTION: Stomal stenosis is the most common complication after the creation of a continent catheterizable channel (CCC), but is challenging to treat. OBJECTIVE: To describe early experience with triamcinolone injection for the treatment of stomal stenosis. MATERIALS AND METHODS: A retrospective review was performed of patients who had undergone a triamcinolone injection (40 mg/ml) for the treatment of stomal stenosis at the present institution. The primary outcome of success was defined as a patient-reported or caregiver-reported return to ease with catheterization, and avoidance of stomal revision or indwelling catheter. The cost of care with various techniques for the treatment of stomal stenosis was also assessed by representing the cost as a percentage of charges for a re-operative Monti ileovesicostomy. RESULTS: A total of 22 injections were performed in 18 CCCs of 17 patients. Demographic and clinical data are provided in the Summary Table. Thirteen CCCs (72%) were successfully treated with a single injection. Three patients (10%) required a total of five repeat injections at a median of 5.1 months between injections (IQR, 4.6-12.4). One patient required a stomal revision at 34.9 months after the initial injection, while one patient also required a Chait cecostomy catheter. The median length of time for ease with catheterization was 11.6 months (IQR, 3.5-18.0) after the initial injection, and 10.4 months (IQR, 4.5-16.0) after any injection. No adverse effects or complications occurred from the injection. There were no variables associated with failure after the initial or any injection on univariate analysis. Represented as a percentage of charges for a reoperative Monti ileovesicostomy, the cost of care was 11.3% for a stomal revision, 5.8% for triamcinolone injection in the operating room, and 0.3% as an office-based procedure. DISCUSSION: The success rate for triamcinolone injection favorably compared with other options for the treatment of stomal stenosis. It surpassed the reported success rate of stomal dilation and approached that of stomal revision. Other studies have similarly observed a minimal risk of adverse effects and complications from both topical and intralesional corticosteroids. The limitations of the present study included its retrospective design at a single institution. A larger cohort of patients with a longer follow-up is necessary to determine its long-term durability. CONCLUSIONS: Triamcinolone injection was an effective and well-tolerated option for the treatment of stomal stenosis in any cutaneous stoma, thereby avoiding the need for a more invasive and costly stomal revision.

Botulinum toxin injection in the pediatric population with medically refractory neuropathic bladder.

INTRODUCTION: Botulinum toxin injection (BTI) has been advocated as a second line therapy in management of neuropathic bladder in pediatric population for refractory patients to conventional medical management such as anticholinergics. The purpose was to review the safety and efficacy of BTI in children with neuropathic bladder refractory to conservative non-surgical measures. We hypothesized that BTI would be an effective alternative to bladder augmentation in certain patients but not all. METHODS: We retrospectively identified 22 patients with neuropathic bladder due to any condition who underwent urologic BTI at our hospital since 2010. Multiple clinicopathologic variables were examined including the following: demographics, use of anticholinergics, the presence of anticholinergic refractoriness or intolerance, dosage of BTI, urodynamic variables, and continence status. RESULTS: The mean patient age at time of BTI was 10 years with a follow up of 12 months. Indications for BTI were anti-cholinergic refractory (AR) urodynamic parameters and/or incontinence and anticholinergic intolerance (AI). Nearly all patients received 300 Units at BTI into detrusor. No complications occurred from BTI. Overall 54% had improved continence after the initial BTI whereas 45% had achieved complete continence between catheterizations. Cystometric capacity increased by 46% and maximum detrusor pressure decreased by 43% following initial BTI (See Table). 75% of AI patients were continent between CIC after BTI compared to 50% of AR patients (P = 0.002). The observed mean duration of clinical improvement after initial BTI was 4.6 months and four patients underwent repeat BTI. Pre BTI % of age expected bladder capacity Post BTI % of age expected bladder capacity % Improvement in Urodynamic Parameter P value Cystometric Capacity (mL) 227 60 331 87 46 0.008 Maximum Detrusor Pressure (cm H2O) 63 44 43 0.002 Compliance (mL/cm H2O) 4.3 8.8 104 0.001. DISCUSSION: Our results are comparable to existing literature with respect to urodynamic parameters. The observed differences may be due to heterogenous patient population of various etiologies of neuropathic bladder and no uniform criteria to proceed with bladder augmentation. The AR patients in our cohort may have had a higher degree of bladder fibrosis which BTI would be less likely to impact and explain the differences in clinical response between AR and AI patients. CONCLUSIONS: BTI is a safe and effective treatment option for pediatric patients with neuropathic bladder refractory to standard therapy. The degree of continence observed after BTI in our series was higher for AI rather than AR patients.

Infant robotic pyeloplasty: comparison with an open cohort.

OBJECTIVE: To present our experience with infant pyeloplasty, comparing outcomes between robotic-assisted laparoscopic pyeloplasty (RALP) and open pyeloplasty (OP). MATERIALS AND METHODS: A retrospective review was performed of all children <1 year of age who underwent unilateral dismembered pyeloplasty at a single pediatric institution since January 2007. Patients with standard laparoscopic pyeloplasty were excluded. Patient demographics, intraoperative details, narcotic usage, and complications were reviewed. RESULTS: A total of 70 infants (51 boys and 19 girls) were identified, with nine RALP and 61 OP performed. Median age was 9.2 months (range, 3.7-11.9 months) for RALP and 4.1 months (range, 1.0-11.6 months) for OP (p = 0.005). Median weight was 8 kg (range, 5.8-10.9 kg) for RALP and 7 kg (range, 4-14 kg) for OP (p = 0.163). Median operative time was 115 min (range, 95-205 min) for RALP and 166 min (range, 79-300 min) for OP (p = 0.028). Median hospital stay was 1 day (range, 1-2 days) for RALP and 3 days (range, 1-7 days) for OP (p < 0.001). Median postoperative narcotic use of morphine equivalent was <0.01 mg/kg/day (range, 0-0.1 mg/kg/day) for RALP and 0.05 mg/kg/day (range, 0-2.2 mg/kg/day) for OP (p < 0.001). Median follow-up was 10 months (range, 7.2-17.8 months) for RALP and 43.6 months (3.4-73.8 months) for OP (p < 0.001). The success rate was 100% for RALP and 98% for OP. CONCLUSIONS: Infant RALP was observed to be feasible and efficacious with shorter operative time, hospital stay, and narcotic utilization than OP.

Cardiac conduction abnormalities in a mouse model of Lyme borreliosis.

BACKGROUND: Borrelia Burgdorferi (BB) induces cardiac conduction abnormalities in infected humans. Mice models of Lyme disease have been developed, however their electrophysiologic (EP) properties of conduction are unknown. METHODS: Seventy-six C3H/J mice (BB infected and age- and gender-matched controls) underwent blinded in vivo EP studies. In a first phase of the study, 40 male C3H/J mice were divided into 2 groups: Group (A) mice were infected at age 3 (weeks) and studied at 5, and Group (B) mice were infected at 9 and studied at 11. In a second phase, 36 female mice were divided into 2 groups: Group (C) mice were infected at 3 weeks and studied at 5, and Group (D) mice were infected at 3 and studied at 11. RESULTS: Infected mice of group (A) and (C) had wider QRS complexes (21.0+/-1.6 versus 17.3+/-1.3ms, p< or =0.0001 and 20.3+/-2.1 versus 18.5+/-1.7, p = 0.05, respectively) compared to the healthy controls (HC). Infected mice of group (B) and group (D) were similar to the HC. In all groups, the presence of conduction abnormalities correlated very closely with the amount of inflammation on pathology. CONCLUSION: This study describes the first EP mouse model of Lyme carditis. C3H/J mice exhibit conduction abnormalities that are reversible 8 weeks after inoculation, closely paralleling the resolution of inflammation on pathology. This model can be a valuable tool in the developing and testing of new modalities for the prevention and treatment of Lyme carditis.

Impact directly over the cardiac silhouette is necessary to produce ventricular fibrillation in an experimental model of commotio cordis.

OBJECTIVES: In an experimental model of sudden death from chest wall impact (commotio cordis), we sought to define the chest wall areas important in the initiation of ventricular fibrillation (VF). BACKGROUND: Sudden death can result from an innocent chest blow by a baseball or other projectile. Observations in humans suggest that these lethal blows occur over the precordium. However, the precise location of impact relative to the risk of sudden death is unknown. METHODS: Fifteen swine received 178 chest impacts with a regulation baseball delivered at 30 mph at three sites over the cardiac silhouette (i.e., directly over the center, base or apex of the left ventricle [LV]) and four noncardiac sites on the left and right chest wall. Chest blows were gated to the vulnerable portion of the cardiac cycle for the induction of VF. RESULTS: Only chest impacts directly over the heart triggered VF (12 of 78: 15% vs. 0 of 100 for noncardiac sites: p < 0.0001). Blows over the center of the heart (7 of 23; 30%) were more likely to initiate VF than impacts at other precordial sites (5 of 55; 9%, p = 0.02). Peak LV pressures generated instantaneously by the chest impact were directly related to the risk of VF (p < 0.0006). CONCLUSIONS: For nonpenetrating, low-energy chest blows to cause sudden death, impact must occur directly over the heart. Initiation of VF may be mediated by an abrupt and substantial increase in intracardiac pressure. Prevention of sudden death from chest blows during sports requires that protective equipment be designed to cover all portions of the chest wall that overlie the heart, even during body movements and positional changes that may occur with athletic activities.

Connexin40-deficient mice exhibit atrioventricular nodal and infra-Hisian conduction abnormalities.

INTRODUCTION: Previous electrophysiologic investigations have described AV conduction disturbances in connexin40 (Cx40)-deficient mice. Because expression of Cx40 occurs predominantly in the atria and His-Purkinje system of the mouse heart, the AV conduction disturbances were thought to be secondary to disruption in His-Purkinje function. However, the lack of a His-bundle electrogram recording in the mouse has limited further investigation of the importance of Cx40. Using a novel technique to record His-bundle recordings in Cx40-deficient mice, we define the physiologic importance of deficiencies in Cx40. METHODS AND RESULTS: Ten Cx40-/- mice and 11 Cx40+/+ controls underwent a blinded, in vivo, closed chest electrophysiology study at 9 to 12 weeks of age. In the Cx40-/- mice, the PR interval was significantly longer compared with Cx40+/+ mice (44.6+/-6.4 msec vs 36.0+/-4.1 msec, P = 0.002). Not only the HV interval (14.0+/-3.0 msec vs 10.4+/-1.2 msec, P = 0.003) but also the AH interval (33.2+/-4.8 msec vs 27.1+/-3.7 msec, P = 0.006), AV Wenckebach cycle lengths, and AV nodal effective and functional refractory periods were prolonged in Cx40-/- compared with Cx40+/+ mice. CONCLUSION: Cx40-deficient mice exhibit significant delay not only in infra-Hisian conduction, as would be expected from the expression of Cx40 in the His-Purkinje system but also in the electrophysiologic parameters that reflect AV nodal conduction. Our data suggest a significant role of Cx40 in atrionodal conduction and/or in proximal His-bundle conduction.

Effect of saline irrigation flow rate on temperature profile during cooled radiofrequency ablation.

INTRODUCTION: Cooled radiofrequency ablation has been developed clinically for the treatment of ventricular tachycardia. Although clinical studies employ a constant saline flow rate for cooling, we hypothesized that varying the flow rates might optimize the temperature profile at depth. METHODS: In excised ovine left ventricle, we compared the temperature profile from a catheter tip electrode thermocouple to those placed at depths of 0.0 mm, 1.0 mm, and 2.0 mm. We compared the following settings: 20 Watts without flow, 20 Watts with 0.3 cc/sec flow, 20 Watts with 0.5cc/sec flow, and 70C surface temperature without flow (temperature control). RESULTS: The temperatures decreased from 77.5 +/-10.5 degrees C, 91.7+/-6.3 degrees C, 65.5 +/- 11.8 degrees C, and 52.5 +/- 11.8 degrees C at 20W without saline irrigation at the tip, 0.0mm, 1.0mm, and 2.0 mm, respectively, to 33.0+/-1.4 degrees C, 63.4 +/- 7.0 degrees C, 57.1+/-5.8 degrees C, 49.9+/-5.8 degrees C+ at 20W with 0.5 ml/sec flow (*p<0.01, +p = 0.09). The lesion volumes were 79.6mm3 for 20W without flow, 64.1 mm3 for 20W with 0.3 ml/sec flow, 47.5 mm3 for 20W with 0.5 ml/sec flow, and 28.6 mm3 for temperature control. CONCLUSIONS: We conclude that 1) the temperature profile greatly depends upon the rate of saline flow for cooling; 2) at high flow rates, the 0.0 mm and 1.0 mm temperatures are similar; 3) even at high irrigation rates, lesion size is greater than for temperature control; 4) the tip temperature significantly underestimates the surface temperature and improved methods of measuring temperature are needed.

Safety and efficacy of a steerable temperature monitoring microwave catheter system for ventricular myocardial ablation.

INTRODUCTION: Radiofrequency current delivered during cardiac ablation is limited by a rise in impedance secondary to coagulum formation on the ablation electrode. Microwave antennas continue to deliver energy despite the presence of coagulum; thus, temperature control of the ablation electrode may be even more important for microwave than for radiofrequency ablations to avoid thromboembolic risks. The purpose of this study was to test the safety and efficacy of an ablation system utilizing a feedback control system to maintain a fixed target temperature for creating lesions with multiple applications of microwave energy. METHODS AND RESULTS: Microwave ablation was assessed using an 8.5-French catheter at 2 to 4 sites in 11 dogs. Microwave energy delivery was performed for 60 seconds three times at the same site. Power was regulated using a feedback control mechanism to maintain a target temperature of 75 degrees C. Ambulatory ECG monitoring was performed before and after ablation to assess arrhythmia occurrence. After follow-up, the dogs were euthanized, and lesion dimensions measured after fixation. The mean power applied to achieve the target temperature of 75 degrees C was 9.3+/-44 W. The mean depth of the lesions was 8.8+/-4.2 mm. The mean volume of the lesions was 304+/-240 mm3. Forty-four percent of the lesions were transmural. No endocardial thrombus was found. Ventricular tachycardia was observed acutely but resolved after 1 week. CONCLUSION: Temperature feedback control systems for microwave ablation using a temperature-controlled system is feasible for myocardial ablation and creates uniform and large lesions; however, such large lesions can be acutely proarrhythmic.

Microwave radiometric thermometry and its potential applicability to ablative therapy.

INTRODUCTION: [corrected] Current techniques for estimating catheter tip temperature in ablative therapy for cardiac arrhythmias rely on thermocouples or thermistors attached to or embedded in the tip electrode. These methods may reflect the electrode temperature rather than the tissue temperature during electrode cooling so that the highest temperature away from the ablation site may go undetected. A microwave radiometer is capable of detecting microwave radiation as a result of molecular motion. In this study, we evaluated microwave radiometric thermometry as a new technique to monitor temperature away from the electrode tip during ablative therapy utilizing a saline model. METHODS AND RESULTS: A microwave radiometer antenna and fluoroptic thermometer were inserted in a test tube with circulating room temperature saline kept constant at 23.5 degrees C while the surrounding saline bath was heated from 37 degrees C to 70 degrees C. For every degree rise in the warm saline bath placed either 5 mm or 8 mm from the radiometer antenna, the radiometer temperature changed 0.26 degrees C and 0.14 degrees C respectively while the fluoroptic temperature probe remained constant at 23.5 degrees C. The radiometer temperature was highly correlated with the warm saline bath temperature (R(2)=0.997 for warm saline 5 mm from the antenna, R(2)=0.991 for warm saline 8 mm from the antenna). CONCLUSIONS: Microwave radiometry can estimate distant temperatures by detecting microwave electromagnetic radiation. The sensitivity of the microwave radiometer is also distance-dependent. The microwave radiometer thus serves as a promising instrument for monitoring temperatures at depth away from the catheter-electrode tip in ablative therapy for cardiac arrhythmias.

Microwave ablation using a spiral antenna design in a porcine thigh muscle preparation: in vivo assessment of temperature profile and lesion geometry.

INTRODUCTION: Theoretical studies have suggested that microwave energy can increase the depth of heating compared with radiofrequency energy. A spiral microwave antenna design may have advantages over previous designs using smaller designs because the resulting power deposition pattern is considerably larger than the catheter diameter. We tested the efficacy of a spiral antenna using microwave energy in a porcine thigh muscle preparation. METHODS AND RESULTS: In five anesthetized pigs, the thigh muscle was exposed and bathed in heparinized bovine blood (36 degrees to 37 degrees C). A helical microwave catheter with a fiberoptic thermometer attached to the distal end was positioned perpendicular to the thigh muscle. The antenna-tissue interface and tissue temperatures at depths of 3.0 and 6.0 mm were measured. A 915-MHz microwave generator delivered energy at one of three power outputs (50, 100, or 150 W) for 60 seconds. Seventy lesions were created: 50 W (n = 23), 100 W (n = 24), and 150 W (n = 23). The mean depths at 50, 100, and 150 W were 4.3 +/- 1.8 mm, 7.2 +/- 1.7 mm, and 9.4 +/- 0.9 mm, respectively. Lesion depth (R = 0.96, P = 0.05), maximum surface dimension (R = 0.99, P = 0.06), and volume (R = 0.99, P = 0.04) were closely correlated to the power applied. CONCLUSION: Power is an important determinant of lesion size using a spiral microwave antenna. A novel, spiral microwave antenna design can create lesions of significant depth that may be applicable for the ablative therapy of ventricular tachycardia.

A 2 1/4-turn spiral antenna for catheter cardiac ablation.

To investigate the delivery of microwave energy by a catheter positioned inside the heart for ablating small abnormal regions producing cardiac arrhythmias, a 2 1/4-turn spiral catheter-based microwave antenna applicator has been developed. The antenna consists of the center conductor with continuous insulating material extending from the coaxial feed cable formed into a spiral antenna. The insulator completely isolates the center conductor from tissue. Phantom experiments were performed on homogeneous tissue equivalent medium. The reflection coefficient of the antenna at different frequencies and for different spiral lengths, the time course and temperature profile of an ablation, and the dosimetry of power versus temperature, all indicate that the high-power heating patterns from this antenna are both wider and deeper than with the other microwave antenna systems and radio-frequency electrodes.

Localization of the sites of conduction abnormalities in a mouse model of myotonic dystrophy.

INTRODUCTION: A mouse strain lacking functional myotonic dystrophy protein kinase (DMPK) has recently been developed. DMPK-/- mice exhibit muscular and conduction abnormalities consistent with the disease; however, the site of abnormal cardiac conduction is unknown. METHODS AND RESULTS: Nine homozygous DMPK-/- mice and seven age matched wild-type (WT) controls underwent in vivo electrophysiologic studies using an endocardial 2-French catheter. Baseline intervals as well as Wenckebach and 2:1 cycle lengths were measured to assess AV and ventriculoatrial (VA) conduction. Effective refractory periods (ERP) and functional refractory periods were determined during atrial and ventricular premature stimulation. His-bundle recordings were obtained on all the studied animals (16/16). DMPK-/- mice had significantly prolonged PR (48.1 +/- 5.5 vs 40.9 +/- 3.9 msec, P = 0.010) and AH (36.7 +/- 4.0 vs 31.6 +/- 4.8 msec, P = 0.037) intervals compared to WT controls. HV intervals were very significantly prolonged as well (14.7 +/- 2.0 vs 10.3 +/- 0.8 msec; P < 0.0001). Three of 9 DMPK-/- and 1 of 7 WT mice exhibited VA block. Atrial ERP was reached before AV node ERP in 2 (22%) of 9 of the knockout mice and 5 (71%) of 7 of the controls (P = 0.06). Only one mouse (DMPK-/-) exhibited infra-Hisian block on premature atrial stimulation. CONCLUSION: In this mouse model of myotonic dystrophy, AV conduction abnormalities were localized to the supra-Hisian and infra-Hisian conduction tissues, with a higher predilection to the latter, a finding similar to the human form of the disease.

Assessment of atrioventricular nodal physiology in the mouse.

Transgenic mice are increasingly being utilized for understanding cardiac electrophysiologic abnormalities. However, little is known about the normal atrioventricular nodal and infraHisian physiology in the mouse because of the prior inability to record a His-bundle deflection. We present the first comprehensive examination of the murine atrioventricular nodal and His-Purkinje systems employing His-bundle recordings. Normal, healthy, male C57BL/6J mice (n = 48) underwent an in vivo electrophysiology study using a 2 F octapolar electrode catheter. Effective refractory periods were determined during premature atrial and ventricular stimulation. The PR interval measured 44 +/- 6 ms with a mean sinus cycle length of 185 +/- 42 ms. Baseline AH intervals were 36 +/- 5 ms and HV intervals were 10 +/- 2 ms. At a pacing cycle length of 140 ms the atrioventricular nodal effective refractory period (AVNERP) and atrial effective refractory period (AERP) were 86 +/- 19 ms and 57 +/- 17 ms, respectively. The mean AV Wenckebach and 2:1 paced cycle length were 103 +/- 14 ms and 84 +/- 13 ms, respectively. Premature atrial stimulation curves were asymptotic without discontinuity. A subset of nine mice was studied after administration of isoproterenol. The sinus cycle length, AVNERP and AERP decreased significantly from baseline measurements. This method establishes a practical and feasible technique to record in vivo His-bundle electrograms in the mouse to assess atrioventricular nodal and infraHisian physiology. Use of this model will allow for the examination of abnormalities of atrioventricular nodal and infraHisian conduction in transgenic murine models.

Selective activation of the K(+)(ATP) channel is a mechanism by which sudden death is produced by low-energy chest-wall impact (Commotio cordis).

BACKGROUND: Sudden death due to relatively innocent chest-wall impact has been described in young individuals (commotio cordis). In our previously reported swine model of commotio cordis, ventricular fibrillation (with T-wave strikes) and ST-segment elevation (with QRS strikes) were produced by 30-mph baseball impacts to the precordium. Because activation of the K(+)(ATP) channel has been implicated in the pathogenesis of ST elevation and ventricular fibrillation in myocardial ischemia, we hypothesized that this channel could be responsible for the electrophysiologic findings in our experimental model and in victims of commotio cordis. METHODS AND RESULTS: In the initial experiment, 6 juvenile swine were given 0.5 mg/kg IV glibenclamide, a selective inhibitor of the K(+)(ATP) channel, and chest impact was given on the QRS. The results of these strikes were compared with animals in which no glibenclamide was given. In the second phase, 20 swine were randomized to receive glibenclamide or a control vehicle (in a double-blind fashion), with chest impact delivered just before the T-wave peak. With QRS impacts, the maximal ST elevation was significantly less in those animals given glibenclamide (0.16+/-0.10 mV) than in controls (0.35+/-0.20 mV; P=0.004). With T-wave impacts, the animals that received glibenclamide had significantly fewer occurrences of ventricular fibrillation (1 episode in 27 impacts; 4%) than controls (6 episodes in 18 impacts; 33%; P=0.01). CONCLUSIONS: In this experimental model of commotio cordis, blockade of the K(+)(ATP) channel reduced the incidence of ventricular fibrillation and the magnitude of ST-segment elevation. Therefore, selective K(+)(ATP) channel activation may be a pivotal mechanism in sudden death resulting from low-energy chest-wall trauma in young people during sporting activities.

An experimental model of sudden death due to low-energy chest-wall impact (commotio cordis)

BACKGROUND: The syndrome of sudden death due to low-energy trauma to the chest wall (commotio cordis) has been described in young sports participants, but the mechanism is unknown. METHODS: We developed a swine model of commotio cordis in which a low-energy impact to the chest wall was produced by a wooden object the size and weight of a regulation baseball. This projectile was thrust at a velocity of 30 miles per hour and was timed to the cardiac cycle. RESULTS: We first studied 18 young pigs, 6 subjected to multiple chest impacts and 12 to single impacts. Of the 10 impacts occurring within the window from 30 to 15 msec before the peak of the T wave on the electrocardiogram, 9 produced ventricular fibrillation. Ventricular fibrillation was not produced by impacts at any other time during the cardiac cycle. Of the 10 impacts sustained during the QRS complex, 4 resulted in transient complete heart block. We also studied whether the use of safety baseballs, which are softer than standard ones, would reduce the risk of arrhythmia. A total of 48 additional animals sustained up to three impacts during the T-wave window of vulnerability to ventricular fibrillation with a regulation baseball and safety baseballs of three degrees of hardness. We found that the likelihood of ventricular fibrillation was proportional to the hardness of the ball, with the softest balls associated with the lowest risk (two instances of ventricular fibrillation after 26 impacts, as compared with eight instances after 23 impacts with regulation baseballs). CONCLUSIONS: This experimental model of commotio cordis closely resembles the clinical profile of this catastrophic event. Whether ventricular fibrillation occurred depended on the precise timing of the impact. Safety baseballs, as compared with regulation balls, may reduce the risk of commotio cordis.