Potential additional indicators for pacemaker requirement in isolated congenital atrioventricular block.

Low heart rate is the predominantly used indication for pacemaker intervention in patients with isolated congenital atrioventricular block (CAVB). The aim of this study was to compare the difference in heart rates recorded with ECG and Holter monitoring between paced (PM) and nonpaced (NPM) patients with isolated CAVB before pacemaker implantation to identify additional predictors for future PM need. Retrospective evaluation of atrial and ventricular rates (electrocardiography) and minimal and maximal (Holter) heart rates in 129 CAVB patients prior to PM implantation (n = 93) was performed, and results are expressed in V adjusted for age and sex. The average V score for the atrial rate was 0.51 (n = 50) in the PM group and 0.60 (n = 22) in the NPM group (not-significant). The average z score for the ventricular (average) rate was -0.91 (n = 83) in the PM group and -0.93 (n = 33) in the NPM group (not-significant). Minimal heart rate was -0.94 (n = 61) in the PM group and -0.86 (n = 25) in the NPM group (not significant). Maximal heart rate was -0.96 (n = 61) in the PM group and -0.95 (n = 26) in the NPM group (not significant). Initial recordings of the average heart rate and the minimal and maximal heart rate recorded during Holter monitoring do not seem to predict future pacemaker need in patients with CAVB. Studies with exercise stress tests are needed to confirm these findings.

Effects of beta-adrenergic antagonists on the QT measurements from exercise stress tests in pediatric patients with long QT syndrome.

It has been proposed that beta-adrenergic antagonist protection against cardiac events in patients with long QT syndrome (LQTS) may be related to a decrease in baseline QTc dispersion. To determine the effects of beta-blocker therapy on QT measurements, we evaluated the exercise tests of 25 pediatric patients with LQTS. Measurements were made of the maximum QTc interval and QTc dispersion during the various segments of the exercise test. There was no statistically significant difference between the pre-beta-blocker and post-beta-blocker maximum QTc interval during the supine (0.473 +/- 0.039 vs 0.470 +/- 0.038 sec), exercise (0.488 +/- 0.044 vs 0.500 +/- 0.026 sec), or recovery (0.490 +/- 0.031 vs 0.493 +/- 0.029 sec) phases of the exercise stress test. There was also no statistically significant difference between the pre-beta-blocker and post-beta-blocker QTc dispersion during the supine (0.047 +/- 0.021 vs 0.058 +/- 0.033 exercise vs 0.063 +/- 0.028 sec), or recovery (0.045 +/- 0.023 vs 0.052 +/- 0.026 sec) phases of the exercise stress test. Therefore, the protection that beta-blockers offer appears not to be related to a reduction of the baseline QTc interval or a decrease of QTc dispersion.

The incidence of arrhythmias in a pediatric cardiac intensive care unit.

A pediatric cardiac intensive care unit (CICU) manages critically ill children and adults with congenital or acquired heart disease. These patients are at increased risk for arrhythmias. The purpose of this study was to prospectively evaluate the incidence of arrhythmias in a pediatric CICU patient population. All patients admitted to the CICU at the Cardiac Center at The Children's Hospital of Philadelphia between December 1, 1997, and November 30, 1998, were evaluated prospectively from CICU admission to hospital discharge via full disclosure telemetry reviewed every 24 hours. Arrhythmias reviewed included nonsustained and sustained ventricular tachycardia (VT), nonsustained and sustained supraventricular tachycardia (SVT), atrial flutter and fibrillation, junctional ectopic tachycardia, and complete heart block. We reviewed 789 admissions consisting of 629 patients (age range, 1 day-45.5 years; median, 8.1 months). Hospital stay ranged from 1 to 155 days (total of 8116 patient days). Surgical interventions (n = 602) included 482 utilizing cardiopulmonary bypass. During the study period, there were 44 deaths [44/629 patients (7.0%)], none of which were directly attributable to a primary arrhythmia. The operative mortality was 5.1%. Overall, 29.0% of admissions had one or more arrhythmias the most common arrhythmia was nonsustained VT (18.0% of admissions), followed by nonsustained SVT (12.9% of admissions). Patients admitted to a pediatric CICU have a high incidence of arrhythmias, most likely associated with their underlying pathophysiology and to the breadth of medical and surgical interventions conducted.

Design and baseline characteristics for the ACE Inhibitor After Anthracycline (AAA) study of cardiac dysfunction in long-term pediatric cancer survivors.

PURPOSE: The ACE Inhibitor After Anthracycline (AAA) study is a randomized, double-blind, controlled clinical trial comparing enalapril with placebo to determine whether treatment can slow the progression of cardiac decline in patients who screen positive for anthracycline cardiotoxicity. METHODS: The primary outcome measure is the rate of decline, over time, in maximal cardiac index (in liters per minute per meters squared) at peak exercise; the secondary outcome measure is the rate of increase in left ventricular end systolic wall stress (in grams per centimeters squared). Patients >2 years off therapy and <4 years from diagnosis, aged 8 years and older, were eligible if they had received anthracyclines and had at least one cardiac abnormality identified at any time after anthracycline exposure. RESULTS: A total of 135 patients were randomized to enalapril or placebo. Baseline characteristics were similar across treatment groups. CONCLUSIONS: The AAA study will provide important information concerning the efficacy of using angiotensin-converting enzyme inhibitors to offset the effects of late anthracycline cardiotoxicity.

Epicardial atrial pacemaker lead placement after multiple cardiac operations.

We describe a simple technique for the implantation of left atrial epicardial pacing leads in children with congenital heart disease who have undergone multiple operations. The pulmonary veins are exposed to reveal the pulmonary venous to atrial confluence using a left thoracotomy. A pacemaker lead is secured to the posterior left atrium inferior to the lower pulmonary vein. This approach provides a reliable site for atrial lead placement without the need for extensive dissection.

Permanent epicardial pacing in pediatric patients: seventeen years of experience and 1200 outpatient visits.

BACKGROUND: The purpose of this study was to evaluate the long-term outcome of all pediatric epicardial pacing leads. METHODS AND RESULTS: All epicardial leads and 1239 outpatient visits between January 1, 1983, and June 30, 2000, were retrospectively reviewed. Pacing and sensing thresholds were reviewed at implant, at 1 month, and at subsequent 6-month intervals. Lead failure was defined as the need for replacement or abandonment due to pacing or sensing problems, lead fracture, or phrenic/muscle stimulation. A total of 123 patients underwent 207 epicardial lead (60 atrial/147 ventricular, 40% steroid) implantations (median age at implant was 4.1 years [range 1 day to 21 years]). Congenital heart disease was present in 103 (84%) of the patients. Epicardial leads were followed for 29 months (range 1 to 207 months). The 1-, 2-, and 5-year lead survival was 96%, 90%, and 74%, respectively. Compared with conventional epicardial leads, both atrial and ventricular steroid leads had better stimulation thresholds 1 month after implantation; however, only ventricular steroid leads had improved chronic pacing thresholds (at 2 years: for steroid leads, 1.9 muJ [from 0.26 to 16 mu]; for nonsteroid leads, 4.7 muJ [from 0.6 to 25 muJ]; P<0.01). Ventricular sensing was significantly better in steroid leads 1 month after lead implantation (at 2 years: for steroid leads, 8 mV [from 4 to 31 mV]; for nonsteroid leads, 4 mV [from 0.7 to 10 mV]; P<0.01). Neither congenital heart disease, lead implantation with a concomitant cardiac operation, age or weight at implantation, nor the chamber paced was predictive of lead failure. CONCLUSIONS: Steroid epicardial leads demonstrated relatively stable acute and chronic pacing and sensing thresholds. In this evaluation of >200 epicardial leads, lead survival was good, with steroid-eluting leads demonstrating results similar to those found with historical conventional endocardial leads.

Dilated cardiomyopathy in isolated congenital complete atrioventricular block: early and long-term risk in children.

OBJECTIVES: We sought to identify the risk factors predicting the development of dilated cardiomyopathy (DCM) in patients with isolated congenital complete atrioventricular block (CCAVB). BACKGROUND: Recently evidence has emerged that a subset of patients with CCAVB develop DCM. METHODS: This was a retrospective study of 149 patients with CCAVB who had heart size and left ventricular (LV) function assessed by echocardiography and chest radiography over a follow-up period of 10 +/- 7 years. RESULTS: Nine patients developed DCM at the age of 6.5 +/- 5 years. No definite cause could be identified. In these nine patients, CCAVB was diagnosed in eight at 23 +/- 2.3 weeks gestation and in one at birth. Maternal SSA/SSB antibodies were confirmed in seven of the nine patients. Pacemakers were implanted in eight patients in the first month and in one patient at five years of age. The initial left ventricular end-diastolic dimension (LVEDD) was in the 96th +/- 2.6 percentile and the cardiothoracic (CT) ratio was 64 +/- 3.8% in the nine patients who developed DCM, and differed significantly in patients with CCAVB (p < 0.005) who did not develop DCM. The LVEDD and CT ratio did not decrease in the patients with CCAVB and DCM, but decreased significantly in the patients with CCAVB without DCM (p < 0.001) once pacing was initiated. Two patients with DCM died within two months of diagnosis; one patient is neurologically compromised; two patients received a heart transplant; and four patients are listed for heart transplantation. CONCLUSIONS: Isolated CCAVB is associated with a long-term risk for the development of DCM. Risk factors may be SSA/SSB antibodies, increased heart size at initial evaluation and the absence of pacemaker-associated improvement.

Epicardial pacemaker implantation and follow-up in patients with a single ventricle after the Fontan operation.

OBJECTIVES: There is an increasing incidence of sinus node dysfunction after the Fontan procedure. Inability to maintain atrioventricular synchrony after the Fontan operation has been associated with an adverse late outcome. Although pacing may be helpful as a primary or adjunct modality after the Fontan procedure, the effects of performing a late thoracotomy or sternotomy for epicardial pacemaker implantation are unknown. In addition, little is known about the long-term effectiveness of epicardial leads in patients with single ventricles. The purpose of this study was to compare the hospital course and follow-up of epicardial pacing lead implantation in patients with Fontan physiology and patients with 2-ventricle physiology. METHODS: We retrospectively reviewed all isolated epicardial pacemaker implantations and outpatient evaluations performed between January 1983 and June 2000. RESULTS: There was no difference in the perioperative course for the 31 Fontan patients (27 atrial and 41 ventricular leads [68 total]) compared with the 56 non-Fontan subjects (9 atrial and 61 ventricular leads [70 total]). The median length of stay in Fontan and non-Fontan patients was 3 and 4 days, respectively. There was no early mortality in either group. Pleural drainage for 5 days or longer was reported in 4% of the Fontan cohort and 3% of the non-Fontan group. Late pleural effusions were identified in only 2 patients in the Fontan group and 2 patients in the non-Fontan group. There was no significant difference in epicardial lead survival between the Fontan group and the non-Fontan group (1 year, 96%; 2 years, 90%; 5 years, 70%). The overall incidence of lead failure was 17% (24/138). CONCLUSIONS: Epicardial leads can be safely placed in Fontan patients at no additional risk compared to patients with biventricular physiology. Sensing and pacing qualities were relatively constant in both the Fontan and non-Fontan groups over the first 2 years after implantation.

Modifications to the cavopulmonary anastomosis do not eliminate early sinus node dysfunction.

OBJECTIVE: To determine whether operations that theoretically jeopardize the sinus node (hemi-Fontan and/or lateral tunnel Fontan procedures) are associated with a greater risk of sinus node dysfunction than those that theoretically spare the sinus node (bidirectional Glenn and/or extracardiac conduit). METHODS: Between January 1, 1996, and December 31, 1999, a prospective cohort study was conducted evaluating the incidence of sinus node dysfunction in patients undergoing a bidirectional Glenn or hemi-Fontan procedure and those in whom the Fontan repair was completed with either an extracardiac conduit or a lateral tunnel. Sinus node dysfunction was defined (1) as a heart rate more than 2 SD below age-adjusted norms or (2) as a predominant junctional rhythm and/or a sinus pause of more than 3 seconds as determined by the resting electrocardiogram and/or ambulatory monitoring at hospital discharge. RESULTS: Fifty-one patients had a bidirectional Glenn shunt (mean age 7.8 +/- 5.1 months) and 79 a hemi-Fontan procedure (mean age 6.9 +/- 2.8 months). The incidence of sinus node dysfunction on postoperative day 1 was significantly higher after the hemi-Fontan (36%) than after the bidirectional Glenn shunt (9.8%); however, by hospital discharge this difference was no longer apparent (hemi-Fontan [8%]; bidirectional Glenn [6%]; P = not significant). No difference in early sinus node dysfunction was discernible after the extracardiac conduit (4/30 [13%]) compared with the lateral tunnel Fontan procedure (6/46 [13%]) (P = not significant). No diagnostic or perioperative variables were predictive of sinus node dysfunction. CONCLUSIONS: Avoidance of surgery near the sinus node has no discernible effect on the development of early sinus node dysfunction. Thus, concerns about early sinus node dysfunction should not override patient anatomy or surgeon preference as determinants of which cavopulmonary anastomosis to perform.

Somatic growth failure after the Fontan operation.

Our study was designed to characterize the patterns of growth, in the medium term, of children with functionally univentricular hearts managed with a hemi-Fontan procedure in infancy, followed by a modified Fontan operation in early childhood. Failure of growth is common in patients with congenital cardiac malformations, and may be related to congestive heart failure and hypoxia. Repair of simple lesions appears to reverse the retardation in growth. Palliation of the functionally single ventricular physiology with a staged Fontan operation reduces the adverse effects of hypoxemia and prolonged ventricular volume overload. The impact of this approach on somatic growth is unknown. Retrospectively, we reviewed the parameters of growth of all children with functionally univentricular hearts followed primarily at our institution who had completed a staged construction of the Fontan circulation between January 1990 and December 1995. Measurements were available on all children prior to surgery, and annually for three years following the Fontan operation. Data was obtained on siblings and parents for comparative purposes. The criterions of eligibility for inclusion were satisfied by 65 patients. The mean Z score for weight was -1.5 +/- 1.2 at the time of the hemi-Fontan operation. Weight improved by the time of completion of the Fontan circulation (-0.91 +/- 0.99), and for the first two years following the Fontan operation, but never normalized. The mean Z scores for height at the hemi-Fontan and Fontan operations were -0.67 +/- 1.1 and -0.89 +/- 1.2 respectively. At most recent follow-up, with a mean age of 6.1 +/- 1.3 years, and a mean time from the Fontan operation of 4.4 +/- 1.4 years, the mean Z score for height was -1.15 +/- 1.2, and was significantly less than comparable Z scores for parents and siblings. In our experience, children with functionally univentricular hearts who have been palliated with a Fontan operation are significantly underweight and shorter than the general population and their siblings.

Population and unit synchrony of fast rhythms in expiratory recurrent laryngeal discharges.

In a decerebrate, vagotomized, gallamine-paralyzed cat that had a prominent bilaterally coherent fast rhythm (50 Hz) in expiratory (E) recurrent laryngeal (RL) nerve discharges, recordings were taken of the firing of nine RL E fibers. This rhythm (called E high-frequency oscillation or EHFO) was seen as a sharp peak in all unit autospectra, all unit-nerve coherence spectra (value range 0.39-0. 91), and all unit-unit coherence spectra (value range 0.27-0.85). In addition, 8/9 units had a sharp autospectral peak in a lower frequency range (19-35 Hz) called E medium-frequency oscillation (EMFO), but there was no coherence at this frequency between signal pairs (unit-unit, unit-nerve, nerve-nerve). The MFOs are specific for each unit and are considered to arise from asynchronous inputs and membrane properties. The HFOs are considered to arise from widespread network interactions that produce a common (correlated) rhythm in virtually all neurons of the RL E network. These phenomena suggest the use of the RL E network as a model system for analyzing rhythmic neural interactions.

Synchronized fast rhythms in inspiratory and expiratory nerve discharges during fictive vocalization.

In precollicular decerebrate and paralyzed cats, respiratory nerve activities were recorded during fictive vocalization (FV), which consisted of a distinctive pattern of 1) decreased inspiratory (I) and expiratory (E) phase durations, 2) marked increase of phrenic activity and moderate changes of recurrent laryngeal (RL) and superior laryngeal (SL) I activities, and 3) massive recruitment of laryngeal and abdominal (ABD; lumbar) E activities. FV was produced by electrical stimulation (100 Hz) in the midbrain periaqueductal gray (PAG) or its putative descending pathways in the ventrolateral pons (VLP). Spectral and correlation analyses revealed three types of effect on fast rhythms during FV. 1) I activities: the coherent high-frequency oscillations in I (I-HFO, 60-90 Hz) present in phrenic and RL discharges during the control state did not change qualitatively, but there was an increase of power and a moderate increase (4-10 Hz) of frequency. Sometimes a distinct relatively weak stimulus-locked rhythm appeared. 2) RL and SL activities during E: in recruited discharges, a prominent intrinsic rhythm (coherent E-HFOs at 50-70 Hz) appeared; sometimes a distinct relatively strong stimulus-locked rhythm appeared. 3) ABD activities during E: this recruited activity had no intrinsic rhythm but had an evoked oscillation locked to the stimulus frequency. Thus FV is characterized by 1) appearance of prominent coherent intrinsic rhythms in RL and SL E discharges, which presumably arise as a result of excitation and increased interactions in laryngeal networks; 2) modification of intrinsic rhythmic interactions in inspiratory networks; and 3) evoked rhythms in augmenting-E neuron networks without occurrence of intrinsic rhythms.

Fast (3 Hz and 10 Hz) and slow (respiratory) rhythms in cervical sympathetic nerve and unit discharges of the cat.

1. In seven decerebrate cats, recordings were taken from the preganglionic cervical sympathetic (CSy) nerves and from 74 individual CSy fibres. Correlation and spectral analyses showed that nerve and fibre discharges had several types of rhythm that were coherent (correlated) between population and unit activity: respiratory, '3 Hz' (2-6 Hz, usually cardiac related), and '10 Hz' (7-13 Hz). 2. Almost all units (73/74) had respiratory modulation of their discharge, either phasic (firing during only one phase) or tonic (firing during both the inspiratory (I) and expiratory (E) phases). The most common pattern consisted of tonic I-modulated firing. When the vagi were intact, lung afferent input during I greatly reduced CSy unit and nerve discharge, as evaluated by the no-inflation test. 3. The incidence of unit-nerve coherent fast rhythms (3 Hz or 10 Hz ranges) depended on unit discharge pattern: they were present in an appreciable fraction (30/58 or 52 %) of tonic units, but in only a small fraction (2/15 or 13 %) of phasic units. 4. When baroreceptor innervation (aortic depressor amd carotid sinus nerves) was intact, rhythms correlated to the cardiac cycle frequency were found in 20/34 (59 %) of units. The cardiac origin of these rhythms was confirmed by residual autospectral and partial coherence analysis and by their absence after baroreceptor denervation. 4. The 10 Hz coherent rhythm was found in 7/34 units when baroreceptor innervation was intact, where it co-existed with the cardiac-locked rhythm; after barodenervation it was found in 9/50 neurones. Where both rhythms were present, the 10 Hz component was sometimes synchronized in a 3:1 ratio to the 3 Hz (cardiac-related) frequency component. 5. The tonic and phasic CSy units seem to form distinct populations, as indicated by the differential responses to cardiac-related afferent inputs when baroreceptor innervation is intact. The high incidence of cardiac-related correlation found among tonic units suggests that they are involved in vasomotor regulation. The high incidence of respiratory modulation of discharge suggests that the CSy units may be involved in regulation of the nasal vasculature and consequent ventilation-related control of nasal airway resistance.

Sinus node function after a systematically staged Fontan procedure.

BACKGROUND: Sinus node dysfunction has been previously reported to occur in 13% to 16% of patients after the Fontan operation. Although there is concern that an intermediate cavopulmonary connection may increase the risk of sinus node dysfunction, previous studies have not reported on patients routinely staged to a Fontan operation. This study sought to determine the early and late incidences of sinus node dysfunction in patients systematically and uniformly staged to a Fontan operation after a prior hemi-Fontan. METHODS AND RESULTS: To determine the early incidence of sinus node dysfunction, hospital records and perioperative ECGs were reviewed in all 287 patients having had a staged Fontan operation between January 1990 and December 1995. A cross-sectional analysis was performed on 220 of 239 surviving patients (92%) to determine the late incidence of sinus node dysfunction. Sinus node dysfunction was present in 7% of the patients before and in 15% after the hemi-Fontan. Although most patients (81%) regained normal sinus node function between the 2 stages, 23% had sinus node dysfunction in the early postoperative period after the Fontan. Of the 95 patients followed for > 4 years after the Fontan operation, 44% had sinus node dysfunction. However, at a mean follow-up of 3.5 +/- 1.7 years, only 16 patients (6.7%) had received a pacemaker and only 10 (4.1%) had documented atrial flutter. CONCLUSIONS: Perioperative sinus node dysfunction is common after both the hemi-Fontan and the Fontan procedures. Although many patients regain sinus node function between the 2 stages, late sinus node dysfunction is common and more likely to occur in patients with early sinus node dysfunction and those with longer follow-up.

Electrophysiologic properties of the atrioventricular node in pediatric patients.

OBJECTIVES: The purpose of this study was to characterize anterograde and retrograde properties of the atrioventricular (AV) node in children and to determine the presence of ventriculoatrial (VA) conduction and dual AV node pathways. BACKGROUND: Although AV node reentry is common in adults, it accounts for 13% of pediatric supraventricular tachycardia (SVT). The age-related changes in the AV node with development are poorly understood. The incidence of dual AV node pathways and VA conduction in the pediatric population is unknown. METHODS: Electrophysiologic studies were performed in 79 patients with normal hearts and no evidence of AV node arrhythmias. Patients were classified into two groups by age: group I = 49 patients (0.39 to 12.8 years old, mean [+/- SD] age 8.5 +/- 3.6); group II = 30 patients (13.4 to 20.0 years old, mean age 15.6 +/- 1.8). RESULTS: There was a significant difference (p < 0.05) in the cycle length (CL) at which anterograde AV block occurred between group I (305 +/- 63 ms) and group II (350 +/- 91 ms). Sixty-one percent of children had VA conduction with no age-related differences. There was no significant difference in the mean CL of retrograde VA block (360 ms). The incidence of dual AV node pathways in group I was 15% and 44% in group II (p < 0.05). CONCLUSIONS: These findings suggest that AV node electrophysiology undergoes maturational changes. The increase in AV node reentrant tachycardia in adults may relate to changes in the relative refractoriness and conduction of the AV node or to differences in autonomic input into the AV node that allow dual pathway physiology to progress to SVT.

High-frequency oscillations in membrane potentials of medullary inspiratory and expiratory neurons (including laryngeal motoneurons).

1. In midcollicular decerebrate, unanesthetized, paralyzed cats ventilated with a cycle-triggered pump system, the properties of high-frequency oscillations (HFOs, 50-100 Hz) in membrane potentials (MPs) of medullary inspiratory (I) and expiratory (E) cells were studied. Simultaneous recordings were taken from bilateral phrenic and recurrent laryngeal (RL) nerves and from cells in the intermediate ventral respiratory group (intVRG, 0-1 mm rostral to the obex) or the caudal ventral respiratory group (cVRG, 2-4 mm caudal to the obex). 2. Spectral coherence analyses were used to detect the presence of HFOs during I in I and E cell MPs. Cross-correlation histograms (CCHs) between the cell and phrenic signals were used to ascertain cell-nerve HFO phase relations and to identify cells as RL motoneurons. Of the 103 cells that had significant HFOs (cell-phrenic coherences > or = 0.1), measurable HFO peak lags in the CCH were seen in 53 cells: 1) RL cells (9 I cells and 7 E cells); and 2) other types of cell (8 intVRG I cells, 18 intVRG E cells, and 11 cVRG E cells). These cells had high HFO correlations; the cell-phrenic coherence range was 0.35-0.94, with a mean HFO frequency of 58 Hz. 3. The cell-phrenic HFO lag (in ms) was measured in the CCH as the lag of the primary peak (peak located nearest to 0 lag). The phase lag was defined as (lag of primary peak in ms)/(HFO period in ms). The phase lags differed markedly between two subsets of cells: 1) RL I cells had HFO depolarization peaks that lagged the phrenic HFO peaks (average cell-phrenic phase lag = -0.18); and 2) the non-RL cells, regardless of location (intVRG or cVRG) and type (I or E), had HFO depolarization peaks leading (preceding) the phrenic HFO peaks (average cell-phrenic phase lag = 0.28). In addition, the cVRG E cells had significantly shorter cell-phrenic phase lags than the intVRG E cells (0.23 vs. 0.31, respectively). 4. These lags can be compared with the (I unit)-phrenic phase lags (average approximately 0.3) found in earlier extracellular studies. 1) There is a transmission delay of about one half HFO cycle from excitatory I cells to RL I cells. 2) Because a depolarization peak in the MP of an E cell corresponds to the start of a hyperpolarizing wave, the excitatory bulbospinal pathways from I cells have transmission times comparable with those of the inhibitory intramedullary pathways from I cells to E cells. 5. These results indicate that study of HFO phase relations can furnish useful information on functional connectivity of medullary respiratory neurons during the I phase.