Respiratory Muscle Blood Flow Research Articles

Respiratory and locomotor muscle blood flow measurements using near-infrared spectroscopy and indocyanine green dye in health and disease.

Measuring respiratory and locomotor muscle blood flow during exercise is pivotal for understanding the factors limiting exercise tolerance in health and disease. Traditional methods to measure muscle blood flow present limitations for exercise testing. This article reviews a method utilising near-infrared spectroscopy (NIRS) in combination with the light-absorbing tracer indocyanine green dye (ICG) to simultaneously assess respiratory and locomotor muscle blood flow during exercise in health and disease. NIRS provides high spatiotemporal resolution and can detect chromophore concentrations. Intravenously administered ICG binds to albumin and undergoes rapid metabolism, making it suitable for repeated measurements. NIRS-ICG allows calculation of local muscle blood flow based on the rate of ICG accumulation in the muscle over time. Studies presented in this review provide evidence of the technical and clinical validity of the NIRS-ICG method in quantifying respiratory and locomotor muscle blood flow. Over the past decade, use of this method during exercise has provided insights into respiratory and locomotor muscle blood flow competition theory and the effect of ergogenic aids and pharmacological agents on local muscle blood flow distribution in COPD. Originally, arterial blood sampling was required via a photodensitometer, though the method has subsequently been adapted to provide a local muscle blood flow index using venous cannulation. In summary, the significance of the NIRS-ICG method is that it provides a minimally invasive tool to simultaneously assess respiratory and locomotor muscle blood flow at rest and during exercise in health and disease to better appreciate the impact of ergogenic aids or pharmacological treatments.

The oxygen transport cascade and exercise: Lessons from comparative physiology

Studies of animal physiology not only provide valuable knowledge for the species in question, but also offer insights into human physiology. This thought is best highlighted by the ‘Krogh Principle’, which states “for many problems there is an animal on which it can be most conveniently studied”. This graphical review focuses on three distinct stages of the oxygen transport cascade in which human exercise physiology knowledge has been enhanced by studies carried out in animal models. We begin by exploring ventilation, and the detrimental effects of cold, dry air on the airways in two sets of elite athletes, the cross-country skier and the racing sled dog. We then discuss the transport of oxygen via hemoglobin in humans and deer mice with relatively shifted oxygen dissociation curves. Finally, we consider the technical difficulties of measuring respiratory muscle blood flow in exercising humans and how an equine model can provide an understanding of the distribution of blood flow during exercise. These cases illustrate the complementary nature of physiological studies across species.

Effects of comorbid type II diabetes mellitus and heart failure on rat hindlimb and respiratory muscle blood flow during treadmill exercise.

In rats with type II diabetes mellitus (T2DM) compared with nondiabetic healthy controls, muscle blood flow (Q̇m) to primarily glycolytic hindlimb muscles and the diaphragm muscle are elevated during submaximal treadmill running consequent to lower skeletal muscle mass, a finding that held even when muscle mass was normalized to body mass. In rats with heart failure with reduced ejection fraction (HF-rEF) compared with healthy controls, hindlimb Q̇m was lower, whereas diaphragm Q̇m is elevated during submaximal treadmill running. Importantly, T2DM is the most common comorbidity present in patients with HF-rEF, but the effect of concurrent T2DM and HF-rEF on limb and respiratory Q̇m during exercise is unknown. We hypothesized that during treadmill running (20 m·min-1; 10% incline), hindlimb and diaphragm Q̇m would be higher in T2DM Goto-Kakizaki rats with HF-rEF (i.e., HF-rEF + T2DM) compared with nondiabetic Wistar rats with HF-rEF. Ejection fractions were not different between groups (HF-rEF: 30 ± 5; HF-rEF + T2DM: 28 ± 8%; P = 0.617), whereas blood glucose was higher in HF-rEF + T2DM (209 ± 150 mg/dL) compared with HF-rEF rats (113 ± 28 mg/dL; P = 0.040). Hindlimb muscle mass normalized to body mass was lower in rats with HF-rEF + T2DM (36.3 ± 1.6 mg/g) than in nondiabetic HF-rEF counterparts (40.3 ± 2.7 mg/g; P < 0.001). During exercise, Q̇m was elevated in rats with HF-rEF + T2DM compared with nondiabetic counterparts to the hindlimb (HF-rEF: 100 ± 28; HF-rEF + T2DM: 139 ± 23 mL·min-1·100 g-1; P < 0.001) and diaphragm (HF-rEF: 177 ± 66; HF-rEF + T2DM: 215 ± 93 mL·min-1·100g-1; P = 0.035). These data suggest that the pathophysiological consequences of T2DM on hindlimb and diaphragm Q̇m during treadmill running in the GK rat persist even in the presence of HF-rEF.NEW & NOTEWORTHY Herein, we demonstrate that rats comorbid with heart failure with reduced ejection fraction (HF-rEF) and type II diabetes mellitus (T2DM) have a higher hindlimb and respiratory muscle blood flow during submaximal treadmill running (20 m·min-1; 10% incline) compared with nondiabetic HF-rEF counterparts. These data may carry important clinical implications for roughly half of all patients with HF-rEF who present with T2DM.

Inspiratory and leg muscle blood flows during inspiratory muscle metaboreflex activation in heart failure with preserved ejection fraction.

The purpose of this study was to determine the cardiovascular consequences elicited by activation of the inspiratory muscle metaboreflex in patients with heart failure with preserved ejection fraction (HFpEF) and controls. Patients with HFpEF (n = 15; 69 ± 10 yr; 33 ± 4 kg/m2) and controls (n = 14; 70 ± 8 yr; 28 ± 4 kg/m2) performed an inspiratory loading trial at 60% maximal inspiratory pressure (PIMAX) until task failure. Mean arterial pressure (MAP) was measured continuously. Near-infrared spectroscopy and bolus injections of indocyanine green dye were used to determine the percent change in blood flow index (%ΔBFI) from baseline to the final minute of inspiratory loading in the vastus lateralis and sternocleidomastoid muscles. Vascular resistance index (VRI) was calculated. Time to task failure was shorter in HFpEF than in controls (339 ± 197 s vs. 626 ± 403 s; P = 0.02). Compared with controls, patients with HFpEF had a greater increase from baseline in MAP (16 ± 7 vs. 10 ± 6 mmHg) and vastus lateralis VRI (76 ± 45 vs. 32 ± 19%) as well as a greater decrease in vastus lateralis %ΔBFI (-32 ± 14 vs. -17 ± 9%) (all, P < 0.05). Sternocleidomastoid %ΔBFI normalized to absolute inspiratory pressure was higher in HFpEF compared with controls (8.0 ± 5.0 vs. 4.0 ± 1.9% per cmH2O·s; P = 0.03). These data indicate that patients with HFpEF exhibit exaggerated cardiovascular responses with inspiratory muscle metaboreflex activation compared with controls.NEW & NOTEWORTHY Respiratory muscle dysfunction is thought to contribute to exercise intolerance in heart failure with preserved ejection fraction (HFpEF); however, the underlying mechanisms are unknown. In the present study, patients with HFpEF had greater increases in leg muscle vascular resistance index and greater decreases in leg muscle blood flow index compared with controls during inspiratory resistive breathing (to activate the metaboreflex). Furthermore, respiratory muscle blood flow index responses normalized to pressure generation during inspiratory resistive breathing were exaggerated in HFpEF compared with controls.

Exercise training decreases intercostal and transversus abdominis muscle blood flows in heart failure rats during submaximal exercise

Diaphragm muscle blood flow (BF) and vascular conductance (VC) are elevated with chronic heart failure (HF) during exercise. Exercise training (ExT) elicits beneficial respiratory muscle and pulmonary system adaptations in HF. We hypothesized that diaphragm BF and VC would be lower in HF rats following ExT than their sedentary counterparts (Sed). Respiratory muscle BFs and mean arterial pressure were measured via radiolabeled microspheres and carotid artery catheter, respectively, during submaximal treadmill exercise (20 m/min, 5 % grade). During exercise, no differences were present between HF + ExT and HF + Sed in diaphragm BFs (201 ± 36 vs. 227 ± 44 mL/min/100 g) or VCs (both, p > 0.05). HF + ExT compared to HF + Sed had lower intercostal BF (27 ± 3 vs. 41 ± 5 mL/min/100 g) and VC (0.21 ± 0.02 vs. 0.31 ± 0.04 mL/min/mmHg/100 g) during exercise (both, p < 0.05). Further, HF + ExT compared to HF + Sed had lower transversus abdominis BF (20 ± 1 vs. 35 ± 6 mL/min/100 g) and VC (0.14 ± 0.02 vs. 0.27 ± 0.05 mL/min/mmHg/100 g) during exercise (both, p < 0.05). These data suggest that exercise training lowers the intercostal and transversus abdominis BF responses in HF rats during submaximal treadmill exercise.

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

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. 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 5min bouts of constant load cycling exercise trials at 30%, 60% and 90% of peak work rate in a randomized order, followed by 5min 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.

Type II diabetes accentuates diaphragm blood flow increases during submaximal exercise in the rat

We investigated the effect of type 2 diabetes mellitus (T2DM) on respiratory muscle blood flow (BF) during exercise. Using the Goto-Kakizaki (GK) rat model of T2DM, we hypothesized that diaphragm, intercostal and transverse abdominis BFs (radiolabeled microspheres) would be higher in male GK rats (n = 10) compared to healthy male Wistar controls (CON; n = 8) during submaximal exercise (20 m/min, 10 % grade). Blood glucose was significantly higher in GK (246 ± 29 mg/dL) compared to CON (103 ± 4 mg/dL; P < 0.01). Respiratory muscle BFs were not different at rest (P> 0.50). From rest to submaximal exercise, respiratory muscle BFs increased in both groups to all muscles (P < 0.01). During submaximal exercise GK rats had higher diaphragm BFs (GK: 189 ± 13; CON: 138 ± 14 mL/min/100 g, P < 0.01), and vascular conductance (GK: 1.4 ± 0.1; CON: 1.0 ± 0.1 mL/min/mmHg/100 g; P < 0.01) compared to CON. There were no differences in intercostal or transverse abdominis BF or VC during exercise (P> 0.15). These findings suggest that submaximal exercise requires a higher diaphragm BF and VC in T2DM compared to healthy counterparts.

Respiratory and locomotor muscle blood flow during exercise in health and chronic obstructive pulmonary disease.

What is the topic of this review? The work presented here focuses mostly on testing the theory of blood flow redistribution from the locomotor to the respiratory muscles during heavy exercise in healthy participants and in patients with COPD. What advances does it highlight? Studies presented and the direct experimental approach to measure muscle blood flow by indocyanine green dye detected by near infrared spectroscopy, show that exercise interferes with respiratory muscle blood flow especially in COPD, but even in healthy. We have developed an indicator-dilution method to measure muscle blood flow at rest and during exercise using the light absorbing tracer indocyanine green dye (ICG) injected as an intravenous bolus, with surface optodes placed over muscles of interest to record the ICG signal by near-infrared spectroscopy. Here we review findings for both quadriceps and intercostal muscle blood flow (measured simultaneously) in trained cyclists and in patients with chronic obstructive pulmonary disease (COPD). During resting hyperpnoea in both athletes and patients, intercostal muscle blood flow increased with ventilation, correlating closely and linearly with the work of breathing, with no change in quadriceps flow. During graded exercise in athletes, intercostal flow at first increased, but then began to fall approaching peak effort. Unexpectedly, in COPD, intercostal muscle blood flow during exercise fell progressively from resting values, contrasting sharply with the response to resting hyperpnoea. During exercise at peak intensity, we found no quadriceps blood flow reduction in favour of the respiratory muscles in either athletes or patients. In COPD at peak exercise, when patients breathed 21% oxygen in helium or 100% oxygen, there was no redistribution of blood flow observed between legs and respiratory muscles in either direction. Evidence of decrease in leg blood flow and increase in respiratory muscle flow was found only when imposing expiratory flow limitation (EFL) during exercise in healthy individuals. However, because EFL caused substantial physiological derangement, lowering arterial oxygen saturation and raising end-tidal and heart rate, these results cannot be projected onto normal exercise.

The hyperpnoea of exercise in health: Respiratory influences on neurovascular control.

What is the topic of this review? Elevated demand is placed on the respiratory muscles during whole-body exercise-induced hyperpnoea. What is the role of elevated demand in neural modulation of cardiovascular control in respiratory and locomotor skeletal muscle, and what are the mechanisms involved? What advances does it highlight? There is a sympathetic restraint of blood flow to locomotor muscles during near-maximal exercise, which might function to maintain blood pressure. During submaximal exercise, respiratory muscle blood flow might be also be reduced if ventilatory load is sufficiently high. Methodological advances (near-infrared spectroscopy with indocyanine green) confirm that blood flow is diverted away from respiratory muscles when the work of breathing is alleviated. It is known that the respiratory muscles have a significant increasing oxygen demand in line with hyperpnoea during whole-body endurance exercise and are susceptible to fatigue, in much the same way as locomotor muscles. The act of ventilation can itself be considered a form of exercise. The manipulation of respiratory load at near-maximal exercise alters leg blood flow significantly, demonstrating a competitive relationship between different skeletal muscle vascular beds to perfuse both sets of muscles adequately with a finite cardiac output. In recent years, the question has moved towards whether this effect exists during submaximal exercise, and the use of more direct measurements of respiratory muscle blood flow itself to confirm assumptions that uphold the concept. Evidence thus far has shown that there is a reciprocal effect on blood flow redistribution during ventilatory load manipulation observed at the respiratory muscles themselves and that the effect is observable during submaximal exercise, where active limb blood flow was reduced in conditions that simulated a high work of breathing. This has clinical applications for populations with respiratory disease and heart failure, where the work of breathing is remarkably high, even during submaximal efforts.

Do rebreathing manoeuvres for non-invasive measurement of cardiac output during maximum exercise test alter the main cardiopulmonary parameters?

Inert gas rebreathing has been recently described as an emergent reliable non-invasive method for cardiac output determination during exercise, allowing a relevant improvement of cardiopulmonary exercise test clinical relevance. For cardiac output measurements by inert gas rebreathing, specific respiratory manoeuvres are needed which might affect pivotal cardiopulmonary exercise test parameters, such as exercise tolerance, oxygen uptake and ventilation vs carbon dioxide output (VE/VCO2) relationship slope. We retrospectively analysed cardiopulmonary exercise testing of 181 heart failure patients who underwent both cardiopulmonary exercise testing and cardiopulmonary exercise test+cardiac output within two months (average 16 ± 15 days). All patients were in stable clinical conditions (New York Heart Association I-III) and on optimal medical therapy. The majority of patients were in New York Heart Association Class I and II (78.8%), with a mean left ventricular ejection fraction of 31 ± 10%. No difference was found between the two tests in oxygen uptake at peak exercise (1101 (interquartile range 870-1418) ml/min at cardiopulmonary exercise test vs 1103 (844-1389) at cardiopulmonary exercise test-cardiac output) and at anaerobic threshold. However, anaerobic threshold and peak heart rate, peak workload (75 (58-101) watts and 64 (42-90), p < 0.01) and carbon dioxide output were significantly higher at cardiopulmonary exercise testing than at cardiopulmonary exercise test+cardiac output, whereas VE/VCO2 slope was higher at cardiopulmonary exercise test+cardiac output (30 (27-35) vs 33 (28-37), p < 0.01). The similar anaerobic threshold and peak oxygen uptake in the two tests with a lower peak workload and higher VE/VCO2 slope at cardiopulmonary exercise test+cardiac output suggest a higher respiratory work and consequent demand for respiratory muscle blood flow secondary to the ventilatory manoeuvres. Accordingly, VE/VCO2 slope and peak workload must be evaluated with caution during cardiopulmonary exercise test+cardiac output.

Intercostal muscle blood flow is elevated in old rats during submaximal exercise

BackgroundRespiratory muscle blood flows (BF) increase substantially during exercise in younger adult rats. As aging is associated with altered pulmonary function, we hypothesized that old rats will have greater intercostal muscle BF and vascular conductances (VC) than young rats during submaximal exercise. MethodsMean arterial pressure and respiratory muscle BFs (via carotid artery catheter and radiolabeled microspheres, respectively) were measured at rest and during submaximal exercise in young (n = 9) and old (n = 7) Fischer 344 X Brown Norway rats. ResultsAt rest, diaphragm, intercostal, and transversus abdominis BFs and VCs were not different between groups (all, p > 0.10). During submaximal exercise, old compared to young rats had greater intercostal BF (40 ± 6 vs 25 ± 2 mL/min/100 g) and VC (0.30 ± 0.05 vs 0.18 ± 0.02 mL/min/mmHg/100 g) (both, p ≤ 0.01). Diaphragm and transversus abdominis BFs and VCs were not different between groups during exercise (all, p > 0.24). ConclusionsThese data demonstrate that intercostal muscle BF and VC are increased in old compared to young rats during submaximal exercise.

Near-infrared spectroscopy using indocyanine green dye for minimally invasive measurement of respiratory and leg muscle blood flow in patients with COPD.

Reliability of near-infrared spectroscopy, measuring indocyanine green (ICG) for minimally invasive assessment of relative muscle blood flow during exercise has been examined in fit young individuals but not in chronic obstructive pulmonary disease (COPD). Here we ask whether it could be used to evaluate respiratory and locomotor muscle perfusion in COPD patients. Vastus lateralis muscle blood flow (MBF, the reference method calculated from arterial and muscle ICG concentration curves) and a blood flow index [BFI, calculated using only the (same) muscle ICG concentration curves] were compared in 10 patients (forced expiratory volume in 1 s: 51 ± 6% predicted) at rest and during cycling at 25, 50, 75, and 100% of peak work rate (WRpeak). Intercostal muscle MBF and BFI were also compared during isocapnic hyperpnea at rest, reproducing ventilation levels up to those at WRpeak. Intercostal and vastus lateralis BFI increased with increasing ventilation during hyperpnea (from 2.5 ± 0.3 to 4.5 ± 0.7 nM/s) and cycling load (from 1.0 ± 0.2 to 12.8 ± 1.9 nM/s), respectively. There were strong correlations between BFI and MBF for both intercostal ( r = 0.993 group mean data, r = 0.872 individual data) and vastus lateralis ( r = 0.994 group mean data, r = 0.895 individual data). Fold changes from rest in BFI and MBF did not differ for either the intercostal muscles or the vastus lateralis. Group mean BFI data showed strong interrelationships with respiratory and cycling workload, and whole body metabolic demand ( r ranged from 0.913 to 0.989) simultaneously recorded during exercise. We conclude that BFI is a reliable and minimally invasive tool for evaluating relative changes in respiratory and locomotor muscle perfusion from rest to peak exercise in COPD patient groups. NEW & NOTEWORTHY We show that noninvasive near-infrared spectroscopic (NIRS) detection of indocyanine green dye (ICG) after peripheral venous injection adequately reflects intercostal and locomotor muscle perfusion during exercise and hyperpnea in patients with chronic obstructive pulmonary disease (COPD). Mean, individual, and fold change responses from rest to exercise or hyperpnea correlated closely with the reference method, which requires arterial sampling. NIRS-ICG is a reliable, robust, and essentially noninvasive tool for assessing relative changes in intercostal and locomotor muscle perfusion in COPD patient groups.

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.

Dietary nitrate supplementation opposes the elevated diaphragm blood flow in chronic heart failure during submaximal exercise

Chronic heart failure (CHF) results in a greater cost of breathing and necessitates an elevated diaphragm blood flow (BF). Dietary nitrate (NO3‾) supplementation lowers the cost of exercise. We hypothesized that dietary NO3‾ supplementation would attenuate the CHF-induced greater cost of breathing and thus the heightened diaphragm BF during exercise. CHF rats received either 5days of NO3‾-rich beetroot (BR) juice (CHF+BR, n=10) or a placebo (CHF, n=10). Respiratory muscle BFs (radiolabeled microspheres) were measured at rest and during submaximal exercise (20m/min, 5% grade). Infarcted left ventricular area and normalized lung weight were not significantly different between groups. During submaximal exercise, diaphragm BF was markedly lower for CHF+BR than CHF (CHF+BR: 195±28; CHF: 309±71mL/min/100g, p=0.04). The change in diaphragm BF from rest to exercise was less (p=0.047) for CHF+BR than CHF. These findings demonstrate that dietary NO3‾ supplementation reduces the elevated diaphragm BF during exercise in CHF rats thus providing additional support for this therapeutic intervention in CHF.

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.

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.

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.

Blood Flow Index Using Near Infrared Spectroscopy and Indocyanine Green Dye as a Minimally Invasive Method for Assessing Respiratory Muscle Blood Flow in Humans

PURPOSE: Previous attempts at measuring respiratory muscle blood flow (RMBF) in humans have required technically demanding and invasive methods on anesthetised subjects. The purpose of this study was to determine if a less invasive method could be used to measure RMBF in conscious humans using near infrared spectroscopy (NIRS) and indocyanine green (ICG) dye.

Last Word on Point:Counterpoint: Exercise-induced intrapulmonary shunting is imaginary vs. real

to the editor: We completely agree with the letter writers ([3][1]) that it is important to apply quantitative techniques for the measurement of intrapulmonary shunt before drawing conclusions. Both MIGET and the 100% oxygen technique are quantitative and have consistently shown insignificant