Brain stem energy metabolism response to acute hypoxia in anaesthetized rats

Changes in local brain stem perfusion that alter extracellular fluid Pco2 and/or [H+] near central chemoreceptors may contribute to the decrease in respiration observed during hypoxia after peripheral chemoreceptor denervation and to the delayed decrease observed during hypoxia in the newborn. In this study, we measured the changes in respiration and brain stem blood flow (BBF) during 2–4 min of hypoxic hypoxia in both intact and denervated piglets and calculated the changes in brain stem Pco2 and [H+] that would be expected to occur as a result of the changes in BBF. All animals were anesthetized, spontaneously breathing, and between 2 and 7 days of age. Respiratory and other variables were measured before and during hypoxia in all animals, and BBF (microspheres) was measured in a subgroup of intact and denervated animals at 0, 30, and 260 s and at 0 and 80 s, respectively. During hypoxia, minute ventilation increased and then decreased (biphasic response) in the intact animals but decreased only in the denervated animals. BBF increased in a near linear fashion, and calculated brain stem extracellular fluid Pco2 and [H+] decreased over the first 80 s both before and after denervation. We speculate that a rapid increase in BBF during acute hypoxia decreases brain stem extracellular fluid Pco2 and [H+], which, in turn, negatively modulate the increase in respiratory drive produced by peripheral chemoreceptor input to the central respiratory generator.

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Decreased energy metabolism in brain stem during central respiratory depression in response to hypoxia

Journal of Applied Physiology ◽

10.1152/jappl.1996.81.4.1772 ◽

1996 ◽

Vol 81 (4) ◽

pp. 1772-1777 ◽

Cited By ~ 27

Author(s):

J. C. Lamanna ◽

M. A. Haxhiu ◽

K. L. Kutina-Nelson ◽

S. Pundik ◽

B. Erokwu ◽

...

Keyword(s):

Energy Metabolism ◽

Brain Stem ◽

Respiratory Depression ◽

Intracellular Ph ◽

Metabolic Changes ◽

Nucleus Ambiguus ◽

Electromyographic Activity ◽

Respiratory Drive ◽

Energy Deficiency ◽

The Brain

LaManna, J. C., M. A. Haxhiu, K. L. Kutina-Nelson, S. Pundik, B. Erokwu, E. R. Yeh, W. D. Lust, and N. S. Cherniack.Decreased energy metabolism in brain stem during central respiratory depression in response to hypoxia. J. Appl. Physiol. 81(4): 1772–1777, 1996.—Metabolic changes in the brain stem were measured at the time when oxygen deprivation-induced respiratory depression occurred. Eucapnic ventilation with 8% oxygen in vagotomized urethan-anesthetized rats resulted in cessation of respiratory drive, monitored by recording diaphragm electromyographic activity, on average within 11 min (range 5–27 min), presumably via central depressant mechanisms. At that time, the brain stems were frozen in situ for metabolic analyses. By using 20-μm lyophilized sections from frozen-fixed brain stem, microregional analyses of ATP, phosphocreatine, lactate, and intracellular pH were made from 1) the ventral portion of the nucleus gigantocellularis and the parapyramidal nucleus; 2) the compact and ventral portions of the nucleus ambiguus; 3) midline neurons; 4) nucleus tractus solitarii; and 5) the spinal trigeminal nucleus. At the time of respiratory depression, lactate was elevated threefold in all regions. Both ATP and phosphocreatine were decreased to 50 and 25% of control, respectively. Intracellular pH was more acidic by 0.2–0.4 unit in these regions but was relatively preserved in the chemosensitive regions near the ventral and dorsal medullary surfaces. These results show that hypoxia-induced respiratory depression was accompanied by metabolic changes within brain stem regions involved in respiratory and cardiovascular control. Thus it appears that there was significant energy deficiency in the brain stem after hypoxia-induced respiratory depression had occurred.

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Effect of antioxidant ionol on energy metabolism and cardiac function in acute hypoxia followed by reoxygenation

Bulletin of Experimental Biology and Medicine ◽

10.1007/bf00840742 ◽

1989 ◽

Vol 107 (6) ◽

pp. 797-800

Author(s):

L. Yu. Golubeva ◽

L. M. Belkina ◽

V. A. Saltykova ◽

F. Z. Meerson

Keyword(s):

Energy Metabolism ◽

Cardiac Function ◽

Acute Hypoxia ◽

Antioxidant Ionol

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Localization of Central Noradrenergic Mechanisms in Cardiovascular Regulation in Rats

Clinical Science ◽

10.1042/cs048277s ◽

1974 ◽

Vol 48 (s2) ◽

pp. 277s-278s ◽

Cited By ~ 2

Author(s):

H. Struyker Boudier ◽

G. Smeets ◽

G. Brouwer ◽

J. Van Rossum

Keyword(s):

Blood Pressure ◽

Heart Rate ◽

Brain Stem ◽

Cardiovascular Regulation ◽

Anterior Hypothalamus ◽

Anaesthetized Rats ◽

Lower Brain Stem ◽

The Brain

1. Various drugs were injected stereotactically into the brain of anaesthetized rats. 2. Noradrenaline injected into the area of the nucleus of the tractus solitarius in the lower brain stem or into the far anterior hypothalamus/pre-optic region induced a fall in blood pressure and in heart rate related to the administered dose. 3. When injected into the anterior hypothalamus/pre-optic region, clonidine and alpha-methyl-noradrenaline induced a long-lasting decrease in blood pressure and heart rate.

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Cardioventilator effects of TRH in anaesthetized rats: Role of the brain stem

European Journal of Pharmacology ◽

10.1016/0014-2999(86)90168-8 ◽

1986 ◽

Vol 122 (1) ◽

pp. 131-134 ◽

Cited By ~ 14

Author(s):

Ilari Paakkari ◽

Marja-Leena Nurminen ◽

Anna-Leena Sirén

Keyword(s):

Brain Stem ◽

Anaesthetized Rats ◽

The Brain

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Protein kinase C modulation of ventilatory response to hypoxia in nucleus tractus solitarii of conscious rats

Journal of Applied Physiology ◽

10.1152/jappl.1998.84.6.1982 ◽

1998 ◽

Vol 84 (6) ◽

pp. 1982-1990 ◽

Cited By ~ 30

Author(s):

Evelyne Gozal ◽

Anisha L. Roussel ◽

Gregory A. Holt ◽

Lyad Gozal ◽

Yair M. Gozal ◽

...

Keyword(s):

Protein Kinase C ◽

Protein Kinase ◽

Brain Stem ◽

Ventilatory Response ◽

Minute Ventilation ◽

Acute Hypoxia ◽

Nucleus Tractus Solitarii ◽

Western Blots ◽

Kinase C ◽

Essential Components

This study aimed to determine the role of protein kinase C (PKC) in signal transduction mechanisms underlying ventilatory regulation in the nucleus tractus solitarii (NTS). Microinjection of phorbol 12-myristate 13-acetate into the commissural NTS of nine chronically instrumented, unrestrained rats elicited significant cardiorespiratory enhancements that lasted for at least 4 h, whereas administration of vehicle ( n = 15) or the inactive phorbol ester 4α-phorbol 12,13-didecanoate ( n = 7) did not elicit minute ventilation (V˙e) changes. Peak hypoxic V˙eresponses (10% O2-balance N2) were measured in 19 additional animals after NTS microinjection of bisindolylmaleimide (BIM) I, a selective PKC inhibitor ( n= 12), BIM V (inactive analog; n = 7), or vehicle (Con; n = 19). In Con,V˙e increased from 139 ± 9 to 285 ± 26 ml/min in room air and hypoxia, respectively, and similar responses occurred after BIM V. BIM I did not affect room airV˙e but markedly attenuated hypoxia-induced V˙e increases (128 ± 12 to 167 ± 18 ml/min; P < 0.02 vs. Con and BIM V). When BIM I was microinjected into the cerebellum ( n = 4), cortex ( n = 4), or spinal cord ( n = 4),V˙e responses were similar to Con. Western blots of subcellular fractions of dorsocaudal brain stem lysates revealed translocation of PKCα, β, γ, δ, ε, and ι isoenzymes during acute hypoxia, and enhanced overall PKC activity was confirmed in the particulate fraction of dorsocaudal brain stem lysates harvested after acute hypoxia. These studies suggest that, in the adult rat, PKC activation in the NTS mediates essential components of the acute hypoxic ventilatory response.

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In vivo modular control analysis of energy metabolism in contracting skeletal muscle

Biochemical Journal ◽

10.1042/bj20080280 ◽

2008 ◽

Vol 414 (3) ◽

pp. 391-397 ◽

Cited By ~ 9

Author(s):

Laurent M. Arsac ◽

Christophe Beuste ◽

Sylvain Miraux ◽

Véronique Deschodt-Arsac ◽

Eric Thiaudiere ◽

...

Keyword(s):

Skeletal Muscle ◽

Energy Metabolism ◽

Contractile Activity ◽

Metabolic Control Analysis ◽

Resonance Spectroscopy ◽

Control Analysis ◽

Modular Control ◽

Anaesthetized Rats ◽

Control Pattern

We used 31P MRS (magnetic resonance spectroscopy) measurements of energetic intermediates [ATP, Pi and PCr (phosphocreatine)] in combination with the analytical tools of metabolic control analysis to study in vivo energy metabolism in the contracting skeletal muscle of anaesthetized rats over a broad range of workload. According to our recent MoCA (modular control analysis) used to describe regulatory mechanisms in beating heart, we defined the energetic system of muscle contraction as two modules (PCr-Producer and PCr-Consumer) connected by the energetic intermediates. Hypoxia and electrical stimulation were used in this in vivo study as reasonably selective modulations of Producer and Consumer respectively. As quantified by elasticity coefficients, the sensitivities of each module to PCr determine the control of steady-state contractile activity and metabolite concentrations. The magnitude of the elasticity of the producer was high (4.3±0.6) at low workloads and decreased 5-fold (to 0.9±0.2) at high workloads. By contrast, the elasticity of the consumer remained low (0.5–1.2) over the range of metabolic rates studied. The control exerted by each module over contraction was calculated from these elasticities. The control of contraction was found on the consumer at low workloads and then swung to the producer, due to the workload-dependent decrease in the elasticity of producer. The workload-dependent elasticity and control pattern of energy production in muscle is a major difference from heart. Since module rate and elasticity depend on the concentrations of substrates and products, the absence of homoeostasis of the energetic intermediates in muscle, by contrast with heart, is probably the origin of the workload-dependent elasticity of the producer module.

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The improved energy metabolism and blood oxygen-carrying capacity for pufferfish, Takifugu fasciatus, against acute hypoxia under the regulation of oxygen sensors

Fish Physiology and Biochemistry ◽

10.1007/s10695-018-0565-2 ◽

2018 ◽

Vol 45 (1) ◽

pp. 323-340

Author(s):

Xinru Li ◽

Tao Wang ◽

Shaowu Yin ◽

Guosong Zhang ◽

Quanquan Cao ◽

...

Keyword(s):

Energy Metabolism ◽

Carrying Capacity ◽

Acute Hypoxia ◽

Oxygen Sensors ◽

Blood Oxygen ◽

Takifugu Fasciatus ◽

Oxygen Carrying Capacity

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Adaptation to hypobaric hypoxia involves GABAA receptors in the pons

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00339.2007 ◽

2008 ◽

Vol 294 (2) ◽

pp. R549-R557 ◽

Cited By ~ 9

Author(s):

Yee-Hsee Hsieh ◽

Thomas E. Dick ◽

Ruth E. Siegel

Keyword(s):

Brain Stem ◽

Hypobaric Hypoxia ◽

Molecular Mechanisms ◽

De Novo ◽

Acute Hypoxia ◽

Receptor Expression ◽

Dependent Manner ◽

Low Oxygen ◽

Subunit Expression ◽

The Brain

Survival in low-oxygen environments requires adaptation of sympathorespiratory control networks located in the brain stem. The molecular mechanisms underlying adaptation are unclear. In naïve animals, acute hypoxia evokes increases in phrenic (respiratory) and splanchnic (sympathetic) nerve activities that persist after repeated challenges (long-term facilitation, LTF). In contrast, our studies show that conditioning rats to chronic hypobaric hypoxia (CHH), an environment characteristic of living at high altitude, diminishes the response to hypoxia and attenuates LTF in a time-dependent manner. Phrenic LTF decreases following 7 days of CHH, and both sympathetic and phrenic LTF disappear following 14 days of CHH. Previous studies demonstrated that GABA is released in the brain stem during hypoxia and depresses respiratory activity. Furthermore, the sensitivity of brain stem neurons to GABA is increased following prolonged hypoxia. In this study, we demonstrate that GABAA receptor expression changes along with the CHH-induced physiological changes. Expression of the GABAA receptor α4 subunit mRNA increases two-fold in animals conditioned to CHH for 7 days. In addition, de novo expression of δ and α6, a subunit normally found exclusively in the cerebellum, is observed after 14 days. Consistent with these changes, diazepam-insensitive binding sites, characteristic of GABAA receptors containing α4 and α6 subunits, increase in the pons. Immunohistochemistry revealed that CHH-induced GABAA receptor subunit expression is localized in regions of sympathorespiratory control within the pons. Our findings suggest that a GABAA receptor mediated-mechanism participates in adaptation of the sympathorespiratory system to hypobaric hypoxia.

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