Changes in pontine and preBötzinger/Bötzinger complex neuronal activity during remifentanil-induced respiratory depression in decerebrate dogs.

Introduction: In vivo studies using selective, localized opioid antagonist injections or localized opioid receptor deletion have identified that systemic opioids dose-dependently depress respiratory output through effects in multiple respiratory-related brainstem areas. Methods: With approval of the subcommittee on animal studies of the Zablocki VA Medical Center, experiments were performed in 53 decerebrate, vagotomized, mechanically ventilated dogs of either sex during isocapnic hyperoxia. We performed single neuron recordings in the Pontine Respiratory Group (PRG, n = 432) and preBötzinger/Bötzinger complex region (preBötC/BötC, n = 213) before and during intravenous remifentanil infusion (0.1-1 mcg/kg/min) and then until complete recovery of phrenic nerve activity. A generalized linear mixed model was used to determine changes in Fn with remifentanil and the statistical association between remifentanil-induced changes in Fn and changes in inspiratory and expiratory duration and peak phrenic activity. Analysis was controlled via random effects for animal, run, and neuron type. Results: Remifentanil decreased Fn in most neuron subtypes in the preBötC/BötC as well as in inspiratory (I), inspiratory-expiratory, expiratory (E) decrementing and non-respiratory modulated neurons in the PRG. The decrease in PRG inspiratory and non-respiratory modulated neuronal activity was associated with an increase in inspiratory duration. In the preBötC, the decrease in I-decrementing neuron activity was associated with an increase in expiratory and of E-decrementing activity with an increase in inspiratory duration. In contrast, decreased activity of I-augmenting neurons was associated with a decrease in inspiratory duration. Discussion: While statistical associations do not necessarily imply a causal relationship, our data suggest mechanisms for the opioid-induced increase in expiratory duration in the PRG and preBötC/BötC and how inspiratory failure at high opioid doses may result from a decrease in activity and decrease in slope of the pre-inspiratory ramp-like activity in preBötC/BötC pre-inspiratory neurons combined with a depression of preBötC/BötC I-augmenting neurons. Additional studies must clarify whether the observed changes in neuronal activity are due to direct neuronal inhibition or decreased excitatory inputs.

Comparison of Prothrombin Complex Concentrate with Activated Factor VII Use for Bleeding Following Cardiopulmonary Bypass in Children.

OBJECTIVE: This study aims to compare the efficacy and safety of activated recombinant factor VII (rFVIIa) and prothrombin complex concentrate (PCC) in the treatment of bleeding complications following surgery requiring cardiopulmonary bypass (CPB) in children. DESIGN/METHODS: This is a retrospective chart review of a single institution comprising patients aged 0 to 18 years old with congenital heart disease. Patients must have received either PCC or rFVIIa after coming off CPB. Our primary efficacy endpoint is time in the operating room from off-CPB to pediatric intensive care unit admission. Our primary safety endpoint is thrombosis through 30 days. RESULTS: Our primary efficacy outcome was significantly shorter in the PCC group compared with the rFVIIa group (P < .0001). Similarly, secondary efficacy outcomes of packed red blood cell administration, chest tube output, and transfusion exposures all significantly favored PCC administration. However, CPB time was significantly longer, and body temperatures were significantly lower, in the rFVIIa group. Safety outcomes, including our primary safety outcome of thrombosis through 30 days, were similar between the two groups. CONCLUSION: This study questions whether PCC could be favored over rFVIIa for hemostasis in children with congenital heart disease following CPB surgery. In addition, this study has found no difference when comparing PCC and rFVIIa in terms of safety outcomes, particularly thrombosis events. There are several limitations to this study due to the retrospective nature of the design and the differences between the two study groups. Despite the limitations, this study suggests that relatively early administration of PCC could be favored over delayed administration of rFVIIa to control recalcitrant post-CPB bleeding in the operating room.

Effects of Arterial Carbon Dioxide Tension on Cerebral and Somatic Regional Tissue Oxygenation and Blood Flow in Neonates After the Norwood Procedure With Deep Hypothermic Cardiopulmonary Bypass.

Neonates undergoing the Norwood procedure for hypoplastic left heart syndrome are at higher risk of impaired systemic oxygen delivery with resultant brain, kidney, and intestinal ischemic injury, shock, and death. Complex developmental, anatomic, and treatment-related influences on cerebral and renal-somatic circulations make individualized treatment strategies physiologically attractive. Monitoring cerebral and renal circulations with near infrared spectroscopy can help drive rational therapeutic interventions. The primary aim of this study was to describe the differential effects of carbon dioxide tension on cerebral and renal circulations in neonates after the Norwood procedure. Using a prospectively-maintained database of postoperative physiologic and hemodynamic parameters, we analyzed the relationship between postoperative arterial carbon dioxide tension and tissue oxygen saturation and arteriovenous saturation difference in cerebral and renal regions, applying univariate and multivariate multilevel mixed regression techniques. Results were available from 7,644 h of data in 178 patients. Increases in arterial carbon dioxide tension were associated with increased cerebral and decreased renal oxygen saturation. Differential changes in arteriovenous saturation difference explained these effects. The cerebral circulation showed more carbon dioxide sensitivity in the early postoperative period, while sensitivity in the renal circulation increased over time. Multivariate models supported the univariate findings and defined complex time-dependent interactions presented graphically. The cerebral and renal circulations may compete for blood flow with critical limitations of cardiac output. The cerebral and renal-somatic beds have different circulatory control mechanisms that can be manipulated to change the distribution of cardiac output by altering the arterial carbon dioxide tension. Monitoring cerebral and renal circulations with near infrared spectroscopy can provide rational physiologic targets for individualized treatment.

Contribution of the caudal medullary raphe to opioid induced respiratory depression.

BACKGROUND: Opioid-induced respiratory depression can be partially antagonized in the preBötzinger Complex and Parabrachial Nucleus/Kölliker-Fuse Complex. We hypothesized that additional opioid antagonism in the caudal medullary raphe completely reverses the opioid effect. METHODS: In adult ventilated, vagotomized, decerebrate rabbits, we administrated remifentanil intravenously at "analgesic", "apneic", and "very high" doses and determined the reversal with sequential naloxone microinjections into the bilateral Parabrachial Nucleus/Kölliker-Fuse Complex, preBötzinger Complex, and caudal medullary raphe. In separate animals, we injected opioid antagonists into the raphe without intravenous remifentanil. RESULTS: Sequential naloxone microinjections completely reversed respiratory rate depression from "analgesic" and "apneic" remifentanil, but not "very high" remifentanil concentrations. Antagonist injection into the caudal medullary raphe without remifentanil independently increased respiratory rate. CONCLUSIONS: Opioid-induced respiratory depression results from a combined effect on the respiratory rhythm generator and respiratory drive. The effect in the caudal medullary raphe is complex as we also observed local antagonism of endogenous opioid receptor activation, which has not been described before.

Dose-dependent Respiratory Depression by Remifentanil in the Rabbit Parabrachial Nucleus/Kölliker-Fuse Complex and Pre-Bötzinger Complex.

BACKGROUND: Recent studies showed partial reversal of opioid-induced respiratory depression in the pre-Bötzinger complex and the parabrachial nucleus/Kölliker-Fuse complex. The hypothesis for this study was that opioid antagonism in the parabrachial nucleus/Kölliker-Fuse complex plus pre-Bötzinger complex completely reverses respiratory depression from clinically relevant opioid concentrations. METHODS: Experiments were performed in 48 adult, artificially ventilated, decerebrate rabbits. The authors decreased baseline respiratory rate ~50% with intravenous, "analgesic" remifentanil infusion or produced apnea with remifentanil boluses and investigated the reversal with naloxone microinjections (1 mM, 700 nl) into the Kölliker-Fuse nucleus, parabrachial nucleus, and pre-Bötzinger complex. In another group of animals, naloxone was injected only into the pre-Bötzinger complex to determine whether prior parabrachial nucleus/Kölliker-Fuse complex injection impacted the naloxone effect. Last, the µ-opioid receptor agonist [d-Ala,2N-MePhe,4Gly-ol]-enkephalin (100 µM, 700 nl) was injected into the parabrachial nucleus/Kölliker-Fuse complex. The data are presented as medians (25 to 75%). RESULTS: Remifentanil infusion reduced the respiratory rate from 36 (31 to 40) to 16 (15 to 21) breaths/min. Naloxone microinjections into the bilateral Kölliker-Fuse nucleus, parabrachial nucleus, and pre-Bötzinger complex increased the rate to 17 (16 to 22, n = 19, P = 0.005), 23 (19 to 29, n = 19, P < 0.001), and 25 (22 to 28) breaths/min (n = 11, P < 0.001), respectively. Naloxone injection into the parabrachial nucleus/Kölliker-Fuse complex prevented apnea in 12 of 17 animals, increasing the respiratory rate to 10 (0 to 12) breaths/min (P < 0.001); subsequent pre-Bötzinger complex injection prevented apnea in all animals (13 [10 to 19] breaths/min, n = 12, P = 0.002). Naloxone injection into the pre-Bötzinger complex alone increased the respiratory rate to 21 (15 to 26) breaths/min during analgesic concentrations (n = 10, P = 0.008) but not during apnea (0 [0 to 0] breaths/min, n = 9, P = 0.500). [d-Ala,2N-MePhe,4Gly-ol]-enkephalin injection into the parabrachial nucleus/Kölliker-Fuse complex decreased respiratory rate to 3 (2 to 6) breaths/min. CONCLUSIONS: Opioid reversal in the parabrachial nucleus/Kölliker-Fuse complex plus pre-Bötzinger complex only partially reversed respiratory depression from analgesic and even less from "apneic" opioid doses. The lack of recovery pointed to opioid-induced depression of respiratory drive that determines the activity of these areas.

Interaction between the pulmonary stretch receptor and pontine control of expiratory duration.

Medial parabrachial nucleus (mPBN) neuronal activity plays a key role in controlling expiratory (E)-duration (TE). Pulmonary stretch receptor (PSR) activity during the E-phase prolongs TE. The aims of this study were to characterize the interaction between the PSR and mPBN control of TE and underlying mechanisms. Decerebrated mechanically ventilated dogs were studied. The mPBN subregion was activated by electrical stimulation via bipolar microelectrode. PSR afferents were activated by low-level currents applied to the transected central vagus nerve. Both stimulus-frequency patterns during the E-phase were synchronized to the phrenic neurogram; TE was measured. A functional mathematical model for the control of TE and extracellular recordings from neurons in the preBötzinger/Bötzinger complex (preBC/BC) were used to understand mechanisms. Findings show that the mPBN gain-modulates, via attenuation, the PSR-mediated reflex. The model suggested functional sites for attenuation and neuronal data suggested correlates. The PSR- and PB-inputs appear to interact on E-decrementing neurons, which synaptically inhibit pre-I neurons, delaying the onset of the next I-phase.

Interventions Associated With Treatment of Low Cardiac Output After Stage 1 Norwood Palliation.

BACKGROUND: Mortality after stage 1 palliation of hypoplastic left heart syndrome remains significant. Both cardiac output (CO) and systemic vascular resistance (SVR) contribute to hemodynamic vulnerability. Simultaneous measures of mean arterial pressure and somatic regional near infrared spectroscopy saturation can classify complex hemodynamics into 4 distinct states, with a low-CO state of higher risk. We sought to identify interventions associated with low-CO state occupancy and transition. METHODS: Perioperative data were prospectively collected in an institutional review board-approved database. Hemodynamic state was classified as high CO, high SVR, low SVR, and low CO using bivariate analysis. Associations of static and dynamic support levels and state classifications over 48 postoperative hours were tested between states and across transitions using mixed regression methods in a quasi-experimental design. RESULTS: Data from 10,272 hours in 214 patients were analyzed. A low-CO state was observed in 142 patients for 1107 hours. Both low CO and extracorporeal membrane oxygenation had increased mortality risk. The low-CO state was characterized by lower milrinone but higher catecholamine dose. Successful transition out of low CO was associated with increased milrinone dose and hemoglobin concentration. Increasing milrinone and hemoglobin levels predicted reduced risk of low CO in future states. CONCLUSIONS: Bivariate classification objectively defines hemodynamic states and transitions with distinct support profiles. Maintaining or increasing inodilator and hemoglobin levels were associated with improved hemodynamic conditions and were predictive of successful future transitions from the low-CO state.

Multi-Level Regulation of Opioid-Induced Respiratory Depression.

Opioids depress minute ventilation primarily by reducing respiratory rate. This results from direct effects on the preBötzinger Complex as well as from depression of the Parabrachial/Kölliker-Fuse Complex, which provides excitatory drive to preBötzinger Complex neurons mediating respiratory phase-switch. Opioids also depress awake drive from the forebrain and chemodrive.

Endogenous glutamatergic inputs to the Parabrachial Nucleus/Kölliker-Fuse Complex determine respiratory rate.

The Kölliker-Fuse Nucleus (KF) has been widely investigated for its contribution to "inspiratory off-switch" while more recent studies showed that activation of the Parabrachial Nucleus (PBN) shortened expiratory duration. This study used an adult, in vivo, decerebrate rabbit model to delineate the contribution of each site to inspiratory and expiratory duration through sequential block of glutamatergic excitation with the receptor antagonists 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo[f]quinoxaline-2,3-dione (NBQX) and d(-)-2-amino-5-phosphonopentanoic acid (AP5). Glutamatergic disfacilitation caused large increases in inspiratory and expiratory duration and minor decrease in peak phrenic activity (PPA). Hypoxia only partially reversed respiratory rate depression but PPA was increased to >200 % of control. The contribution of PBN activity to inspiratory and expiratory duration was equal while block of the KF affected inspiratory duration more than expiratory. We conclude that in the in vivo preparation respiratory rate greatly depends on PBN/KF activity, which contributes to the "inspiratory on- "and "off-switch", but is of minor importance for the magnitude of phrenic motor output.

Identification of Time-Dependent Risks of Hemodynamic States After Stage 1 Norwood Palliation.

BACKGROUND: Mortality after stage 1 palliation of hypoplastic left heart syndrome remains significant. Hemodynamic changes result from interaction of cardiac output (CO) and systemic vascular resistance (SVR). We sought to identify time-dependent changes in postoperative hemodynamic states and their associations with mortality. METHODS: Perioperative data were prospectively collected in an institutional review board-approved database. Hemodynamic state was classified as high CO, high SVR, low SVR, and low CO using bivariate analysis of mean arterial pressure and somatic regional near-infrared spectroscopic oximetry saturation. State classifications over 48 postoperative hours were modelled using multinomial logistic regressions for association with mortality. RESULTS: Data from 9614 of 10,272 hours in 214 patients were analyzed. Operative survival was 91%. The predominant state was high CO (46% time). Low CO state without extracorporeal membrane oxygenation (ECMO) was found in 52% of patients for 9.7% time. ECMO was employed in 24 (11.2%) patients for 10.4% time. State stability was 33%, with high SVR the least stable (17%) and high CO the most stable (53%). Transition from high CO increased in hours 1 to 12, mainly to low SVR. Transition to low CO was 18.4%, increasing in hours 1 to 12, mainly from high SVR. The transition risk to ECMO was 0.32%, and 0.74% during hours 1 to 12, only from low CO. Both low CO and ECMO had increased mortality risk. CONCLUSIONS: Bivariate classification defines hemodynamic states with distinct physiologic, transition, and mortality risk profiles. High SVR state was unstable. Transition to ECMO occurred only from low CO, while the low SVR and high CO states were safest.

Platelet Function Changes during Neonatal Cardiopulmonary Bypass Surgery: Mechanistic Basis and Lack of Correlation with Excessive Bleeding.

Thrombocytopenia and platelet dysfunction induced by extracorporeal blood circulation are thought to contribute to postsurgical bleeding complications in neonates undergoing cardiac surgery with cardiopulmonary bypass (CPB). In this study, we examined how changes in platelet function relate to changes in platelet count and to excessive bleeding in neonatal CPB surgery. Platelet counts and platelet P-selectin exposure in response to agonist stimulation were measured at four times before, during, and after CPB surgery in neonates with normal versus excessive levels of postsurgical bleeding. Relative to baseline, platelet counts were reduced in patients while on CPB, as was platelet activation by the thromboxane A2 analog U46619, thrombin receptor activating peptide (TRAP), and collagen-related peptide (CRP). Platelet activation by adenosine diphosphate (ADP) was instead reduced after platelet transfusion. We provide evidence that thrombocytopenia is a likely contributor to CPB-associated defects in platelet responsiveness to U46619 and TRAP, CPB-induced collagen receptor downregulation likely contributes to defective platelet responsiveness to CRP, and platelet transfusion may contribute to defective platelet responses to ADP. Platelet transfusion restored to baseline levels platelet counts and responsiveness to all agonists except ADP but did not prevent excessive bleeding in all patients. We conclude that platelet count and function defects are characteristic of neonatal CPB surgery and that platelet transfusion corrects these defects. However, since CPB-associated coagulopathy is multifactorial, platelet transfusion alone is insufficient to treat bleeding events in all patients. Therefore, platelet transfusion must be combined with treatment of other factors that contribute to the coagulopathy to prevent excessive bleeding.

Inputs to medullary respiratory neurons from a pontine subregion that controls breathing frequency.

Neurons in a subregion of the medial parabrachial (PB) complex control expiratory duration (TE) and the inspiratory on-switch. To better understanding the underlying mechanisms, this study aimed to determine the types of medullary neurons in the rhythmogenic preBötzinger/Bötzinger Complex (preBötC/BötC) and adjacent areas that receive synaptic inputs from the PB subregion and whether these inputs are excitatory or inhibitory in nature. Highly localized electrical stimuli in the PB subregion combined with multi-electrode recordings from respiratory neurons and phrenic nerve activities were used to generate stimulus-to-spike event histograms to detect correlations in decerebrate, vagotomized dogs during isocapnic hyperoxia. Short-time scale correlations were found in 237/442 or ∼54% of the ventral respiratory column (VRC) neurons. Inhibition of E-neurons was ∼2.5X greater than for I-neurons, while Pre-I and I-neurons were excited. These findings indicate that the control of TE and the inspiratory on-switch by the PB subregion are mediated by a marked inhibition of BötC E-neurons combined with an excitation of I-neurons, especially pre-I neurons.

The contribution of endogenous glutamatergic input in the ventral respiratory column to respiratory rhythm.

Glutamate is the predominant excitatory neurotransmitter in the ventral respiratory column; however, the contribution of glutamatergic excitation in the individual subregions to respiratory rhythm generation has not been fully delineated. In an adult, in vivo, decerebrate rabbit model during conditions of mild hyperoxic hypercapnia we blocked glutamatergic excitation using the receptor antagonists 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo[f]quinoxaline-2,3-dione (NBQX) and d(-)-2-amino-5-phosphonopentanoic acid (AP5). Disfacilitation of the preBötzinger Complex caused a decrease in inspiratory and expiratory duration as well as peak phrenic amplitude and ultimately apnea. Disfacilitation of the Bötzinger Complex caused a decrease in inspiratory and expiratory duration; subsequent disfacilitation of the preBötzinger Complex resulted in complete loss of the respiratory pattern but maintained tonic inspiratory activity. We conclude that glutamatergic drive to the preBötzinger Complex is essential for respiratory rhythm generation. Glutamatergic drive to the Bötzinger Complex significantly affects inspiratory and expiratory phase duration. Bötzinger Complex neurons are responsible for maintaining the silent expiratory phase of the phrenic neurogram.

Rotational Thromboelastometry Rapidly Predicts Thrombocytopenia and Hypofibrinogenemia During Neonatal Cardiopulmonary Bypass.

BACKGROUND: Thrombocytopenia and hypofibrinogenemia during neonatal cardiopulmonary bypass (CPB) contribute to bleeding and morbidity. Rotational thromboelastometry (ROTEM) is a viscoelastic assay with a rapid turnaround time. Data validating ROTEM during neonatal cardiac surgery remain limited. This study examined perioperative hemostatic trends in neonates treated with standardized platelet and cryoprecipitate transfusion during CPB. We hypothesized that ROTEM would predict thrombocytopenia, hypofibrinogenemia, and the correction thereof. METHODS: Forty-four neonates undergoing CPB were included in this prospective observational study. Blood samples were obtained at Baseline, On CPB, Post-CPB, and Postoperative. The ROTEM analysis included extrinsically activated (Extem) and fibrinogen-specific (Fibtem) assays. Platelet-specific thromboelastometry (Pltem) values were calculated. Platelet and cryoprecipitate transfusion was initiated prior to termination of CPB. RESULTS: Platelet count and Extem amplitude decreased significantly On CPB ( P < .0001), increased significantly Post-CPB ( P < .0001), and Postoperative values were not significantly different from Baseline. Extem amplitude at 10 minutes (A10) > 46.5 mm (AUC = 0.941) and Pltem A10 > 37.5 mm [area under curve (AUC) = 0.960] predicted platelet count > 100 × 103/µL, and they highly correlated with platelet count ( R = 0.89 and R = 0.90, respectively). Fibrinogen concentration and Fibtem amplitude decreased significantly On CPB ( P ≤ .0001) and normalized after cryoprecipitate transfusion. Fibtem A10 > 9.5 mm predicted fibrinogen >200 mg/dL (AUC = 0.817), but it correlated less well with fibrinogen concentration ( R = 0.65). CONCLUSIONS: ROTEM analysis during neonatal cardiac surgery is sensitive and specific for thrombocytopenia and hypofibrinogenemia, identifying deficits within 10 minutes. Platelet and cryoprecipitate transfusion during neonatal CPB normalizes platelet count, fibrinogen level, and ROTEM amplitudes.

A Subregion of the Parabrachial Nucleus Partially Mediates Respiratory Rate Depression from Intravenous Remifentanil in Young and Adult Rabbits.

BACKGROUND: The efficacy of opioid administration to reduce postoperative pain is limited by respiratory depression. We investigated whether clinically relevant opioid concentrations altered the respiratory pattern in the parabrachial nucleus, a pontine region contributing to respiratory pattern generation, and compared these effects with a medullary respiratory site, the pre-Bötzinger complex. METHODS: Studies were performed in 40 young and 55 adult artificially ventilated, decerebrate rabbits. We identified an area in the parabrachial nucleus where α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid microinjections elicited tachypnea. Two protocols were performed in separate sets of animals. First, bilateral microinjections of the µ-opioid receptor agonist [D-Ala, N-MePhe, Gly-ol]-enkephalin (100 µM) into the "tachypneic area" determined the effect of maximal µ-opioid receptor activation. Second, respiratory rate was decreased with continuous IV infusions of remifentanil. The opioid antagonist naloxone (1 mM) was then microinjected bilaterally into the "tachypneic area" of the parabrachial nucleus to determine whether the respiratory rate depression could be locally reversed. RESULTS: Average respiratory rate was 27 ± 10 breaths/min. First, [D-Ala, N-MePhe, Gly-ol]-enkephalin injections decreased respiratory rate by 62 ± 20% in young and 45 ± 26% in adult rabbits (both P < 0.001). Second, during IV remifentanil infusion, bilateral naloxone injections into the "tachypneic area" of the parabrachial nucleus reversed respiratory rate depression from 55 ± 9% to 20 ± 14% in young and from 46 ± 20% to 18 ± 27% in adult rabbits (both P < 0.001). The effects of bilateral [D-Ala, N-MePhe, Gly-ol]-enkephalin injection and IV remifentanil on respiratory phase duration in the "tachypneic area" of the parabrachial nucleus was significantly different from the pre-Bötzinger complex. CONCLUSIONS: The "tachypneic area" of the parabrachial nucleus is highly sensitive to µ-opioid receptor activation and mediates part of the respiratory rate depression by clinically relevant administration of opioids.

Scimitar Syndrome-Complex Surgical Revision 3 Decades After Repair.

We present a case of a 39-year-old woman with scimitar syndrome who had a 2-patch repair 3 decades previously and presented with a right-to-left shunt of the inferior vena cava (IVC) to the left atrium resulting from baffle dehiscence. We discuss details of our reoperative repair.

Characteristics of breathing rate control mediated by a subregion within the pontine parabrachial complex.

The role of the dorsolateral pons in the control of expiratory duration (Te) and breathing frequency is incompletely understood. A subregion of the pontine parabrachial-Kölliker-Fuse (PB-KF) complex of dogs was identified via microinjections, in which localized pharmacologically induced increases in neuronal activity produced increases in breathing rate while decreases in neuronal activity produced decreases in breathing rate. This subregion is also very sensitive to local and systemic opioids. The purpose of this study was to precisely characterize the relationship between the PB-KF subregion pattern of altered neuronal activity and the control of respiratory phase timing as well as the time course of the phrenic nerve activity/neurogram (PNG). Pulse train electrical stimulation patterns synchronized with the onset of the expiratory (E) and/or phrenic inspiratory (I) phase were delivered via a small concentric bipolar electrode while the PNG was recorded in decerebrate, vagotomized dogs. Step frequency patterns during the E phase produced a marked frequency-dependent decrease in Te, while similar step inputs during the I phase increased inspiratory duration (Ti) by 14 ± 3%. Delayed pulse trains were capable of pacing the breathing rate by terminating the E phase and also of triggering a consistent stereotypical inspiratory PNG pattern, even when evoked during apnea. This property suggests that the I-phase pattern generator functions in a monostable circuit mode with a stable E phase and a transient I phase. Thus the I-pattern generator must contain neurons with nonlinear pacemaker-like properties, which allow the network to rapidly obtain a full on-state followed by relatively slow inactivation. The activated network can be further modulated and supplies excitatory drive to the neurons involved with pattern generation.NEW & NOTEWORTHY A circumscribed subregion of the pontine medial parabrachial nucleus plays a key role in the control of breathing frequency primarily via changes in expiratory duration. Excitation of this subregion triggers the onset of the inspiratory phase, resulting in a stereotypical ramplike phrenic activity pattern independent of time within the expiratory phase. The ability to pace the I-burst rate suggests that the in vivo I-pattern generating network must contain functioning pacemaker neurons.

Near-infrared spectroscopy provides continuous monitoring of compromised lower extremity perfusion during cardiac surgery.

Near-infrared spectroscopy (NIRS) is more frequently used to monitor regional oxygenation/perfusion of the cerebral and somatorenal vascular bed during congenital heart surgery. However, NIRS probes can be placed elsewhere to assess regional perfusion. We report the intraoperative use of NIRS probes on both calves of an infant to continuously monitor changes in the regional oxygenation/perfusion of a lower extremity whose perfusion was compromised after femoral arterial line placement. The NIRS trend of the compromised limb was compared with the contralateral limb throughout congenital heart surgery including the period on cardiopulmonary bypass (CPB). Our case report illustrates that NIRS technology can be used to monitor ongoing lower extremity vascular compromise during congenital heart surgery when it is not practical to directly access and continuously assess the limb. Transient vascular compromise after invasive femoral arterial line or sheath placement for cardiac catheterization in small infants is not infrequent. NIRS technology in such circumstances may help to decide whether watchful waiting is acceptable or immediate interventions are indicated. Continuous NIRS monitoring showed that limb regional oxygenation remained depressed during CPB but dramatically increased in the post-CPB period.