bluuebunny/crossref_metadata_2025 huggingface dataset:
Partitioning of lung tissue response and inhomogeneous airway constriction at the airway opening
Authors: Suki Béla , Yuan Huichin , Zhang Qin , Lutchen Kenneth R.
Published: December 2017

Suki, Béla, Huichin Yuan, Qin Zhang, and Kenneth R. Lutchen. Partitioning of lung tissue response and inhomogeneous airway constriction at the airway opening. J. Appl. Physiol. 82(4): 1349–1359, 1997.—During a bronchial challenge, much of the observed response of lung tissues is an artifactual consequence of inhomogeneous airway constriction. Inhomogeneities, in the sense of time constant inequalities, are an inherently linear phenomenon. Conversely, if lung tissues respond to a bronchoagonist, they become more nonlinear. On the basis of these distinct responses, we present an approach to separate real tissue changes from airway inhomogeneities. We developed a lung model that includes airway inhomogeneities in the form of a continuous distribution of airway resistances and nonlinear viscoelastic tissues. Because time domain data are dominated by nonlinearities, whereas frequency domain data are most sensitive to inhomogeneities, we apply a combined time-frequency domain identification scheme. This model was tested with simulated data from a morphometrically based airway model mimicking gross peripheral airway inhomogeneities and shown capable of recovering all tissue parameters to within 15% error. Application to our previously measured data suggests that in dogs during histamine infusion 1) the distribution of airway resistances increases widely and 2) lung tissues do respond but less so than previously reported. This approach, then, is unique in its ability to differentiate between airway and tissue responses to an agonist from a single broadband measurement made at the airway opening.
Twenty-year follow-up of aerobic power and body composition of older track athletes
Authors: Pollock Michael L. , Mengelkoch Larry J. , Graves James E. , Lowenthal David T. , Limacher Marian C. , Foster Carl , Wilmore Jack H.
Published: December 2017

Pollock, Michael L., Larry J. Mengelkoch, James E. Graves, David T. Lowenthal, Marian C. Limacher, Carl Foster, and Jack H. Wilmore. Twenty-year follow-up of aerobic power and body composition of older track athletes. J. Appl. Physiol. 82(5): 1508–1516, 1997.—The purpose was to determine the aerobic power (maximal oxygen uptake) and body composition of older track athletes after a 20-yr follow-up (T3). At 20 yr, 21 subjects [mean ages: 50.5 ± 8.5 yr at initial evaluation (T1), 60.2 ± 8.8 yr at 10-yr follow-up (T2), and 70.4 ± 8.8 yr at 20-yr follow-up (T3)] were divided into three intensity groups: high (H; remained elite; n = 9); moderate (M; continued frequent moderate-to-rigorous endurance training; n = 10); and low (L; greatly reduced training; n = 2). All groups decreased in maximal oxygen uptake at each testing point (H, 8 and 15%; M, 13 and 14%; and L, 18 and 34% from T1 to T2 and T2 to T3, respectively). Maximal heart rate showed a linear decrease of ∼5–7 beats ⋅ min−1⋅ decade−1and was independent of training status. Body weight remained stable for the H and M groups and percent fat increased ∼2–2.5%/decade. Although fat-free weight decreased at each testing point, there was a trend for those who began weight-training exercise to better maintain it. Cross-sectional analysis at T3 showed that leg strength and bone mineral density were generally maintained from age 60 to 89 yr. Those who performed weight training had a greater arm region bone mineral density than those who did not. These longitudinal data show that the physiological capacities of older athletes are reduced despite continued vigorous endurance exercise over a 20-yr period (∼8–15%/decade). Changes in body composition appeared to be less than those shown for the healthy sedentary population and were related to changes in training habits.
A permanent prosthesis for converting in situ muscle contractions into hydraulic power for cardiac assist
Authors: Trumble Dennis R. , Magovern James A.
Published: December 2017

Trumble, Dennis R., and James A. Magovern. A permanent prosthesis for converting in situ muscle contractions into hydraulic power for cardiac assist. J. Appl. Physiol. 82(5): 1704–1711, 1997.—The key to utilizing muscle power for circulatory support lies with the development of a practical scheme by which contractile energy may be collected and efficiently delivered to the bloodstream. This work describes initial in vitro testing of a prototype muscle energy converter (MEC) designed to transform the power of in situ muscle contractions into hydraulic form. The MEC resembles a simple piston pump and is designed for implant beneath the humeral insertion of the latissimus dorsi muscle. Bench tests were conducted to measure component function and to characterize device performance under various hydraulic loads. Under simulated muscle-pull conditions, MEC energy transfer capacity was found to be 170 mJ/stroke while operating at peak efficiencies (i.e., >98% of input power converted into hydraulic energy and preload work). Transfer efficiencies dropped from 96 to 38% as mean generated pressures increased from 23 to 36 N/cm2due to metal bellows flexion. These results demonstrate that a significant amount of contractile energy can be efficiently transformed to hydraulic power via this mechanism.
Tone-entropy analysis on cardiac recovery after dynamic exercise
Authors: Oida Eiichi , Moritani Toshio , Yamori Yukio
Published: December 2017

Oida, Eiichi, Toshio Moritani, and Yukio Yamori.Tone-entropy analysis on cardiac recovery after dynamic exercise. J. Appl. Physiol. 82(6): 1794–1801, 1997.—Autonomic controls on heart rate variability have been investigated; however, sympathovagal interactive modulations remain unexplored. The purpose of this study is to present a new method, tone-entropy analysis (T-E analysis) of heart period fluctuations, and to make clear an intensive cooperation of autonomic networks in heart recovery. On the basis of evidence obtained in animal experiments, we hypothesized that heart periods are lengthened or shortened beat to beat by assumed physiological mediators: accelerator and inhibitor. Their operations were evaluated through a normalized successive variation of the period, that is, the percentage index (PI). The process was described through PI distributions by using two indexes, tone and entropy, standard values of which were obtained through pharmacological autonomic blockade experiment. T-E analysis was applied to heart recovery (70 min) after dynamic exercise by 12 female athletes. Interactive autonomic modulations were expressed by a curved path in tone-entropy space. Results suggested that heart rate decay proceeds not by withdrawal of one pathway but by increasing activity of both pathways as vagosympathetic balance inclines slightly but significantly to the vagus division in the course of recovery. The process was examined through Fourier spectral analysis as well.
Muscle chemoreflex increases renal sympathetic nerve activity during exercise
Authors: O’Hagan Kathleen P. , Casey Susan M. , Clifford Philip S.
Published: December 2017

O’Hagan, Kathleen P., Susan M. Casey, and Philip S. Clifford. Muscle chemoreflex increases renal sympathetic nerve activity during exercise. J. Appl. Physiol. 82(6): 1818–1825, 1997.—Activation of the muscle chemoreflex increases sympathetic drive to skeletal muscle in humans. This study investigated whether activation of the muscle chemoreflex augments the renal sympathetic nerve activity (RSNA) response to dynamic exercise in rabbits. The muscle chemoreflex was evoked by hindlimb ischemia during exercise on a motorized treadmill. Seven New Zealand White rabbits performed a nonischemic control protocol and a hindlimb ischemia protocol in which terminal aortic blood flow (Q˙ta) was reduced to 51 ± 2% of preocclusion Q˙ta by partial aortic occlusion after 1.5 min of exercise. Mean arterial pressure (MAP), heart rate, RSNA andQ˙ta increased in response to exercise and were similar between trials during the first 1.5 min of exercise. In the control trial, Q˙ta, MAP, and RSNA were stable at an elevated level through an additional 3.5 min of exercise. Hindlimb ischemia produced a potent pressor response that plateaued after 2.5 min (Δ+17 ± 4 mmHg, where Δ designates change). RSNA began to increase after 1.5 min of ischemic exercise and was significantly elevated relative to preocclusion RSNA at 2.5 (Δ+25 ± 9%) and 3.5 (Δ+47 ± 12%) min of occlusion. These results suggest that the muscle chemoreflex can augment sympathoexcitatory drive to the kidney during dynamic exercise.
Blood volume and cardiac index in rats after exchange transfusion with hemoglobin-based oxygen carriers
Authors: Migita Russell , Gonzales Armando , Gonzales Maria L. , Vandegriff Kim D. , Winslow Robert M.
Published: December 2017

Migita, Russell, Armando Gonzales, Maria L. Gonzales, Kim D. Vandegriff, and Robert M. Winslow. Blood volume and cardiac index in rats after exchange transfusion with hemoglobin-based oxygen carriers. J. Appl. Physiol. 82(6): 1995–2002, 1997.—We have measured plasma volume and cardiac index in rats after 50% isovolemic exchange transfusion with human hemoglobin cross-linked between the α-chains with bis(3,5-dibromosalicyl)fumarate (ααHb) and with bovine hemoglobin modified with polyethylene glycol (PEGHb). ααHb and PEGHb differ in colloid osmotic pressure (23.4 and 118.0 Torr, respectively), oxygen affinity (oxygen half-saturation pressure of hemoglobin = 30.0 and 10.2 Torr, respectively), viscosity (1.00 and 3.39 cP, respectively), and molecular weight (64,400 and 105,000, respectively). Plasma volume was measured by Evans blue dye dilution modified for interference by plasma hemoglobin. Blood volumes in PEGHb-treated animals were significantly elevated (74.0 ± 3.5 ml/kg) compared with animals treated with ααHb (49.0 ± 1.2 ml/kg) or Ringer lactate (48.0 ± 2.0 ml/kg) or with controls (58.2 ± 1.9 ml/kg). Heart rate reduction after ααHb exchange is opposite to that expected with blood volume contraction, suggesting that ααHb may have a direct myocardial depressant action. The apparently slow elimination of PEGHb during the 2 h after its injection is a consequence of plasma volume expansion: when absolute hemoglobin (concentration × plasma volume) is compared for PEGHb and ααHb, no difference in their elimination rates is found. These studies emphasize the need to understand blood volume regulation when the effects of cell-free hemoglobin on hemodynamic measurements are evaluated.
Pathophysiology of neonatal lung injury induced by monoclonal antibody to surfactant protein B
Authors: Grossmann Gertie , Suzuki Yasuhiro , Robertson Bengt , Kobayashi Tsutomu , Berggren Per , Li Wen-Zhi , Song Guo-Wei , Sun Bo
Published: December 2017

Grossmann, Gertie, Yasuhiro Suzuki, Bengt Robertson, Tsutomu Kobayashi, Per Berggren, Wen-Zhi Li, Guo-Wei Song, and Bo Sun.Pathophysiology of neonatal lung injury induced by monoclonal antibody to surfactant protein B. J. Appl. Physiol. 82(6): 2003–2010, 1997.—Near-term newborn rabbits were exposed via the airways to a monoclonal antibody to surfactant protein B and ventilated for 0–120 min. Control animals received nonspecific rabbit or mouse immunoglobulin G, saline, or no material via the airways. Administration of the antibody at ≥40 mg/kg elicited an immediate, significant fall in lung-thorax compliance associated with progressive intra-alveolar edema and/or alveolar collapse and necrosis and desquamation of airway epithelium, and hyaline membranes. The vascular-to-alveolar leak of human albumin and human immunoglobulin G, injected intravenously at birth and determined in lung lavage fluid 60–120 min after instillation of the antibody, was 1.8% for the left lung, with no difference between the markers. The average leak in control animals ventilated for 120 min was <0.3% ( P < 0.05). Cytospin preparations of lung lavage fluid from animals exposed to the antibody showed significantly increased recruitment of neutrophilic granulocytes. The pathology and pathophysiology of neonatal lung injury induced by the monoclonal antibody to surfactant protein B probably reflect a combination of direct inactivation of surfactant and an inflammatory response triggered by the immune reaction.
A relationship between heat loss and sleepiness: effects of postural change and melatonin administration
Authors: Kräuchi Kurt , Cajochen Christian , Wirz-Justice Anna
Published: December 2017

Kräuchi, Kurt, Christian Cajochen, and Anna Wirz-Justice. A relationship between heat loss and sleepiness: effects of postural change and melatonin administration. J. Appl. Physiol. 83(1): 134–139, 1997.—Both the pineal hormone melatonin (Mel) and postural changes have thermoregulatory sequelae. The purpose of the study was to evaluate their relationship to subjective sleepiness. Eight healthy young men were investigated under the unmasking conditions of a constant routine protocol. Heart rate, rectal temperature (Tre), skin temperatures (foot, Tfo; and stomach), and subjective sleepiness ratings were continuously recorded from 1000 to 1700. Mel (5 mg po) was administered at 1300, a time when Mel should not phase shift the circadian system. Both the postural change at 1000 from upright to a supine position (lying down in bed) and Mel administration at 1300 reduced Treand increased Tfoin parallel with increased sleepiness. These findings suggest that under comfortable ambient temperature conditions, heat loss via the distal skin regions (e.g., feet) is a key mechanism for induction of sleepiness as core body temperature declines.
Acute and chronic effects of exercise on leptin levels in humans
Authors: Pérusse Louis , Collier Gregory , Gagnon Jacques , Leon Arthur S. , Rao D. C. , Skinner James S. , Wilmore Jack H. , Nadeau André , Zimmet Paul Z. , Bouchard Claude
Published: December 2017

Pérusse, Louis, Gregory Collier, Jacques Gagnon, Arthur S. Leon, D. C. Rao, James S. Skinner, Jack H. Wilmore, André Nadeau, Paul Z. Zimmet, and Claude Bouchard. Acute and chronic effects of exercise on leptin levels in humans. J. Appl. Physiol. 83(1): 5–10, 1997.—The acute (single bout of exercise) and chronic (exercise training) effects of exercise on plasma leptin were investigated in 97 sedentary adult men ( n = 51) and women ( n = 46) participating in the HERITAGE Family Study. Exercise training consisted of a standardized 20-wk endurance training program performed in the laboratory on a computer-controlled cycle ergometer. Maximal oxygen uptake, body composition assessed by hydrostatic weighing, and fasting insulin level were also measured before and after training. Pre- and posttraining blood samples were obtained before and after completion of a maximal exercise test on the cycle ergometer. Exercise training resulted in significant changes in maximal oxygen uptake (increase in both genders) and body compostion (reduction of fat mass in men and increase in fat-free mass in women). There were considerable interindividual differences in the leptin response to acute and chronic effects of exercise, some individuals showing either increase or reduction in leptin, others showing almost no change. On average, leptin levels were not acutely affected by exercise. After endurance training was completed, leptin levels decreased significantly in men (from 4.6 to 3.9 ng/ml; P = 0.004) but not in women. However, after the training-induced changes in body fat mass were accounted for, the effects of exercise training were no longer significant. Most of the variation observed in leptin levels after acute exercise or endurance training appears to be within the confidence intervals of the leptin assay. We conclude that there are no meaningful acute or chronic effects of exercise, independent of the amount of body fat, on leptin levels in humans.
Acutely administered melatonin reduces oxidative damage in lung and brain induced by hyperbaric oxygen
Authors: Pablos Marta I. , Reiter Russel J. , Chuang Jin-Ing , Ortiz Genaro G. , Guerrero Juan M. , Sewerynek Ewa , Agapito Maria T. , Melchiorri Daniela , Lawrence Richard , Deneke Susan M.
Published: December 2017

Pablos, Marta I., Russel J. Reiter, Jin-Ing Chuang, Genaro G. Ortiz, Juan M. Guerrero, Ewa Sewerynek, Maria T. Agapito, Daniela Melchiorri, Richard Lawrence, and Susan M. Deneke. Acutely administered melatonin reduces oxidative damage in lung and brain induced by hyperbaric oxygen. J. Appl. Physiol. 83(2): 354–358, 1997.—Hyperbaric oxygen exposure rapidly induces lipid peroxidation and cellular damage in a variety of organs. In this study, we demonstrate that the exposure of rats to 4 atmospheres of 100% oxygen for 90 min is associated with increased levels of lipid peroxidation products [malonaldehyde (MDA) and 4-hydroxyalkenals (4-HDA)] and with changes in the activities of two antioxidative enzymes [glutathione peroxidase (GPX) and glutathione reductase (GR)], as well as in the glutathione status in the lungs and in the brain. Products of lipid peroxidation increased after hyperbaric hyperoxia, both GPX and GR activities were decreased, and levels of total glutathione (reduced+oxidized) and glutathione disulfide (oxidized glutathione) increased in both lung and brain areas (cerebral cortex, hippocampus, hypothalamus, striatum, and cerebellum) but not in liver. When animals were injected with melatonin (10 mg/kg) immediately before the 90-min hyperbaric oxygen exposure, all measurements of oxidative damage were prevented and were similar to those in untreated control animals. Melatonin’s actions may be related to a variety of mechanisms, some of which remain to be identified, including its ability to directly scavenge free radicals and its induction of antioxidative enzymes via specific melatonin receptors.
Mechanism of the exercise hyperkalemia: an alternate hypothesis
Authors: Wasserman Karlman , Stringer William W. , Casaburi Richard , Zhang Yong-Yu
Published: December 2017

Wasserman, Karlman, William W. Stringer, Richard Casaburi, and Yong-Yu Zhang. Mechanism of the exercise hyperkalemia: an alternate hypothesis. J. Appl. Physiol. 83(2): 631–643, 1997.—A progressive hyperkalemia is observed as exercise intensity increases. The current most popular hypothesis for the hyperkalemia is that the Na+-K+pump cannot keep pace with the K+efflux from muscle during the depolarization-repolarization process of the sarcolemmal membrane during muscle contraction. In this report, we present data that suggest an alternate hypothesis to those previously described. Because phosphocreatine (PCr) is a highly dissociated acid and creatine is neutral at cell pH, the concentration of nondiffusible anions decreases, and an alkaline reaction takes place when PCr hydrolyzes. This creates a state of cation (K+) excess and H+ depletion in the cell. To examine the balance of K+ and H+ for exercising muscle during the early period of exercise when PCr changes most rapidly, catheters were inserted into the brachial artery and femoral vein (FV) in five healthy subjects who performed two 6-min cycle ergometer exercise tests at 40 and 85% of peak oxygen uptake. FV blood was sampled every 5 s during the first 2 min, then every 30 s for the remaining 4 min of exercise and the first 3 min of recovery, and then less frequently for the next 12 min. Arterial sampling was every 30 s during exercise and simultaneous with FV sampling during recovery. Arterial K+ concentration ([K+]) increase lagged FV [K+] increase. The hyperkalemia observed during early exercise results from K+ release from skeletal muscle. FV [K+] increased by 5 s of the start of exercise and followed the rate of H+ loss from the FV blood for the first 30 s of exercise. FV lactate and Na+ kinetics differed from K+ kinetics during exercise and recovery. As predicted from the PCr hydrolysis reaction, the exercising limb took up H+ and released K+ at the start of exercise (first 30 s) at both exercise intensities, resulting in a FV metabolic alkalosis. K+ release was essentially complete by 3 min, the time at which oxygen uptake (and, presumably, PCr) reached its asymptote. These findings lead us to hypothesize that the early K+release by the cell takes place with H+ exchange and that the major mechanism for the exercise hyperkalemia is the reduction in nondiffusible intracellular anions in the myocyte as PCr hydrolyzes.
Effects of edema on small airway narrowing
Authors: Wagner Elizabeth M.
Published: December 2017

Wagner, Elizabeth M. Effects of edema on small airway narrowing. J. Appl. Physiol. 83(3): 784–791, 1997.—Numerous mediators of inflammation have been demonstrated to cause airway microvascular fluid and protein extravasation. That fluid extravasation results in airway wall edema leading to airway narrowing and enhanced reactivity has not been confirmed. In anesthetized, ventilated sheep ( n = 30), airway vascular fluid extravasation was induced by infusing bradykinin (10−6 M) through a cannulated, blood-perfused bronchial artery. Airway wall edema and luminal narrowing were determined morphometrically. Airway reactivity to methacholine (MCh; 10 μg/ml, intrabronchial artery) was determined by measuring conducting airway resistance (Raw) by forced oscillation. Raw measurements were made and lung lobes were excised and quick frozen before or after a 1-h bradykinin infusion. In 10 airways per lobe (range 0.2- to 2.0-mm relaxed diameter), wall area occupied 32 ± 2% (SE) of the total normalized airway area ( n = 9). Bradykinin infusion increased wall area to 42 ± 5% ( P = 0.02); luminal area decreased by <5%; and smooth muscle perimeter, a measure of smooth muscle constriction, was not altered ( n = 5). Raw showed no change from baseline (1.4 ± 0.4 cmH2O ⋅ l−1 ⋅ s) after bradykinin infusion ( n = 10). During MCh challenge, Raw increased by 3.2 ± 04 cmH2O ⋅ l−1 ⋅ s, and this change did not differ after administration of bradykinin. MCh challenge caused similar decreases in smooth muscle perimeter (10%) and luminal area (72 vs. 68%) before and after bradykinin infusion. However, the time constant of recovery of Raw from MCh constriction was increased from control (40 ± 3 s) to 57 ± 10 s after bradykinin infusion ( P = 0.03). When lung lobes were excised at the same time after MCh challenge was terminated ( n = 5), luminal area was greater before bradykinin infusion than after (86 vs. 78%; P = 0.007), as was smooth muscle perimeter. The results of this study demonstrate that airway wall edema limits relaxation after induced constriction rather than enhancing constriction.
Exercise-associated hyponatremia in Alaskan sled dogs: urinary and hormonal responses
Authors: Hinchcliff K. W. , Reinhart G. A. , Burr J. R. , Swenson R. A.
Published: December 2017

Hinchcliff, K. W., G. A. Reinhart, J. R. Burr, R. A. Swenson. Exercise-associated hyponatremia in Alaskan sled dogs: urinary and hormonal responses. J. Appl. Physiol. 83(3): 824–829, 1997.—Exercise-associated hyponatremia occurs in horses and humans, both species that sweat, and in sled dogs, which do not sweat. To investigate the mechanism of exercise-associated hyponatremia in sled dogs, we measured water turnover, serum electrolyte concentrations and osmolality, plasma renal hormone concentrations, and urine composition of 12 fit Alaskan sled dogs before, during, and after a 490-km sled dog race (Ex group). Water turnover and serum electrolyte concentrations were measured in six similarly fit dogs that did not run (Sed group). Water turnover was significantly larger ( P < 0.001) in Ex [190 ± 19 (SD) ml ⋅ kg−1⋅ day−1] than in Sed dogs (51 ± 13 ml ⋅ kg−1⋅ day−1). There were significant ( P < 0.001) decreases in serum sodium concentration (from 148.6 ± 2.8 to 139.7 ± 1.9 mmol/l) and osmolality (from 306 ± 9 to 296 ± 5 mosmol/kgH2O) of Ex, but not Sed, dogs during the race. Plasma concentrations of arginine vasopressin decreased, whereas aldosterone and plasma renin activity increased significantly ( P < 0.01) during the race. Urine osmolality was unchanged, whereas urine sodium, potassium, and chloride concentrations decreased significantly ( P < 0.05) and urine urea concentration increased ( P = 0.06). These results demonstrate increased water turnover associated with hyponatremia and renal sodium conservation with maintained high urine osmolality in exercising Alaskan sled dogs.
Autonomic and behavioral thermoregulation in guinea pigs during postnatal maturation
Authors: Fewell James E. , Kang Maria , Eliason Heather L.
Published: December 2017

Fewell, James E., Maria Kang, and Heather L. Eliason.Autonomic and behavioral thermoregulation in guinea pigs during postnatal maturation. J. Appl. Physiol. 83(3): 830–836, 1997.—Serial experiments were carried out on seven chronically instrumented Hartley-strain guinea pigs at 1, 3, and 5 wk of age to define their autonomic and behavioral thermoregulatory profiles and to test the hypothesis that they have the mechanisms in place shortly after birth that allow them to optimize their energy expenditure for thermoregulation by selecting a thermal environment that requires the lowest metabolic oxygen requirements. Each animal was studied in both a thermocline to determine selected ambient temperature and in a metabolic chamber to determine the thermoregulatory response to forced changes in ambient temperature. In the thermocline, the guinea pigs at all postnatal ages selected an ambient temperature that placed core temperature, oxygen consumption, thermal conductance, heart rate, and respiratory rate at levels comparable to those observed at ambient temperatures in which minimal oxygen consumption occurred in the metabolic chamber. Thus our experiments provide evidence that guinea pigs have the neurophysiological mechanisms in place shortly after birth that allow them to optimize their energy expenditure for thermoregulation by selecting a thermal environment that corresponds to the lowest metabolic oxygen requirements.
Cardiac output and mixed venous oxygen content measurements by a tracer bolus method: theory
Authors: Clark Justin S. , Lin Yuxiang J. , Criddle Michael J. , Cutillo Antonio G. , Bigler Adelbert H. , Farr Fred L. , Renzetti Attilio D.
Published: December 2017

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[Formula: see text]Reduction in recirculation error is made possible by 1) replacement of sinusoidal input functions with impulse inputs and 2) 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 and[Formula: see text] from 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 and[Formula: see text] 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.
Gut and liver fat metabolism in depancreatized dogs: effects of exercise and acute insulin infusion
Authors: Namdaran Kiarash , Bracy Deanna P. , Lacy D. Brooks , Johnson Janice L. , Bupp Jennifer L. , Wasserman David H.
Published: December 2017

Namdaran, Kiarash, Deanna P. Bracy, D. Brooks Lacy, Janice L. Johnson, Jennifer L. Bupp, and David H. Wasserman. Gut and liver fat metabolism in depancreatized dogs: effects of exercise and acute insulin infusion. J. Appl. Physiol. 83(4): 1339–1347, 1997.—Excessive circulating fat levels are a defining feature of poor metabolic control in diabetes. Splanchnic adipose tissue is a source of free fatty acids (FFA), and the liver is a key site of FFA utilization and the sole source of ketones. Despite the role of splanchnic tissues in fat metabolism, little is known about how these tissues respond to diabetes under divergent metabolic conditions. Therefore, splanchnic fat metabolism was studied in poorly controlled diabetes under two conditions. First, it was studied during exercise, a stimulus that enhances FFA flux. Second, it was studied while insulin was being acutely infused to achieve levels normally present during exercise, a treatment that may be expected to inhibit lipolysis. For this purpose, liver and gut arteriovenous differences were used during rest and 2.5 h of treadmill exercise in insulin-deficient ( n = 6) and acutely insulin-infused ( n = 4) depancreatized (PX) dogs. The data show that 1) exercise, in insulin-deficient PX dogs, leads to an increase in net FFA release from mesenteric fat that is equal in magnitude to the response in nondiabetic dogs; 2) net hepatic fractional FFA extraction is increased twofold during exercise in both insulin-deficient PX dogs and nondiabetic control dogs; 3) during exercise, ∼40 and 75% of the FFA consumed by the liver is effectively transferred from fat stores mobilized from splanchnic adipose tissue in insulin-deficient PX and nondiabetic dogs, respectively; 4) hepatic ketogenic efficiency is elevated during rest three- to fourfold in insulin-deficient PX dogs compared with nondiabetic control dogs and remains elevated during exercise; and 5) surprisingly, acute insulin replacement is ineffective in normalizing net gut, hepatic, or splanchnic FFA or ketone body balances in PX dogs.
rG-CSF reduces endotoxemia and improves survival duringE. colipneumonia
Authors: Freeman Bradley D. , Quezado Zenaide , Zeni Fabrice , Natanson Charles , Danner Robert L. , Banks Steven , Quezado Marcello , Fitz Yvonne , Bacher John , Eichacker Peter Q.
Published: December 2017

Freeman, Bradley D., Zenaide Quezado, Fabrice Zeni, Charles Natanson, Robert L. Danner, Steven Banks, Marcello Quezado, Yvonne Fitz, John Bacher, and Peter Q. Eichacker. rG-CSF reduces endotoxemia and improves survival during E. coli pneumonia. J. Appl. Physiol. 83(5): 1467–1475, 1997.—We investigated the effects of recombinant granulocyte colony-stimulating factor (rG-CSF) during canine bacterial pneumonia. Beagles with chronic tracheostomies received daily subcutaneous rG-CSF (5 μg/kg body wt) or placebo for 14 days, beginning 9 days before intrabronchial inoculation with E. coli. Animals received antibiotics and fluid support; a subset received humidified oxygen (fractional inspired O20.40). Compared with controls, rG-CSF increased circulating neutrophil counts (57.4 vs. 11.0 × 103/mm3, day 1 after infection; P = 0.0001), decreased plasma endotoxin (7.5 vs. 1.1 EU/ml at 8 h; P< 0.01) and serum tumor necrosis factor-α (3,402 vs. 729 pg/ml at 2 h; P = 0.01) levels, and prolonged survival (relative risk of death = 0.45, 95% confidence interval 0.21–0.97; P = 0.038). Also, rG-CSF attenuated sepsis-associated myocardial dysfunction ( P < 0.001). rG-CSF had no effect on pulmonary function or on blood and lung bacteria counts (all P = not significant). Other animals challenged with endotoxin (4 mg/kg iv) after similar treatment with rG-CSF had lower serum endotoxin levels (7.62 vs. 5.81 log EU/ml at 6 h; P < 0.01) and less cardiovascular dysfunction ( P < 0.05 to < 0.002) but similar tumor necrosis factor-α levels ( P = not significant) compared with controls. Thus prophylactic rG-CSF sufficient to increase circulating neutrophils during bacterial pneumonia may improve cardiovascular function and survival by mechanisms that in part enhance the clearance of bacterial toxins but do not improve lung function.
Inhibition of surfactant function by copper-zinc superoxide dismutase (CuZn-SOD)
Authors: Haddad Imad Y. , Nieves-Cruz Bedford , Matalon Sadis
Published: December 2017

Haddad, Imad Y., Bedford Nieves-Cruz, and Sadis Matalon.Inhibition of surfactant function by copper-zinc superoxide dismutase (CuZn-SOD). J. Appl. Physiol. 83(5): 1545–1550, 1997.—The efficacy of antioxidant enzymes to limit oxidant lung injury by instillation with surfactant mixtures in preterm infants with hyaline membrane disease is under investigation. However, there is concern that instillation of proteins in the alveolar space may inactivate pulmonary surfactant. We studied the effects of bovine copper-zinc superoxide dismutase (CuZn-SOD) on the biophysical properties of two distinct surfactant preparations. Incubation of calf lung surfactant extract (CLSE, 1 mg phospholipid/ml) and Exosurf (0.1 mg phospholipid/ml) with CuZn-SOD (1–10 mg/ml) prevented the fall of surface tension at minimal bubble radius (Tmin) to low values with dynamic compression in a pulsating bubble surfactometer. CuZn-SOD also enhanced the sensitivity to inactivation by albumin, normal human serum, and after treatment with peroxynitrite. The inhibitory effects of CuZn-SOD on CLSE, but not Exosurf, were abolished at high lipid concentrations (3 mg/ml) and after the addition of human surfactant protein A (by weight). We conclude that CuZn-SOD may interfere with the surface activity of surfactant mixtures, leading to decreased effectiveness of surfactant replacement therapy.
Influence of nicotine on the core temperature response to a novel environment in pregnant rats
Authors: Fewell James E. , Tang Patricia A.
Published: December 2017

Fewell, James E., and Patricia A. Tang. Influence of nicotine on the core temperature response to a novel environment in pregnant rats. J. Appl. Physiol.83(5): 1612–1616, 1997.—Exposure of a male or nonpregnant female rat to a novel environment, such as a simulated open field, induces a transient increase in core temperature, which is often called stress-induced hyperthermia. Pregnancy alters this response such that the core temperature index increases significantly during exposure to a simulated open field on day 10 but not on days 15 and 20 of gestation in rats. The present experiments were carried to investigate the effect of chronic administration of nicotine (0, 1, 2, 4, or 8 mg ⋅ kg−1 ⋅ 24 h−1 for 13–15 days) on the core temperature response to a simulated open field in chronically instrumented pregnant ( day 20 or 21 of gestation) and nonpregnant Sprague-Dawley rats. In nonpregnant rats, the core temperature index increased more during exposure to a simulated open field after chronic administration of nicotine at all doses than after chronic administration of vehicle; the core temperature response was not dependent on the dose of nicotine. In pregnant rats, significant increases in core temperature as well as in the core temperature index occurred only during exposure to a simulated open field after chronic administration of nicotine in doses of 2, 4, or 8 mg ⋅ kg−1 ⋅ 24 h−1; the core temperature response was dependent on the dose of nicotine. Our data provide evidence that chronic exposure to nicotine enhances the core temperature response to a simulated open field in nonpregnant rats and unmasks a maternal thermogenic response that is not seen to the same stimulus near term of pregnancy. The possible physiological consequences for the fetus are presently unknown and require investigation.
Prostaglandin production contributes to exercise-induced vasodilation in heart failure
Authors: Lang Chim C. , Chomsky Don B. , Butler Javed , Kapoor Shiv , Wilson John R.
Published: December 2017

Lang, Chim C., Don B. Chomsky, Javed Butler, Shiv Kapoor, and John R. Wilson. Prostaglandin production contributes to exercise-induced vasodilation in heart failure. J. Appl. Physiol. 83(6): 1933–1940, 1997.—Endothelial release of prostaglandins may contribute to exercise-induced skeletal muscle arteriolar vasodilation in patients with heart failure. To test this hypothesis, we examined the effect of indomethacin on leg circulation and metabolism in eight chronic heart failure patients, aged 55 ± 4 yr. Central hemodynamics and leg blood flow, determined by thermodilution, and leg metabolic parameters were measured during maximum treadmill exercise before and 2 h after oral administration of indomethacin (75 mg). Leg release of 6-ketoprostaglandin F1α was also measured. During control exercise, leg blood flow increased from 0.34 ± 0.03 to 1.99 ± 0.19 l/min ( P < 0.001), leg O2 consumption from 13.6 ± 1.8 to 164.5 ± 16.2 ml/min ( P < 0.001), and leg prostanoid release from 54.1 ± 8.5 to 267.4 ± 35.8 pg/min ( P < 0.001). Indomethacin suppressed release of prostaglandin F1α( P < 0.001) throughout exercise and decreased leg blood flow during exercise ( P < 0.05). This was associated with a corresponding decrease in leg O2 consumption ( P < 0.05) and a higher level of femoral venous lactate at peak exercise ( P < 0.01). These data suggest that release of vasodilatory prostaglandins contributes to skeletal muscle arteriolar vasodilation in patients with heart failure.
Effects of training and a single session of exercise on lipids and apolipoproteins in hypercholesterolemic men
Authors: Crouse Stephen F. , O’Brien Barbara C. , Grandjean Peter W. , Lowe Robert C. , Rohack J. James , Green John S.
Published: December 2017

Crouse, Stephen F., Barbara C. O’Brien, Peter W. Grandjean, Robert C. Lowe, J. James Rohack, and John S. Green. Effects of training and a single session of exercise on lipids and apolipoproteins in hypercholesterolemic men. J. Appl. Physiol. 83(6): 2019–2028, 1997.—To differentiate between transient (acute) and training (chronic) effects of exercise at two different intensities on blood lipids and apolipoproteins (apo), 26 hypercholesterolemic men (cholesterol = 258 mg/dl, age = 47 yr, weight = 81.9 kg) trained three times per week for 24 wk, 350 kcal/session at high (80% maximal O2uptake, n = 12) or moderate (50% maximal O2uptake, n = 14) intensity. Serum lipid and apolipoprotein (apo) concentrations (plasma volume adjusted) were measured before and immediately, 24, and 48 h after exercise on four different occasions corresponding to 0, 8, 16, and 24 wk of training. Data were analyzed using three-way repeated-measures multivariate analysis of variance followed by analysis of variance and Duncan’s procedures (α = 0.05). A transient 6% rise in low-density-lipoprotein cholesterol measured before training at the 24-h time point was no longer evident after training. Triglycerides fell and total cholesterol, high-density-lipoprotein cholesterol (HDL-C), HDL3-C, apo A-I, and apo B rose 24–48 h after exercise regardless of training or intensity. Total cholesterol, HDL3-C, apo A-I, and apo B were lower and HDL2-C was higher after training than before training. Thus exercise training and a single session of exercise exert distinct and interactive effects on lipids and apolipoproteins. These results support the practice of training at least every other day to obtain optimal exercise benefits.
Effects of head-down-tilt bed rest on cerebral hemodynamics during orthostatic stress
Authors: Zhang Rong , Zuckerman Julie H. , Pawelczyk James A. , Levine Benjamin D.
Published: December 2017

Zhang, Rong, Julie H. Zuckerman, James A. Pawelczyk, and Benjamin D. Levine. Effects of head-down-tilt bed rest on cerebral hemodynamics during orthostatic stress. J. Appl. Physiol. 83(6): 2139–2145, 1997.—Our aim was to determine whether the adaptation to simulated microgravity (μG) impairs regulation of cerebral blood flow (CBF) during orthostatic stress and contributes to orthostatic intolerance. Twelve healthy subjects (aged 24 ± 5 yr) underwent 2 wk of −6° head-down-tilt (HDT) bed rest to simulate hemodynamic changes that occur when humans are exposed to μG. CBF velocity in the middle cerebral artery (transcranial Doppler), blood pressure, cardiac output (acetylene rebreathing), and forearm blood flow were measured at each level of a ramped protocol of lower body negative pressure (LBNP; −15, −30, and −40 mmHg × 5 min, −50 mmHg × 3 min, then −10 mmHg every 3 min to presyncope) before and after bed rest. Orthostatic tolerance was assessed by using the cumulative stress index (CSI; mmHg × minutes) for the LBNP protocol. After bed rest, each individual’s orthostatic tolerance was reduced, with the group CSI decreased by 24% associated with greater decreases in cardiac output and greater increases in systemic vascular resistance at each level of LBNP. Before bed rest, mean CBF velocity decreased by 14, 10, and 45% at −40 mmHg, −50 mmHg, and maximal LBNP, respectively. After bed rest, mean velocity decreased by 16% at −30 mmHg and by 21, 35, and 39% at −40 mmHg, −50 mmHg, and maximal LBNP, respectively. Compared with pre-bed rest, post-bed-rest mean velocity was less by 11, 10, and 21% at −30, −40, and −50 mmHg, respectively. However, there was no significant difference at maximal LBNP. We conclude that cerebral autoregulation during orthostatic stress is impaired by adaptation to simulated μG as evidenced by an earlier and greater fall in CBF velocity during LBNP. We speculate that impairment of cerebral autoregulation may contribute to the reduced orthostatic tolerance after bed rest.
Cardiopulmonary effects of inhaled nitric oxide in normal dogs and during E. coli pneumonia and sepsis
Authors: Quezado Zenaide M. N. , Natanson Charles , Karzai Waheedullah , Danner Robert L. , Koev Cezar A. , Fitz Yvonne , Dolan Donald P. , Richmond Steven , Banks Steven M. , Wilson Laura , Eichacker Peter Q.
Published: December 2017

Quezado, Zenaide M. N., Charles Natanson, Waheedullah Karzai, Robert L. Danner, Cezar A. Koev, Yvonne Fitz, Donald P. Dolan, Steven Richmond, Steven M. Banks, Laura Wilson, and Peter Q. Eichacker.Cardiopulmonary effects of inhaled nitric oxide in normal dogs and during E. coli pneumonia and sepsis. J. Appl. Physiol. 84(1): 107–115, 1998.—We investigated the effect of inhaled nitric oxide (NO) at increasing fractional inspired O2concentrations ([Formula: see text]) on hemodynamic and pulmonary function during Escherichia coli pneumonia. Thirty-eight conscious, spontaneously breathing, tracheotomized 2-yr-old beagles had intrabronchial inoculation with either 0.75 or 1.5 × 1010 colony-forming units/kg of E. coli 0111:B4 (infected) or 0.9% saline (noninfected) in one or four pulmonary lobes. We found that neither the severity nor distribution (lobar vs. diffuse) of bacterial pneumonia altered the effects of NO. However, in infected animals, with increasing[Formula: see text] (0.08, 0.21, 0.50, and 0.85), NO (80 parts/million) progressively increased arterial[Formula: see text] [−0.3 ± 0.6, 3 ± 1, 13 ± 4, 10 ± 9 (mean ± SE) Torr, respectively] and decreased the mean arterial-alveolar O2 gradient (0.5 ± 0.3, 4 ± 2, −8 ± 7, −10 ± 9 Torr, respectively). In contrast, in noninfected animals, the effect of NO was significantly different and opposite; NO progressively decreased mean[Formula: see text] with increasing[Formula: see text] (2 ± 1, −5 ± 3, −2 ± 3, and −12 ± 5 Torr, respectively; P < 0.05 compared with infected animals) and increased mean arterial-alveolar O2 gradient (0.3 ± 0.04, 2 ± 2, 1 ± 3, 11 ± 5 Torr; P< 0.05 compared with infected animals). In normal and infected animals alike, only at [Formula: see text]≤0.21 did NO significantly lower mean pulmonary artery pressure, pulmonary artery occlusion pressure, and pulmonary vascular resistance index (all P < 0.01). However, inhaled NO had no significant effect on increases in mean pulmonay artery pressure associated with bacterial pneumonia. Thus, during bacterial pneumonia, inhaled NO had only modest effects on oxygenation dependent on high[Formula: see text] and did not affect sepsis-induced pulmonary hypertension. These data do not support a role for inhaled NO in bacterial pneumonia. Further studies are necessary to determine whether, in combination with ventilatory support, NO may have more pronounced effects.
Cardiovascular and humoral responses to sustained muscle metaboreflex activation in humans
Authors: Nishiyasu Takeshi , Tan Nobusuke , Morimoto Keiko , Sone Ryoko , Murakami Naotoshi
Published: December 2017

Nishiyasu, Takeshi, Nobusuke Tan, Keiko Morimoto, Ryoko Sone, and Naotoshi Murakami. Cardiovascular and humoral responses to sustained muscle metaboreflex activation in humans. J. Appl. Physiol. 84(1): 116–122, 1998.—The cardiovascular and humoral responses to sustained muscle metaboreflex activation were examined in eight male volunteers while they performed two 24-min exercise protocols. Each of these consisted of six 1-min bouts of isometric handgrip exercise (the left and right hands being used alternately) at 50% of maximal voluntary contraction; after each bout, there was either 3-min postexercise occlusion (occlusion protocol) or 3-min rest (control protocol). In the occlusion protocol, mean arterial blood pressure was ∼25 mmHg higher than during the control protocol, indicating that the muscle metaboreflex was activated during occlusion. During the control protocol, plasma renin activity, plasma vasopressin, and adrenocorticotropic hormone values were not significantly different from the values at rest. During the occlusion protocol, however, plasma renin activity, plasma vasopressin, and adrenocorticotropic hormone were all significantly increased at 25 min. These data demonstrate that, in humans, the sustained activation of the muscle metaboreflex causes the secretion of several hormones originating from different regions.
Ovalbumin increases macromolecular efflux from the in situ nasal mucosa of allergic hamsters
Authors: Gao Xiao-Pei , Akhter Syed R. , Rubinstein Israel
Published: December 2017

Gao, Xiao-Pei, Syed R. Akhter, and Israel Rubinstein.Ovalbumin increases macromolecular efflux from the in situ nasal mucosa of allergic hamsters. J. Appl. Physiol. 84(1): 169–176, 1998.—The purpose of this study was to determine whether bradykinin mediates ovalbumin-induced increase in macromolecular efflux from the nasal mucosa of ovalbumin-sensitized hamsters in vivo and, if so, whether thel-arginine/nitric oxide biosynthetic pathway transduces, in part, this response. We found that suffusion of ovalbumin onto the in situ nasal mucosa of ovalbumin-sensitized hamsters, but not of controls, elicited a significant time- and concentration-dependent increase in clearance of fluorescein isothiocyanate-labeled dextran (mol mass, 70 kDa; P < 0.05). HOE-140, but not des-Arg9,[Leu8]-bradykinin, and NG-l-arginine methyl ester (l-NAME), but not NG-d-arginine methyl ester, significantly attenuated ovalbumin-induced responses.l-Arginine, but notd-arginine, abolished the effects ofl-NAME.l-NAME also significantly attenuated bradykinin-, but not adenosine- induced increase in macromolecular efflux from the in situ nasal mucosa. Overall, these data suggest that ovalbumin increases macromolecular efflux from the in situ nasal mucosa of ovalbumin-sensitized hamsters, in part, by producing bradykinin with subsequent activation of thel-arginine/nitric oxide biosynthetic pathway.