Biomedical subjects

J E Fewell

Publications and source records attributed to J E Fewell.

At least 19 recordsLinked to original sources

PubMed1999

Arginine vasopressin does not mediate the attenuated febrile response to intravenous IL-1beta in pregnant rats.

Rats have an attenuated febrile response to intravenous endogenous pyrogen [e.g., interleukin-1beta (IL-1beta)] near the term of pregnancy. The present experiments were carried out on 25 nonpregnant and 32 pregnant rats to test the hypothesis that arginine vasopressin functioning as an endogenous antipyretic substance in the central nervous system mediates this attenuated febrile response. An intravenous injection of recombinant rat IL-1beta (rrIL-1beta) after intracerebroventricular vehicle produced a significant increase in core temperature in both nonpregnant and pregnant animals, the magnitude and duration of which was greater in the nonpregnant rats. In nonpregnant rats, intravenous rrIL-1beta after intracerebroventricular vasopressin V1-receptor antagonist accentuated the core temperature response compared with that observed with intravenous rrIL-1beta after intracerebroventricular vehicle. In pregnant animals, however, intravenous rrIL-1beta after intracerebroventricular vasopressin V1-receptor antagonist produced a decrease in core temperature rather than an increase in core temperature, which was observed with intravenous rrIL-1beta after intracerebroventricular vehicle. Thus our data do not support the hypothesis that a pregnancy-related activation of arginine vasopressin as an endogenous antipyretic substance in the central nervous system attenuates the febrile response to intravenous rrIL-1beta near the term of pregnancy in rats.

Animals↗

PubMed1999

Role of AVP in mediating the altered core temperature response to a simulated open field in pregnant rats.

Near the term of pregnancy, rats have an attenuated core temperature response on exposure to a novel environment (e.g., a simulated open field) compared with that observed early in pregnancy or in nonpregnant rats. The present experiments were carried out on 26 nonpregnant and 26 pregnant rats to test the hypothesis that arginine vasopressin, functioning as an endogenous antipyretic substance in the central nervous system, mediates this attenuated core temperature response. Exposure to a simulated open field after intracerebroventricular (ICV) vehicle produced a significant increase in core temperature in both nonpregnant and pregnant animals, the magnitude and duration of which were greater in the nonpregnant rats. In nonpregnant rats, exposure to a simulated open field after ICV vasopressin V(1)-receptor antagonist altered the pattern of the core temperature response but not the core temperature index compared with that observed on exposure to a simulated open field after ICV vehicle. In pregnant animals, ICV vasopressin V(1)-receptor antagonist did not alter the core temperature response to a simulated open field compared with that observed after ICV vehicle. Thus our data do not support the hypothesis that a pregnancy-related activation of arginine vasopressin attenuates the core temperature response to a simulated open field in rats near the term of pregnancy.

Animals↗

PubMed1998

Cerebral cortex does not modulate "regulated" decrease in core temperature during hypoxemia in rats.

In newborns and adults of a number of species including humans, exposure to acute hypoxemia produces a "regulated" decrease in core temperature, the mechanism of which is unknown. Considering that various cortical areas participate in autonomic regulation including thermoregulation, the present experiments were carried out to test the hypothesis that the cerebral cortex plays a role in modulating the regulated decrease in core temperature during acute hypoxemia. This hypothesis was tested by determining the core temperature response to acute hypoxemia in chronically instrumented adult Sprague-Dawley rats before and after cortical spreading depression (i.e., functional decortication) was produced by the local application of potassium chloride to the dura overlying the cerebral hemispheres. There was no effect of cortical spreading depression on baseline core temperature. Core temperature decreased during acute hypoxemia in a similar fashion when the cerebral cortex was intact as well as during functional decortication. Thus our data do not support the hypothesis that the cerebral cortex modulates the regulated decrease in core temperature that occurs in adult rats during acute hypoxemia.

Acute Disease↗

PubMed1998

Coordination of autonomic and behavioral thermoregulatory responses during exposure to a novel stimulus in rats.

The induction of psychological stress in rats is accompanied by an elevation of core temperature. Our experiments were carried out to determine whether the latency, duration, magnitude, or effector mechanisms of the core temperature response to psychological stress would be altered when rats were allowed to use behavioral as well as autonomic thermoregulation. Core temperature, oxygen consumption, and ambient temperature were measured in adult rats before and after handling and a sham intraperitoneal injection. Seven rats were studied in a thermocline (gradient of 7 to 42 degrees C) and eight rats were studied in a metabolic chamber (25 degrees C). The rats studied in the thermocline selected a warm ambient temperature following the sham intraperitoneal injection and exhibited an increase in core temperature of shorter latency, greater magnitude, and greater duration than those studied in the metabolic chamber. The rats studied in the metabolic chamber exhibited an oxygen consumption response of greater magnitude and duration than the animals studied in the thermocline. Thus the characteristics in addition to the effector mechanisms of the core temperature response to psychological stress are altered when rats are allowed to use behavioral as well as autonomic thermoregulatory effectors.

Animals↗

PubMed1998

AVP mediates the attenuated febrile response to administration of PGE1 in rats near term of pregnancy.

Rats have an attenuated febrile response to intracerebroventricular injection of PGE1 near the term of pregnancy, the mechanism of which is unknown. The present experiments were carried out to test the hypothesis that arginine vasopressin (AVP), functioning as an endogenous antipyretic substance in the central nervous system, mediates this attenuated febrile response. The febrile response to intracerebroventricular injection of 0.2 microg PGE1 was determined in pregnant and nonpregnant rats after an intracerebroventricular injection of either vehicle or a vasopressin V1-receptor antagonist. After intracerebroventricular administration of vehicle, intracerebroventricular administration of 0.2 microg PGE1 produced significant increases in core temperature in both nonpregnant and pregnant animals. The increase in core temperature, however, was attenuated both in magnitude and duration in pregnant compared with nonpregnant animals. After intracerebroventricular administration of a vasopressin V1-receptor antagonist, intracerebroventricular administration of 0.2 microg PGE1 produced significant increases in core temperature that were similar in nonpregnant and pregnant animals. Our data support the hypothesis that a pregnancy-related activation of AVP as an endogenous antipyretic substance in the central nervous system attenuates the febrile response to intracerebroventricular administration of PGE1 near term of pregnancy in rats.

Alprostadil↗

PubMed1998

Naloxone does not alter the "regulated" decrease in core temperature during hypoxemia in guinea pigs.

In newborns and adults of a number of species, exposure to acute hypoxemia produces a "regulated" decrease in core temperature, the mechanism of which is unknown. The present experiments were carried out in chronically instrumented newborn (5-10 days of age; n = 59) and older (25-30 days of age; n = 61) guinea pigs to test the hypothesis that the endogenous opioids mediate this regulated decrease in core temperature. During an experiment, core temperature, oxygen consumption, and selected ambient temperature were measured in a thermocline (linear temperature gradient of 10-40 degreesC) during a control period of normoxemia, an experimental period of normoxemia or hypoxemia (inspired oxygen fraction 0.10), and during a recovery period of normoxemia following an intraperitoneal injection of naloxone hydrochloride (a nonspecific opioid antagonist; 1, 2, or 4 mg/kg) or vehicle. Naloxone did not significantly alter basal core temperature or the core temperature response to acute hypoxemia in newborn or older guinea pigs. Naloxone did, however, decrease basal oxygen consumption in newborn and older guinea pigs and altered the thermoregulatory effector mechanism used to decrease core temperature during hypoxemia in the newborn guinea pigs. Our data do not support the hypothesis that the endogenous opioids mediate the regulated decrease in core temperature that occurs in newborn and older guinea pigs during exposure to acute hypoxemia.

Animals↗

PubMed1998

Perinatal nicotine exposure impairs ability of newborn rats to autoresuscitate from apnea during hypoxia.

Failure to autoresuscitate by hypoxic gasping during prolonged sleep apnea has been suggested to play a role in sudden infant death. Furthermore, maternal smoking has been repeatedly shown to be a risk factor for sudden infant death. The present experiments were carried out on newborn rat pups to investigate the influence of perinatal exposure to nicotine (the primary pharmacological and addictive agent in tobacco) on their time to last gasp during a single hypoxic exposure and on their ability to autoresuscitate during repeated exposure to hypoxia. Pregnant rats received either nicotine (6 mg. kg-1. 24 h-1) or vehicle continuously from day 6 of gestation to days 5 or 6 postpartum via an osmotic minipump. On days 5 or 6 postpartum, pups were exposed either to a single period of hypoxia (97% N2-3% CO2) and their time to last gasp was determined, or they were exposed repeatedly to hypoxia and their ability to autoresuscitate from primary apnea was determined. Perinatal exposure to nicotine did not alter the time to last gasp, but it did impair the ability of pups to autoresuscitate from primary apnea. After vehicle, the pups were able to autoresuscitate from 18 +/- 1 (SD) periods of hypoxia, whereas, after nicotine, the pups were able to autoresuscitate from only 12 +/- 2 periods (P < 0.001) of hypoxia. Thus our data provide evidence that perinatal exposure to nicotine impairs the ability of newborn rats to autoresuscitate from primary apnea during repeated exposure to hypoxia, such as may occur during episodes of prolonged sleep apnea.

Animals↗

PubMed1997

Oxygen transport and utilization during feeding in the young lamb.

1. Five lambs (19-27 days old) were studied to determine the effects of feeding on cardiorespiratory function. 2. Each lamb was instrumented to record cardiac output, aortic and pulmonary artery pressure and arterial and mixed venous oxyhaemoglobin saturations (Sa,O2 and Sv,O2). 3. During feeding, arterial haemoglobin desaturated and resaturated sequentially during the periods of sucking and non-sucking. The nadir of these Sa,O2 desaturations (83 +/- 2%, mean +/- S.E.M.) was significantly lower than the baseline value (92 +/- 2%, P < or = 0.05, ANOVA). Sa,O2 returned to the baseline level between periods of sucking. Sv,O2 also decreased (55 +/- 3% baseline, 46 +/- 3% sucking, P < or = 0.05) but, in contrast to Sa,O2, it remained significantly lower than baseline levels in the pauses between periods of sucking. 4. Arterial pressure increased during feeding (94 +/- 4 mmHg baseline, 113 +/- 6 mmHg feeding, P < or = 0.05), while heart rate and cardiac index did not change. 5. Total body oxygen consumption rose during the pauses between sucking periods (10.9 +/- 1.1 ml O2 min-1 kg-1 baseline, 13.9 +/- 1.2 ml O2 min-1 kg-1 non-sucking, P < or = 0.05) and was provided for by a significant increase in total body oxygen extraction as systemic oxygen transport was unchanged. 6. Our results reveal that during feeding in young lambs oxygen consumption increases and body stores of oxygen (e.g. Sv,O2) become depleted; this combination may promote rapid arterial desaturation and cyanosis during feeding.

Analysis of Variance↗

PubMed1997

Influence of carotid denervation on the body-core temperature and metabolic responses to changes in ambient temperature during normoxemia and acute hypoxemia in guinea pigs during postnatal maturation.

Acute hypoxemia produces a decrease in body-core temperature (Tbc) in guinea pigs during postnatal maturation, although the factors mediating the response remain unknown. Experiments were therefore carried out to test the hypothesis that the carotid chemoreceptors and (or) baroreceptors mediate the decrease in Tbc during acute hypoxemia. Twelve guinea pigs, six carotid intact and six carotid denervated, were studied in a metabolic chamber to determine the influence of carotid denervation on the Tbc and metabolic (i.e., oxygen consumption) responses to changes in ambient temperature during normoxemia and during acute hypoxemia at 2, 3, and 4 weeks of age. Carotid denervation accentuated the decrease in Tbc in response to a decrease in ambient temperature during normoxemia at 2 and 3 weeks of age but not at 4 weeks of age without altering the metabolic response. This suggests that carotid denervation disrupted heat conservation mechanisms rather than heat production mechanisms in an age-specific manner. Furthermore, carotid denervation accentuated the decrease in Tbc and oxygen consumption in response to acute hypoxemia at all ages studied. This provides evidence that the carotid chemoreceptors and (or) baroreceptors do not mediate the decrease in Tbc that occurs in response to acute hypoxemia in guinea pigs during postnatal maturation.

Animals↗

PubMed1997

Endocrine effects of pregnancy and exposure to a simulated open field in rats.

In adult rats, exposure to a novel environment, such as a simulated open field, elicits an increase in body core temperature. We have recently shown that this response is attenuated in midpregnancy and abolished at term of pregnancy in rats. We postulated that this gestation-dependent response resulted from alterations in the hypothalamic-pituitary-adrenal axis. To test this hypothesis, we measured the effects of pregnancy on renin, corticosterone, and arginine vasopressin (AVP) responses to exposure to either a simulated open field (30 or 120 min) or to the home cage (30 or 120 min) in rats. Pregnancy increased renin and corticosterone levels but not plasma AVP levels. Exposure to an open field decreased renin and increased plasma AVP levels in nonpregnant rats and on days 15 and 20 of gestation in pregnant rats, compared with home cage responses. Serum corticosterone levels were elevated after exposure to an open field in nonpregnant and pregnant rats, compared with home cage rats, the effect being more prolonged on day 20 of gestation. These observations provide new information on endocrine changes during pregnancy in rats and may help to explain the attenuated stress-induced hyperthermic response to exposure to a novel environment seen near term of pregnancy.

Animals↗

PubMed1997

Pregnancy alters body-core temperature response to a simulated open field in rats.

Exposure of a rat to a novel environment (e.g., a simulated open field) induces a transient increase in body-core temperature, which is often called stress-induced hyperthermia. Although pregnancy is known to influence thermoregulatory control, its effect on stress-induced hyperthermia is unknown. Therefore, 24 Sprague-Dawley rats (8 nonpregnant and 16 pregnant) were studied to test the hypothesis that pregnancy would alter the development of stress-induced hyperthermia after exposure to a simulated open field. Body-core temperature index increased significantly after exposure to a simulated open field in nonpregnant and gestation day-10 rats but not in gestation day-15 and day-20 rats. Thus our data provide evidence that pregnancy influences the body-core temperature response of rats exposed to a simulated open field in a gestation-dependent fashion. The functional consequences as well as the mechanisms involved remain to be determined.

Animals↗

PubMed1997

Influence of pregnancy on the febrile response to ICV administration of PGE1 in rats studied in a thermocline.

Rats near term of pregnancy have an attenuated febrile response to intracerebroventricular (ICV) injection of prostaglandin E1 (PGE1) when they are studied at an ambient temperature below their thermoneutral zone. Given that nonshivering thermogenesis in brown adipose tissue is impaired in rodents near term of pregnancy, it is possible that the attenuated febrile response is forced by impairment of this component of the autonomic thermoregulatory response. If this were the case, then near-term pregnant rats should develop a "normal" fever after PGE1 administration if they were studied in a thermocline where they could utilize behavioral as well as autonomic thermoregulatory effectors to increase their body core temperature (Tbc). Experiments were, therefore, carried out on 13 nonpregnant and 14 pregnant chronically instrumented rats in a thermocline (temperature gradient 10-40 degrees C) to investigate their Tbc responses to ICV injection of PGE1. ICV injection of 0.2 microgram PGE1 produced significant increases in Tbc and fever index in both nonpregnant and pregnant animals (day 19 of gestation); the increases, however, were significantly attenuated in the pregnant compared with the nonpregnant rats. Behavioral (e.g., selected ambient temperature) and autonomic (e.g., oxygen consumption) thermoregulatory effectors were activated to increase Tbc after ICV PGE1 in both groups of animals, but the duration of activation was shortened in pregnant compared with nonpregnant rats. The abbreviated thermoregulatory effector responses and the resulting attenuated febrile response to PGE1 in the pregnant rats may have resulted from a pregnancy-related activation of an endogenous antipyretic system.

Alprostadil↗

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↗