Biomedical subjects

J E Fewell

Publications and source records attributed to J E Fewell.

At least 37 records · Page 2Linked to original sources

PubMed1997

Autonomic and behavioral thermoregulation in guinea pigs during postnatal maturation.

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.

Aging↗

PubMed1997

Thermoregulatory control during pregnancy and lactation in rats.

Although the mechanisms remain unknown, maternal core temperature (Tc) decreases near term of pregnancy and is increased throughout lactation in rats. The purpose of our present experiments was to determine whether pregnancy and lactation shift the thermoneutral zone of rats and to investigate whether the changes in maternal Tc during pregnancy and lactation result from "forced" or "regulated" thermoregulatory responses. Conscious, chronically instrumented nonpregnant and pregnant and lactating rats were studied both in a thermocline (a chamber with a linear temperature gradient from 12 to 36 degrees C) and in a metabolic chamber to determine the influence of pregnancy and lactation on selected ambient temperature as well as the thermoregulatory response to changes in ambient temperature. We found that selected ambient temperature, oxygen consumption, and thermal conductance did not change in rats studied in a thermocline as Tc decreased near term of pregnancy. There was, however, a downward shift in the thermoneutral zone of rats studied in a metabolic chamber near term of pregnancy. During lactation, selected ambient temperature decreased in rats studied in a thermocline as oxygen consumption and Tc increased. The thermoneutral zone of lactating rats was not different from that of nonpregnant animals. Thus our data provide evidence that the decrease in Tc near term of pregnancy in rats results from a regulated thermoregulatory response, whereas the increase in Tc during lactation results from a forced thermoregulatory response.

Animals↗

PubMed1997

Influence of nicotine on the core temperature response to a novel environment in pregnant rats.

Exposure of a male or nonpregnant female rat to a novel environment, such as a simulated open field, induces a transient increase in core temperature, which is often called stress-induced hyperthermia. Pregnancy alters this response such that the core temperature index increases significantly during exposure to a simulated open field on day 10 but not on days 15 and 20 of gestation in rats. The present experiments were carried to investigate the effect of chronic administration of nicotine (0, 1, 2, 4, or 8 mg.kg-1.24 h-1 for 13-15 days) on the core temperature response to a simulated open field in chronically instrumented pregnant (day 20 or 21 of gestation) and nonpregnant Sprague-Dawley rats. In nonpregnant rats, the core temperature index increased more during exposure to a simulated open field after chronic administration of nicotine at all doses than after chronic administration of vehicle; the core temperature response was not dependent on the dose of nicotine. In pregnant rats, significant increases in core temperature as well as in the core temperature index occurred only during exposure to a simulated open field after chronic administration of nicotine in doses of 2, 4, or 8 mg.kg-1.24 h-1; the core temperature response was dependent on the dose of nicotine. Our data provide evidence that chronic exposure to nicotine enhances the core temperature response to a simulated open field in nonpregnant rats and unmasks a maternal thermogenic response that is not seen to the same stimulus near term of pregnancy. The possible physiological consequences for the fetus are presently unknown and require investigation.

Animals↗

PubMed1996

Influence of pregnancy on the febrile response to intracerebroventricular administration of PGE1 in rats.

Rats have an attenuated or absent febrile response to exogenous pyrogen (e.g., bacterial endotoxin) and endogenous pyrogen (e.g., interleukin-1 beta) near term of pregnancy. The present experiments have been carried out on 19 nonpregnant and 18 time-bred pregnant Long-Evans rats to investigate the febrile response to intracerebroventricular (ICV) administration of prostaglandin E1 (PGE1). Each rat was anesthetized, a biotelemetry device was placed in the peritoneal cavity for measurement of body core temperature (Tbc), and guide cannulas were placed above the lateral cerebral ventricles for ICV injection of PGE1. At least 6 days were allowed to lapse between surgery and the experiments. ICV injection of 0.2 micrograms PGE1 produced significant increases in Tbc in both nonpregnant and pregnant animals (day 19 of gestation). The increase in Tbc as well as the fever index, however, were significantly attenuated in the pregnant compared with the nonpregnant rats. Vehicle had no effect on Tbc or fever index in either group of animals. The attenuated febrile response to PGE1 in the pregnant rats may have resulted from a pregnancy-related activation of endogenous antipyretics and/or impaired thermoregulatory effector mechanisms.

Alprostadil↗

PubMed1996

Decreased body-core temperature during acute hypoxemia in guinea pigs during postnatal maturation: a regulated thermoregulatory response.

In newborn mammals, hypoxemia produces a decrease in body-core temperature (Tbc), the mechanism of which is unknown. Experiments were therefore carried out to determine whether this decrease results from a regulated or a forced thermoregulatory response. Seven Hartley strain guinea pigs were studied on postnatal days 2, 5, 10, 15, and 26 following implantation of a biotelemetry transmitter into the peritoneal cavity on day 1 to measure Tbc. During each experiment, Tbc and selected ambient temperature were determined in a thermocline (15-40 degrees C gradient) during a control period of normoxemia, an experimental period of hypoxemia (produced by decreasing the fraction of inspired oxygen from 0.21 to 0.10), and a recovery period of normoxemia. We reasoned that no change or a decrease in selected ambient temperature while Tbc decreased during hypoxemia would indicate a regulated thermoregulatory response, whereas an increase in selected ambient temperature while Tbc decreased during hypoxemia would indicate a forced thermoregulatory response. Tbc decreased during hypoxemia at all ages; the response was accentuated on days 15 and 26 compared with day 2. Selected ambient temperature decreased during hypoxemia in the youngest animals but remained the same in the older animals. Our data provide evidence that postnatal maturation influences the thermoregulatory response to hypoxemia in guinea pigs and support the hypothesis that the decrease in Tbc during hypoxemia results from a regulated thermoregulatory response.

Acute Disease↗

PubMed1995

Automated scoring of sleep in the neonatal lamb.

The study of sleep is an important and rapidly expanding area of research that generates large bodies of data. Manual scoring of sleep states from polygraph recordings is a laborious and often subjective task. Even when care is taken, the opportunity for disagreement between investigators and between laboratories remains great. To avoid this difficulty and to reduce the subjectivity of sleep state scoring we have designed a computer-based algorithm for scoring sleep state in the lamb. The algorithm underlying the system relies upon spectral analysis of the electrocorticogram and upon amplitude analysis of the electrooculogram and nuchal electromyogram. Partitioning the spectral power observed within the electrocorticogram (1-4 Hz frequency range) reliably identifies deep quiet sleep. Wakefulness and active sleep are then identified based upon threshold crossings of the electrooculogram and of the electromyogram of the nuchal muscles. We compared the sleep states returned by the algorithm to those scored visually by trained personnel for 1 hour of data collected from each of five 19-day-old lambs. There was good agreement between the two methods of scoring sleep. The percents agreement between the algorithm-derived scores and visual scores were as follows: active wakefulness 97%, quiet wakefulness 87%, quite sleep 85% and phasic active sleep 82%. As such, our algorithm provides a fast, reliable and objective method for scoring sleep state in the young lamb.

Algorithms↗

PubMed1995

Body temperature regulation in rats near term of pregnancy.

Experiments were carried out to define the effects of pregnancy on body temperature (Tb) regulation in rats. Tb was measured by biotelemetry in six animals from day 10 of pregnancy (term day 21) to postpartum day 10. Average 24-h Tb decreased from day 15 of gestation to the time of parturition. Furthermore, there was a loss of the normal circadian variation of Tb late in gestation, which was again present by postpartum day 2. The decrease in 24-h Tb on day 15 of gestation resulted from this loss of circadian variation, as Tb did not increase during the dark period. The further decrease in Tb on day 20 of gestation resulted from an overall decrease in Tb during the light and dark periods as well as from a loss of the circadian variation in Tb. Tb increased dramatically within 4 h of birth of the first pup, which always occurred on day 21 during the light period. The mechanisms responsible for these dramatic changes in thermoregulation during late gestation and around the time of parturition are presently unknown.

Animals↗

PubMed1995

Influence of sleep and myometrial activity on systemic and uteroplacental hemodynamics in pregnant ewes.

Little is known about the influence of sleep on systemic and uteroplacental hemodynamics during pregnancy. Experiments were therefore carried out on six chronically instrumented pregnant ewes (125-133 days of gestation) to investigate the influence of sleep on systemic and uteroplacental hemodynamics. Because nonlabor myometrial activity influences uteroplacental hemodynamics, we made measurements during quiet wakefulness, quiet sleep, and active sleep in the presence and absence of myometrial activity. Cardiac output, heart rate, and systemic arterial pressure were decreased in active sleep compared with quiet wakefulness; these variables were not significantly altered by myometrial activity. The interaction between sleep and myometrial activity was such that the lowest values of uteroplacental blood flow, as estimated from middle uterine artery blood flow to the pregnant uterine horn and, hence, uteroplacental oxygen delivery occurred during active sleep in the presence of myometrial activity (i.e., decreased approximately 19% compared with quiet wakefulness and the absence of myometrial activity). Further investigation is required to determine the possible fetal consequences of a reduced uteroplacental perfusion in the presence of myometrial activity during sleep.

Animals↗

PubMed1995

Body temperature response to IL-1 beta in pregnant rats.

Rats have an attenuated or absent febrile response to exogenous pyrogen (e.g., bacterial endotoxin) near term of pregnancy. With the aim of providing insight into possible mechanism(s) of the altered febrile response to exogenous pyrogen, experiments have been carried out on 67 time-bred Sprague-Dawley rats to investigate the febrile response to endogenous pyrogen [i.e., interleukin-1 beta (IL-1 beta)]. On day 13 of gestation, intravenous injection of IL-1 beta produced a significant increase in body temperature with a latency of approximately 30 min and a duration of approximately 120 min. In contrast, on days 17 and 21 of gestation as well as on the day of delivery, intravenous injection of IL-1 beta produced significant decreases in body temperature. Thus rats do not develop fever in response to endogenous pyrogen near term of pregnancy but rather become hypothermic. The mechanism of the altered body temperature response to exogenous pyrogen as pregnancy proceeds remains unknown. We speculate, however, that it most likely lies downstream from the formation of endogenous pyrogen.

Animals↗

PubMed1994

Body-core temperature decreases during hypoxic hypoxia in Long-Evans and Brattleboro rats.

In newborn mammals, hypoxic hypoxia produces a regulated decrease in body-core temperature, the mechanism of which is unknown. Since plasma and cerebrospinal fluid levels of arginine vasopressin increase during hypoxemia and intracerebroventricular administration of arginine vasopressin decreases body-core temperature, it has been hypothesized that an increase in central arginine vasopressin may mediate this response. Experiments were therefore carried out to test the hypothesis that the body-core temperature response to hypoxic hypoxia would be different in Brattleboro rats (which lack arginine vasopressin containing cells in the central nervous system) compared with that observed in Long-Evans rats (which have arginine vasopressin containing cells in the central nervous system). Both mild (15% oxygen) and severe (10% oxygen) hypoxic hypoxia decreased body-core temperature in both strains of rats, the decrease actually being accentuated in the Brattleboro rats. Thus, our data do not support the hypothesis that an increase in central arginine vasopressin mediates the regulated decrease in body-core temperature during hypoxic hypoxia in rats.

Animals↗

PubMed1994

Hypoxia similarly impairs metabolic responses to cutaneous and core cold stimuli in conscious rats.

Cold exposure elicits several thermoregulatory responses, including an increased metabolic heat production from shivering and nonshivering thermogenesis. The increased metabolism can be in response to body core and/or body cutaneous cooling. Hypoxic hypoxia has been shown to attenuate the metabolic response to cutaneous cooling. We measured metabolic heat production in adult conscious rats during independent cutaneous and core cooling, during normoxia and hypoxia, to 1) test the hypothesis that hypoxia suppresses the metabolic response to independent core cooling and 2) determine whether hypoxia acts preferentially on the response to cutaneous or core cooling. The animals were studied in a temperature-controlled metabolic chamber, and body core temperature was controlled by an abdominal heat exchange coil. Ambient temperature was varied (10, 19, and 28 degrees C) while core temperature was clamped at 37 degrees C or core temperature was varied (33, 35, and 37 degrees C) at a stable ambient temperature of 28 degrees C. Our data indicate that although the sensitivity of the metabolic response to core cooling is about five to six times that to cutaneous cooling. Hypoxia similarly attenuates thermoregulatory responses to both stimuli.

Animals↗

PubMed1994

Arousal response from sleep to tracheal obstruction in lambs during postnatal maturation.

Experiments were carried out to investigate the arousal response from sleep to tracheal obstruction in lambs during postnatal maturation. Ten fetal sheep were instrumented with electrodes for sleep staging and a tracheotomy was done. After spontaneous vaginal delivery, serial experiments were carried out on the lambs at five postnatal ages: 18-48 h and 4, 6, 11, and 18 d. During an experiment, a 5F balloon-tipped catheter was inserted into the tracheostomy tube so that tracheal obstruction could be produced by inflating the balloon. Measurements were made in quiet sleep and active sleep during control periods of tidal respiration and during experimental periods of tracheal obstruction. Neither sleep state nor age influenced control arterial Hb oxygen saturation (SaO2). SaO2 decreased significantly before arousal during tracheal obstruction in quiet sleep at 18-48 h and in active sleep at all ages. The SaO2 at arousal was always lower in active sleep than in quiet sleep. Overall, however, there were no significant effects of age on the change in SaO2 before arousal in either quiet sleep or active sleep. The time to arousal during tracheal obstruction increased between 18-48 h and 6 d of postnatal life in active sleep but not in quite sleep. Our data provide evidence that the arousal response to tracheal obstruction is functional by 18 h of postnatal life in lambs. The increase in time to arousal after tracheal obstruction in active sleep most likely results from state-specific changes in the factors governing oxygen supply and demand.

Aging↗

PubMed1993

Ontogeny of a circadian rhythm in body temperature in newborn lambs reared independently of maternal time cues.

To investigate the ontogeny of a circadian rhythm in body temperature, we performed 24-h temperature measurements at six postnatal ages in ten newborn lambs reared independently of their ewes. At 18 to 48 h of age, a significant time-of-day variation in body temperature was found, the variation achieving a peak between 5.00 pm and 6.00 pm. Over the next two weeks, this time-of-day variation disappeared, reappearing at 18 days of age, although the phase had shifted such that the peak temperature was achieved between 8.00 am and 9.00 am. At 26 days of age, the time-of-day variation in body temperature was still present, maintaining the same phase relationship as at 18 days of age. It is possible that the significant time-of-day variation observed in the two oldest groups is due to the emergence of a discernable circadian rhythm in body temperature entrained to the light-dark cycle during the second or third week of life, whereas the time-of-day variation observed in the 18 to 48-h old is due to residual effects of entrainment to maternal zeitgebers. We speculate that the lack of any observable time-of-day variation in the 4, 6 and 11 days-old lambs may denote the presence of no rhythm or possibly a free-running rhythm in body temperature in subjects not yet able to entrain to photic zeitgebers.

Animals↗

PubMed1993

Influence of sleep on systemic and coronary hemodynamics in lambs.

Experiments were done on seven lambs between the ages of 18 and 24 days to investigate the effects of sleep on systemic and coronary hemodynamics. Each lamb was anesthetized and instrumented for recordings of electrocorticogram, electro-oculogram and nuchal electromyograms, and for measurements of cardiac output and coronary blood flow as well as systemic arterial blood pressure and arterial-, mixed-venous- and coronary-sinus- hemoglobin oxygen saturations. No sooner than three days after surgery, measurements were made during periods of quiet wakefulness (QW), quiet sleep (QS) and active sleep (AS) at an ambient temperature of 25 degrees C. Cardiac output and heart rate were decreased during AS compared to QW and QS. A significant increase in systemic vascular resistance during AS prevented more than a slight decrease in systemic arterial blood pressure. Coronary blood flow decreased during AS compared to QW and QS. Furthermore, myocardial work as estimated from the product of systolic blood pressure and heart rate decreased during AS compared to QW and QS as did myocardial oxygen consumption and myocardial oxygen transport. Transient hypertensive phases--defined as transient increases in mean blood pressure of greater than 15 mmHg above the mean blood pressure for a period of AS--occurred during eight of 13 periods of AS in four of the seven animals. These transient hypertensive phases were caused primarily by an increase in systemic vascular resistance; surprisingly, coronary vascular resistance also increased at this time when estimated myocardial work was increased.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Fever in young lambs: carotid denervation alters the febrile response to a small dose of bacterial pyrogen.

Experiments were done on 13 young lambs to determine if carotid denervation influences the cardiovascular and metabolic responses to i.v. administration of bacterial pyrogen [Salmonella abortus equi (SAE) 0.3 micrograms]. Each lamb was anesthetized with halothane and prepared for measurements of cardiac output, arterial and mixed venous oxygen saturations, and body core temperature. No sooner than 3 d after surgery, measurements were made during a control period and at 10-min intervals for 120 min after i.v. administration of SAE in seven carotid-intact lambs and six carotid-denervated lambs. Administration of SAE produced a short-lived fever of about 1 degrees C in the carotid-intact lambs, whereas no change in body core temperature was observed in the carotid-denervated lambs. In carotid-intact lambs, the rise in body core temperature began approximately 40 min after administration of SAE and continued for approximately 50 min. This rise in body core temperature was preceded by the onset of shivering and an increase in total body oxygen consumption. Carotid denervation produced changes in some of the cardiovascular variables during the control period (i.e. arterial oxygen content, cardiac index, heart rate, and pulmonary blood pressure); however, there were no additional significant changes in any of the metabolic or cardiovascular variables after administration of SAE. The mechanism of these unexpected findings remains to be determined.

Animals↗

PubMed1992

Naloxone does not alter the arousal response decrement after repeated exposure to hypoxemia during sleep in lambs.

Experiments were done to determine if endogenous opiates cause the arousal response decrement that follows repeated exposure to hypoxemia during sleep in lambs. Five lambs were anesthetized and instrumented for sleep staging and measurement of arterial Hb oxygen saturation. No sooner than 3 d after surgery, measurements were made in quiet sleep and active sleep during control periods when the lambs were breathing 21% oxygen and during experimental periods when the lambs were breathing 5% oxygen. The experimental period was terminated during each epoch by changing the inspired gas mixture back to 21% oxygen, once the lamb aroused from sleep. After each lamb had been exposed to 5% oxygen during 100 consecutive epochs of sleep, naloxone--an opiate antagonist--was given i.v. in a dose of 3 mg/kg as a bolus. The animals continued to be exposed to 5% oxygen during six more epochs of sleep after the administration of naloxone. Arousal occurred from both sleep states during rapidly developing hypoxemia but was delayed in active sleep compared to quiet sleep. The arterial Hb oxygen saturation at arousal was significantly lower, and the time to arousal was significantly longer with repeated exposure to hypoxemia during both quiet sleep and active sleep. Naloxone did not alter this arousal response decrement to hypoxemia. Thus, our data provide evidence that endogenous opiates do not play a major role in causing the arousal response decrement that follows repeated exposure to hypoxemia during sleep in lambs.

Animals↗

PubMed1992

Fever in young lambs: hypoxemia alters the febrile response to a small dose of bacterial pyrogen.

Experiments were done on eight young lambs to investigate the effects of hypoxemia on the body temperature, metabolic and cardiovascular responses to intravenous administration of a small dose of bacterial pyrogen (0.3 micrograms lipopolysaccharide extracted from Salmonella Abortus Equi; SAE). Each lamb was anaesthetized with halothane and prepared for sleep staging and measurements of cardiac output, arterial and mixed-venous haemoglobin oxygen saturations, body-core and ear-skin temperatures. Three experiments were done on each lamb, the first being done no sooner than three days after surgery. The first experiment consisted of establishing the thermal neutral environment during normoxemia (ie, environmental temperature at which total body oxygen consumption was minimal while body temperature was maintained) for each lamb. The second and third experiments were done at the lamb's thermoneutral environment as determined on day 1. One experiment was done during normoxemia (ie, control condition, SaO2 approximately 90%) and one experiment was done during hypoxemia (ie, experimental condition, SaO2 approximately 50%). Measurements were made during a control period and during one-minute experimental periods at 10 minute intervals for 120 minutes following administration of 0.3 micrograms of bacterial pyrogen in sterile saline. Administration of SAE produced a short-lived fever of about 0.8 degrees C in the normoxemic lambs, whereas no change in body-core temperature was observed in the hypoxemic lambs. During normoxemia, the increase in body-core temperature was preceded by peripheral vasoconstriction, the onset of shivering, and a surge in total body oxygen consumption. The increase in total body oxygen consumption was met primarily by an increase in total body oxygen extraction during the development of fever. Cardiac index, heart rate, and systemic oxygen transport increased during the peak body-core temperature response. Systemic arterial blood pressure did not change significantly during the febrile response; however, pulmonic arterial blood pressure increased. During hypoxemia, peripheral vasoconstriction and shivering occurred following administration of SAE, but there was no change in total body oxygen consumption or body-core temperature. Thus, our data provide evidence that hypoxemia alters the febrile response of young lambs to bacterial pyrogen. The precise mechanism remains to be determined.

Animals↗

PubMed1991

Arousal response to upper airway obstruction in young lambs: comparison of nasal and tracheal occlusion.

Experiments were done on seven lambs to determine if site of occlusion--nasal versus tracheal--influences the cardiopulmonary and arousal responses from sleep to upper airway obstruction. Each lamb was anesthetized and instrumented for sleep staging and measurements of heart rate and arterial hemoglobin oxygen saturation. A tracheostomy was also done and a fenestrated tracheostomy tube placed in the trachea. Prior to an experiment, A 5F balloon-tipped catheter was inserted through the decannulation cannula into the tracheostomy tube so that tracheal occlusions could be accomplished by inflating the balloon. In addition, a 5F balloon-tipped catheter was inserted into the inlet of a pre-formed silicone mask sealed to the animals snout with silicone rubber foam so that nasal occlusions could be accomplished by inflating the balloon. During an experiment, measurements were made in quiet sleep and in active sleep during control periods of tidal breathing and during experimental periods of nasal or tracheal occlusion. Upper airway obstruction was terminated by deflating the balloon once the animal aroused from sleep. Arousal occurred sooner following nasal occlusion than during tracheal occlusion in quiet sleep; 64 percent of arousals occurred within five seconds of nasal occlusion whereas only 14 percent of arousals occurred within five seconds of tracheal occlusion in quiet sleep. In addition, SaO2 and heart rate decreased more before arousal following tracheal occlusion than following nasal occlusion. However, there was not a significant effect of site of obstruction on time to arousal or the change in SaO2 before arousal in active sleep.(ABSTRACT TRUNCATED AT 250 WORDS)

Airway Obstruction↗