scholarly journals Quantifying hypoxia-induced chemoreceptor sensitivity in the awake rodent

2014 ◽  
Vol 117 (7) ◽  
pp. 816-824 ◽  
Author(s):  
Barbara J. Morgan ◽  
Russell Adrian ◽  
Melissa L. Bates ◽  
John M. Dopp ◽  
Jerome A. Dempsey
Keyword(s):  
Arterial Oxygen Saturation ◽  
Linear Regression Analysis ◽  
Carbon Dioxide Production ◽  
Complete Characterization ◽  
Arterial Oxygen ◽  
Respiratory Drive ◽  
Sprague Dawley ◽  
Conscious Rat ◽  
Stimulus Response ◽  
Sprague Dawley Rats

We evaluated several methods for characterizing hypoxic chemosensitivity in the conscious rat. Adult Sprague-Dawley rats ( n = 30) were exposed to normobaric hypoxia [inspired oxygen fraction (Fio2) 0.15, 0.12, and 0.09]. We measured ventilation (V̇e; barometric plethysmography), arterial oxygen saturation (SpO2; pulse oximeter), and oxygen consumption and carbon dioxide production (V̇o2 and V̇co2; analysis of expired air). Linear regression analysis was used to define stimulus-response relationships. Testing was performed on 2 days to assess day-to-day reproducibility. Exposure to graded, steady-state hypoxia caused progressive reductions in SpO2 that were, for any given Fio2, quite variable (SpO2 range, 20–30%) among individuals. Hypoxia produced progressive increases in V̇e caused by increases in both tidal volume (VT) and breathing frequency. Hypoxia also increased the VT:inspiratory time (Ti) ratio, an indicator of central respiratory “drive.” Hypoxia caused consistent, progressive declines in V̇o2, V̇co2, and core temperature (>20% at the lowest SpO2). We propose that optimal quantification of carotid chemoreceptor hypoxic sensitivity in the unanesthetized rodent should employ SpO2 [a surrogate for arterial Po2 (PaO2)] as the stimulus variable and the ventilatory equivalent for V̇co2 (V̇e/V̇co2) and/or mean inspiratory flow rate (VT/Ti) normalized for V̇co2 as the response variables. Both metrics take into account not only the important influence of a falling metabolic rate, but also SpO2, which represents the hypoxic stimulus at the carotid body. Because of the somewhat curvilinear nature of these responses, exposure to multiple levels of graded hypoxia provides the most complete characterization of hypoxic chemosensitivity.

scholarly journals Chronic intermittent hypoxia alters ventilatory and metabolic responses to acute hypoxia in rats

2016 ◽  
Vol 120 (10) ◽  
pp. 1186-1195 ◽  
Author(s):  
Barbara J. Morgan ◽  
Russell Adrian ◽  
Zun-yi Wang ◽  
Melissa L. Bates ◽  
John M. Dopp
Keyword(s):  
Intermittent Hypoxia ◽  
Acute Hypoxia ◽  
Sprague Dawley ◽  
Glomus Cell ◽  
Stimulus Response ◽  
Sprague Dawley Rats ◽  
Ventilatory Equivalent ◽  
Before And After ◽  
Conscious Animals ◽  
Carotid Body Glomus Cells

We determined the effects of chronic exposure to intermittent hypoxia (CIH) on chemoreflex control of ventilation in conscious animals. Adult male Sprague-Dawley rats were exposed to CIH [nadir oxygen saturation (SpO2), 75%; 15 events/h; 10 h/day] or normoxia (NORM) for 21 days. We assessed the following responses to acute, graded hypoxia before and after exposures: ventilation (V̇e, via barometric plethysmography), V̇o2 and V̇co2 (analysis of expired air), heart rate (HR), and SpO2 (pulse oximetry via neck collar). We quantified hypoxia-induced chemoreceptor sensitivity by calculating the stimulus-response relationship between SpO2 and the ventilatory equivalent for V̇co2 (linear regression). An additional aim was to determine whether CIH causes proliferation of carotid body glomus cells (using bromodeoxyuridine). CIH exposure increased the slope of the V̇e/V̇co2/SpO2 relationship and caused hyperventilation in normoxia. Bromodeoxyuridine staining was comparable in CIH and NORM. Thus our CIH paradigm augmented hypoxic chemosensitivity without causing glomus cell proliferation.

Pulmonary Effects of Sustained Periods of High-G Acceleration Relevant to Suborbital Spaceflight

2021 ◽  
Vol 92 (8) ◽  
pp. 633-641
Author(s):  
Ross D. Pollock ◽  
Caroline J. Jolley ◽  
Nadia Abid ◽  
John H. Couper ◽  
Luis Estrada-Petrocelli ◽  
...  
Keyword(s):  
Work Of Breathing ◽  
Arterial Oxygen Saturation ◽  
Regional Distribution ◽  
Blood Gases ◽  
Respiratory Physiology ◽  
Arterial Oxygen ◽  
Relative Distribution ◽  
Respiratory Drive ◽  
Impedance Tomography ◽  
Arterial Blood

AbstractBACKGROUND: Members of the public will soon be taking commercial suborbital spaceflights with significant Gx (chest-to-back) acceleration potentially reaching up to 6 Gx. Pulmonary physiology is gravity-dependent and is likely to be affected, which may have clinical implications for medically susceptible individuals.METHODS: During 2-min centrifuge exposures ranging up to 6 Gx, 11 healthy subjects were studied using advanced respiratory techniques. These sustained exposures were intended to allow characterization of the underlying pulmonary response and did not replicate actual suborbital G profiles. Regional distribution of ventilation in the lungs was determined using electrical impedance tomography. Neural respiratory drive (from diaphragm electromyography) and work of breathing (from transdiaphragmatic pressures) were obtained via nasoesophageal catheters. Arterial blood gases were measured in a subset of subjects. Measurements were conducted while breathing air and breathing 15 oxygen to simulate anticipated cabin pressurization conditions.RESULTS: Acceleration caused hypoxemia that worsened with increasing magnitude and duration of Gx. Minimum arterial oxygen saturation at 6 Gx was 86 1 breathing air and 79 1 breathing 15 oxygen. With increasing Gx the alveolar-arterial (A-a) oxygen gradient widened progressively and the relative distribution of ventilation reversed from posterior to anterior lung regions with substantial gas-trapping anteriorly. Severe breathlessness accompanied large progressive increases in work of breathing and neural respiratory drive.DISCUSSION: Sustained high-G acceleration at magnitudes relevant to suborbital flight profoundly affects respiratory physiology. These effects may become clinically important in the most medically susceptible passengers, in whom the potential role of centrifuge-based preflight evaluation requires further investigation.Pollock RD, Jolley CJ, Abid N, Couper JH, Estrada-Petrocelli L, Hodkinson PD, Leonhardt S, Mago-Elliott S, Menden T, Rafferty G, Richmond G, Robbins PA, Ritchie GAD, Segal MJ, Stevenson AT, Tank HD, Smith TG. Pulmonary effects of sustained periods of high-G acceleration relevant to suborbital spaceflight. Aerosp Med Hum Perform. 2021; 92(7):633641.

Patterns of EMG activity of rat plantaris muscle during swimming and other locomotor activities

1987 ◽  
Vol 63 (2) ◽  
pp. 713-718 ◽  
Author(s):  
B. J. Jasmin ◽  
P. F. Gardiner
Keyword(s):  
Maximum Amplitude ◽  
Treadmill Walking ◽  
Emg Activity ◽  
Sprague Dawley ◽  
Plantaris Muscle ◽  
Conscious Rat ◽  
Bipolar Electrodes ◽  
Sprague Dawley Rats ◽  
Locomotor Activities ◽  
Stabilization Period

The purpose of the study was to examine the patterns of electromyographic (EMG) activity of the rat plantaris during loaded swimming in comparison with other locomotor activities. Five female Sprague-Dawley rats were implanted with chronic bipolar electrodes in the plantaris muscle of the left hindlimb under pentobarbital anesthesia. Characteristics of EMG bursts recorded while the conscious rat was performing treadmill walking (0.24 m/s) were stable and reproducible 10–14 days postsurgery. Following this stabilization period, records of EMG activity were obtained during walking, loaded swimming (6.5 g attached to tail), and several other locomotor tasks. Compared to walking, EMG bursts during loaded swimming were significantly higher (67%) in maximum amplitude, one-third as long in duration, and occurred at a greater rate (4.4 vs. 1.7 bursts/s, P less than 0.05). Swimming bursts were of higher amplitudes than those of all other activities examined and reached 65% of the EMG amplitude recorded following stimulation of the sciatic nerve with supramaximal voltage. The addition of a mass to the animal's tail during swimming did not increase the EMG burst amplitudes but resulted in a higher frequency of bursts. Compared with treadmill walking, loaded swimming elicited burst of high variability in amplitude. Swimming in the rat involves rapid, extensive activation of plantaris, thus providing an exercise model to study the adaptability of the neuromuscular system to prolonged activity of this type.

scholarly journals Impact of ageing and pregnancy on the minute ventilation/carbon dioxide production response to exercise

2021 ◽  
Vol 30 (161) ◽  
pp. 200225
Author(s):  
Michele R. Schaeffer ◽  
Jordan A. Guenette ◽  
Dennis Jensen
Keyword(s):  
Equilibrium Point ◽  
Minute Ventilation ◽  
Arterial Oxygen Saturation ◽  
Carbon Dioxide Production ◽  
Arterial Oxygen ◽  
Critical Threshold ◽  
Primary Role ◽  
Physiological Factors ◽  
Age Related ◽  
Increased Risk

Ventilatory efficiency can be evaluated using the relationship between minute ventilation (V′E) and the rate of CO2 production (V′CO2). In accordance with the modified alveolar ventilation equation, this relationship is determined by changes in dead space volume (VD) and/or the arterial CO2 tension (PaCO2) equilibrium point. In this review, we summarise the physiological factors that may account for normative ageing and pregnancy induced increases in V′E/V′CO2 during exercise. Evidence suggests that age-related increases in VD and pregnancy-related decreases in the PaCO2 equilibrium point are mechanistically linked to the increased V′E/V′CO2 during exercise. Importantly, the resultant increase in V′E/V′CO2 (ratio or slope), with normal ageing or pregnancy, remains below the critical threshold for prognostic indication in cardiopulmonary disease, is not associated with increased risk of adverse health outcomes, and does not affect the respiratory system's ability to fulfil its primary role of eliminating CO2 and maintaining arterial oxygen saturation during exercise.

Abstract 17908: Milrinone Lacks Acute Inotropic And Lusitropic Effects Under Constant Afterload Conditions

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Elizabeth S DeWitt ◽  
Katherine Black ◽  
Kimberly I Mills ◽  
Lauren Ruoss ◽  
James A DiNardo ◽  
...  
Keyword(s):  
Cardiac Output ◽  
Left Atrium ◽  
Linear Regression Analysis ◽  
Aortic Pressure ◽  
Conductance Catheter ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Patients With Heart Failure ◽  
Phosphodiesterase Iii Inhibitors ◽  
Phosphodiesterase Iii

Introduction: Phosphodiesterase III inhibitors are known to improve cardiac output in patients with heart failure. Whether this is due to a reduction in afterload, a positive inotropic effect, or an interaction of these factors is uncertain. We compared the inotropic and lusitropic effects of milrinone to those of commonly used catecholamines in a working Langendorff model under constant loading conditions. Methods: Sprague Dawley rats (n=35, 350-400 grams) were anesthetized and heparinized for cardiac explantation. The aorta and left atrium were immediately cannulated by a single experimenter. Left atrial pressure (10 mmHg) and aortic pressure (90 mmHg) were fixed. A conductance catheter (Millar) was inserted into the left ventricle. Following baseline measurements, infusions of milrinone, dopamine, dobutamine, epinephrine, or norephinephrine, alone and in commonly-used combinations, were initiated into the left atrium for 10 minute periods. Changes in cardiac output, contractility (dP/dTmax), diastolic performance (-dP/dT and Tau) relative to baseline were compared between groups by linear regression analysis. Results: Cardiac output increased in linear fashion for each of the catecholamines: Dobutamine>>Dopamine>Norepinephrine>Epinephrine (P<0.001 for each). Dobutamine, Norepinephrine, and Dopamine (P<0.05) significantly increased diastolic function, including negative dP/dT (C) and Tau (D), none of which were changed by Milrinone infusion. Conclusions: When afterload is fixed using a Starling resistor, milrinone at commonly used doses does not acutely change systolic or diastolic performance or cardiac output. It is possible that clinical improvements are due to milrinone’s vasodilatory properties.

scholarly journals Large BP-dependent and -independent differences in susceptibility to nephropathy after nitric oxide inhibition in Sprague-Dawley rats from two major suppliers

2012 ◽  
Vol 302 (1) ◽  
pp. F173-F182 ◽  
Author(s):  
Karen Griffin ◽  
Aaron Polichnowski ◽  
Hector Licea-Vargas ◽  
Maria Picken ◽  
Jianrui Long ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Linear Regression Analysis ◽  
Sprague Dawley ◽  
Glomerular Injury ◽  
Renal Vasoconstriction ◽  
Renal Autoregulation ◽  
Sprague Dawley Rats ◽  
The Relationship ◽  
Dose Dependent

The Nω-nitro-l-arginine methyl ester (l-NAME) model is widely employed to investigate the role of nitric oxide (NO) in renal injury. The present studies show that Sprague-Dawley rats from Harlan (H) and Charles River (CR) exhibit strikingly large differences in susceptibility to l-NAME nephropathy. After 4 wk of l-NAME (∼50 mg·kg−1·day−1 in drinking water), H rats ( n = 13) exhibited the expected hypertension [average radiotelemetric systolic blood pressure (BP), 180 ± 3 mmHg], proteinuria (136 ± 17 mg/24 h), and glomerular injury (GI) (12 ± 2%). By contrast, CR rats developed less hypertension (142 ± 4), but surprisingly no proteinuria or GI, indicating a lack of glomerular hypertension. Additional studies showed that conscious H, but not CR, rats exhibit dose-dependent renal vasoconstriction after l-NAME. To further investigate these susceptibility differences, l-NAME was given 2 wk after 3/4 normotensive nephrectomy (NX) and comparably impaired renal autoregulation in CR-NX and H-NX rats. CR-NX rats, nevertheless, still failed to develop proteinuria and GI despite moderate hypertension (144 ± 2 mmHg, n = 29). By contrast, despite an 80–90% l-NAME dose reduction and lesser BP increases (169 ± 4 mmHg), H-NX rats ( n = 20) developed greater GI (26 ± 3%) compared with intact H rats. Linear regression analysis showed significant ( P < 0.01) differences in the slope of the relationship between BP and GI between H-NX (slope 0.56 ± 0.14; r = 0.69; P < 0.008) and CR-NX (slope 0.09 ± 0.06; r = 0.29; P = 0.12) rats. These data indicate that blunted BP responses to l-NAME in the CR rats are associated with BP-independent resistance to nephropathy, possibly mediated by a resistance to the renal (efferent arteriolar) vasoconstrictive effects of NO inhibition.

Comparison of ultradian and circadian oscillations of carbon dioxide production by various endotherms

1995 ◽  
Vol 268 (1) ◽  
pp. R253-R265 ◽  
Author(s):  
M. Stupfel ◽  
V. Gourlet ◽  
A. Perramon ◽  
P. Merat ◽  
G. Putet ◽  
...  
Keyword(s):  
Carbon Dioxide ◽  
Premature Infants ◽  
Guinea Pigs ◽  
Carbon Dioxide Emission ◽  
Continuous Light ◽  
Co2 Concentration ◽  
Carbon Dioxide Production ◽  
Sprague Dawley ◽  
Cynomolgus Monkeys ◽  
Sprague Dawley Rats

Carbon dioxide emission (VCO2) was computed every 20 min from continuous CO2 concentration recordings taken during 3-30 consecutive days, in strictly controlled environmental conditions, in 54 OF1 mice, 99 Japanese quail, 66 Sprague-Dawley rats, 50 Hartley guinea pigs, 7 chicks, for 7-15 days on 2 Cynomolgus monkeys, and for 24 h on 7 premature infants. This VCO2 shows circadian and ultradian oscillations that were analyzed for frequencies and amplitudes in light-dark 12-h alternation (LD 12:12), continuous light (LL), and continuous dark (DD). Circadians were not always identified or were often masked in LL or DD (mostly in guinea pigs, quail, and rats), while ultradians (tau > or = 40 min) were found in all species, at every time, and in all light regimens. Analysis of variance and chi 2 show significant (P < 0.001) interspecies differences for ultradian (1.07 < tau < 1.40 h) intervals and for circadian and ultradian VCO2 amplitudes. Relationships between ultradian and circadian VCO2 oscillations differ according to the species, ultradians appearing as an entity characteristic for each endotherm species.

scholarly journals Ventilatory long-term facilitation in unanesthetized rats

2001 ◽  
Vol 91 (2) ◽  
pp. 709-716 ◽  
Author(s):  
E. B. Olson ◽  
C. J. Bohne ◽  
M. R. Dwinell ◽  
A. Podolsky ◽  
E. H. Vidruk ◽  
...  
Keyword(s):  
Intermittent Hypoxia ◽  
Time Course ◽  
Minute Ventilation ◽  
Carbon Dioxide Production ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Baseline Values ◽  
Long Term Facilitation ◽  
Feedback Time

We tested the hypothesis that unanesthetized rats exhibit ventilatory long-term facilitation (LTF) after intermittent, but not continuous, hypoxia. Minute ventilation (V˙e) and carbon dioxide production (V˙co 2) were measured in unanesthetized, unrestrained male Sprague-Dawley rats via barometric plethysmography before, during, and after exposure to continuous or intermittent hypoxia. Hypoxia was either isocapnic [inspired O2 fraction (Fi O2 ) = 0.08–0.09 and inspired CO2 fraction (Fi CO2 ) = 0.04] or poikilocapnic (Fi O2 = 0.11 and Fi CO2 = 0.00). Sixty minutes after intermittent hypoxia, V˙e orV˙e/V˙co 2 was significantly greater than baseline in both isocapnic and poikilocapnic conditions. In contrast, 60 min after continuous hypoxia,V˙e andV˙e/V˙co 2 were not significantly different from baseline values. These data demonstrate ventilatory LTF after intermittent hypoxia in unanesthetized rats. Ventilatory LTF appeared similar in its magnitude (after accounting for CO2 feedback), time course, and dependence on intermittent hypoxia to phrenic LTF previously observed in anesthetized, vagotomized, paralyzed rats.

scholarly journals Phasic respiratory modulation of pharyngeal collapsibility via neuromuscular mechanisms in rats

2012 ◽  
Vol 112 (5) ◽  
pp. 695-703 ◽  
Author(s):  
Ying Cao ◽  
Michelle McGuire ◽  
Chun Liu ◽  
Atul Malhotra ◽  
Liming Ling
Keyword(s):  
Superior Laryngeal Nerve ◽  
Upper Airway ◽  
Respiratory Drive ◽  
Sprague Dawley ◽  
Lung Inflation ◽  
Sprague Dawley Rats ◽  
Dilator Muscle ◽  
Obstructive Sleep ◽  
Before And After ◽  
Patients Experience

Obstructive sleep apnea patients experience recurrent upper airway (UA) collapse due to decreases in the UA dilator muscle activity during sleep. In contrast, activation of UA dilators reduces pharyngeal critical pressure (Pcrit, an index of pharyngeal collapsibility), suggesting an inverse relationship between pharyngeal collapsibility and dilator activity. Since most UA muscles display phasic respiratory activity, we hypothesized that pharyngeal collapsibility is modulated by respiratory drive via neuromuscular mechanisms. Adult male Sprague-Dawley rats were anesthetized, vagotomized, and ventilated (normocapnia). In one group, integrated genioglossal activity, Pcrit, and maximal airflow (Vmax) were measured at three expiration and five inspiration time points within the breathing cycle. Pcrit was closely and inversely related to phasic genioglossal activity, with the value measured at peak inspiration being the lowest. In other groups, the variables were measured during expiration and peak inspiration, before and after each of five manipulations. Pcrit was 26% more negative (−15.0 ± 1.0 cmH2O, −18.9 ± 1.2 cmH2O; n = 23), Vmax was 7% larger (31.0 ± 1.0 ml/s, 33.2 ± 1.1 ml/s), nasal resistance was 12% bigger [0.49 ± 0.05 cmH2O/(ml/s), 0.59 ± 0.05 cmH2O/(ml/s)], and latency to induced UA closure was 14% longer (55 ± 4 ms, 63 ± 5 ms) during peak inspiration vs. expiration (all P < 0.005). The expiration-inspiration difference in Pcrit was abolished with neuromuscular blockade, hypocapnic apnea, or death but was not reduced by the superior laryngeal nerve transection or altered by tracheal displacement. Collectively, these results suggest that pharyngeal collapsibility is moment-by-moment modulated by respiratory drive and this phasic modulation requires neuromuscular mechanisms, but not the UA negative pressure reflex or tracheal displacement by phasic lung inflation.

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