Search

A paper published by Harry H. Pennes in Volume 1 of theJournal of Applied Physiologydefined the theoretical basis for a considerable body of analysis performed by many investigators during the ensuing half century. However, during the past decade, the Pennes’ model of heat transfer in perfused tissue has been criticized for various reasons, one of which is that his own experimental data seemed to be at variance with the model. More specifically, the shape of the mean temperature-depth relationship measured by Pennes was distinctly different from the shape of the theoretical curve. In this paper, I show that Pennes used an inappropriate procedure to analyze his data and that, when the data are analyzed in a more rigorous manner, they support his theory. Additional support for Pennes’ theory is provided by the experimental data of H. Barcroft and O. G. Edholm [J. Physiol. (Lond.)102: 5–20, 1942 and 104: 366–376, 1946], who had previously studied cooling of the forearm during immersion in water at various temperatures.

A paper published by Harry H. Pennes in Volume 1 of the Journal of Applied Physiology defined the theoretical basis for a considerable body of analysis performed by many investigators during the ensuing half century. However, during the past decade, the Pennes' model of heat transfer in perfused tissue has been criticized for various reasons, one of which is that his own experimental data seemed to be at variance with the model. More specifically, the shape of the mean temperature-depth relationship measured by Pennes was distinctly different from the shape of the theoretical curve. In this paper, I show that Pennes used an inappropriate procedure to analyze his data and that, when the data are analyzed in a more rigorous manner, they support his theory. Additional support for Pennes' theory is provided by the experimental data of H. Barcroft and O. G. Edholm [J. Physiol. (Lond.) 102: 5-20, 1942 and 104: 366-376, 1946], who had previously studied cooling of the forearm during immersion in water at various temperatures.

A dynamic model predicting human thermal responses in cold, cool, neutral, warm, and hot environments is presented in a two-part study. This, the first paper, is concerned with aspects of the passive system:1) modeling the human body, 2) modeling heat-transport mechanisms within the body and at its periphery, and 3) the numerical procedure. A paper in preparation will describe the active system and compare the model predictions with experimental data and the predictions by other models. Here, emphasis is given to a detailed modeling of the heat exchange with the environment: local variations of surface convection, directional radiation exchange, evaporation and moisture collection at the skin, and the nonuniformity of clothing ensembles. Other thermal effects are also modeled: the impact of activity level on work efficacy and the change of the effective radiant body area with posture. A stable and accurate hybrid numerical scheme was used to solve the set of differential equations. Predictions of the passive system model are compared with available analytic solutions for cylinders and spheres and show good agreement and stable numerical behavior even for large time steps.

This paper reports that the selective β2-adrenergic receptor agonist clenbuterol affects bone metabolism in growing 3-mo-old male Wistar rats treated over 8 wk. Thirty-two 3-mo-old growing Wistar rats weighing 234 ± 2 g were assigned to a progressive isometric force, strength-training exercise program plus oral clenbuterol (2 mg · kg body wt−1· day−1) for 5 days each week, exercise program without clenbuterol 5 days each week, no exercise program plus oral clenbuterol (2 mg · kg−1· day−1) for 5 days each week, or no exercise without clenbuterol 5 days each week. At the end of 8 wk, lean mass, fat mass, and right total femoral, distal metaphyseal femoral, and diaphyseal femoral bone mineral density were measured by Hologic QDR 4500 dual X-ray absorptiometry (DEXA) technique. Left femoral bones were harvested after death on day 58, and femoral resistance was determined by three-point bending testing. We found that fat mass was decreased in rats given strength training exercise and decreased further in rats treated with clenbuterol. Lean mass was increased in clenbuterol-treated animals. Strength-training exercise appeared to have no effect on bone mineral density, serum osteocalcin, or urinary deoxypyridinoline. However, clenbuterol treatment decreased femoral length, diameter, bone mineral density, and mechanical resistance. Clenbuterol had no effect on osteocalcin but increased urinary deoxypyridinoline. We concluded that clenbuterol treatment decreased bone mineral density and increased bone resorption independent of the level of exercise rats were given.

To determine the effect of hyperpnea on the characteristics of periciliary liquid, we collected airway surface fluid (ASF) and measured its osmolarity in 11 normal people while they breathed dry, frigid air (−17 ± 1.2°C) at minute ventilations (V˙e) of 10, 40, and 80 l/min through a heat exchanger. The ASF was collected at the fifth tracheal ring by absorption onto filter paper pledgets inserted via fiber-optic bronchoscopy. Hyperpnea had no influence on the amount of ASF recovered (ASF volume at a V˙eof 10 l/min = 12.0 ± 2.0 μl; at 80 l/min = 8.8 ± 1.5 μl; P= 0.28) or its osmolarity (at a V˙eof 10, 40, and 80 l/min = 326 ± 15, 323 ± 11, and 337 ± 12 mosM, respectively; P= 0.65). These findings demonstrate that the tracheal mucosa of normal subjects does not desiccate during hyperpnea and that hypertonicity of the periciliary fluid does not develop even at high levels of ventilation.

Since its inception at the National Aeronautics and Space Administration (NASA) Ames Research Center in the mid-1970s, many laboratories around the world have used the rat hindlimb unloading model to simulate weightlessness and to study various aspects of musculoskeletal loading. In this model, the hindlimbs of rodents are elevated to produce a 30° head-down tilt, which results in a cephalad fluid shift and avoids weightbearing by the hindquarters. Although several reviews have described scientific results obtained with this model, this is the first review to focus on the technical aspects of hindlimb unloading. This review includes a history of the technique, a brief comparison with spaceflight data, technical details, extension of the model to mice, and other important technical considerations (e.g., housing, room temperature, unloading angle, the potential need for multiple control groups, age, body weight, the use of the forelimb tissues as internal controls, and when to remove animals from experiments). This paper is intended as a reference for researchers, reviewers of manuscripts, and institutional animal care and use committees. Over 800 references, related to the hindlimb unloading model, can be accessed via the electronic version of this article.

In this paper, selected historical aspects of thermoregulation and fever are presented as background to the application of molecular biology to thermoregulation. Temperature-sensing mechanisms, coordination of thermal information, thermoregulatory circuitry, efferent responses to thermal stimuli, set point mechanisms, and some of the mechanisms and consequences of fever and hyperthermia are highlighted. Neurotransmitters used in thermoregulatory circuits are also discussed. An attempt is made to include information from comparative physiological sources. Possible future avenues of research in the light of recent new technologies are also presented.

The purpose of this paper was to determine the effects of stimulation pattern and frequency on repetitive human knee movements. Quadriceps femoris muscles were stimulated against a load equal to 10% of each subject's maximum voluntary isometric force. The main variable of interest was the number of repetitions in which the leg reached a target angle of 40° of knee extension. Sixteen different trains were tested, including1) six constant-frequency trains with frequencies ranging from 9 to 100 Hz, 2) five variable-frequency trains with an initial 5-ms triplet and mean frequencies ranging from 11 to 35 Hz, and3) five doublet-frequency trains, which used doublets (2 pulses with a 5-ms interpulse interval) to replace single pulses, with mean frequencies of 17–57 Hz. Testing was stopped when the subject failed to reach the target angle for three consecutive activations. Results showed that no single pattern was best for all subjects. The 33- and 100-Hz constant-frequency trains, 35-Hz variable-frequency trains, and 27- and 36-Hz doublet frequency trains each met the target the most times for some subjects. The results showed that, under our testing conditions, higher frequency trains were better suited for producing repetitive knee movements than lower frequency trains.

During isometric contractions of increasing strength, motor units (MUs) are recruited by the central nervous system in an orderly manner starting with the smallest, with muscle fibers that usually show the lowest conduction velocity (CV). Theory predicts that the higher the velocity of propagation of the action potential, the higher the power at high frequencies of the detected surface signal. These considerations suggest that the power spectral density of the surface detected electromyogram (EMG) signal may give indications about the MU recruitment process. The purpose of this paper is to investigate the potential and limitations of spectral analysis of the surface EMG signal as a technique for the investigation of muscle force control. The study is based on a simulation approach and on an experimental investigation of the properties of surface EMG signals detected from the biceps brachii during isometric linearly increasing torque contractions. Both simulation and experimental data indicate that volume conductor properties play an important role as confounding factors that may mask any relation between EMG spectral variables and estimated CV as a size principle parameter during ramp contractions. The correlation between spectral variables and CV is thus significantly lower when the MU pool is not stable than during constant-torque isometric contractions. Our results do not support the establishment of a general relationship between spectral EMG variables and torque or recruitment strategy.

This minireview provides an overview of known and potential gender differences in physiological responses to spaceflight. The paper covers cardiovascular and exercise physiology, barophysiology and decompression sickness, renal stone risk, immunology, neurovestibular and sensorimotor function, nutrition, pharmacotherapeutics, and reproduction. Potential health and functional impacts associated with the various physiological changes during spaceflight are discussed, and areas needing additional research are highlighted. Historically, studies of physiological responses to microgravity have not been aimed at examining gender-specific differences in the astronaut population. Insufficient data exist in most of the discipline areas at this time to draw valid conclusions about gender-specific differences in astronauts, in part due to the small ratio of women to men. The only astronaut health issue for which a large enough data set exists to allow valid conclusions to be drawn about gender differences is orthostatic intolerance following shuttle missions, in which women have a significantly higher incidence of presyncope during stand tests than do men. The most common observation across disciplines is that individual differences in physiological responses within genders are usually as large as, or larger than, differences between genders. Individual characteristics usually outweigh gender differences per se.

In this paper, we describe the effects of voluntary cage wheel exercise on mouse cardiac and skeletal muscle. Inbred male C57/Bl6 mice (age 8–10 wk; n= 12) ran an average of 4.3 h/24 h, for an average distance of 6.8 km/24 h, and at an average speed of 26.4 m/min. A significant increase in the ratio of heart mass to body mass (mg/g) was evident after 2 wk of voluntary exercise, and cardiac atrial natriuretic factor and brain natriuretic peptide mRNA levels were significantly increased in the ventricles after 4 wk of voluntary exercise. A significant increase in the percentage of fibers expressing myosin heavy chain (MHC) IIa was observed in both the gastrocnemius and the tibialis anterior (TA) by 2 wk, and a significant decrease in the percentage of fibers expressing IIb MHC was evident in both muscles after 4 wk of voluntary exercise. The TA muscle showed a greater increase in the percentage of IIa MHC-expressing fibers than did the gastrocnemius muscle (40 and 20%, respectively, compared with 10% for nonexercised). Finally, the number of oxidative fibers as revealed by NADH-tetrazolium reductase histochemical staining was increased in the TA but not the gastrocnemius after 4 wk of voluntary exercise. All results are relative to age-matched mice housed without access to running wheels. Together these data demonstrate that voluntary exercise in mice results in cardiac and skeletal muscle adaptations consistent with endurance exercise.

Functional electrical stimulation (FES) is used to provide paralyzed human subjects with postural support and a limited range of movements. Problems encountered with FES include jerky movements from tension oscillations during stimulation and rapid muscle fatigue. In this paper, we report experiments on anesthetized cats that test a new, computer-controlled method of stimulation of the muscle nerve supply, distributed across several inputs, which reduces these problems. After 5 min of continuous, distributed stimulation of the medial gastrocnemius muscle at 6 pulses per second (pps) across 6 channels, tension fell to 55.9 ± 3.9% (SE) of its original value. In comparison, after 5 min of synchronous stimulation of one muscle portion at 36 pps, tension fell to 11 ± 3.7%. At higher stimulation rates, 10 pps per channel (distributed) and 60 pps (synchronous), the differences in fatigue were even greater. Similar results were obtained when an intermittent, rather than a continuous, stimulation protocol was used. These findings indicate that distributed stimulation has important advantages over other methods for applications such as FES.

Transdermal extraction of clinically relevant analytes offers a potentially noninvasive method of diagnostics. However, development of such a method is limited by the low permeability of skin. In this paper, we present a potential method for noninvasive diagnostics based on ultrasonic skin permeabilization and subsequent extraction of interstitial fluid (ISF) across the skin using vacuum. ISF extracted by this method was collected and analyzed for glucose and other analytes. Glucose concentration in the extracted fluid correlates well with blood glucose concentration over a range of 50–250 mg/dl. A mathematical model describing vacuum-induced transport of ISF through ultrasonically permeabilized skin is presented as well. The model accounts for convective, as well as diffusive, transport processes across blood capillaries, epidermis, and the stratum corneum. The overall predictions of the model compare favorably with the experimental observations.

In the present paper, the study of the ventricular motion during systole was addressed by means of a computational model of ventricular ejection. In particular, the implications of ventricular motion on blood acceleration and velocity measurements at the valvular plane (VP) were evaluated. An algorithm was developed to assess the force exchange between the ventricle and the surrounding tissue, i.e., the inflow and outflow vessels of the heart. The algorithm, based on the momentum equation for a transitory flowing system, was used in a fluid-structure model of the ventricle that includes the contractile behavior of the fibers and the viscous and inertial forces of the intraventricular fluid. The model calculates the ventricular center of mass motion, the VP motion, and intraventricular pressure gradients. Results indicate that the motion of the ventricle affects the noninvasive estimation of the transvalvular pressure gradient using Doppler ultrasound. The VP motion can lead to an underestimation equal to 12.4 ± 6.6%.

This paper describes and quantifies acute responses of the kidneys in correcting plasma volume, acid-base, and ion disturbances resulting from NaHCO3and KHCO3ingestion. Renal excretion of ions and water was studied in five men after ingestion of 3.57 mmol/kg body mass of sodium bicarbonate (NaHCO3) and, in a separate trial, potassium bicarbonate (KHCO3). Subjects had a Foley catheter inserted into the bladder and indwelling catheters placed into an antecubital vein and a brachial artery. Blood and urine were sampled in the 30-min period before, the 60-min period during, and the 210-min period after ingestion of the solutions. NaHCO3ingestion resulted in a rapid, transient diuresis and natriuresis. Cumulative urine output was 44 ± 11% of ingested volume, resulting in a 555 ± 119 ml increase in total body water at the end of the experiment. The cumulative increase (above basal levels) in renal Na+excretion accounted for 24 ± 2% of ingested Na+. In the KHCO3trial, arterial plasma K+concentration rapidly increased from 4.25 ± 0.10 to a peak of 7.17 ± 0.13 meq/l 140 min after the beginning of ingestion. This increase resulted in a pronounced, transient diuresis, with cumulative urine output at 270 min similar to the volume ingested, natriuresis, and a pronounced kaliuresis that was maintained until the end of the experiment. Cumulative (above basal) renal K+excretion at 270 min accounted for 26 ± 5% of ingested K+. The kidneys were important in mediating rapid corrections of substantial portions of the fluid and electrolyte disturbances resulting from ingestion of KHCO3and NaHCO3solutions.

This paper describes and quantifies acute responses of the kidneys in correcting plasma volume, acid-base, and ion disturbances resulting from NaHCO3 and KHCO3 ingestion. Renal excretion of ions and water was studied in five men after ingestion of 3.57 mmol/kg body mass of sodium bicarbonate (NaHCO3) and, in a separate trial, potassium bicarbonate (KHCO3). Subjects had a Foley catheter inserted into the bladder and indwelling catheters placed into an antecubital vein and a brachial artery. Blood and urine were sampled in the 30-min period before, the 60-min period during, and the 210-min period after ingestion of the solutions. NaHCO3 ingestion resulted in a rapid, transient diuresis and natriuresis. Cumulative urine output was 44 ± 11% of ingested volume, resulting in a 555 ± 119 ml increase in total body water at the end of the experiment. The cumulative increase (above basal levels) in renal Na⁺ excretion accounted for 24 ± 2% of ingested Na⁺. In the KHCO3 trial, arterial plasma K⁺ concentration rapidly increased from 4.25 ± 0.10 to a peak of 7.17 ± 0.13 meq/l 140 min after the beginning of ingestion. This increase resulted in a pronounced, transient diuresis, with cumulative urine output at 270 min similar to the volume ingested, natriuresis, and a pronounced kaliuresis that was maintained until the end of the experiment. Cumulative (above basal) renal K⁺ excretion at 270 min accounted for 26 ± 5% of ingested K⁺. The kidneys were important in mediating rapid corrections of substantial portions of the fluid and electrolyte disturbances resulting from ingestion of KHCO3 and NaHCO3 solutions.

Development of drug treatments for obstructive sleep-disordered breathing has been impeded by the lack of animal models. The obese pig may be a suitable animal model, as it has been reported to experience sleep-disordered breathing resembling human obstructive sleep apnea. The purpose of this paper is to describe in detail techniques for chronic instrumentation of the obese Vietnamese pot-bellied pig and to study respiratory function during sleep. Under general anesthesia, four obese pigs were instrumented for long-term recording of intrapleural and tracheal pressures, genioglossal EMG, and bioelectric signals related to sleep. A custom-fitted face mask was used to record respiratory variables including airflow, snoring, and expired CO2. Most chronic instrumentation provided robust signals for up to 6 wk after installation. All pigs displayed sleep-disordered breathing characterized by increased resistance to airflow, snoring, inspiratory flow limitation, and possible sleep disruption. Apneas and hypopneas were not a feature of breathing during sleep in these animals. Nonetheless, this animal preparation may be useful for exploring possible drug treatments for obstructive sleep-disordered breathing.

Active and passive shortening of muscle bundles in the canine diaphragm were measured with the objective of testing a consequence of the minimal-work hypothesis: namely, that the ratio of active to passive shortening is the same for all active muscles. Lengths of six muscle bundles in the costal diaphragm and two muscle bundles in the crural diaphragm of each of four bred-for-research beagle dogs were measured by the radiopaque marker technique during the following maneuvers: a passive deflation maneuver from total lung capacity to functional residual capacity, quiet breathing, and forceful inspiratory efforts against an occluded airway at different lung volumes. Shortening per liter increase in lung volume was, on average, 70% greater during quiet breathing than during passive inflation in the prone posture and 40% greater in the supine posture. For the prone posture, the ratio of active to passive shortening was larger in the ventral and midcostal diaphragm than at the dorsal end of the costal diaphragm. For both postures, active shortening during quiet breathing was poorly correlated with passive shortening. However, shortening during forceful inspiratory efforts was highly correlated with passive shortening. The average ratios of active to passive shortening were 1.23 ± 0.02 and 1.32 ± 0.03 for the prone and supine postures, respectively. These data, taken together with the data reported in the companion paper (T. A. Wilson, M. Angelillo, A. Legrand, and A. De Troyer,J. Appl. Physiol. 87: 554-560, 1999), support the hypothesis that, during forceful inspiratory efforts, the inspiratory muscles drive the chest wall along the minimal-work trajectory.

We investigated whether hyperosmolar saline (HS), applied via paper disk onto the septum of one nostril, induces a nasal secretory response. Furthermore, we examined whether this response is accentuated in patients with active allergic rhinitis (AR) compared with healthy volunteers. Unilateral HS produced significant nasal secretions both ipsilateral and contralateral to the site of challenge in the AR group and only ipsilaterally in the healthy group. The HS-induced nasal secretions were significantly greater in the AR vs. the healthy subjects. In a separate study, we ascertained that the nasal response to HS is neurally mediated and found that ipsilateral nerve blockade with lidocaine significantly attenuates the HS-induced secretions bilaterally. In another group of AR subjects, we determined whether nociceptive fibers were involved in this response and found that sensory nerve desensitization with repeated application of capsaicin attenuated the HS-induced nasal secretions. Finally, we determined whether the secretory hyperresponsiveness in AR is attributable to increased reactivity of submucosal glands rather than of nerves. We found that the dose response to methacholine, which directly stimulates the glands, was identical among AR and healthy subjects. We conclude that, in AR, nasal challenge with HS induces significantly greater reflex secretions involving capsaicin-sensitive nerve fibers, consistent with the notion of neural hyperresponsiveness in this disease.

Exercise training results in several muscle adaptations, one of which is angiogenesis. Acutely, exercise leads to release of nitric oxide, prostacyclin (PGI2), and adenosine (A) in the skeletal muscles. In this paper, we asked whether any of these locally released vasodilators, as well as other known dilator prostaglandins (PGE1and PGE2), have the potential to increase angiogenic growth factor gene expression in resting skeletal muscle. Seven groups of 5–7 female Wistar rats (age 8–12 wk, weight 250 ± 10 g) were anesthetized and instrumented for carotid artery pressure and electromagnetic femoral artery blood flow measurement. One group acted as control while the other groups each received one of the following six agents by constant arterial infusion (dose in μg/min): A (200), nitroprusside (NP, 4.2), acetylcholine (100), PGE1(1.9), PGE2(1.7), and PGI2(1.7). Each agent reduced peripheral vascular resistance to a similar extent (at least twofold). Densitometric mRNA/18S levels for vascular endothelial growth factor (VEGF) were increased 50% by NP and acetylcholine, were unaffected by PGE1and PGE2, and were reduced 40% by PGI2. For basic fibroblast growth factor, only PGI2had any effect, reducing mRNA/18S ∼25%. For transforming growth factor-β1, A, NP, and PGE1led to reduced mRNA/18S, whereas PGE2slightly increased mRNA/18S. For the principal putative angiogenic growth factor, VEGF, these data suggest that naturally secreted vasodilators in contracting skeletal muscle could be involved in regulation of gene expression, namely, nitric oxide in a positive and PGI2in a negative direction.

Curran-Everett, Douglas, Yiming Zhang, M. Douglas Jones, Jr., and Richard H. Jones.An improved statistical methodology to estimate and analyze impedances and transfer functions. J. Appl. Physiol.83: 2146–2157, 1997.—Estimating the mathematical relationship between pulsatile time series (e.g., pressure and flow) is an effective technique for studying dynamic systems. The frequency-domain relationship between time series, often calculated as an impedance (pressure/flow), is known more generally as a frequency-response or transfer function (output/input). Current statistical methods for transfer function analysis 1) assume erroneously that repeated observations on a subject are independent,2) have limited statistical value and power, or 3) are restricted to use in single subjects rather than in an entire sample. This paper develops a regression model for transfer function analysis that corrects each of these deficiencies. Spectral densities of the input and output time series and the cross-spectral density between them are first estimated from discrete Fourier transforms and then used to obtain regression estimates of the transfer function. Statistical comparisons of the transfer function estimates use a test statistic that is distributed as χ2. Confidence intervals for amplitude and phase can also be calculated. By correctly modeling repeated observations on each subject, this improved statistical approach to transfer function estimation and analysis permits the simultaneous analysis of data from all subjects in a sample, improves the power of the transfer function model, and has broad relevance to the study of dynamic physiological systems.

Clark, Justin S., Yuxiang J. Lin, Michael J. Criddle, Antonio G. Cutillo, Adelbert H. Bigler, Fred L. Farr, and Attilio D. Renzetti, Jr.Cardiac output and mixed venous oxygen content measurements by a tracer bolus method: theory. J. Appl. Physiol.83(3): 884–896, 1997.—We present a bolus method of inert-gas delivery to the lungs that facilitates application of multiple inert gases and the multiple inert-gas-exchange technique (MIGET) model to noninvasive measurements of cardiac output (CO) and central mixed venous oxygen content(Cv¯O2).Reduction in recirculation error is made possible by 1) replacement of sinusoidal input functions with impulse inputs and2) replacement of steady-state analyses with transient analyses. Recirculation error reduction increases the inert-gas selection to include common gases without unusually high (and difficult to find) tissue-to-blood partition coefficients for maximizing the systemic filtering efficiency. This paper also presents a practical method for determining the recirculation contributions to inert expired profiles in animals and determining their specific contributions to errors in the calculations of CO andCv¯O2from simulations applied to published ventilation-perfusion ratio (V˙/Q˙) profiles. Recirculation errors from common gases were found to be reducible to the order of 5% or less for both CO andCv¯O2,whereas simulation studies indicate that measurement bias contributions from recirculation, V˙/Q˙ mismatch, and the V˙/Q˙ extraction process can be limited to 15% for subjects with severeV˙/Q˙ mismatch and high inspired oxygen fraction levels. These studies demonstrate a decreasing influence of V˙/Q˙ mismatch on parameter extraction bias as the number of inert gases are increased. However, the influence of measurement uncertainty on parameter extraction error limits improvement to six gases.

Mijailovich, Srboljub, Steven Treppo, and José G. Venegas.Effects of lung motion and tracer kinetics corrections on PET imaging of pulmonary function. J. Appl. Physiol.82(4): 1154–1162, 1997.—A method to assess the three-dimensional distribution of alveolar ventilation-perfusion ratio (V˙a/Q˙) by imaging the lungs with positron emission tomography (PET) during a constant-rate intravenous infusion of 13NN-labeled saline solution was developed by C. G. Rhodes, S. O. Valind, L. H. Brudin, P. E. Wollmer, T. Jones, P. D. Buckingham, and J. M. B. Hughes (J. Appl. Physiol.66: 1896–1904 and 1905–1913, 1989). We have modified this methodology to obtain high-resolution, low-noise PET images of local V˙a/Q˙where lung motion artifact was eliminated by respiratory gating of image collection. In addition, we have refined and implemented the methods to assess local alveolar ventilation by imaging the washout of equilibrated 13NN and local perfusion by imaging the distribution of an intravenous bolus of13NN-labeled saline solution during apnea. This paper experimentally evaluates the effect of the implemented modifications in mechanically ventilated and anesthetized dogs. We found that the lack of gating had no significant effect on the average recoveredV˙a/Q˙, but the spatial heterogeneity [pixel-by-pixel coefficient of variation squared (CV2) = SD2/mean2] was underestimated by 14%. The lack of gating during the washout underestimated the average specific ventilation by 11% and decreased the corresponding CV2by 50%.

Specific muscle training and chronic contractile measurements are difficult in rodents, especially in the mouse. The primary reason for this is the lack of a means for stimulating the motor nerve that does not damage the nerve and that permits reproducible measurements of contractility. In this paper, we describe procedures for the construction and implantation of a stimulating nerve cuff for use on the mouse common peroneal nerve. We demonstrate that nerve cuff implantation success rates can be high (i.e., 75–93%), as determined from measurements of maximal isometric torque produced by the anterior crural muscles. Isometric torque production is not adversely affected by the nerve cuff because the torque produced matches that observed in our established percutaneous stimulation model. We also demonstrate that use of the nerve cuff for stimulation is compatible with electromyographic measurements made on the tibialis anterior muscle, with no sign of stimulation artifact in the electromyographic signal.

Few commercial products are available for investigators who wish to monitor multiple physiological and behavioral variables in unrestrained subjects. When telemetry is not practical, e.g., in studies of at-sea diving physiology, one of the only options is to design and build a custom data-logging instrument. This paper describes how a data logger was developed for the successful long-term monitoring of dive depth, swim speed, heart rate, water temperature, and multiple body temperatures from free-ranging northern elephant seals. The task was facilitated by using a commercially available single-board computer designed specifically for portable multichannel data acquisition and, where possible, off-the-shelf sensors/transducers available with integrated signal-conditioning circuits. A smaller data logger for monitoring the electrocardiogram, body temperature, and dive behavior of double-crested cormorants is also described to illustrate the flexibility and simplicity of this approach. Although it is customized for diving animals, with incorporation of the appropriate sensors the basic design should be applicable to studies of comparative, environmental, or exercise physiology involving most medium-to-large animals, including humans.

Two near-infrared spectroscopy (NIRS) methods are available for measuring changes (Δ) in total cerebral hemoglobin concentration (CHC): 1) a continuous measurement of the changes in total hemoglobin concentration (Δ[Hb]tot) and 2) the difference between two absolute measurements of CHC, each derived from a small, controlled change in inspired O2fraction. This paper investigates the internal consistency of these two methods by using an experimental and theoretical comparison. NIRS was used to measure [Hb]totin five newborn piglets before and after a change in arterialPCO2. Δ[Hb]totdemonstrated a low coefficient of variation of 2.8 ± 2.8 (SD) % which allowed changes in CO2-cerebral blood volume reactivity to be clearly discriminated. However, a high coefficient of variation of 22.8 ± 3.5% on the ΔCHC measurements obscured any CO2reactivity changes. A theoretical analysis demonstrates the effects of optical pathlength, background absorption, scatter, and blood vessel diameter on both methods. For more accurate monitoring of CHC, individual measurements of optical pathlength and more accurate pulse oximetry are required.

Early in spaceflight, an apparently paradoxical condition occurs in which, despite an externally visible headward fluid shift, measured central venous pressure is lower but stroke volume and cardiac output are higher, and heart rate is unchanged from reference measurements made before flight. This paper presents a set of studies in which a simple three-compartment, steady-state model of cardiovascular function is used, providing insight into the contributions made by the major mechanisms that could be responsible for these events. On the basis of these studies, we conclude that, during weightless spaceflight, the chest relaxes with a concomitant shape change that increases the volume of the closed chest cavity. This leads to a decrease in intrapleural pressure, ultimately causing a shift of blood into the vessels of the chest, increasing the transmural filling pressure of the heart, and decreasing the central venous pressure. The increase in the transmural filling pressure of the heart is responsible, through a Starling-type mechanism, for the observed increases in heart size, left ventricular end-diastolic volume, stroke volume, and cardiac output.

To investigate the temporal relationships of mediator release and physiological changes during the early response to allergen, we challenged allergic individuals intranasally with antigen and followed their responses. This was done by using small filter paper disks to challenge one nostril and collect secretions from both the challenged and the contralateral nostril, thus enabling us to evaluate the nasonasal reflex. There was a significant increase in sneezing after allergen challenge that peaked within 2 min and returned to baseline. The weights of nasal secretions as well as nasal symptoms increased immediately and remained significantly elevated for 20 min in both nostrils. Nasal airway resistance increased slowly, reaching its peak at ∼6 min after challenge on the ipsilateral side, but it did not change on the contralateral side. Histamine levels peaked 30 s after removal of the allergen disk on the side of challenge, whereas albumin levels peaked after those of histamine. Lactoferrin paralleled the increase in secretion weights and occurred in both nostrils. Increasing doses of antigen produced dose-dependent increases in all parameters, whereas control challenges produced no response. These studies describe a human model for the evaluation of the allergic response that is capable of simultaneously measuring mediator release and the physiological response, including the nasonasal reflex. This model should prove useful in studying the mechanism of allergic rhinitis in humans.

The following are the abstracts of the articles discussed in the subsequent letter:Huang, Yuh-Chin T., Aneysa C. Sane, Steven G. Simonson, Thomas A. Fawcett, Richard E. Moon, Philip J. Fracica, Margaret G. Menache, Claude A. Piantadosi, and Stephen L. Young.Artificial surfactant attenuates hyperoxic lung injury in primates. I. Physiology and biochemistry. J. Appl. Physiol.78(5): 1816–1822, 1995.—Prolonged exposure to O2causes diffuse alveolar damage and surfactant dysfunction that contribute to the pathophysiology of hyperoxic lung injury. We hypothesized that exogenous surfactant would improve lung function during O2exposure in primates. Sixteen healthy male baboons (10–15 kg) were anesthetized and mechanically ventilated for 96 h. The animals received either 100% O2(n= 6) or 100% O2plus aerosolized artificial surfactant (Exosurf; n= 5). A third group of animals (n= 5) was ventilated with an inspired fraction of O2of 0.21 to control for the effects of sedation and mechanical ventilation. Hemodynamic parameters were obtained every 12 h, and ventilation-perfusion distribution (V˙A/Q˙) was measured daily using a multiple inert-gas elimination technique. Positive end-expiratory pressure was kept at 2.5 cmH2O and was intermittently raised to 10 cmH2O for 30 min to obtain additional measurements ofV˙A/Q˙. After the experiments, lungs were obtained for biochemical and histological assessment of injury. O2exposures altered hemodynamics, progressively worsenedV˙A/Q˙, altered lung phospholipid composition, and produced severe lung edema. Artificial surfactant therapy significantly increased disaturated phosphatidylcholine in lavage fluid and improved intrapulmonary shunt, arterial Po2, and lung edema. Surfactant also enhanced the shunt-reducing effect of positive end-expiratory pressure. We conclude that an aerosolized protein-free surfactant decreased the progression of pulmonary O2toxicity in baboons.Piantadosi, Claude A., Philip J. Fracica, Francis G. Duhaylongsod, Y.-C. T. Huang, Karen E. Welty-Wolf, James D. Crapo, and Stephen L. Young.Artificial surfactant attenuates hyperoxic lung injury in primates. II. Morphometric analysis. J. Appl. Physiol.78(5): 1823–1831, 1995.—Diffuse lung injury from hyperoxia is accompanied by low compliance and hypoxemia with disruption of endothelial and alveolar epithelial cell layers. Because both function and content of surfactant in diffuse lung injury decrease in animals and in humans, changes in the extent of injury during continuous hyperoxia were evaluated after treatments with a protein-free surfactant in primates. Ten baboons were ventilated with 100% O2for 96 h and five were intermittently given an aerosol of an artificial surfactant (Exosurf). Physiological and biochemical measurements of the effects of the surfactant treatment are presented in a companion paper (Y.-C. T. Huang, A. C. Sane, S. G. Simonson, T. A. Fawcett, R. E. Moon, P. J. Fracica, M. G. Menache, C. A. Piantadosi, and S. L. Young. J. Appl. Physiol.78: 1823–1829, 1995.) After O2exposures, lungs were fixed and processed for electron microscopy. The cellular responses to O2included epithelial and endothelial cell injuries, interstitial edema, and inflammation. Morphometry was used to quantitate changes in lungs of animals treated with the artificial surfactant during O2exposure and to compare them with the untreated animals. The surfactant decreased neutrophil accumulation, increased fibroblast proliferation, and decreased changes in the volume of type I epithelial cells. Surfactant-treated animals also demonstrated better preservation of endothelial cell integrity. These responses indicate ameliorating effects of the surfactant on the pulmonary response to hyperoxia, including protection against epithelial and endothelial cell destruction. Significant interstitial inflammation and fibroblast proliferation remained, however, in surfactant-treated lungs exposed to continuous hyperoxia.