Respiratory Pump Research Articles

Intraspinal Electrical Stimulation Reliably Triggers Respiratory Activity in the in situ Rodent Model

Cervical spinal cord injury impairs ventilation by preventing brainstem generated respiratory activity from reaching motor pools in the spinal cord which drive respiratory pump muscles. Epidural high frequency thoracic spinal cord stimulation is a method of producing respiratory efforts independent of centrally generated signals, which is effective at eliciting diaphragmatic EMG in anesthetized animal preparations. However, the exact spinal pathways and circuitry involved in producing these respiratory efforts are unknown. We hypothesize that targeted electrical stimulation within the spinal cord will identify pathways relaying the stimulus to the phrenic motoneurons. To investigate this, we monitored bilateral phrenic nerve activity (PNA) in the in situ rat preparation (n=6) and applied either bipolar epidural or intraspinal stimulation (ISS) (300ms, 100‐300Hz, 200μs pd) in the rostral thoracic spinal cord (T2‐6). Our initial findings demonstrated that epidural stimulation was only intermittently effective in eliciting PNA, while ISS reliably produced site and current dependent (10‐500μA) responses. We conclude that, in comparison to epidural stimulation, low current thoracic ISS more efficiently and reliably activates the phrenic motor circuit in the in situ model. Ongoing studies are focused on identifying the neural circuits activated by ISS. Funded by the UF College of Veterinary Medicine, APS UGSRF, and NIH 1R01NS080180‐01A1

Simulating Free Radical Production from Complex I

Complex I is a respiratory pump (NADH:quinone oxidoreductase) in the electron transport chain of mitochondria that can produce a significant amount of reactive oxygen species (ROS) in the form of superoxide and hydrogen peroxide. Hydrogen peroxide is formed at the flavin mononucleotide (FMN), but the location of superoxide production is less certain. A computer model fit to kinetic data is used to determine the location and rates of ROS production. The model includes the major redox centers in the complex: the FMN, iron-sulfur cluster N2, and semiquinone. The analysis identifies that the fully reduced FMN and semiquinone are the major sources of superoxide with little to no production from the iron-sulfur cluster N2. Also, the FMN radical only produces superoxide when turnover at the quinone-reductase site is blocked. When electron flow through the complex is reversed, ROS production is maximized with the FMN and semiquinone producing similar amounts. Moreover, high membrane potentials and alkaline matrix pH stimulate ROS production. Of all the ROS produced, the majority originates from the FMN. The Complex I model is integrated into a larger model of the respiratory chain that includes ROS production from Complex III, and the relative rates of ROS production from each complex is determined under a variety of simulated conditions.

Persistent Pulmonary Atelectasis in Duchenne Muscular Dystrophy Treated with High Frequency Chest Wall Oscillation

Patients with neuromuscular disease that affects the respiratory pump can experience mild to profound limitation in both ventilation and cough. They frequently present recurrent pulmonary infections, respiratory failure, hypoventilation and atelectasis. We describe the case of a 22-years-old patient with Duchenne Muscular Dystrophy, he was referred to our hospital with persisten fever (>38°C), dyspnea and respiratory failure. Chest CT showed parenchymal consolidation. The patient was treated with antibiotics and rehabilitation therapy, bronchial endoscopy, cough assist, but only with the use of High Frequency Chest Wall Oscillation followed by mechanical in-exsufflation (MI-E) for cough assistance, we observed clinical and radiological improvement. We suggest that High Frequency Chest Wall Oscillation can be helpful for neuromuscular patient, particularly in cases of difficult clinical management hospedalizations.

Defining inhibitory neurone function in respiratory circuits: opportunities with optogenetics?

Pharmacological and mathematical modelling studies support the view that synaptic inhibition in mammalian brainstem respiratory circuits is essential for generating normal and stable breathing movements. GABAergic and glycinergic neurones are known components of these circuits but their precise functional roles have not been established, especially within key microcircuits of the respiratory pre-Bötzinger (pre-BötC) and Bötzinger (BötC) complexes involved in phasic control of respiratory pump and airway muscles. Here, we review briefly current concepts of relevant complexities of inhibitory synapses and the importance of synaptic inhibition in the operation of these microcircuits. We highlight results and limitations of classical pharmacological studies that have suggested critical functions of synaptic inhibition. We then explore the potential opportunities for optogenetic strategies that represent a promising new approach for interrogating function of inhibitory circuits, including a hypothetical wish list for optogenetic approaches to allow expedient application of this technology. We conclude that recent technical advances in optogenetics should provide a means to understand the role of functionally select and regionally confined subsets of inhibitory neurones in key respiratory circuits such as those in the pre-BötC and BötC.

Functional results after chest wall stabilization with a new screwless fixation device.

This is the experience with the Stratos system in two surgical centres for the management of two types of rib fractures: flail chest and multiple dislocated rib fractures with significant chest wall deformity. From January 2009 to May 2012, 94 consecutive patients were included. Selected indications were extended anterolateral flail chest (n = 68) and dislocated painful rib fractures (n = 26). The open reduction internal fixation (ORIF) system consists of flexible titanium rib clamps and connecting plates. The postoperative course was assessed. Clinical and functional outcomes were evaluated at 6 months. Functional assessment consisted of measurement of the functional vital capacity (FVC) and magnetic resonance imaging (MRI) examination with determination of the radiological vital capacity (rVC) in patients with a flail chest. The median operation time and length of hospital stay were 122 min and 19 days, respectively, in patients with a flail chest, and 67 min and 11 days, respectively, in patients with dislocated painful rib fractures. The morbidity rate was 6.4% and the overall 30-day mortality rate was 1.1%. Clinical evaluation and pulmonary function testing at 6 months revealed no deformity of the chest wall, symmetrical shoulder girdle mobility in 88% and a feeling of stiffness on the operated side in 19% of the patients operated for a flail chest. Median ratio of FVC was 88%, not suggesting any restriction after stabilization. MRI was performed in 53% (36 of 68) of the patients with a flail chest. The analysis of the rVC showed, on average, no clinically relevant restriction related to the operation, with a mean rVC of the operated relative to the non-operated side of 92% (95% confidence interval: 83, 100). Stabilization of more than four ribs was associated with a lower median rVC than stabilization of four or less ribs. Our results suggest that stabilization of the chest wall with this screwless rib fixation device can be performed with a low morbidity and lead to early restoration of chest wall integrity and respiratory pump function, without clinically relevant functional restriction. Owing to the simplicity of the fixation technique, indications for stabilization can be safely enlarged to selected patients with dislocated and painful rib fractures.

Neural drive to respiratory muscles in the spontaneously breathing rat pup

The neonatal rodent serves as useful and appropriate model within which to study respiratory system development. Despite an extensive literature that documents respiratory control in vitro, in vivo studies have relied upon whole body plethysmography to determine measures of respiratory frequency and tidal volume. However, plethysmography restricts access to the animal and thus, respiratory muscle electromyographic (EMG) activities have not been recorded in these studies previously. Electromyography yields accurate information about neural respiratory center output to the musculature and therefore, about the control of breathing in the intact animal. In this case, we documented neural drive to respiratory pump and upper airway muscles, electrocardiogram (ECG) and chest wall motions in rat pups up to 10 days of age noting sighs, spontaneous central apneas and hypopneas in room air and with successive increments in fractional inspired CO2 (FICO2). Our findings underscore the advantages of EMG recordings for purposes of determining the magnitude and distribution of neural drive to respiratory muscles and for characterizing the full range of breathing behaviors exhibited by rats in the early postnatal period.

Respiratory pump contributes to increased physiological reserve for compensation during simulated haemorrhage.

Intrathoracic pressure regulation (IPR) represents a therapy for increasing systemic circulation through the creation of negative intrathoracic pressure. We hypothesized that using this 'respiratory pump' effect would slow the diminution of the physiological reserve to compensate during progressive reductions in central blood volume. The compensatory reserve index (CRI) algorithm was used to measure the proportion (from 100 to 0%) of reserve capacity that remained to compensate for central volume loss before the onset of cardiovascular decompensation. Continuous analog recordings of arterial waveforms were extracted from data files of seven healthy volunteers. Subjects had previously participated in experiments designed to induce haemodynamic decompensation (presyncope) by progressive reduction in central blood volume using graded lower-body negative pressure. The lower-body negative pressure protocol was completed while breathing spontaneously through a standard medical face mask without (placebo) and with a resistance (approximately -7cmH2O; active IPR) applied during inspiration. At the onset of presyncope in the placebo conditions, CRI was smaller than the CRI observed at the same time point in the active IPR conditions. The CRI at the onset of presyncope during active IPR (0.08±0.01) was similar to the CRI at presyncope with placebo. Kaplan-Meier and log rank tests indicated that CRI survival curves were shifted to the right by active IPR. Optimizing the respiratory pump contributed a small but significant effect of increasing tolerance to progressive reductions in central blood volume by extending the compensatory reserve.

Nichtinvasive Beatmung beim Patienten mit persistierender Hyperkapnie

Chronic respiratory failure is caused by insufficiency of the inspiratory muscles, i.e. mainly the diaphragm, which represents the so-called "respiratory pump". Insufficiency of the respiratory pump causes hypercapnia. Diseases with chronic hypercapnia are characterized by reduced survival. Mechanical ventilation-mostly applied as noninvasive mechanical ventilation (NIV)-improves ventilation and unloads the inspiratory muscles. Strong evidence supports the use of domiciliary NIV already in mild degrees of chronic respiratory failure caused by neuromuscular diseases, thoracic restrictions and obesity hypoventilation. In these diseases long-term NIV improves both physiological parameters (such as blood gases) and clinical outcome, e.g. exercise capacity, right heart dysfunction, sleep quality, disease-specific aspects of health-related quality of life (HRQL) and survival rate. In contrast, its influence on long-term survival in chronic obstructive pulmonary disease (COPD) patients is not clearly proven. Prescription of home NIV in COPD should therefore be restricted to severe degrees of chronic respiratory failure. Finally, there is an indication for domiciliary NIV in patients after prolonged weaning from mechanical ventilation. This paper elaborates underlying pathophysiology, diseases and how NIV works in chronic hypercapnic respiratory failure.

Techniques for the Measurement and Monitoring of Carbon Dioxide in the Blood

The relationship between an elevated partial pressure of carbon dioxide (Pco2) and reduced alveolar ventilation resulting from respiratory failure primarily affecting the respiratory pump was first reported during the 1952 Copenhagen polio epidemic. Several methods for Pco2 estimation, such as blood gas analyses, capnography, and transcutaneous Pco2 measurements, have since been developed to assess alveolar ventilation. The clinical setting in which CO2 measurement is valuable includes acute and chronic respiratory failure, transport, cardiopulmonary resuscitation, patient-controlled analgesia, and procedural sedation. The techniques that are currently available differ considerably regarding their accuracy, capacity to facilitate continuous assessment, side effects, availability, and their ability to assess additional information. Importantly, each technique has its own spectrum of indications and applications. Therefore, the different techniques are not competitive but, rather, complementary. As a consequence, it is reasonable to combine different techniques depending on specific clinical scenarios. This review summarizes the physiological background, historical development, instrument-specific technical aspects, and current recommendations for the clinical application of Pco2 assessment.

Respiratory pump contributes to increased physiological reserve for compensation during reductions in central blood volume (707.4)

The impedance threshold device (ITD) represents a therapy for increasing systemic circulation through creation of negative intrathoracic pressure. PURPOSE: To evaluate the respiratory pump effect on the diminution of compensatory responses during progressive reductions in central blood volume. METHODS: The Compensatory Reserve Index (CRI) algorithm measured compensation capacity to reduced central blood volume. Continuous analog recordings of arterial waveforms were extracted from data files of 7 volunteers. Subjects had previously participated in experiments designed to induce hemodynamic decompensation by application of graded lower body negative pressure (LBNP). The LBNP protocol was completed while spontaneously breathing through a standard medical facemask without (sham ITD) and with (active ITD) a resistance (~‐7cmH2O). RESULTS: At the onset of pre‐syncope in the sham ITD, CRI (0.08±0.02) was smaller (P=0.05) than CRI at the same time point in the active ITD (0.09±0.01). CRI at pre‐syncope in the active ITD (0.08±0.01) was similar (P=0.19) to CRI at pre‐syncope in the sham ITD. Kaplan‐Meier and log rank tests indicated that CRI survival curves shifted to the right (P=0.04) by the active ITD. CONCLUSIONS: Optimizing the respiratory pump contributed a small but significant effect of increasing tolerance to progressive reductions in central blood volume by extending the compensatory reserve.Grant Funding Source: U.S. Army MRMC Combat Casualty Care Research Program

Therapeutic Range of Spontaneous Breathing during Mechanical Ventilation

In the 4th century before the common era, the Greek philosopher and physician Hippocrates expressed his wisdom on the value of activity to the sick and the healthy by stating that: “The sick will of course profit to a great extent from gymnastics with regard to the restoration of their health and the healthy will profit with regard to its maintenance” (On Regimen in Acute Diseases, 3, 400 BCE). In contemporary critical care medicine, driven by the goal of protecting our patients from self-inflicted injury, pain, and anxiety – and in contrast to Hippoctrates’ suggestions – we have built a culture of immobilizing our patients: we prescribe high doses of opioids, sedatives, anxiolytics, and anti-pychotics, and with the best intentions, place bed-rest and restraints orders. In patients with severe respiratory failure, we frequently use immobilizing ventilator settings such as volume control ventilation. Recent data have been increasingly challenging this tenet in relation to the fields of neuropsychiatry, rehabilitation, and respiratory medicine1–5. In this issue of Anesthesiology, two papers bring new information on why the concept of muscle activity is also relevant to lung biochemistry and regional function. Guldner et al.6 and Bruells et al.7 provide important experimental data on the relationship between the dose of diaphragmatic activity (spontaneous contribution to breathing during mechanical ventilation) and the resulting response in terms of lung mechanical stress, gas exchange, and markers of muscle deconditioning. As the main respiratory muscle, the diaphragm contributes 72% for tidal breathing8 and its role in respiratory mechanics and gas exchange goes well beyond this global number. One of the reasons is its curvature during spontaneous breathing in the supine position, which facilitates expansion of dependent lung regions9, optimizes the regional distribution of lung ventilation, and prevents loss of dependent lung aeration and increase in shunt observed when muscle paralysis is produced10. Accordingly, modes of ventilation proposed since the 1970s tried to explore those advantages in patients with acute respiratory failure. The beneficial effects of maintaining continuous spontaneous breathing during mechanical ventilation of patients with acute respiratory failure have been described by Putensen and coworkers in two well-designed studies11,12. However, in patients with severe respiratory failure, barriers to spontaneous breathing during mechanical ventilation including patient-ventilator asynchrony, high oxygen consumption of the respiratory pump muscles, and the risk of barotrauma, have hindered a clear determination of the value of spontaneous breathing during mechanical ventilation.

Interaction between respiration and right versus left ventricular volumes at rest and during exercise: a real-time cardiac magnetic resonance study

Breathing-induced changes in intrathoracic pressures influence left ventricular (LV) and right ventricular (RV) volumes, the exact nature and extent of which have not previously been evaluated in humans. We sought to examine this "respiratory pump" using novel real-time cardiac magnetic resonance (CMR) imaging. Eight healthy subjects underwent serial multislice real-time CMR during normal breathing, breath holding, and the Valsalva maneuver. Subsequently, a separate cohort of nine subjects underwent real-time CMR at rest and during incremental exercise. LV and RV end-diastolic volume (EDV) and end-systolic volume (ESV) and diastolic and systolic eccentricity indexes were determined at peak inspiration and expiration. During normal breathing, inspiration resulted in an increase in RV volumes [RVEDV: +18 ± 8%, RVESV: +14 ± 12%, and RV stroke volume (SV): +21 ± 10%, P < 0.01] and an opposing decrease in LV volumes (P < 0.0001 for interaction). During end-inspiratory breath holding, RV SV decreased by 9 ± 10% (P = 0.046), whereas LV SV did not change. During the Valsalva maneuver, volumes decreased in both ventricles (RVEDV: -29 ± 11%, RVESV: -16 ± 14%, RV SV: -36 ± 14%, LVEDV: -22 ± 17%, and LV SV: -25 ± 17%, P < 0.01). The reciprocal effect of respiration on LV and RV volumes was maintained throughout exercise. The diastolic and systolic eccentricity indexes were greater during inspiration than during expiration, both at rest and during exercise (P < 0.0001 for both). In conclusion, ventricular volumes oscillate with respiratory phase such that RV and LV volumes are maximal at peak inspiration and expiration, respectively. Thus, interpretation of RV versus LV volumes requires careful definition of the exact respiratory time point for proper interpretation, both at rest and during exercise.

Assessing sinus aerosol deposition: Benefits of SPECT–CT imaging

Aerosol inhalation therapy is one of the methods to treat rhinosinusitis. However the topical drug delivery to the posterior nose and paranasal sinuses shows only limited efficiency. A precise sinusal targeting remains a main challenge for aerosol treatment of sinus disorders. This paper proposes a comparative study of the nasal deposition patterns of micron and submicron particles using planar gamma-scintigraphy imaging vs. a new 3-dimensional (3D) imaging approach based on SPECT-CT measurements. Radiolabelled nebulizations have been performed on a plastinated model of human nasal cast coupled with a respiratory pump. First, the benefits provided by SPECT-CT imaging were compared with 2D gamma-scintigraphy and radioactive quantification of maxillary sinus lavage as reference for the sonic 2.8 μm aerosol sinusal deposition. Then, the impact on nasal deposition of various airborne particle sizes was assessed. The 2D methodology overestimates aerosol deposition in the maxillary sinuses by a factor 9 whereas the 3D methodology is in agreement with the maxillary sinus lavage reference methodology. Then with the SPECT-CT approach we highlighted that the higher particle size was mainly deposited in the central nasal cavity contrary to the submicron aerosol particles (33.8 ± 0.6% of total deposition for the 2.8 μm particles vs. 1 ± 0.3% for the 230 nm particles). Benefits of SPECT/CT for the assessment of radiolabelled aerosol deposition in rhinology are clearly demonstrated. This 3D methodology should be preferentially used for scintigraphic imaging of sinusal deposition in Human.

Blood pressure regulation X: what happens when the muscle pump is lost? Post-exercise hypotension and syncope

Syncope which occurs suddenly in the setting of recovery from exercise, known as post-exercise syncope, represents a failure of integrative physiology during recovery from exercise. We estimate that between 50 and 80% of healthy individuals will develop pre-syncopal signs and symptoms if subjected to a 15-min head-up tilt following exercise. Post-exercise syncope is most often neurally mediated syncope during recovery from exercise, with a combination of factors associated with post-exercise hypotension and loss of the muscle pump contributing to the onset of the event. One can consider the initiating reduction in blood pressure as the tip of the proverbial iceberg. What is needed is a clear model of what lies under the surface; a model that puts the observational variations in context and provides a rational framework for developing strategic physical or pharmacological countermeasures to ultimately protect cerebral perfusion and avert loss of consciousness. This review summarizes the current mechanistic understanding of post-exercise syncope and attempts to categorize the variation of the physiological processes that arise in multiple exercise settings. Newer investigations into the basic integrative physiology of recovery from exercise provide insight into the mechanisms and potential interventions that could be developed as countermeasures against post-exercise syncope. While physical counter maneuvers designed to engage the muscle pump and augment venous return are often found to be beneficial in preventing a significant drop in blood pressure after exercise, countermeasures that target the respiratory pump and pharmacological countermeasures based on the involvement of histamine receptors show promise.

Amélioration de la perfusion des organes vitaux par la valve d’impédance inspiratoire et le concept de pompe respiratoire : rationnel physiologique et application clinique

ObjectiveIn this article, we review the effects of the respiratory pump to improve vital organ perfusion by the use of an inspiratory threshold device. Data sourcesMedline and MeSH database. Study selectionAll papers with a level of proof of I to III have been used. Data extractionThe analysis of the papers has focused on the physiological modifications induced by intrathoracic pressure regulation. Data synthesisPrimary function of breathing is to provide gas exchange. Studies of the mechanisms involved in animals and humans provide the physiological underpinnings for “the other side of breathing”: to increase circulation to the heart and brain. We describe studies that focus on the fundamental relationship between the generation of negative intrathoracic pressure during inspiration through a low-level of resistance created by an impedance threshold device and the physiologic effects of a respiratory pump. A decrease in intrathoracic pressure during inspiration through a fixed resistance resulting in an intrathoracic pressure of −7 cmH2O has multiple physiological benefits including: enhanced venous return, cardiac stroke volume and aortic blood pressure; lower intracranial pressure; resetting of the cardiac baroreflex; elevated cerebral blood flow oscillations and increased tissue blood flow/pressure gradient. ConclusionThe clinical and animal studies support the use of the intrathoracic pump to treat different clinical conditions: hemorrhagic shock, orthostatic hypotension, septic shock, and cardiac arrest.

Changes in biventricular volumes during respiration: assessment of the respiratory pump using real-time cardiac magnetic resonance imaging during exercise

Background: Real-time cardiac magnetic resonance (CMR) imaging has emerged as an accurate and reproducible tool for biventricular volume assessment during free-breathing and whilst exercising. The aim of this study was to examine the degree to which the respiratory pump influenced cardiac filling and performance at rest and during exercise. Methods: Nine healthy subjects (8 male, 1 female) underwent CMR during free-breathing using an ungated real-time CMR sequence. ECG and respiratory movements were retrospectively synchronized enabling compensation for cardiac cycle and respiratory phase and cardiac volumes were determined for the left and right ventricles (LV and RV) from stacks of bi-plane cine images using customized software. End-diastolic and end-systolic volumes (EDV and ESV) as well as diastolic and systolic eccentricity indexes were measured for the LV and RV during peak inspiration and peak expiration, both at rest (heart rate 58±10 bpm) and whilst cycling at low (110±17 bpm), moderate (138±18 bpm) and strenuous (153±20 bpm) workload intensities. Results: As compared with expiration, there was an increase in RV volumes during inspiration (RVEDV +11%, RVESV +12%, RVSV +10%, p<0.05) In contrast, LV EDV, LV ESV and LV SV reduced during inspiration (-6%, -6%, -6%, p<0.05). LVEF and RVEF did not change with respiration, at rest or during exercise. During inspiration, RV SV tended to be larger than LV SV (p=0.064), whilst LV SV was significantly larger than RV SV during expiration (p<0.0001). Mean SV, defined as the average of peak-inspiratory and peak expiratory SV, was slightly greater (5%, p=0.047) for the LV than for the RV, possibly reflecting the expected physiological excess due to the bronchial and thebesian circulation. The interventricular septum pushed toward the LV during inspiration as evidenced by a greater eccentricity index during inspiration than during expiration, which was greatest in diastole (+ 16%, p<0.0001) but also evident during systole (+ 6%, p=0.019). Conclusions: Ventricular volumes oscillate with respiratory phase such that RV volumes and LV volumes are maximal during inspiration and expiration, respectively. Thus, instantaneous measures of stroke volume should not be expected to be equal. Real-time CMR provides a novel means of quantifying the degree to which pulmonary disorders may impact on cardiac performance.

Extrinsic Bronchial Obstruction Caused by Scoliosis

A case report. To emphasize the importance of monitoring the breathing capacity in patients with moderate to severe scoliosis, even in adulthood. Diseases that disturb the structure of the chest wall affect the function of the respiratory pump. Restrictive respiratory pattern is caused by severe scoliosis. However, scoliosis may provoke obstructive changes due to compression of the airways. It can be a direct compression because of imprinting of vertebral bodies, or an indirect one, due to rotation forces. METHODS.: We have collected data from the patients' clinical history and have reviewed similar published cases. a white female, with frequent respiratory tract infections during her childhood. She was diagnosed as having 55° right T5-T11 scoliosis. At age of 26, an increase of her pulmonary symptoms appeared with difficulty to expel mucus and medium efforts dyspnea. A computed axial tomographic scan showed T8 vertebral body pushing against the right intermediate bronchus. A bronchoscopy found a decrease in the bronchial area, with near contact between the walls. Lung function test: 41% forced vital capacity (FVC), 43% forced expiratory volume in 1 second (FEV1), and 91 FEV1/FVC1. The patient underwent surgical correction using rods and pedicle screws; she had improvement of symptoms, image tests, and pulmonary function (70% FVC, 71% FEV1, and 101 FEV1/FVC). Increased frequency and severity of respiratory tract infections, difficulty in expelling mucus and dyspnea are warning signs of compromised airways. Spirometry tests and image tests such as computed axial tomography and bronchoscopy are essential for diagnosis. Surgical approach may be the treatment of choice.

EComment. Pectus excavatum surgical repair improves cardiopulmonary function in adults

Jayaramakrishnan et al. recently addressed the question: Does repair of pectus excavatum (PEx) improve cardiopulmonary function? [1]. Using an adequate keyword-based search strategy, the authors concluded that surgical repair using minimally invasive Nuss technique and Ravitch procedure caused an early, moderate decrease in pulmonary function tests (which are typically minimally impaired in PEx patients). In addition, cardiac function at rest improved during the early postoperative period, which is typically sustained in the mid-term. Here, we take the opportunity to mention that Jayaramakrishnan et al. have failed to identify our previous study based on a large series of 70 patients, which was recently published in the European Journal of Cardio-Thoracic Surgery [2]. We think this omission is critical regarding the clinical bottom-line proposed by Jayaramakrishnan et al. because our study clearly demonstrated that the modified Ravitch-type repair [3] in young adults significantly improved maximal oxygen uptake (VO2max) and O2 pulse [2]. Increase of O2 pulse (a surrogate of heart stroke volume) after surgery suggested that aerobic capacity (VO2max) improvement was the result of a better cardiovascular adaptation at maximal workload. In a short series of PE patients, we recently reported that normalization of thoracic geometry by PEx repair could restore adequate negative pulmonary pressure during ventilation (i.e., respiratory pump) that is necessary to enhanced venous return, heart filling and cardiac output [4, 5] . Overall, we would like to offer the possibility to include our results [2, 4] in the present evidence-based medicine proposal to support the conclusion by Jayaramakrishnan et al. [1] that PEx repair improves cardiopulmonary function and supports aerobic capacity. Conflict of interest: none declared.

Response to Letter Regarding Article, “Cardiac Magnetic Resonance Imaging: A New Gold Standard for Ventricular Volume Quantification During High-Intensity Exercise”

HomeCirculation: Cardiovascular ImagingVol. 6, No. 3Response to Letter Regarding Article, “Cardiac Magnetic Resonance Imaging: A New Gold Standard for Ventricular Volume Quantification During High-Intensity Exercise” Free AccessResearch ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessResearch ArticlePDF/EPUBResponse to Letter Regarding Article, “Cardiac Magnetic Resonance Imaging: A New Gold Standard for Ventricular Volume Quantification During High-Intensity Exercise” Andre La Gerche, MD, PhD, Guido Claessen, MD, Alexander Van de Bruaene, MD, Nele Pattyn, MSc, Johan Van Cleemput, MD, PhD, Marc Gewillig, MD, PhD, Jan Bogaert, MD, PhD, Steven Dymarkowski, MD, PhD, Piet Claus, PhD and Hein Heidbuchel, MD, PhD Andre La GercheAndre La Gerche University Hospital of LeuvenLeuven, Belgium Search for more papers by this author , Guido ClaessenGuido Claessen University Hospital of LeuvenLeuven, Belgium Search for more papers by this author , Alexander Van de BruaeneAlexander Van de Bruaene University Hospital of LeuvenLeuven, Belgium Search for more papers by this author , Nele PattynNele Pattyn University Hospital of LeuvenLeuven, Belgium Search for more papers by this author , Johan Van CleemputJohan Van Cleemput University Hospital of LeuvenLeuven, Belgium Search for more papers by this author , Marc GewilligMarc Gewillig University Hospital of LeuvenLeuven, Belgium Search for more papers by this author , Jan BogaertJan Bogaert University Hospital of LeuvenLeuven, Belgium Search for more papers by this author , Steven DymarkowskiSteven Dymarkowski University Hospital of LeuvenLeuven, Belgium Search for more papers by this author , Piet ClausPiet Claus University Hospital of LeuvenLeuven, Belgium Search for more papers by this author and Hein HeidbuchelHein Heidbuchel University Hospital of LeuvenLeuven, Belgium Search for more papers by this author Originally published1 May 2013https://doi.org/10.1161/CIRCIMAGING.113.000389Circulation: Cardiovascular Imaging. 2013;6:e20We thank Drs Yoneyama and Akashi for their important reference to the confounding influence of respiration on biventricular volume assessment by real-time cardiac magnetic resonance imaging. As we noted in the Discussion, changes in biventricular volumes “may be caused by physiological differences in preload attributable to the fall in intrathoracic pressures during inspiration and cardiac translation through the imaging plane.”1 Real-time cardiac magnetic resonance imaging provides a novel means of expanding on the eloquent work of Natarajan et al2 on assessing the influence of the respiratory pump on cardiac filling and function. This interaction between breathing and cardiac function has received limited attention, but now we have an excellent noninvasive tool for very accurately detailing changes in both right and left ventricular volumes with various respiratory maneuvers. We hope to provide novel data in the peer-reviewed literature soon that will detail the importance of this respiratory pump in enhancing cardiac filling. We slightly disagree with the assertion that breath-hold imaging should be considered a gold standard. Breath-holding is a nonphysiological surrogate that has previously been necessary to enable gating of cardiac magnetic resonance images. Real-time imaging enables the investigator to apply the accuracy of cardiac magnetic resonance to real physiological settings. We can neither ignore the fact that our patients breathe nor ignore the fact that most of our patients develop symptoms with exertion. This new methodology finally enables us to accurately measure cardiac function when it really matters.Andre La Gerche, MD, PhDGuido Claessen, MDAlexander Van de Bruaene, MDNele Pattyn, MScJohan Van Cleemput, MD, PhDMarc Gewillig, MD, PhDJan Bogaert, MD, PhDSteven Dymarkowski, MD, PhDPiet Claus, PhDHein Heidbuchel, MD, PhDUniversity Hospital of LeuvenLeuven, BelgiumDisclosuresNone.

Functional nasal morphology of chimaerid fishes

Holocephalans (chimaeras) are a group of marine fishes comprising three families: the Callorhinchidae (callorhinchid fishes), the Rhinochimaeridae (rhinochimaerid fishes) and the Chimaeridae (chimaerid fishes). We have used X-ray microcomputed tomography and magnetic resonance imaging to characterise in detail the nasal anatomy of three species of chimaerid fishes: Chimaera monstrosa, C. phantasma and Hydrolagus colliei. We have shown that the nasal chamber of these three species is linked to the external environment by an incurrent channel and to the oral cavity by an excurrent channel via an oral groove. A protrusion of variable morphology is present on the medial wall of the incurrent channel in all three species, but is absent in members of the two other holocephalan families that we inspected. A third nasal channel, the lateral channel, functionally connects the incurrent nostril to the oral cavity, by-passing the nasal chamber. From anatomical reconstructions, we have proposed a model for the circulation of water, and therefore the transport of odorant, in the chimaerid nasal region. In this model, water could flow through the nasal region via the nasal chamber or the lateral channel. In either case, the direction of flow could be reversed. Circulation through the entire nasal region is likely to be driven primarily by the respiratory pump. We have identified several anatomical features that may segregate, distribute, facilitate and regulate flow in the nasal region and have considered the consequences of flow reversal. The non-sensory cilia lining the olfactory sensory channels appear to be mucus-propelling, suggesting that these cilia have a common protective role in cartilaginous fishes (sharks, rays and chimaeras). The nasal region of chimaerid fishes shows at least two adaptations to a benthic lifestyle, and suggests good olfactory sensitivity, with secondary folding enhancing the hypothetical flat sensory surface area by up to 70%.