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

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.

1995 ◽  
Vol 82 (2) ◽  
pp. 491-501 ◽  
Author(s):  
Andrea Dicker ◽  
Kerstin B. E. Ohlson ◽  
Lennart Johnson ◽  
Barbara Cannon ◽  
Sten G.E. Lindahl ◽  
...  

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.


1977 ◽  
Vol 42 (2) ◽  
pp. 154-158 ◽  
Author(s):  
C. A. Fuller ◽  
J. M. Horowitz ◽  
B. A. Horwitz

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.


1997 ◽  
Vol 83 (3) ◽  
pp. 830-836 ◽  
Author(s):  
James E. Fewell ◽  
Maria Kang ◽  
Heather L. Eliason

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.


1981 ◽  
Vol 15 (4) ◽  
pp. 313-317 ◽  
Author(s):  
B. G. Miller ◽  
J. K. Kirkwood ◽  
K. Howard ◽  
A. Tuddenham ◽  
A. J. F. Webster

The calorimeter has special features which make it independent of changes in ambient temperature and pressure and therefore able to record precisely not only the integral of respiratory exchange over periods of 24 h but also the rate of oxygen consumption over short periods. Experiments with mice and kestrels ( Falco tinnunculus) are presented to illustrate the accuracy of the apparatus.


1964 ◽  
Vol 15 (1) ◽  
pp. 311-317 ◽  
Author(s):  
Arnold A. Gerall ◽  
William S. Berg

The normal rate of O2 consumption of 10 mature male guinea pigs was compared with that produced during the first several days in the novel situation and by sexual satiation and frustration. A higher than normal rate of O2 consumption recorded on the first day was followed by a lower than normal rate on the second and third days. Neither sexual satiation derived from ejaculation nor frustration produced by interrupting the copulatory pattern after the first intromission was found to modify significantly the normal rate of metabolism. In an attempt to explain these results, several hypotheses were suggested based on either the tendency of the guinea pig to crouch when frightened or the nature of the stimuli in the chamber of the metabolism apparatus.


1975 ◽  
Vol 228 (5) ◽  
pp. 1519-1524 ◽  
Author(s):  
CA Fuller ◽  
BA Horwitz ◽  
JM Horowitz

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.


1957 ◽  
Vol 190 (3) ◽  
pp. 425-428 ◽  
Author(s):  
Richard M. Hoar ◽  
William C. Young

Oxygen consumption and heart rate during pregnancy were measured in untreated, thyroxin-injected and thyroidectomized guinea pigs given I131. From impregnation until parturition, oxygen consumption increased 7.9% in untreated females. The increase continued until 5 days postpartum when a sharp decrease occurred. The increase is not accounted for by growth of the fetal mass. Comparable increases occurred in thyroxin-injected (16.2%) and thyroidectomized (11.9%) females, although the levels throughout were higher and lower, respectively, than in intact females. Heart rate did not increase. On the contrary, statistically significant decreases occurred in the untreated and thyroxin-injected females. Although the mechanism associated with the increased metabolic rate is not known, the possibility of thyroid participation would seem to be excluded. Involvement of the adrenal cortex is suggested by morphological differences in the cells of the zona fasciculata in pregnant and nonpregnant females and by evidence cited from other studies.


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.


1996 ◽  
Vol 271 (3) ◽  
pp. F717-F722
Author(s):  
G. Bajaj ◽  
M. Baum

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.


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