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Biomedical subjects

R W Hubbard

Publications and source records attributed to R W Hubbard.

At least 91 records · Page 5Linked to original sources

Chronic low-sodium diet in rats: hormonal and physiological effects during exercise in the heat.

To elucidate the effects of sodium (Na+) deficiency on the ability to work in the heat, immature rats were fed a diet deficient in Na+ for approximately 2 mo. Rates of weight gain were severely affected (P less than 0.01) in the Na+-deficient rats (1.7 vs. 7.2 g/day in controls), although fluid consumption was unaffected. The low-Na+ diet effected no alterations in endurance or weight loss during exercise in the heat to hyperthermic exhaustion, but final core and skin temperatures were significantly reduced in the low-Na+ group (P less than 0.02) and hematocrit ratios were significantly (P less than 0.001) increased. Circulating Na+ and potassium (K+) concentrations were significantly (P less than 0.05) increased in both groups after hyperthermic exhaustion. In the Na+-deficient groups, plasma levels of both aldosterone and cortisol/corticosterone were significantly (P less than 0.05) increased, and these increments were exacerbated following exercise to hyperthermic exhaustion. Consumption of the low-Na+ diet elicited significant increments in circulating levels of lactate (P less than 0.01) and creatinine (P less than 0.01), both of which were increased further after exercise. We concluded that hormonal adaptations prevented circulatory hyponatremia and decrements in physical performance, but other clinical and metabolic effects of the low-Na+ diet were noted.

Adrenal Cortex Hormones↗

Heat-stressed rat: effects of atropine, desalivation, or restraint.

Heat-stressed rats thermoregulate behaviorally by spreading saliva onto body surfaces and thus lose body water through evaporative cooling. Prior to exploring the role of dehydration in our rat heatstroke model, we sought to compare the abilities of physical restraint, surgical desalivation, and/or atropine to increase the rate of body heat storage by inhibiting body water loss and evaporative cooling during heat exposure. In these experiments, male Sprague-Dawley rats were stressed at an ambient temperature of 41.5 degrees C either in their own cages or in a restraining device until a rectal temperature of 42.6 degrees C was attained. Unrestrained control rats heat-stressed at this temperature lost approximately 8% of body weight (water) during a 258-min exposure. Physical restraint or desalivation reduced both the exposure time and body weight loss by about 72%. Surgically desalivated, heat-stressed rats were observed to engage in voluntary urine-spreading behavior. Maximal heat storage and therefore maximal reduction in exposure time and inhibition of body weight loss to less than 10% of control values were achieved by either physical restraint plus desalivation or by a 500-micrograms dose of atropine.

Animals↗

Physiological and hematologic responses to summer and winter dry-heat acclimation.

Differences between acclimation to heat at the end of winter (W) and at the end of summer (S) were studied on the same eight male volunteers. Subjects were exposed to 40 degrees C, 30% rh for 10 consecutive days on two separate occasions approximately 5 mo apart (S and W). Daily exposures lasted 120 min: 10 min rest, 50 min walking 1.34 m . s-1 on the level, 10 min rest, 50 min walking. During W acclimation, rectal temperature (Tre) and heart rate (HR) decreased, sweat rate (msw) remained unchanged, and plasma and red cell volume of the blood expanded. During S acclimation, HR decreased while Tre and msw remained unchanged, and plasma volume increased. The Tre of the acclimated subjects remained higher in W, and the msw lower, than in S. It was concluded that acclimation does not totally eliminate the seasonal differences in thermoregulatory set point and sweating sensitivity. Further, acclimation to a more severe heat did not lower the thermoregulatory set point that was achieved by natural acclimatization to a milder heat but affected the cardiovascular adjustment and caused greater plasma volume expansion. W acclimation caused both plasma and blood cell volume expansion, whereas S acclimation affected only plasma volume.

Acclimatization↗

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↗

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↗

Effects of exercise in the heat on predisposition to heatstroke.

This article reviews briefly the historical origins for both the cardiovascular and neural-anhidrotic concepts of heatstroke pathophysiology. It describes how deemphasis of the role of anhidrosis as the primary cause of heatstroke has resulted in: (a) an increased acceptance of animal models for heatstroke research; (b) further evidence that rigid reliance on the classic heatstroke symptoms (coma, anhidrosis, and a fever over 106 degrees F) can result in underdiagnosis; and (c) new research consistant with the hypothesis that exhaustive physical effort, by worsening circulatory collapse and metabolic acidosis predisposes tissue to hyperthermic injury and, as a result, substantially lowers the threshold for heatstroke injury and mortality. Thus, a new hypothesis combining the essential features of both direct thermal injury and cardiovascular origins of heatstroke pathophysiology may be necessary.

Adult↗

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↗

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↗

Rat model of acute heatstroke mortality.

A total of 252 untrained, unacclimatized, and unanesthetized laboratory rats weighing between 485 and 545 g were fasted and either run to exhaustion at 5, 20, 23, or 26 degrees C or were restrained and heated at an ambient temperature of 41.5 degrees C. The incidence of mortality associated with a wide range of work-induced hyperthermias was compared to the lethality of equivalent heat loads in the absence of physical effort. The severity of hyperthermia was calculated in degree-minutes above a base-line core temperature of 40.4 degrees C. The LD25's of run-exhausted versus restrained-heated rats were 16.8 and 30.1 deg-min, respectively. Survivors had a faster cooling rate than fatalities, but run-exhausted survivors had a slower cooling rate than restrained-heating survivors. Results indicate that 1) both the incidence of mortality and the survival time can be predicted from the severity of core heating, 2) work-related factors contribute to an increased rate of heatstroke death at low thermal loads, and 3) retrospectively, both heat-sensitive and heat-resistant groups were identified.

Animals↗

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↗

Compensatory adaptations of skeletal muscle composition to a long-term functional overload.

Compensatory hypertrophy of rat plantaris muscle was induced by ablating the synergistic gastrocnemius muscle. The sham-operated contralateral muscle served as a control. Within 5, 30 and 60 days postoperatively, the wet weight of the hypertrophied plantaris was 40, 64, and 109% greater, respectively, than the contralateral control. Two patterns of changing muscle composition emerged with compensatory hypertrophy: (1) an early (less than or equal to 5 days) increase in DNA content (+190%) which resulted in a sharp decline in the wet weight per nucleus ratio (-50%). This coincided with an increase in sarcoplasmic and stromal proteins and a fall in myofibrillar protein concentration. These changes were followed by (2) a secondary increase (30-60 days postoperatively) in the proportions of myofibrillar proteins with a corresponding decline in sarcoplasmic proteins.

Adaptation, Physiological↗