Epidemiological analysis of intramuscular hemorrhage of respiratory and accessory respiratory muscles in fatal drowning cases.

The postmortem diagnosis of drowning death and understanding the mechanisms leading to drowning require a comprehensive judgment based on numerous morphological findings in order to determine the pathogenesis and epidemiological characteristics of the findings. Effortful breathing during the drowning process can result in intramuscular hemorrhage in respiratory and accessory respiratory muscles. However, the characteristics of this phenomenon have not been investigated. We analyzed the epidemiological characteristics of 145 cases diagnosed as drowning, in which hemorrhage, not due to trauma, was found in the respiratory muscles and accessory respiratory muscles. Hemorrhage was observed in 31.7% of these cases, and the incidence did not differ by gender or drowning location. The frequency of hemorrhage was significantly higher in months with a mean temperature below 20°C than in months above 20°C, suggesting a relationship between the occurrence of hemorrhage and low environmental temperature. Moreover, the frequency of hemorrhage was significantly higher in the elderly (aged ≥65 years) compared to those <65 years old. In the elderly, the weakening of muscles due to aging may contribute to the susceptibility for intramuscular hemorrhage. Moreover, these intramuscular hemorrhages do not need to be considered in cases of a potential bleeding tendency due to disease such as cirrhosis or medication such as anticoagulants. Our results indicate that intramuscular hemorrhage in respiratory and accessory respiratory muscles can serve as an additional criterion to differentiate between fatal drowning and other causes of death, as long as no cutaneous or subcutaneous hematomas above the muscles with hemorrhages are observed. In addition, the epidemiological features that such intramuscular hemorrhage is more common in cold environments and in the elderly may provide useful information for the differentiation.

Near-infrared spectroscopy measures of sternocleidomastoid blood flow during exercise and hyperpnoea.

NEW FINDINGS: What is the central question of this study? How does sternocleidomastoid blood flow change in response to increasing ventilation and whole-body exercise intensity? What is the main finding and its importance? Sternocleidomastoid blood flow increased with increasing ventilation. For a given ventilation, sternocleidomastoid blood flow was lower during whole-body exercise compared to resting hyperpnoea. These findings suggest that locomotor muscle work exerts an effect on respiratory muscle blood flow that can be observed in the sternocleidomastoid. ABSTRACT: Respiratory muscle work influences the distribution of blood flow during exercise. Most studies have focused on blood flow to the locomotor musculature rather than the respiratory muscles, owing to the complex anatomical arrangement of respiratory muscles. The purpose of this study was to examine how accessory respiratory (i.e. sternocleidomastoid, and muscles in the intercostal space) muscle blood flow changes in response to locomotor muscle work. Seven men performed 5 min bouts of constant load cycling exercise trials at 30%, 60% and 90% of peak work rate in a randomized order, followed by 5 min bouts of voluntary hyperpnoea (VH) matching the ventilation achieved during each exercise (EX) trial. Blood-flow index (BFI) of the vastus lateralis, sternocleidomastoid (SCM) and seventh intercostal space (IC) were estimated using near-infrared spectroscopy and indocyanine green and expressed relative to resting levels. BFISCM was greater during VH compared to EX (P = 0.002) and increased with increasing exercise intensity (P = 0.036). BFISCM reached 493 ± 219% and 301 ± 215% rest during VH and EX at 90% peak work rate, respectively. BFIIC increased to 242 ± 178% and 210 ± 117% rest at 30% peak work rate during VH and EX, respectively. No statistically significant differences in BFIIC were observed with increased work rate during VH or EX (both P > 0.05). Moreover, there was no observed difference in BFIIC between conditions (P > 0.05). BFISCM was lower for a given minute ventilation during EX compared to VH, suggesting that accessory respiratory muscle blood flow is influenced by whole-body exercise.

Competition for blood flow distribution between respiratory and locomotor muscles: implications for muscle fatigue.

Sympathetically induced vasoconstrictor modulation of local vasodilation occurs in contracting skeletal muscle during exercise to ensure appropriate perfusion of a large active muscle mass and to maintain also arterial blood pressure. In this synthesis, we discuss the contribution of group III-IV muscle afferents to the sympathetic modulation of blood flow distribution to locomotor and respiratory muscles during exercise. This is followed by an examination of the conditions under which diaphragm and locomotor muscle fatigue occur. Emphasis is given to those studies in humans and animal models that experimentally changed respiratory muscle work to evaluate blood flow redistribution and its effects on locomotor muscle fatigue, and conversely, those that evaluated the influence of coincident limb muscle contraction on respiratory muscle blood flow and fatigue. We propose the concept of a "two-way street of sympathetic vasoconstrictor activity" emanating from both limb and respiratory muscle metaboreceptors during exercise, which constrains blood flow and O2 transport thereby promoting fatigue of both sets of muscles. We end with considerations of a hierarchy of blood flow distribution during exercise between respiratory versus locomotor musculatures and the clinical implications of muscle afferent feedback influences on muscle perfusion, fatigue, and exercise tolerance.

Effects of inspiratory muscle training in professional women football players: a randomized sham-controlled trial.

This study was conducted to determine the effects of inspiratory muscle training (IMT) on respiratory and peripheral muscles oxygenation during a maximal exercise tolerance test and on repeated-sprint ability (RSA) performance in professional women football players. Eighteen athletes were randomly assigned to one of the following groups: SHAM (n = 8) or IMT (n = 10). After a maximal incremental exercise test, all participants performed (on a different day) a time-to-exhaustion (Tlim) test. Peripheral and respiratory muscles oxygenation by near-infrared spectroscopy, breath-by-breath ventilatory and metabolic variables, and blood lactate concentration were measured. The RSA test was performed on a grass field. After a 6 week intervention, all athletes were reevaluated. Both groups showed increases in inspiratory muscles strength, exercise tolerance and RSA performance, however only the IMT group presented lower deoxyhemoglobin and total hemoglobin blood concentrations on intercostal muscles concomitantly to an increased oxyhemoglobin and total hemoglobin blood concentrations on vastus lateralis muscle during Tlim. In conclusion, these results may indicate the potential role of IMT to attenuate inspiratory muscles metaboreflex and consequently improve oxygen and blood supply to limb muscles during high-intensity exercise, with a potential impact on inspiratory muscle strength, exercise tolerance and sprints performance in professional women football players.

Effects of respiratory muscle work on respiratory and locomotor blood flow during exercise.

NEW FINDINGS: What is the central question of this study? Does manipulation of the work of breathing during high-intensity exercise alter respiratory and locomotor muscle blood flow? What is the main finding and its importance? We found that when the work of breathing was reduced during exercise, respiratory muscle blood flow decreased, while locomotor muscle blood flow increased. Conversely, when the work of breathing was increased, respiratory muscle blood flow increased, while locomotor muscle blood flow decreased. Our findings support the theory of a competitive relationship between locomotor and respiratory muscles during intense exercise. Manipulation of the work of breathing (WOB) during near-maximal exercise influences leg blood flow, but the effects on respiratory muscle blood flow are equivocal. We sought to assess leg and respiratory muscle blood flow simultaneously during intense exercise while manipulating WOB. Our hypotheses were as follows: (i) increasing the WOB would increase respiratory muscle blood flow and decrease leg blood flow; and (ii) decreasing the WOB would decrease respiratory muscle blood flow and increase leg blood flow. Eight healthy subjects (n = 5 men, n = 3 women) performed a maximal cycle test (day 1) and a series of constant-load exercise trials at 90% of peak work rate (day 2). On day 2, WOB was assessed with oesophageal balloon catheters and was increased (via resistors), decreased (via proportional assist ventilation) or unchanged (control) during the trials. Blood flow was assessed using near-infrared spectroscopy optodes placed over quadriceps and the sternocleidomastoid muscles, coupled with a venous Indocyanine Green dye injection. Changes in WOB were significantly and positively related to changes in respiratory muscle blood flow (r = 0.73), whereby increasing the WOB increased blood flow. Conversely, changes in WOB were significantly and inversely related to changes in locomotor blood flow (r = 0.57), whereby decreasing the WOB increased locomotor blood flow. Oxygen uptake was not different during the control and resistor trials (3.8 ± 0.9 versus 3.7 ± 0.8 l min-1 , P > 0.05), but was lower on the proportional assist ventilator trial (3.4 ± 0.7 l min-1 , P < 0.05) compared with control. Our findings support the concept that respiratory muscle work significantly influences the distribution of blood flow to both respiratory and locomotor muscles.

Effect of chronic heart failure in older rats on respiratory muscle and hindlimb blood flow during submaximal exercise.

Submaximal exercise diaphragm blood flow (BF) is elevated in young chronic heart failure (CHF) rats, while it is unknown if this occurs in older animals. Respiratory and hindlimb muscle BFs (radiolabeled microspheres) were measured at rest and during submaximal exercise (20m/min, 5% grade) in older healthy (n=7) and CHF (n=6) Fischer 344X Brown Norway rats (27-29 mo old). Older CHF, compared to healthy, rats had greater (p<0.01) left ventricular end-diastolic pressure and right ventricle and lung weight (normalized to body weight). During submaximal exercise, respiratory and hindlimb muscle BFs increased (p<0.02) in both groups, while diaphragm BF was higher (CHF: 257±32; healthy: 121±9mL/min/100g, p<0.01) and hindlimb BF lower (CHF: 111±10; healthy: 133±12mL/min/100g, p=0.04) in older CHF compared to healthy rats. Submaximal exercise hindlimb BF was negatively related (r=-0.93; p=0.03) to diaphragm BF in older CHF rats. During submaximal exercise, diaphragm BF is elevated in older CHF compared to healthy rats in proportion to the compromised hindlimb BF.

Respiratory muscle blood flow during exercise: Effects of sex and ovarian cycle.

Sex and ovarian cycle have been speculated to modify respiratory muscle blood flow control during exercise, but the findings are inconclusive. We tested the hypotheses that females would have higher respiratory muscle blood flow and vascular conductance (VC) compared with males during exercise and that this difference would be accentuated in proestrus vs. ovariectomized (OVA) females. Mean arterial pressure (carotid artery catheter) and respiratory muscle blood flow (radiolabeled microspheres) were measured during moderate-intensity (24 m/min, 10% grade) exercise in male (n = 9), female (n = 9), and OVA female (n = 7) rats and near-maximal (60 m/min, 5% grade) exercise in male (n = 5) and female (n = 7) rats. At rest, diaphragm, intercostal, and transversus abdominis blood flow were not different (P = 0.33) among groups. During moderate-intensity exercise, diaphragm (M: 124 ± 16; F: 140 ± 14; OVA: 140 ± 20 ml·min-1·100 g-1), intercostal (M: 33 ± 5; F: 34 ± 5; OVA: 30 ± 5 ml·min-1·100 g-1), and transversus abdominis blood flow (M: 24 ± 4; F: 35 ± 7; OVA: 35 ± 9 ml·min-1·100 g-1) significantly increased in all groups compared with rest but were not different (P = 0.12) among groups. From rest to moderate-intensity exercise, diaphragm (P < 0.03) and transversus abdominis (P < 0.04) VC increased in all groups, whereas intercostal VC increased only for males and females (P = 0.01). No differences (P > 0.13) existed in VC among groups. During near-maximal exercise, diaphragm (M: 304 ± 62; F: 283 ± 17 ml·min-1·100 g-1), intercostal (M: 29 ± 8; F: 40 ± 6 ml·min-1·100 g-1), and transversus abdominis (M: 85 ± 14; F: 86 ± 9 ml·min-1·100 g-1) blood flow and VC were not different (P > 0.27) between males and females. These data demonstrate that respiratory muscle blood flow and vascular conductance at rest and during exercise are not affected by sex or ovarian cycle in rats.NEW & NOTEWORTHY It has been proposed that sex and ovarian cycle modulate respiratory muscle blood flow control during exercise. We demonstrate herein that neither sex nor ovarian cycle influences respiratory muscle blood flow or vascular conductance at rest or during exercise in rats.

Effect of acute hypoxia on inspiratory muscle oxygenation during incremental inspiratory loading in healthy adults.

PURPOSE: To non-invasively examine the effect of acute hypoxia and inspiratory threshold loading (ITL) on inspiratory muscles [sternocleidomastoid (SCM), scalene (SA) and parasternal (PS)] oxygenation in healthy adults using near-infrared spectroscopy (NIRS). METHODS: Twenty healthy adults (12 M/8 F) were randomly assigned to perform two ITL tests while breathing a normoxic or hypoxic (FIO2 = 15 %) gas mixture. NIRS devices were placed over the SCM, PS, SA, and a control muscle, tibialis anterior (TA), to monitor oxygenated (O2Hb), deoxygenated (HHb), total hemoglobin (tHb) and tissue saturation index (TSI). With the nose occluded, subjects breathed normally for 4 min through a mouthpiece that was connected to a weighted threshold loading device. ITL began by adding a 100-g weight to the ITL device. Then, every 2 min 50-g was added until task failure. Vital signs, ECG and ventilatory measures were monitored throughout the protocol. RESULT: Participants were 31 ± 12 year and had normal spirometry. At task failure, the maximum load and ventilatory parameters did not differ between the hypoxic and normoxic ITL. At hypoxic ITL task failure, SpO2 was significantly lower, and ∆HHb increased more so in SA, SCM and PS than normoxic values. SCM ∆TSI decreased more so during hypoxic compared to normoxic ITL. ∆tHb in the inspiratory muscles (SCM, PS and SA) increased significantly compared to the decrease in TA during both hypoxic and normoxic ITL. CONCLUSION: The SCM, an accessory inspiratory muscle was the most vulnerable to deoxygenation during incremental loading and this response was accentuated by acute hypoxia.

Increased intrinsic excitability of muscle vasoconstrictor preganglionic neurons may contribute to the elevated sympathetic activity in hypertensive rats.

Hypertension is associated with pathologically increased sympathetic drive to the vasculature. This has been attributed to increased excitatory drive to sympathetic preganglionic neurons (SPN) from brainstem cardiovascular control centers. However, there is also evidence supporting increased intrinsic excitability of SPN. To test this hypothesis, we made whole cell recordings of muscle vasoconstrictor-like (MVClike) SPN in the working-heart brainstem preparation of spontaneously hypertensive (SH) and normotensive Wistar-Kyoto (WKY) rats. The MVClike SPN have a higher spontaneous firing frequency in the SH rat (3.85 ± 0.4 vs. 2.44 ± 0.4 Hz in WKY; P = 0.011) with greater respiratory modulation of their activity. The action potentials of SH SPN had smaller, shorter afterhyperpolarizations (AHPs) and showed diminished transient rectification indicating suppression of an A-type potassium conductance (IA). We developed mathematical models of the SPN to establish if changes in their intrinsic properties in SH rats could account for their altered firing. Reduction of the maximal conductance density of IA by 15-30% changed the excitability and output of the model from the WKY to a SH profile, with increased firing frequency, amplified respiratory modulation, and smaller AHPs. This change in output is predominantly a consequence of altered synaptic integration. Consistent with these in silico predictions, we found that intrathecal 4-aminopyridine (4-AP) increased sympathetic nerve activity, elevated perfusion pressure, and augmented Traube-Hering waves. Our findings indicate that IA acts as a powerful filter on incoming synaptic drive to SPN and that its diminution in the SH rat is potentially sufficient to account for the increased sympathetic output underlying hypertension.

Rib cage deformities alter respiratory muscle action and chest wall function in patients with severe osteogenesis imperfecta.

BACKGROUND: Osteogenesis imperfecta (OI) is an inherited connective tissue disorder characterized by bone fragility, multiple fractures and significant chest wall deformities. Cardiopulmonary insufficiency is the leading cause of death in these patients. METHODS: Seven patients with severe OI type III, 15 with moderate OI type IV and 26 healthy subjects were studied. In addition to standard spirometry, rib cage geometry, breathing pattern and regional chest wall volume changes at rest in seated and supine position were assessed by opto-electronic plethysmography to investigate if structural modifications of the rib cage in OI have consequences on ventilatory pattern. One-way or two-way analysis of variance was performed to compare the results between the three groups and the two postures. RESULTS: Both OI type III and IV patients showed reduced FVC and FEV(1) compared to predicted values, on condition that updated reference equations are considered. In both positions, ventilation was lower in OI patients than control because of lower tidal volume (p<0.01). In contrast to OI type IV patients, whose chest wall geometry and function was normal, OI type III patients were characterized by reduced (p<0.01) angle at the sternum (pectus carinatum), paradoxical inspiratory inward motion of the pulmonary rib cage, significant thoraco-abdominal asynchronies and rib cage distortions in supine position (p<0.001). CONCLUSIONS: In conclusion, the restrictive respiratory pattern of Osteogenesis Imperfecta is closely related to the severity of the disease and to the sternal deformities. Pectus carinatum characterizes OI type III patients and alters respiratory muscles coordination, leading to chest wall and rib cage distortions and an inefficient ventilator pattern. OI type IV is characterized by lower alterations in the respiratory function. These findings suggest that functional assessment and treatment of OI should be differentiated in these two forms of the disease.

Limitations of respiratory muscle and vastus lateralis blood flow during continuous exercise.

Measurement of regional blood flow to the respiratory muscles has traditionally been invasive. The blood flow index (BFI), a minimally invasive method using indocyanine green dye (ICG) and near infrared spectroscopy, allows assessment of within subject changes in regional blood flow. This study assessed regional BFI to the vastus lateralis muscle (QBFI) and the superficial respiratory muscles in the seventh intercostal space (RMBFI). Eight healthy subjects cycled continuously at incrementally more difficulty stages to exhaustion. In our subjects, QBFI declined between 83% and 100% of maximal exertion (p=0.002) and no statistically significant changes in RMBFI were seen despite steadily increasing ventilatory workloads. Post hoc pairwise comparisons demonstrated that QBFI at 83% work (0.015µmoless(-1)±0.005) was significantly higher than at maximum work output (0.011µmoless(-1)±0.004, p=0.007). There were no other significant differences of QBFI between maximum work output and different levels of work. The current study suggests that respiratory and locomotor muscle blood flow during sub-maximal and maximal exertion is unable to match increasing workloads.

Ventilation and respiratory mechanics.

During dynamic exercise, the healthy pulmonary system faces several major challenges, including decreases in mixed venous oxygen content and increases in mixed venous carbon dioxide. As such, the ventilatory demand is increased, while the rising cardiac output means that blood will have considerably less time in the pulmonary capillaries to accomplish gas exchange. Blood gas homeostasis must be accomplished by precise regulation of alveolar ventilation via medullary neural networks and sensory reflex mechanisms. It is equally important that cardiovascular and pulmonary system responses to exercise be precisely matched to the increase in metabolic requirements, and that the substantial gas transport needs of both respiratory and locomotor muscles be considered. Our article addresses each of these topics with emphasis on the healthy, young adult exercising in normoxia. We review recent evidence concerning how exercise hyperpnea influences sympathetic vasoconstrictor outflow and the effect this might have on the ability to perform muscular work. We also review sex-based differences in lung mechanics.

Sternocleidomastoid muscle deoxygenation in response to incremental inspiratory threshold loading measured by near infrared spectroscopy.

This study investigated the pattern of changes in muscle oxygenation, deoxygenation and blood volume in the sternocleidomastoid (SCM) in comparison with the parasternal (PS) and intercostal (IC) muscles during a bout of incremental inspiratory threshold loading (ITL) in healthy subjects using near-infrared spectroscopy. During progressive loading, the PS and IC showed a significant increase in oxygenated hemoglobin (5.9 ± 2.3 and 6.8 ± 2.4 µM, P<0.05) and the SCM showed an increase in deoxygenated hemoglobin (17.3 ± 3.8 µM, P<0.05). Total hemoglobin also steadily increased in the SCM whereas it decreased in the quiescent vastus lateralis muscle (20.7 ± 6.1µM vs. -6.6 ± 2.4 µM, P<0.05), which was used as the control muscle during the ITL. Our data suggests that the SCM is recruited progressively during progressive ITL and is accompanied by an increased blood volume and maintenance of O(2)Hb. Blood redistribution away from the nonactive limb muscles during the ITL may provide one source of maintaining inspiratory muscle blood volume and oxygenation during high respiratory motor output.

Effect of helium breathing on intercostal and quadriceps muscle blood flow during exercise in COPD patients.

Emerging evidence indicates that, besides dyspnea relief, an improvement in locomotor muscle oxygen delivery may also contribute to enhanced exercise tolerance following normoxic heliox (replacement of inspired nitrogen by helium) administration in patients with chronic obstructive pulmonary disease (COPD). Whether blood flow redistribution from intercostal to locomotor muscles contributes to this improvement currently remains unknown. Accordingly, the objective of this study was to investigate whether such redistribution plays a role in improving locomotor muscle oxygen delivery while breathing heliox at near-maximal [75% peak work rate (WR(peak))], maximal (100%WR(peak)), and supramaximal (115%WR(peak)) exercise in COPD. Intercostal and vastus lateralis muscle perfusion was measured in 10 COPD patients (FEV(1) = 50.5 ± 5.5% predicted) by near-infrared spectroscopy using indocyanine green dye. Patients undertook exercise tests at 75 and 100%WR(peak) breathing either air or heliox and at 115%WR(peak) breathing heliox only. Patients did not exhibit exercise-induced hyperinflation. Normoxic heliox reduced respiratory muscle work and relieved dyspnea across all exercise intensities. During near-maximal exercise, quadriceps and intercostal muscle blood flows were greater, while breathing normoxic heliox compared with air (35.8 ± 7.0 vs. 29.0 ± 6.5 and 6.0 ± 1.3 vs. 4.9 ± 1.2 ml·min(-1)·100 g(-1), respectively; P < 0.05; mean ± SE). In addition, compared with air, normoxic heliox administration increased arterial oxygen content, as well as oxygen delivery to quadriceps and intercostal muscles (from 47 ± 9 to 60 ± 12, and from 8 ± 1 to 13 ± 3 mlO(2)·min(-1)·100 g(-1), respectively; P < 0.05). In contrast, normoxic heliox had neither an effect on systemic nor an effect on quadriceps or intercostal muscle blood flow and oxygen delivery during maximal or supramaximal exercise. Since intercostal muscle blood flow did not decrease by normoxic heliox administration, blood flow redistribution from intercostal to locomotor muscles does not represent a likely mechanism of improvement in locomotor muscle oxygen delivery. Our findings might not be applicable to patients who hyperinflate during exercise.

Blood flow index using near-infrared spectroscopy and indocyanine green as a minimally invasive tool to assess respiratory muscle blood flow in humans.

Near-infrared spectroscopy (NIRS) in combination with indocyanine green (ICG) dye has recently been used to measure respiratory muscle blood flow (RMBF) in humans. This method is based on the Fick principle and is determined by measuring ICG in the respiratory muscles using transcutaneous NIRS in relation to the [ICG] in arterial blood as measured using photodensitometry. This method is invasive since it requires arterial cannulation, repeated blood withdrawals, and reinfusions. A less invasive alternative is to calculate a relative measure of blood flow known as the blood flow index (BFI), which is based solely on the NIRS ICG curve, thus negating the need for arterial cannulation. Accordingly, the purpose of this study was to determine whether BFI can be used to measure RMBF at rest and during voluntary isocapnic hyperpnea at 25, 40, 55, and 70% of maximal voluntary ventilation in seven healthy humans. BFI was calculated as the change in maximal [ICG] divided by the rise time of the NIRS-derived ICG curve. Intercostal and sternocleidomastoid muscle BFI were correlated with simultaneously measured work of breathing and electromyography (EMG) data from the same muscles. BFI showed strong relationships with the work of breathing and EMG for both respiratory muscles. The coefficients of determination (R(2)) comparing BFI vs. the work of breathing for the intercostal and sternocleidomastoid muscles were 0.887 (P < 0.001) and 0.863 (P < 0.001), respectively, whereas the R(2) for BFI vs. EMG for the intercostal and sternocleidomastoid muscles were 0.879 (P < 0.001) and 0.930 (P < 0.001), respectively. These data suggest that the BFI closely reflects RMBF in conscious humans across a wide range of ventilations and provides a less invasive and less technically demanding alternative to measuring RMBF.

Muscle and cerebral oxygenation during exercise performance after short-term respiratory work.

The purpose of the study was to investigate the effect of 30-min voluntary hyperpnoea on cerebral, respiratory and leg muscle balance between O(2) delivery and utilization during a subsequent constant-power test. Eight males performed a V˙O(2max) test, and two exercise tests at 85% of peak power output: (a) a control constant-power test (CPT), and (b) a constant-power test after a respiratory maneuver (CPT(RM)). Oxygenated (Δ[O(2)Hb]), deoxygenated (Δ[HHb]) and total (Δ[tHb]) hemoglobin in cerebral, intercostal and vastus lateralis were monitored with near-infrared spectroscopy. The performance time dropped ∼15% in CPT(RM) (6:55±2:52min) compared to CPT (8:03±2:33min), but the difference was not statistically significant. The vastus lateralis and intercostal Δ[tHb] and Δ[HHb] were lower in CPT(RM) than in CPT (P≤0.05). There were no differences in cerebral oxygenation between the trials. Thus, respiratory work prior to an exercise test influences the oxygenation during exercise in the leg and respiratory muscles, but not in the frontal cortex.

Contribution of respiratory muscle blood flow to exercise-induced diaphragmatic fatigue in trained cyclists.

We investigated whether the greater degree of exercise-induced diaphragmatic fatigue previously reported in highly trained athletes in hypoxia (compared with normoxia) could have a contribution from limited respiratory muscle blood flow. Seven trained cyclists completed three constant load 5 min exercise tests at inspired O(2) fractions (FIO2) of 0.13, 0.21 and 1.00 in balanced order. Work rates were selected to produce the same tidal volume, breathing frequency and respiratory muscle load at each FIO2 (63 +/- 1, 78 +/- 1 and 87 +/- 1% of normoxic maximal work rate, respectively). Intercostals and quadriceps muscle blood flow (IMBF and QMBF, respectively) were measured by near-infrared spectroscopy over the left 7th intercostal space and the left vastus lateralis muscle, respectively, using indocyanine green dye. The mean pressure time product of the diaphragm and the work of breathing did not differ across the three exercise tests. After hypoxic exercise, twitch transdiaphragmatic pressure fell by 33.3 +/- 4.8%, significantly (P < 0.05) more than after both normoxic (25.6 +/- 3.5% reduction) and hyperoxic (26.6 +/- 3.3% reduction) exercise, confirming greater fatigue in hypoxia. Despite lower leg power output in hypoxia, neither cardiac output nor QMBF (27.6 +/- 1.2 l min(-1) and 100.4 +/- 8.7 ml (100 ml)(-1) min(-1), respectively) were significantly different compared with normoxia (28.4 +/- 1.9 l min(-1) and 94.4 +/- 5.2 ml (100 ml)(-1) min(-1), respectively) and hyperoxia (27.8 +/- 1.6 l min(-1) and 95.1 +/- 7.8 ml (100 ml)(-1) min(-1), respectively). Neither IMBF was different across hypoxia, normoxia and hyperoxia (53.6 +/- 8.5, 49.9 +/- 5.9 and 52.9 +/- 5.9 ml (100 ml)(-1) min(-1), respectively). We conclude that when respiratory muscle energy requirement is not different between normoxia and hypoxia, diaphragmatic fatigue is greater in hypoxia as intercostal muscle blood flow is not increased (compared with normoxia) to compensate for the reduction in PaO2, thus further compromising O(2) supply to the respiratory muscles.

Effects of respiratory muscle unloading on leg muscle oxygenation and blood volume during high-intensity exercise in chronic heart failure.

Blood flow requirements of the respiratory muscles (RM) increase markedly during exercise in chronic heart failure (CHF). We reasoned that if the RM could subtract a fraction of the limited cardiac output (QT) from the peripheral muscles, RM unloading would improve locomotor muscle perfusion. Nine patients with CHF (left ventricle ejection fraction = 26 +/- 7%) undertook constant-work rate tests (70-80% peak) receiving proportional assisted ventilation (PAV) or sham ventilation. Relative changes (Delta%) in deoxy-hemoglobyn, oxi-Hb ([O2Hb]), tissue oxygenation index, and total Hb ([HbTOT], an index of local blood volume) in the vastus lateralis were measured by near infrared spectroscopy. In addition, QT was monitored by impedance cardiography and arterial O2 saturation by pulse oximetry (SpO2). There were significant improvements in exercise tolerance (Tlim) with PAV. Blood lactate, leg effort/Tlim and dyspnea/Tlim were lower with PAV compared with sham ventilation (P < 0.05). There were no significant effects of RM unloading on systemic O2 delivery as QT and SpO2 at submaximal exercise and at Tlim did not differ between PAV and sham ventilation (P > 0.05). Unloaded breathing, however, was related to enhanced leg muscle oxygenation and local blood volume compared with sham, i.e., higher Delta[O2Hb]% and Delta[HbTOT]%, respectively (P < 0.05). We conclude that RM unloading had beneficial effects on the oxygenation status and blood volume of the exercising muscles at similar systemic O2 delivery in patients with advanced CHF. These data suggest that blood flow was redistributed from respiratory to locomotor muscles during unloaded breathing.

Human respiratory muscle blood flow measured by near-infrared spectroscopy and indocyanine green.

Measurement of respiratory muscle blood flow (RMBF) in humans has important implications for understanding patterns of blood flow distribution during exercise in healthy individuals and those with chronic disease. Previous studies examining RMBF in humans have required invasive methods on anesthetized subjects. To assess RMBF in awake subjects, we applied an indicator-dilution method using near-infrared spectroscopy (NIRS) and the light-absorbing tracer indocyanine green dye (ICG). NIRS optodes were placed on the left seventh intercostal space at the apposition of the costal diaphragm and on an inactive control muscle (vastus lateralis). The primary respiratory muscles within view of the NIRS optodes include the internal and external intercostals. Intravenous bolus injection of ICG allowed for cardiac output (by the conventional dye-dilution method with arterial sampling), RMBF, and vastus lateralis blood flow to be quantified simultaneously. Esophageal and gastric pressures were also measured to calculate the work of breathing and transdiaphragmatic pressure. Measurements were obtained in five conscious humans during both resting breathing and three separate 5-min bouts of constant isocapnic hyperpnea at 27.1 +/- 3.2, 56.0 +/- 6.1, and 75.9 +/- 5.7% of maximum minute ventilation as determined on a previous maximal exercise test. RMBF progressively increased (9.9 +/- 0.6, 14.8 +/- 2.7, 29.9 +/- 5.8, and 50.1 +/- 12.5 ml 100 ml(-1) min(-1), respectively) with increasing levels of ventilation while blood flow to the inactive control muscle remained constant (10.4 +/- 1.4, 8.7 +/- 0.7, 12.9 +/- 1.7, and 12.2 +/- 1.8 ml 100 ml(-1) min(-1), respectively). As ventilation rose, RMBF was closely and significantly correlated with 1) cardiac output (r = 0.994, P = 0.006), 2) the work of breathing (r = 0.995, P = 0.005), and 3) transdiaphragmatic pressure (r = 0.998, P = 0.002). These data suggest that the NIRS-ICG technique provides a feasible and sensitive index of RMBF at different levels of ventilation in humans.

Microscopic polyangiitis presenting as a "pulmonary-muscle" syndrome: is subclinical alveolar hemorrhage the mechanism of pulmonary fibrosis?

Microscopic polyangiitis (MPA) may present with a syndrome that resembles idiopathic pulmonary fibrosis (IPF). We describe an MPA patient with the clinical presentation of a "pulmonary-muscle" syndrome in which interstitial lung disease antedated the onset of myopathy. Identification of vasculitis on muscle biopsy was instrumental in recognizing clinical, radiographic, and histopathologic features that were more characteristic of MPA than of IPF. Institution of glucocorticoid and cyclophosphamide therapy led to the induction of a complete remission. The histologic findings in this case implicate subclinical episodes of alveolar hemorrhage as the mechanism of interstitial lung disease in MPA.