A potential early physiological marker for CNS oxygen toxicity: hyperoxic hyperpnea precedes seizure in unanesthetized rats breathing hyperbaric oxygen

2013 ◽  
Vol 114 (8) ◽  
pp. 1009-1020 ◽  
Author(s):  
Raffaele Pilla ◽  
Carol S. Landon ◽  
Jay B. Dean
Keyword(s):  
Hyperbaric Oxygen ◽  
Ventilatory Response ◽  
Minute Ventilation ◽  
Phase 1 ◽  
Oxygen Toxicity ◽  
Sprague Dawley ◽  
Hyperbaric Chamber ◽  
Phase 3 ◽  
Sprague Dawley Rats ◽  
Animal Chamber

Hyperbaric oxygen (HBO2) stimulates presumptive central CO2-chemoreceptor neurons, increases minute ventilation (V̇min), decreases heart rate (HR) and, if breathed sufficiently long, produces central nervous system oxygen toxicity (CNS-OT; i.e., seizures). The risk of seizures when breathing HBO2 is variable between individuals and its onset is difficult to predict. We have tested the hypothesis that a predictable pattern of cardiorespiration precedes an impending seizure when breathing HBO2. To test this hypothesis, 27 adult male Sprague-Dawley rats were implanted with radiotelemetry transmitters to assess diaphragmatic/abdominal electromyogram, electrocardiogram, and electroencephalogram. Seven days after surgery, each rat was placed in a sealed, continuously ventilated animal chamber inside a hyperbaric chamber. Both chambers were pressurized in parallel using poikilocapnic 100% O2 (animal chamber) and air (hyperbaric chamber) to 4, 5, or 6 atmospheres absolute (ATA). Breathing 1 ATA O2 initially decreased V̇min and HR ( Phase 1 of the compound hyperoxic ventilatory response). With continued exposure to normobaric hyperoxia, however, V̇min began increasing toward the end of exposure in one-third of the animals tested. Breathing HBO2 induced an early transient increase in V̇min ( Phase 2) and HR during the chamber pressurization, followed by a second significant increase of V̇min ≤8 min prior to seizure ( Phase 3). HR, which subsequently decreased during sustained hyperoxia, showed no additional changes prior to seizure. We conclude that hyperoxic hyperpnea ( Phase 3 of the compound hyperoxic ventilatory response) is a predictor of an impending seizure while breathing poikilocapnic HBO2 at rest in unanesthetized rats.

scholarly journals Ventilatory responses to ozone are reduced in immature rats

2000 ◽  
Vol 88 (6) ◽  
pp. 2023-2030 ◽  
Author(s):  
S. A. Shore ◽  
J. H. Abraham ◽  
I. N. Schwartzman ◽  
G. G. Krishna Murthy ◽  
J. D. Laporte
Keyword(s):  
Bronchoalveolar Lavage ◽  
Ventilatory Response ◽  
Minute Ventilation ◽  
Sprague Dawley ◽  
Adult Rats ◽  
Ventilatory Responses ◽  
Sprague Dawley Rats ◽  
Immature Rats ◽  
Old Rats ◽  
Induced Changes

During ozone (O3) exposure, adult rats decrease their minute ventilation (V˙e). To determine whether such changes are also observed in immature animals, Sprague-Dawley rats, aged 2, 4, 6, 8, or 12 wk, were exposed to O3(2 ppm) in nose-only-exposure plethysmographs. BaselineV˙e normalized for body weight decreased with age from 2.1 ± 0.1 ml ⋅ min−1⋅ g−1in 2-wk-old rats to 0.72 ± 0.03 ml ⋅ min−1⋅ g−1in 12-wk-old rats, consistent with the higher metabolic rates of younger animals. In adult (8- and 12-wk-old) rats, O3caused 40–50% decreases in V˙e that occurred primarily as the result of a decrease in tidal volume. In 6-wk-old rats, O3-induced changes inV˙e were significantly less, and in 2- and 4-wk-old rats, no significant changes inV˙e were observed during O3exposure. The increased baseline V˙e and the smaller decrements in V˙e induced by O3in the immature rats imply that their delivered dose of O3is much higher than in adult rats. To determine whether these differences in O3dose influence the extent of injury, we measured bronchoalveolar lavage protein concentrations. The magnitude of the changes in bronchoalveolar lavage induced by O3was significantly greater in 2- than in 8-wk-old rats (267 ± 47 vs. 165 ± 22%, respectively, P < 0.05). O3exposure also caused a significant increase in PGE2in 2-wk-old but not in adult rats. The results indicate that the ventilatory response to O3is absent in 2-wk-old rats and that lack of this response, in conjunction with a greater specific ventilation, leads to greater lung injury.

Changes in respiratory timing induced by hypercapnia in maturing rats

1999 ◽  
Vol 87 (2) ◽  
pp. 484-490 ◽  
Author(s):  
Jalal M. Abu-Shaweesh ◽  
Ismail A. Dreshaj ◽  
Agnes J. Thomas ◽  
Musa A. Haxhiu ◽  
Kingman P. Strohl ◽  
...  
Keyword(s):  
Ventilatory Response ◽  
Minute Ventilation ◽  
Aminobutyric Acid ◽  
Whole Body ◽  
Sprague Dawley ◽  
Newborn Rat ◽  
Rat Pups ◽  
Significant Prolongation ◽  
Sprague Dawley Rats ◽  
Central Origin

Premature infants respond to hypercapnia by an attenuated ventilatory response that is characterized by a decrease in respiratory frequency. We hypothesized that this impaired hypercapnic ventilatory response is of central origin and is mediated via γ-aminobutyric acid-ergic (GABAergic) pathways. We therefore studied two groups of maturing Sprague-Dawley rats: unrestrained rats in a whole body plethysmograph at four postnatal ages (5, 16–17, 22–23, and 41–42 days); and ventilated, decerebrate, vagotomized, paralyzed rats in which phrenic nerve responses to hypercapnia were measured at 4–6 and 37–39 days of age. In the unrestrained group, the increase in minute ventilation induced by hypercapnia was significantly lower at 5 days vs. beyond 16 days. Although there was an increase in tidal volume at all ages, frequency decreased significantly from baseline at 5 days, whereas it increased significantly at 16–17, 22–23, and 41–42 days. The decrease in frequency at 5 days of age was mainly due to a significant prolongation in expiratory duration (Te). In the ventilated group, hypercapnia also caused prolongation in Te at 4–6 days but not at 37–39 days of age. Intravenous administration of bicuculline (GABAA-receptor blocker) abolished the prolongation of Te in response to hypercapnia in the newborn rats. We conclude that newborn rat pups exhibit a characteristic ventilatory response to CO2 expressed as a centrally mediated prolongation of Te that appears to be mediated by GABAergic mechanisms.

scholarly journals Seizures Caused by Exposure to Hyperbaric Oxygen in Rats Can Be Predicted by Early Changes in Electrodermal Activity

2022 ◽  
Vol 12 ◽  
Author(s):  
Hugo F. Posada-Quintero ◽  
Carol S. Landon ◽  
Nicole M. Stavitzski ◽  
Jay B. Dean ◽  
Ki H. Chon
Keyword(s):  
Nervous System ◽  
Hyperbaric Oxygen ◽  
Electrodermal Activity ◽  
Radio Telemetry ◽  
Core Body Temperature ◽  
Ambient Pressure ◽  
Oxygen Toxicity ◽  
Hyperbaric Chamber ◽  
Generalized Seizures ◽  
Animal Chamber

Hyperbaric oxygen (HBO2) is breathed during undersea operations and in hyperbaric medicine. However, breathing HBO2 by divers and patients increases the risk of central nervous system oxygen toxicity (CNS-OT), which ultimately manifests as sympathetic stimulation producing tachycardia and hypertension, hyperventilation, and ultimately generalized seizures and cardiogenic pulmonary edema. In this study, we have tested the hypothesis that changes in electrodermal activity (EDA), a measure of sympathetic nervous system activation, precedes seizures in rats breathing 5 atmospheres absolute (ATA) HBO2. Radio telemetry and a rodent tether apparatus were adapted for use inside a sealed hyperbaric chamber. The tethered rat was free to move inside a ventilated animal chamber that was flushed with air or 100% O2. The animal chamber and hyperbaric chamber (air) were pressurized in parallel at ~1 atmosphere/min. EDA activity was recorded simultaneously with cortical electroencephalogram (EEG) activity, core body temperature, and ambient pressure. We have captured the dynamics of EDA using time-varying spectral analysis of raw EDA (TVSymp), previously developed as a tool for sympathetic tone assessment in humans, adjusted to detect the dynamic changes of EDA in rats that occur prior to onset of CNS-OT seizures. The results show that a significant increase in the amplitude of TVSymp values derived from EDA recordings occurs on average (±SD) 1.9 ± 1.6 min before HBO2-induced seizures. These results, if corroborated in humans, support the use of changes in TVSymp activity as an early “physio-marker” of impending and potentially fatal seizures in divers and patients.

scholarly journals Potentiation of hypoxic ventilatory response by hyperoxia in the conscious rat: putative role of nitric oxide

1998 ◽  
Vol 85 (1) ◽  
pp. 129-132 ◽  
Author(s):  
David Gozal
Keyword(s):  
Nitric Oxide ◽  
Ventilatory Response ◽  
Minute Ventilation ◽  
Hypoxic Ventilatory Response ◽  
Sprague Dawley ◽  
Conscious Rat ◽  
Adult Rats ◽  
Hyperoxic Exposure ◽  
Essential Components ◽  
Oxide Synthase

In humans, the hypoxic ventilatory response (HVR) is augmented when preceded by a short hyperoxic exposure (Y. Honda, H. Tani, A. Masuda, T. Kobayashi, T. Nishino, H. Kimura, S. Masuyama, and T. Kuriyama. J. Appl. Physiol. 81: 1627–1632, 1996). To examine whether neuronal nitric oxide synthase (nNOS) is involved in such hyperoxia-induced HVR potentiation, 17 male Sprague-Dawley adult rats underwent hypoxic challenges (10% O2-5% CO2-balance N2) preceded either by 10 min of room air (−O2) or of 100% O2(+O2). At least 48 h later, similar challenges were performed after the animals received the selective nNOS inhibitor 7-nitroindazole (25 mg/kg ip). In −O2 runs, minute ventilation (V˙e) increased from 121.3 ± 20.5 (SD) ml/min in room air to 191.7 ± 23.8 ml/min in hypoxia ( P< 0.01). After +O2,V˙e increased from 114.1 ± 19.8 ml/min in room air to 218.4 ± 47.0 ml/min in hypoxia (+O2 vs. −O2: P < 0.005, ANOVA). After 7-nitroindazole administration, HVR was not affected in the −O2 treatment group withV˙e increasing from 113.7 ± 17.8 ml/min in room air to 185.8 ± 35.0 ml/min in hypoxia ( P < 0.01). However, HVR potentiation in +O2-exposed animals was abolished (111.8 ± 18.0 ml/min in room air to 184.1 ± 35.6 ml/min in hypoxia; +O2 vs. −O2: P not significant). We conclude that in the conscious rat nNOS activation mediates essential components of the HVR potentiation elicited by a previous short hyperoxic exposure.

scholarly journals Reevaluation of CNS Oxygen Toxicity Seizures in Male Sprague‐Dawley Rats

2017 ◽  
Vol 31 (S1) ◽  
Author(s):  
Christopher M. Hinojo ◽  
Nicole M. Stavitzski ◽  
Carol S. Landon ◽  
Jay B. Dean
Keyword(s):  
Oxygen Toxicity ◽  
Sprague Dawley ◽  
Sprague Dawley Rats

Ketone Ester Supplementation Does Not Impair Cognitive or Motor Performance and Delays CNS Oxygen Toxicity in Male Sprague‐Dawley Rats

2020 ◽  
Vol 34 (S1) ◽  
pp. 1-1
Author(s):  
Nicole M. Stavtizski ◽  
Carol S. Landon ◽  
Christopher M. Hinojo ◽  
Angela M. Poff ◽  
Christopher Q. Rogers ◽  
...  
Keyword(s):  
Motor Performance ◽  
Oxygen Toxicity ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Ketone Ester

Effects of 4-h ischemia and 1-h reperfusion on rat muscle sarcoplasmic reticulum function

2001 ◽  
Vol 281 (4) ◽  
pp. E867-E877 ◽  
Author(s):  
R. Tupling ◽  
H. Green ◽  
G. Senisterra ◽  
J. Lepock ◽  
N. McKee
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Phase 1 ◽  
Late Phase ◽  
Maximal Activity ◽  
Hill Coefficient ◽  
Sprague Dawley ◽  
Rapid Phase ◽  
Sprague Dawley Rats ◽  
The Hill

To investigate the hypothesis that ischemia and reperfusion would impair sarcoplasmic reticulum (SR) Ca2+ regulation in skeletal muscle, Sprague-Dawley rats ( n = 20) weighing 290 ± 3.5 g were randomly assigned to either a control control (CC) group, in which only the effects of anesthetization were studied, or to a group in which the muscles in one hindlimb were made ischemic for 4 h and allowed to recover for 1 h (I). The nonischemic, contralateral muscles served as control (C). Measurements of Ca2+-ATPase properties in homogenates and SR vesicles, in mixed gastrocnemius and tibialis anterior muscles, indicated no differences between groups on maximal activity, the Hill coefficient, and Ca50, defined as the Ca2+concentration needed to elicit 50% of maximal activity. In homogenates, Ca2+ uptake was lower ( P < 0.05) by 20–25%, measured at 0.5 and 1.0 μM of free Ca2+ ([Ca2+]f) in C compared with CC. In SR vesicles, Ca2+ uptake was lower ( P < 0.05) by 30–38% in I compared with CC at [Ca2+]f between 0.5 and 1.5 μM. Silver nitrate induced Ca2+ release, assessed during both the initial, early rapid ( phase 1), and slower, prolonged late ( phase 2) phases, in homogenates and SR vesicles, indicated a higher ( P < 0.05) release only in phase 1in SR vesicles in I compared with CC. These results indicate that the alterations in SR Ca2+ regulation, previously observed after prolonged ischemia by our group, are reversed within 1 h of reperfusion. However, the lower Ca2+ uptake observed in long-term, nonischemic homogenates suggests that altered regulation may occur in the absence of ischemia.

Effects of ischemia on sarcoplasmic reticulum Ca2+ uptake and Ca2+ release in rat skeletal muscle

2001 ◽  
Vol 281 (2) ◽  
pp. E224-E232 ◽  
Author(s):  
R. Tupling ◽  
H. Green ◽  
G. Senisterra ◽  
J. Lepock ◽  
N. McKee
Keyword(s):  
Skeletal Muscle ◽  
Sarcoplasmic Reticulum ◽  
Phase 1 ◽  
Tibialis Anterior Muscle ◽  
Tissue Preparation ◽  
Phase 2 ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Two Phases

In this study, we investigated the hypothesis that prolonged ischemia would impair both sarcoplasmic reticulum (SR) Ca2+ uptake and Ca2+ release in skeletal muscle. To induce total ischemia (I), a tourniquet was placed around the upper hindlimb in 30 female Sprague-Dawley rats [wt = 256 ± 6.7 (SE) g] and inflated to 350 mmHg for 4 h. The contralateral limb served as control (C). Immediately after the 4 h of ischemia, mixed gastrocnemius and tibialis anterior muscle was sampled from both limbs, and both crude muscle homogenates and SR vesicles were prepared. In another 10 control animals (CC), muscles were sampled and prepared exactly the same way, but immediately after anesthetization. Ca2+ uptake and Ca2+ release were measured in vitro with Indo-I on both homogenates and SR vesicles. As hypothesized, submaximal Ca2+ uptake was lower ( P < 0.05) in I compared with CC and C, by 25 and 45% in homogenates and SR vesicles, respectively. Silver nitrate (AgNO3)-induced Ca2+ release, which occurred in two phases ( phase 1 and phase 2), was also altered in I compared with CC and C, in both muscle homogenates and SR vesicles. With ischemia, phase 1 peak Ca2+ release was 26% lower ( P < 0.05) in SR vesicles only. For phase 2, peak Ca2+ release was 54 and 24% lower ( P < 0.05) in SR vesicles and homogenates, respectively. These results demonstrate that prolonged skeletal muscle ischemia leads to a reduced SR Ca2+uptake in both homogenates and SR vesicles. The effects of ischemia on SR Ca2+ release, however, depend on both the phase examined and the type of tissue preparation.

Loss of diaphragm glutathione is associated with respiratory failure induced by resistive breathing

1994 ◽  
Vol 76 (6) ◽  
pp. 2825-2831 ◽  
Author(s):  
G. Borzone ◽  
M. W. Julian ◽  
A. J. Merola ◽  
T. L. Clanton
Keyword(s):  
Respiratory Failure ◽  
Minute Ventilation ◽  
Oxidant Stress ◽  
Respiratory Muscles ◽  
Redox Status ◽  
Sprague Dawley ◽  
Liver Glutathione ◽  
Sprague Dawley Rats ◽  
Resistive Breathing ◽  
Glutathione Oxidation

It has been suggested that oxidant stress may contribute to dysfunction of respiratory muscles undergoing severe work loads. We examined changes in glutathione content and redox status in the diaphragm and intercostal muscles of anesthetized Sprague-Dawley rats exposed to prolonged inspiratory resistive loading while breathing 70% O2. These results were compared with those from control groups breathing air or 70% O2. Changes in liver glutathione were also examined. Freeze-clamping and an enzymatic recycling assay were used. Results show that 1) in controls, glutathione content was higher in the diaphragm than in the intercostals, 2) severe hypercapnic acidosis without hypoxemia was present with loading, 3) total diaphragm glutathione decreased approximately 35% with no increase in glutathione oxidation with resistive breathing, whereas intercostal and liver glutathione remained unchanged, and 4) the drop in diaphragm glutathione correlated significantly with the drop in minute ventilation and the increase in arterial PCO2, whereas it was not directly related to intensity of respiratory muscle activity. In conclusion, although diaphragm susceptibility to oxidant stress may be increased with resistive breathing, it is unlikely that the modest decrease in total glutathione contributed significantly to respiratory failure in this model.

scholarly journals Systemic Administration of Tempol Attenuates the Cardiorespiratory Depressant Effects of Fentanyl

2021 ◽  
Vol 12 ◽  
Author(s):  
Santhosh Baby ◽  
Ryan Gruber ◽  
Joseph Discala ◽  
Veljko Puskovic ◽  
Nijo Jose ◽  
...  
Keyword(s):  
Minute Ventilation ◽  
Oxidant Stress ◽  
Sprague Dawley ◽  
Systemic Injection ◽  
Analgesic Effects ◽  
Opioid Receptor Agonist ◽  
Sprague Dawley Rats ◽  
Freely Moving ◽  
Dose Dependent ◽  
Prior Administration

Fentanyl is a high-potency opioid receptor agonist that elicits profound analgesia and suppression of breathing in humans and animals. To date, there is limited evidence as to whether changes in oxidant stress are important factors in any of the actions of acutely administered fentanyl. This study determined whether the clinically approved superoxide dismutase mimetic, Tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl), or a potent antioxidant, N-acetyl-L-cysteine methyl ester (L-NACme), modify the cardiorespiratory and analgesic actions of fentanyl. We examined whether the prior systemic injection of Tempol or L-NACme affects the cardiorespiratory and/or analgesic responses elicited by the subsequent injection of fentanyl in isoflurane-anesthetized and/or freely moving male Sprague-Dawley rats. Bolus injections of Tempol (25, 50 or 100 mg/kg, IV) elicited minor increases in frequency of breathing, tidal volume and minute ventilation. The ventilatory-depressant effects of fentanyl (5 μg/kg, IV) given 15 min later were dose-dependently inhibited by prior injections of Tempol. Tempol elicited dose-dependent and transient hypotension that had (except for the highest dose) resolved when fentanyl was injected. The hypotensive responses elicited by fentanyl were markedly blunted after Tempol pretreatment. The analgesic actions of fentanyl (25 μg/kg, IV) were not affected by Tempol (100 mg/kg, IV). L-NACme did not modify any of the effects of fentanyl. We conclude that prior administration of Tempol attenuates the cardiorespiratory actions of fentanyl without affecting the analgesic effects of this potent opioid. As such, Tempol may not directly affect opioid-receptors that elicit the effects of fentanyl. Whether, the effects of Tempol are solely due to alterations in oxidative stress is in doubt since the powerful antioxidant, L-NACme, did not affect fentanyl-induced suppression of breathing.

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