PubMed Health⌕ Search

Biomedical subjects

M Mager

Publications and source records attributed to M Mager.

At least 37 records · Page 2Linked to original sources
PubMed1981

Effect of low-potassium diet on rat exercise hyperthermia and heatstroke mortality.

A total of 182 male Sprague-Dawley rats weighing 250-300 g were fed either a control (n = 122) diet for 32 days. The diets contained either 125 or 8 meq potassium/kg, respectively. Rats fed the low-K diet gained weight at only one-third the rate of controls (1.7 vs. 5.2 g/day), and their skeletal muscle and plasma potassium levels were reduced by 28 and 47%, respectively. When run to exhaustion at either 15 or 20 degrees C, low K+-fed rats accomplished less than one-half of the work done by the controls (26 vs. 53 kg. m) but exhibited a markedly greater rate of heat gain per kilogram-meter of work than controls (0.12 vs. 0.05 degrees C)ambient temperature of 20 degrees C, the rats of the low-K+ group despite large differences in body weight (-25%), run time temperature and twice (33 vs 17%) the mortality rate of the controls. Postexercise increases in circulating potassium (less than 90%) of heat-injured rats raised the plasma levels of low K+-fed rats to normal (5.9 +/- 2.2 meq/l). These results appear to characterize the existence of an insidious and, therefore, undocumented form of fatal exertion-induced heat illness.

Animals↗
PubMed1980

5-Thio-D-glucose: hypothermic responses in mice.

Adult male mice were administered several doses of 5-thio-D-glucose (5-TG) at two environmental temperatures, 4 and 22 degrees C. Both intracerebroventricular (icv) and intraperitoneal (ip) administration of 5-TG resulted in significant (P < 0.05 to P < 0.001) decrements in rectal temperature (Tre) that were dose dependent. After 30 min, the hypothermic effects were significantly (P < 0.001, icv, 100 microgram) exacerbated by cold exposure (4 vs. 22 degrees C) and were likewise intensified significantly (P < 0.005, 45 min, fed vs. 18 h fasted) by food deprivation. These reductions in Tre were accompanied by significant (P < 0.001) increases in circulating levels of glucose. The present results indicate that 5-TG may be eliciting both central and peripheral cellular glucopenia concomitant with circulatory hyperglycemia; thus, the resultant hypothermia may be arising from competitive inhibition of glycolysis by 5-TG intermediates as well as reduced availability of tissue glucose.

Animals↗
PubMed1980

Hypothermia following injection of 2-deoxy-D-glucose into selected hypothalamic sites.

From our previous studies with 2-deoxy-D-glucose (2-DG) an inhibitor of glucose utilization, we postulated that the resultant intracellular glucopenia affects central neuronal pathways involved in the control of peripheral heat production. In this investigation, we have delineated these thermoregulatory sites by stereotaxically injecting microquantities of 2-DG into the hypothalamus of the rat and monitoring core temperature (Tre). After stabilization of Tre at a room temperature of 23 +/- 1 degree C, 20 microgram of 2-DG in 2 microliter was injected into 350- to 400-g rats. Significant decreases in Tre were noted after injections into the anterior hypothalamic, ventromedial, and dorsomedial nuclei as well as the lateral and posterior hypothalamic areas. Mean nadir Tre decreased 1.5 degrees C 1 h after, was significantly depressed 3.5 h after, and returned to basal values 4 h after administration of 2-DG into the ventral premammillary nucleus (PMV). Dose-dependent response was observed for injections into the PMV only. Of a total of 21 sites studied in the anterior and posterior hypothalamus, the PMV, an area of unknown physiological function, was the most sensitive to glucose deprivation.

Animals↗
PubMed1980

2-Deoxy-D-glucose-induced hypothermia: thermoregulatory pathways in rat.

2-Deoxy-D-glucose (2-DG) elicits significant and prolonged hypothermia in a variety of animals when administered either peripherally or centrally. From our current studies it would appear that, in high concentrations (250 mg/kg or more, ip), 2-DG can act directly on peripheral tissues in the rat by competitively interfering with glucose metabolism and consequently with normal heat producing mechanisms. When a low concentration of 2-DG (20 micrograms) is injected centrally, the ensuing glucopenia results in vagal stimulation and subsequent diminution of peripheral heat production. Vagal involvement is concluded from studies with atropine, which demonstrated total inhibition of the usual 2-DG depression of body temperature by administration to the ventral premammillary nucleus (PMV), a site that is normally extremely sensitive to this analog of glucose. Additionally, from studies with PMV-lesioned rats, it was concluded that an intact nucleus is necessary for thermoregulation in a normal, a hot, or a cold environment.

Animals↗
PubMed1980

Hypothermia induced by 5-thio-D-glucose: Effects on treadmill performance in the heat.

In continuing our studies on the effects of preinduced hypothermia on the endurance capacities, thermoregulatory responses, and clinical chemical indices of heat injury, 10 mg of 5-thio-D-glucose (5-TG) were administered intravenously to restrained rats kept at 4 degrees C. When rectal temperatures (Tre) fell to 29-30 degrees C, the rats were removed to a hot environment (35 degrees C), where they exercised on a level treadmill (9.14 m/min) to hyperthermic exhaustion (Tre = 41.5-43 degrees C). Preinduced hypothermia was effective in significantly (p < 0.001) prolonging the time to hyperthermic exhaustion. In these hypothermic rats, increments in Tre (degree C/min) while on the treadmill were significantly (p < 0.001) increased while rates of skin temperature (Tsk) heating were significantly (p < 0.001) reduced when compared to normothermic controls. Administration of 5-TG effected significant (p < 0.001) hyperglycemia, which returned to control levels following the exhaustive run in the heat. Prolonged endurance times among the hypothermic rats caused slight increases in the levels of circulating plasma indices of heat/exercise injury. We concluded from these studies that hypothermia induced by 5-TG administration and cold exposure is effective in increasing the endurance capacity of rats exercising in the heat. However, homeostatic mechanisms supercede to increase the heating rate, and thus return Tre to equilibrium levels.

Animals↗
PubMed1979

Diagnostic significance of selected serum enzymes in a rat heatstroke model.

A total of 171 untrained, unacclimatized, and unanesthetized rats were either exercised to exhaustion at one of four ambient temperatures (5, 20, 26, or 30 degrees C), or were restrained and heated at an ambient temperature of 41.5 degrees C until their core temperatures reached a preselected end point between 41.0 and 43.3 degrees C. The serum levels of creatine phosphokinase (CRK) and two transaminases (SGOT and SGPT) were determined at 30 min, 24, 48, 72, and 96 h posttreatment. Peak enzyme activity for CPK was noted primarily at the 30-min sampling period and at 24 h for the transaminases. The data indicated that under these conditions a) the transaminase SGOT was elevated in the serum as a consequence of the extent and duration of prior hyperthermia, b) the transaminase SGOT was released in moderate amounts after exhaustive exercise but reached its greatest activity levels following hyperthermia, and c) the activity of CPK was increased by the duration of exhaustive exercise and was less sensitive than either transaminase to prior hyperthermia. As a result, each of the three experimental conditions: a) exercise without hyperthermia, b) exercise with hyperthermia, and c) sedentary hyperthermia, produced a unique pattern of serum enzyme activity that would appear useful in diagnosing a variety of heat- and/or work-induced disorders.

Alanine Transaminase↗
PubMed1979

Hypothermia induced by chlorpromazine or L-tryptophan: effects on treadmill performance in the heat.

To study the effects of preinduced hypothermia on the physiological and thermoregulatory responses to exercise in the heat rats were intravenously administered either 100 micrograms of chlorpromazine (CPZ) or 200 mg/kg of L-tryptophan (L-Trp) under restraint in a cold (4 degrees C) environment. When rectal temperatures (Tre) reached 32-33 degrees C the rats were removed to a hot environment (35 degrees C) where they ran on a level treadmill (9.14 m/min) to hyperthermic exhaustion (Tre, 42.5-43 degrees C). Both CPZ and L-trp hypothermia was effective in increasing significantly (P less than 0.001) the time to hyperthermic exhaustion. However, the maximal Tre and skin temperatures (Tsk) attained were unaffected by either treatment. When the rats exercised on the treadmill, increments (degrees C/min) in Tre and Tsk were significantly (P less than 0.02, minimal) greater for the initially hypothermic animals compared to normothermic controls. Cooling rates were unaffected by either treatment. We concluded from these studies that, although preinduced hypothermia is extremely effective in prolonging the time to hyperthermic exhaustion, no additional beneficial thermoregulatory responses accrued as a result of this treatment.

Animals↗
PubMed1979

Heat- and exercise-induced hyperthermia: effects on high-energy phosphates.

To assess the role of high-energy phosphate compounds in the etiology of heat injury with respect to the release of intracellular constituents, the susceptibility of selected tissues to heat injury, and the shock-like demise of the animals, rats were exercised on a treadmill (9.14 m/min) in a hot environment (34.5-35 degrees C) to a rectal temperature (Tre) of 42.5-43 degrees C. In the heart, kidney, left lateral lobe of the liver, and gastrocnemius muscle extricated from animals immediately upon termination of the treadmill run, levels of glucose-6-phosphate (G-6-P), adenosine triphosphate (ATP), and creatine phosphate (CP) were unchanged when compared with sedentary controls. In animals which had been resuscitated by infusion of isotonic saline into a jugular catheter, levels of CP were significantly (p less than 0.025) elevated in gastrocnemius muscle. In rats which were unconscious and succumbing to the effects of hyperthermic injury, levels of hepatic G-6-P and ATP were significantly reduced (p less than 0.05, p less than 0.02, respectively). These results indicate that the combination of exhaustive excercise/heat injury had the most deleterious effects upon hepatic metabolism. However, while resuscitation with physiological saline may be accompanied by an increased synthesis of CP, hyperthermic exhaustion and the concomitant efflux of cellular constituents cannot be attributed to a depletion or even a decrement of high-energy phosphates in vital tissues.

Adenosine Triphosphate↗
PubMed1978

Heat-injured rats: pathochemical indices and survival time.

Rats were exercised on a treadmill (9.14 m/min) in a hot environment (34.5 degrees C, 30% rh) until a rectal temperature of 42.0--42.5 degrees C was reached. Analysis of plasma constituents in subsequent serial blood samples demonstrated a highly significant inverse correlation between lactate concentration (P less than 0.001) and potassium levels (P less than 0.005) in blood samples taken immediately postexercise when both of these were correlated to survival time. Alternatively, plasma creatine phosphokinase (CPK) activity in these samples, although significantly elevated over control levels (P less than 0.001), was not correlated with either survival time or lactate-potassium concentrations. When fluid was administered prior to the run and immediately thereafter to repress pathological effects, there occurred no changes in plasma lactate and potassium levels between the postrun sample and a second sample taken 60 min later, while CPK levels were significantly reduced (P less than 0.01) in the second sample. However, levels of all three indices were significantly elevated (P less than 0.01) in a third sample taken terminally despite the fact that the animals were restrained and sedentary during this interval. These findings indicate that the hyperthermic injury may have had fundamental pathological effects on metabolism and membrane integrity producing lactacidemia and hyperkalemia of sufficient magnitude to compromise cardiovascular performance.

Animals↗
PubMed1978

Role of physical effort in the etiology of rat heatstroke injury and mortality.

A total of 171 untrained, unacclimatized, and unanesthetized rats were used to evaluate the effects of sedentary and work-induced hyperthermia on the incidence of mortality and cellular injury, 24 h postexposure. Cellular injury was defined as serum transaminase activity (SGPT and SGOT) exceeding 1,000 IU/l (heatstroke levels). Both the percent mortality and the percentage of 24-h survivors with transaminase levels above 1,000 IU/l were plotted against maximum core temperatures. Exertion-induced hyperthermia produced a significantly higher incidence of cellular injury and heatstroke death at lower core temperatures than hyperthermia alone. With hyperthermia only, the SGPT and SGOT dose-response curves were identical. When work was combined with hyperthermia, there was a greater incidence of elevated SGOT at lower core temperatures. These curves bore a striking resemblance to curves reflecting heat- and/or work-induced mortality in humans. The results suggest a direct role of physical effort in causing heatstroke injury and mortality.

Alanine Transaminase↗
PubMed1978

L-dopa absorption and the pituitary-hypothalamic axis.

Administration of oral L-dopa is often used as a neuropharmacological probe to evaluate the pituitary hypothalamic axis. The effect of gastrointestinal absorption of L-dopa on the changes in plasma GH, PRL, and body temperature which occur after ingestion of this amino acid is unknown. Plasma L-dopa, GH, PRL, and rectal and skin temperatures were measured in 14 male volunteers after oral administration of 1.0 g measured in 24 men after random administration of L-dopa and a placebo. L-Dopa levels rose to 1.85 +/- 1.33 microgram/ml (mean +/- SD), but maximum plasma levels occurred at variable times from 30-230 min after drug administration. Plasma GH levels increased to 23.7 +/- 14.7 ng/ml, while PRL levels fell to 46.7 +/- 12.3% of the mean basal values. Rectal temperature decreased significantly in 3 of the men after L-dopa ingestion. Plasma GH levels after L-dopa correlated with the absorption of the drug (P less than 0.05) and inversely with the basal level of GH before L-dopa administration. There was no correlation between the basal PRL level or basal body temperature and the magnitude of the fall in PRL or body temperature after L-dopa administration. The variability of responses in GH, PRL, and body temperature after oral L-dopa ingestion is not the result of differences in absorption in the amino acid alone, and indicate either that there is a different sensitivity in the mechanisms that stimulate GH secretion and lower plasma PRL and body temperature, or that L-dopa acts at different sites to bring about each of these changes.

Adolescent↗
PubMed1978

Alterations of rat liver subsequent to heat overload.

Since pathological changes in the liver are among the consistent findings in humans subsequent to heatstroke, specimens were taken from the liver in rats during a study to assess the rat as a model for human heatstroke. Tissues from four groups of rats were processed for light and electron microscopy. The groups consisted of control rats, rats run to exhaustion at 5 C, rats exhausted at 26 C, and rats restrained at 41.5 C until their rectal temperatures reached 42.3 C. Exhaustive exercise at 5 C produced neither fatalities nor pathological changes in the livers. Exhaustive exercise at 26 C and restraint at 41.5 C were fatal for most rats. Histological and/or ultrastructural changes, which included centrilobular necrosis, vacuolization and diminution of hepatocellular microvilli, and loss of sinusoidal endothelium, were observed in livers from rats that were run to exhaustion at 26 C and from those rats restrained at 41.5 C. This work supports the validity of the rat model, since human heatstroke results in similar hepatic changes.

Animals↗
PubMed1976

Thermoregulatory effects of monoamine potentiators and inhibitors in the rat.

Exogenously administered monoamines may elicit variable thermoregulatory responses dependent on dosage, species, site of administration, ambient temperature, etc. In an attempt to reconcile several inconsistencies, we have undertaken a series of studies related to monoaminergic control of temperature regulation. Thus, intraventricular administration of serotonin (2.64-26.4 mug) and norepinephrine (3.3-32.8 mug) in rats evoked acute (15-60 min) dose-dependent hypothermic responses (delta Tre = 2 degrees C) that were gradually superseded by significant, more persistent hyperthermia (delta Tre = 1 degreee C). Administration of chlorimipramine or imipramine (total dose 40 mug), even in monoamine-depleted animals, caused long-lasting hyperthermic responses, presumably by the prevention of reuptake of serotonin and norepinephrine at nerve terminals involved in thermoregulation. Pretreatment with the serotonin inhibitor cyproheptadine (4o mug) attenuated the hyperthermia achieved by central administration of chlorimipramine alone. We conclude that both monoamines can act as thermogenic agents under the conditions of these experiments.

Animals↗
PubMed1976

The laboratory rat as a model for hyperthermic syndromes in humans.

To assess the lethal effects of work-induced hyperthermia on exercising animals, untrained rats were run to exhaustion at 5 and 20-26 degrees C or restrained at 41.5 degrees C. An exercise-induced core temperature of 40.4 degrees C represented a base line above which mortalities occurred. With increasing core temperature at exhaustion (between 40.4 and 43 degrees C), mortality increased within 24 h. A dose-respones curve with an LD50 equivalent to a core temperature of 41.5 +/- 0.1 degrees C was calculated. Although differences in body weight loss, core temperature at exhaustion, and cooling rate will clearly distinguish between survivors and fatalities, the severity of heat injury as inferred from survival times is best measured by the time versus intensity of hyperthermia in degree-minutes.

Acclimatization↗
PubMed1976

Drug modification of hypothermia induced by CNS glucopenia in the mouse.

2-Deoxy-D-glucose (2-DG), insulin, or norepinephrine (NE), when injected into the cerebral ventricles of conscious mice, produce decreased rates of O2 consumption and hypothermia. These changes are accompanied by hyperglycemia with 2-DG, hypoglycemia with insulin, and normoglycemia with NE. Desipramine blocks the reduction in body temperature and O2 consumption produced by each of these agents, but does not modify significantly their effects on plasma glucose. The latter suggests that the thermal and oxidative responses to central glucopenia can be dissociated from concurrent alterations in circulating glucose. Propranolol enhances the hypothermic response produced by administered 2-DG, insulin, or NE. Phentolamine, however, antagonizes the hypothermia only with NE, indicating the 2-DG and insulin are probably not acting through the release of endogenous NE.

Animals↗
PubMed1975

Effect of limb regeneration on size increase at molt of the shore crabs Hemigrapsus oregonensis and Pachygrapsus crassipes.

Size increase at molt is reduced following multiple limb regeneration in the shore crabs, Hemigrapsus oregonensis and Pachygrapsus crassipes. Limb loss per se does not influence postmolt size. Effect of increasing number of regenerating limbs is additive. Postmolt size is programmed early in the premolt period of the preceding instar and is probably not readily influenced by water uptake mechanics at ecdysis. A simple model for growth, molting, and regeneration in heavily calcified Crustacea is developed from the viewpoint of adaptive strategies and energetic considerations.

Animals↗
PubMed1975

Salicylate, tryptophan, and tyrosine hypothermia.

The intraperitoneal administration of sodium salicylate, L-tryptophan, and tyrosine resulted in significant hypothermia when rats were exposed to a 4degree C ambient temperature. Salicylate and tryptophan increased plasma levels of nonprotein-bound tryptophan while total and bound tryptophan were reduced in salicylate-treated rats. Tryptophan concentrations were unaffected by tyrosine administration. Concomitant with increases in free plasma tryptophan, there occurred significant rises in brain levels of tryptophan in both groups of rats, while brain tyrosine levels were increased in those rats receiving tyrosine. Similarly, significant increments in hypothalamic serotonin levels in rats receiving salicylate or L-tryptophan and increases in hypothalamic norepinephrine in tyrosine-treated rats seem to reflect the increased availability of tryptophan and tyrosine for monamine synthesis. However, alternative mechanisms of hypothermiaseem to be operative since oxygen consumption studies demonstrate dissimilar results for tryptophan and salicylate administration.

Animals↗