Halothane Selectively Inhibits Nonshivering Thermogenesis 

1995 ◽  
Vol 82 (2) ◽  
pp. 491-501 ◽  
Author(s):  
Andrea Dicker ◽  
Kerstin B. E. Ohlson ◽  
Lennart Johnson ◽  
Barbara Cannon ◽  
Sten G.E. Lindahl ◽  
...  
Keyword(s):  
Oxygen Consumption ◽  
Inhibitory Effect ◽  
Nonshivering Thermogenesis ◽  
Halothane Anesthesia ◽  
Control Series ◽  
Mechanically Ventilated ◽  
Anesthetized Rats ◽  
Rate Of Oxygen Consumption ◽  
Spontaneously Breathing ◽  
Thermogenic Response

Background During halothane anesthesia, infants fail to increase oxygen consumption in response to a cold stimulus in the form of an increase in temperature gradient between body and environment. Based on recent observations with isolated brown-fat cells, it seemed feasible that this inability to respond could be due to an inhibition of nonshivering thermogenesis during halothane anesthesia. Methods The rate of oxygen consumption was measured in cold-acclimated hamsters and rats. The rate evoked by norepinephrine injection in hamsters at an environmental temperature of approximately 24 degrees C was used as a measure of the capacity for nonshivering thermogenesis. Anesthesia was induced by 3% halothane and maintained by 1.5% halothane. One experimental series with spontaneously breathing hamsters and a second control series with spontaneously breathing rats and with rats whose lungs were mechanically ventilated were conducted. Results Norepinephrine injection led to a fourfold increase in the rate of oxygen consumption in control hamsters; after this response had subsided, a second injection led to a similar effect. Halothane anesthesia caused an approximately 20% decrease in resting metabolic rate (P < 0.05) and a 70% inhibition of the thermogenic response to norepinephrine (P < 0.001). The halothane concentration yielding half-maximal inhibitory effect was estimated to be less than 1.0%. After the animals had recovered from halothane anesthesia, a completely restored thermogenic response to norepinephrine was observed. The inhibitory effect of halothane also was observed in hamsters maintained at normothermia and was therefore not secondary to the slight hypothermia that otherwise developed during anesthesia. In a series of control experiments, it was confirmed that rats also showed large thermogenic responses to norepinephrine injections, and it was found that, in spontaneously breathing halothane-anesthetized rats, the thermogenic response to norepinephrine was also much inhibited. Further, in halothane-anesthetized rats whose lungs were mechanically ventilated, and where blood gases were kept at virtually normal levels, the thermogenic response to norepinephrine was found to be similarly markedly inhibited. Conclusions A much diminished or abolished thermogenic response to injected norepinephrine was demonstrated in halothane-anesthetized animals. This implies that there would be a diminished ability to elicit nonshivering thermogenesis even when this process is physiologically induced. Such a diminished ability could in part explain the susceptibility of neonates and infants to hypothermia during halothane anesthesia.

Responses of cold- and warm-adapted dogs to infused norepinephrine and acute body cooling

1965 ◽  
Vol 209 (1) ◽  
pp. 227-230 ◽  
Author(s):  
Tetsuo Nagasaka ◽  
Loren D. Carlson
Keyword(s):  
Heart Rate ◽  
Oxygen Consumption ◽  
Cold Exposure ◽  
Nonshivering Thermogenesis ◽  
Mechanically Ventilated ◽  
Cold Adapted ◽  
Pentobarbital Sodium ◽  
Acute Cold Exposure ◽  
Increased Sensitivity ◽  
Body Cooling

Oxygen consumption, heart rate, and colonic, pinna, and paw temperatures were recorded continuously in warm-adapted (W-A) and cold-adapted (C-A) dogs anesthetized with pentobarbital sodium (30 mg/kg), paralyzed with Flaxedil (5 mg/kg per hr), and mechanically ventilated. The dogs were infused with norepinephrine (1.25 µg/kg per min) for 20 min at 30 C and after 45 min of acute cold exposure to 5 C. Oxygen consumption of C-A dogs increased with a slight increase in the heart rate during the initial 18–20 min of body cooling. O2 consumption decreased continuously during cold exposure in W-A dogs. Calorigenic effects of infused noradrenaline were similar in C-A and W-A dogs at 30 C and 5 C. Heart rate increased in W-A dogs at 30 and 5 C. These results show that nonshivering thermogenesis is well developed by cold acclimation in dogs, and suggest that the increase may be due to an increase in noradrenaline in blood rather than to increased sensitivity of the animals to the calorigenic effects of noradrenaline.

Role of serotonin3 receptors in the nucleus tractus solitarii on the carotid chemoreflex

1997 ◽  
Vol 272 (3) ◽  
pp. H1250-H1259 ◽  
Author(s):  
C. Sevoz ◽  
J. C. Callera ◽  
B. H. Machado ◽  
M. Hamon ◽  
R. Laguzzi
Keyword(s):  
Inhibitory Effect ◽  
Nucleus Tractus Solitarii ◽  
Inhibitory Influence ◽  
Dependent Manner ◽  
Gamma Aminobutyric Acid ◽  
Receptor Stimulation ◽  
Gaba A ◽  
Anesthetized Rats ◽  
Carotid Body Chemoreceptors ◽  
Spontaneously Breathing

The effects of serotonin3 (5-HT3)-receptor stimulation in the nucleus tractus solitarii (NTS) on the cardiovagal, sympathetic, and respiratory responses to activation of carotid body chemoreceptors were investigated in anesthetized rats. The chemoreflex responses were triggered by an intravenous administration of KCN (40 microg/kg) in spontaneously breathing urethan-chloralose-anesthetized rats or by an intracarotid administration of saline saturated with 100% CO2 in pancuronium bromide-paralyzed and artificially ventilated urethan-anesthetized rats. Microinjections of 5-HT (2.5-5 nmol) or the 5-HT3 agonist 1-(m-chlorophenyl)-biguanide (CPBG, 300-1,200 pmol) into the commissural NTS blocked in a dose-dependent manner the atropine-sensitive chemoreflex bradycardia elicited by KCN. However, neither 5-HT nor CPBG affected the KCN-induced increase in respiratory volume and the CO2-induced increases in blood pressure and lumbar sympathetic nerve discharge. The inhibitory effect of 5-HT or CPBG on KCN-induced bradycardia was blocked by prior intra-NTS microinjection of a 5-HT3 antagonist, such as zacopride (100 pmol) or ondansetron (100 pmol), or the A-type gamma-aminobutyric acid (GABA(A)) antagonist bicuculline (10 pmol). In contrast, local microinjections of antagonists acting at 5-HT1 and 5-HT2 receptors, such as methysergide (100 pmol) and ketanserin (10 pmol), respectively, did not prevent the actions of 5-HT or CPBG. These data show that the stimulation of 5-HT3 receptors in the NTS exerted an inhibitory influence, probably through the activation of a local GABAergic system, on the cardiovagal component of the chemoreflex. Because similar effects of 5-HT3-receptor stimulation in the NTS were previously found on the baroreflex and Bezold-Jarisch reflex responses, it can be inferred that NTS 5-HT3 receptors play a key modulatory role in the reflex control of the heart rate.

Spinal cord thermosensitivity and sorting of neural signals in cold-exposed rats

1977 ◽  
Vol 42 (2) ◽  
pp. 154-158 ◽  
Author(s):  
C. A. Fuller ◽  
J. M. Horowitz ◽  
B. A. Horwitz
Keyword(s):  
Spinal Cord ◽  
Oxygen Consumption ◽  
Study Data ◽  
Direct Influence ◽  
Nonshivering Thermogenesis ◽  
Neural Signals ◽  
Spinal Cord Temperature ◽  
Identical Manner ◽  
Rate Of Oxygen Consumption ◽  
Spinal Cord Thermosensitivity

In the present study, data relevant to the presence or absence of sorting of neural signals were obtained by evaluating the thermal responses to spinal warming in the chronically prepared rat. Specifically, shivering activity and the rate of oxygen consumption (VO2) were measured in unanesthetized rats during cold exposure (10–16 degrees C). Warming the spinal cord at the level of T2 resulted in a significant decrease in shivering (P less than 0.001), without a significant change in VO2. The shivering response was reversed upon cessation of heating. These results are interpreted as indicating a direct influence of spinal cord temperature on shivering but not nonshivering thermogenesis in the rat. Similarly, in previous work with the rat, we have obtained data supporting hypothalamic receptor control of nonshivering but not shivering heat production. These findings are thus consistent with the suggestion that in the rat there occurs a sorting of neural signals. That is, impulses from the three thermoreceptor locations are not integrated in an identical manner for the control of shivering and nonshivering thermogenesis.

scholarly journals THE OXYGEN CONSUMPTION ASSOCIATED WITH GROWTH IN ESCHERICHIA COLI AND THE EFFECT OF SULFATHIAZOLE AND OF n-PROPYL CARBAMATE ON IT

1947 ◽  
Vol 30 (3) ◽  
pp. 279-289 ◽  
Author(s):  
Florence H. Armstrong ◽  
Kenneth C. Fisher
Keyword(s):  
Oxygen Consumption ◽  
Viable Cell ◽  
Sole Source ◽  
Inhibitory Effect ◽  
Total Oxygen ◽  
E Coli ◽  
Inhibition Of Growth ◽  
Cell Counts ◽  
Growing Cell ◽  
Rate Of Oxygen Consumption

1. The rate of oxygen consumption by E. coli has been observed both in the presence and absence of ammonia which substance is used by this organism in these experiments as the sole source of nitrogen for growth. 2. After the ammonia has been completely taken up in a culture of E. coli, the rate of oxygen consumption by the culture is observed to fall rapidly. It becomes relatively constant again at a rate approximately 45 per cent of that existing immediately prior to the exhaustion of the nitrogen source. It appears that the fixation of ammonia, that is, growth, requires approximately 55 per cent of the oxygen consumed by the growing cell. 3. Inhibition of the oxygen consumption which is associated with ammonia fixation, by both sulfathiazole (ST) and n-propyl carbamate (PC) closely parallels the inhibition of growth by these compounds (as measured by viable cell counts, etc.). 4. The concentrations of ST and PC which inhibit growth exert little or no inhibitory effect on the rate of oxygen consumption by cells after the rate has fallen to the resting value. 5. It is pointed out that the above observations would be adequately accounted for if growth depended on a discrete fraction of the total oxygen consumption of the growing cell. 6. It is noted that PC, but not ST, has a significant accelerating effect on the oxygen consumption of the resting cell; and that for a given inhibition of growth, PC produces less inhibition of the total oxygen consumption of the cells, than does ST. The latter of these two observations would follow from the former if the resting oxygen consumption were a discrete entity.

Thermogenesis Inhibition in Brown Adipocytes Is a Specific Property of Volatile Anesthetics

2003 ◽  
Vol 98 (2) ◽  
pp. 437-448 ◽  
Author(s):  
Kerstin B.E. Ohlson ◽  
Sten G.E. Lindahl ◽  
Barbara Cannon ◽  
Jan Nedergaard
Keyword(s):  
Oxygen Consumption ◽  
Heat Production ◽  
Specific Property ◽  
Clinical Importance ◽  
Volatile Anesthetics ◽  
Oxygen Electrode ◽  
Inhibitory Effect ◽  
Nonshivering Thermogenesis ◽  
Brown Adipocytes ◽  
Anesthetic Agents

Background This investigation examined the possibility that the inhibitory effect of halothane on nonshivering thermogenesis (heat production) in brown adipocytes is not a universal effect of all anesthetic agents but related to the type of anesthetic. Methods Brown adipocytes from hamster were isolated with a collagenase digestion method and incubated with anesthetic agents. The rate of oxygen consumption was measured with an oxygen electrode. The effect of clinically relevant (and higher) doses of anesthetics of different classes on basal and norepinephrine-induced thermogenesis (oxygen consumption) was tested. Results Two distinct groups of anesthetics could be distinguished: thermogenesis inhibitors and noninhibitors. Thermogenesis inhibitors include volatile anesthetics such as halothane (IC(50), 1.1 mm), ether (IC(50), 20 mm), and chloroform (IC(50), 2.2 mm) (nominal concentrations), but also tribromoethanol (IC(50), 0.6 mm), all inducing inhibition of norepinephrine-induced thermogenesis without affecting the EC for norepinephrine. Thermogenesis noninhibitors include the nonvolatile anesthetics pentobarbital, propofol, ketamine, and urethane, the inhalation anesthetic nitrous oxide, and, notably, also the volatile nonanesthetics (nonimmobilizers) 1,2-dichlorohexafluorocyclobutane and 2,3-dichlorooctafluorobutane; none of these compounds had any effect on norepinephrine-induced thermogenesis at any concentration tested. Conclusions There are two distinct classes of anesthetics with regard to effects on thermogenesis, thermogenesis inhibitors and thermogenesis noninhibitors. The results are important for the interpretation of studies in thermal biology in general; specifically, they indicate that conclusions concerning regulation of nonshivering thermogenesis during anesthesia depend on the type of anesthetic used. Of clinical importance is that the volatile anesthetics are inhibitory for nonshivering thermogenesis and thus for an alternative heat production when myorelaxants prevent shivering. As the distinction between thermogenesis inhibitors and thermogenesis noninhibitors corresponds to the distinction between volatile and nonvolatile anesthetics, it may be related to the mode of action of the volatile anesthetics.

Shivering and nonshivering thermogenic responses of cold-exposed rats to hypothalamic warming

1975 ◽  
Vol 228 (5) ◽  
pp. 1519-1524 ◽  
Author(s):  
CA Fuller ◽  
BA Horwitz ◽  
JM Horowitz
Keyword(s):  
Oxygen Consumption ◽  
Heat Production ◽  
Neural Control ◽  
Nonshivering Thermogenesis ◽  
Neural Controllers ◽  
Rate Of Oxygen Consumption ◽  
Exposed Animal ◽  
Unanesthetized Animals ◽  
Shivering Thermogenesis ◽  
Rule Out

The concurrent neural control of two thermoregulatory responses, shivering thermogenesis (ST) and nonshivering thermogenesis (NST), was investigated in chronically implanted cold-exposed rats. The effects of heating the preoptic/anterior hypothalamus (POAH) on shivering and on the rate of oxygen consumption (Vo2) were measured in these unanesthetized animals. With ambient temperature maintained constant (at some value between 10 and 16 degrees C), warming the hypothalamus 2-3 degrees C resulted in a significant decrease in Vo2 (Psmaller than 0.001) and an increase in shivering (Psmaller than .01), these responses being reversed on cessation of hypothalamic warming. These results are consistent with the proposal that, in the cold-exposed animal, elevated POAH temperatures directly inhibit NST even though shivering may increase (possibly as a compensation for the decrease in nonshivering heat production). They also rule out the possibility that, in the rat, signals from cutaneous and hypothalamic thermoreceptors are integrated in an indentical manner by the neural controllers for ST and NST.

Effect of propranolol on endotoxin-induced pyrogenesis in newborn and adult guinea pigs

1976 ◽  
Vol 40 (1) ◽  
pp. 35-39 ◽  
Author(s):  
C. M. Blatteis
Keyword(s):  
Oxygen Consumption ◽  
Ambient Temperature ◽  
Guinea Pigs ◽  
Salmonella Enteritidis ◽  
Nonshivering Thermogenesis ◽  
Fat Pad ◽  
Adrenergic Blocker ◽  
Rate Of Oxygen Consumption ◽  
Propranolol Administration ◽  
Newborn Animals

Previous studied have shown that nonshivering thermogenesis (NST) is the prevailing mechanism of fever production in both newborn (during the first 2–3 wk of life) and adult cold-acclimated guinea pigs. This study was undertaken to determine whether this process may be mediated by noradrenergic sympathetics. The temperatures in the interscapular brown fat pad (Tbat) and the colon (Tre), the rate of oxygen consumption (VO2), and shivering activity were measured continuously for 5 h at 27 degrees C ambient temperature in 8- and 16-day-old and adult cold-acclimated guinea pigs following 2 mug/kg iv of Salmonella enteritidis endotoxin, with and without 6.0 mg/kg of propranolol (a beta-adrenergic blocker) injected ip 2 min before the endotoxin. In the older animals, the increase in Tbat normally produced by endotoxin was reduced by propranolol administration, but shivering set in, maintaining both VO2 and Tre at their febrile levels. In the newborn animals, Tbat also was decreased by propranolol, but shivering did not set in, so that VO2 and Tre fell below their febrile values. It is concluded that endotoxin-induced NST is controlled by noradrenergic sympathetics. The failure of NST to be replaced in the present newborn guinea pigs by visible shivering might be related to other observations that the onset of shivering at this age occurs only when Tre is significantly reduced.

scholarly journals Recovery heat in muscular contraction without lactic acid formation

1931 ◽  
Vol 108 (757) ◽  
pp. 279-301 ◽  
Keyword(s):  
Acetic Acid ◽  
Oxygen Consumption ◽  
Lactic Acid ◽  
Muscular Contraction ◽  
Acid Formation ◽  
Anaerobic Conditions ◽  
Spontaneous Breakdown ◽  
Rate Of Oxygen Consumption ◽  
Resting Muscle

In a comparison of muscles poisoned with mono-iodo-acetic acid (IAA) in the presence and in the absence of oxygen respectively, Lundsgaard (1930) found:- (1) That the spontaneous breakdown of phosphagen in poisoned resting muscle is much more rapid under anaerobic conditions. (2) That the onset of the characteristic contracture produced by IAA is accompanied always by an increase in the rate of oxygen consumption.

Proximal tubule dysfunction in cystine-loaded tubules: effect of phosphate and metabolic substrates

1996 ◽  
Vol 271 (3) ◽  
pp. F717-F722
Author(s):  
G. Bajaj ◽  
M. Baum
Keyword(s):  
Oxygen Consumption ◽  
Proximal Tubule ◽  
Tricarboxylic Acid Cycle ◽  
Dimethyl Ester ◽  
Proximal Tubules ◽  
Intracellular Atp ◽  
Metabolic Substrates ◽  
Rate Of Oxygen Consumption ◽  
Intracellular Phosphate

Intracellular cystine loading by use of cystine dimethyl ester (CDME) results in a generalized inhibition in proximal tubule transport due, in part, to a decrease in intracellular ATP. The present study examined the importance of phosphate and metabolic substrates in the proximal tubule dysfunction produced by cystine loading. Proximal tubule intracellular phosphorus was 1.8 +/- 0.1 in control tubules and 1.1 +/- 0.1 nmol/mg protein in proximal tubules incubated in vitro with CDME P < 0.001). Infusion of sodium phosphate in rabbits and subsequent incubation of proximal tubules with a high-phosphate medium attenuated the decrease in proximal tubule respiration and prevented the decrease in intracellular ATP with cystine loading. Tricarboxylic acid cycle intermediates have been shown to preserve oxidative metabolism in phosphate-depleted proximal tubules. In proximal tubules incubated with either 1 mM valerate or butyrate, there was a 42 and 34% reduction (both P < 0.05) in the rate of oxygen consumption with cystine loading. However, tubules incubated with 1 mM succinate or citrate had only a 13 and 14% P = NS) reduction in the rate of oxygen consumption, respectively. These data are consistent with a limitation of intracellular phosphate in the pathogenesis of the proximal tubule dysfunction with cystine loading.

Viability and respiratory activity ofPseudomonas syringaecells starved in buffer

1995 ◽  
Vol 41 (4-5) ◽  
pp. 372-377 ◽  
Author(s):  
João P. S. Cabral
Keyword(s):  
Oxygen Consumption ◽  
Electron Transport ◽  
Pseudomonas Syringae ◽  
Respiratory Activity ◽  
Bacterial Cells ◽  
Intact Cells ◽  
Rate Of Oxygen Consumption ◽  
Metabolic Activities ◽  
Different Levels ◽  
Number Of Cells

Pseudomonas syringae cells starved in buffer released orcinol-reactive molecules and materials that absorbed ultraviolet light. The number of cells culturable in nutrient medium decreased more rapidly than the number of intact particles determined by microscopy. The results suggested that starvation resulted in the lysis of an increasing number of cells, and that a fraction of the intact particles were not culturable. Starvation also resulted in a decrease in the rate of oxygen consumption with acetate, glycerol, and succinate, but at different levels. Whereas the respiration of acetate and glycerol decreased concomitantly with culturability, the respiration of succinate decreased to levels similar to the concentration of intact cells, suggesting that all intact particles respired the succinate, but only the culturable cells respired the acetate and glycerol. The results suggest that measuring the activity of the electron-transport system can overestimate the viability of starved bacterial cells, and that complex metabolic activities such as the respiration of acetate and glycerol are probably better suited for the evaluation of this parameter.Key words: Pseudomonas syringae, starvation, culturability, viability, respiration.

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