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Biomedical subjects

R W Hubbard

Publications and source records attributed to R W Hubbard.

At least 73 records · Page 4Linked to original sources
PubMed1986

An atropinized heat-stressed rat model: dose response effects and pharmacokinetics.

Atropine and other anticholinergic drugs are widely used in common medications and in the treatment of organophosphate poisoning. Man dissipates heat by the evaporation of sweat. Analogously, rats spread saliva over their bodies for evaporative cooling. Atropine inhibits both sweating and salivation. Therefore, we sought to quantitate the effects of atropine in our rat heatstroke model. While heat-stressing adult male rats of 500 or 250 g at 41.5 degrees C, we measured the effects of i.v. atropine (10-4000 micrograms X kg-1) on the following: heating rate (HR), % wt loss (saliva production), and fecal loss (intestinal motility). HR (degree C X min-1) was the most sensitive index of drug activity with a 200 micrograms X kg-1 dose (equivalent to 2 mg in man for organophosphate poisoning) eliciting an increased HR from 0.022 degrees C (saline) to 0.087 degrees C X min-1 (atropine). Atropine (200 micrograms X kg-1) increased HR even if administered 3 h prior to heat exposure. Large (500 g) rats showed an increase in HR with 25 micrograms X kg-1 of atropine, but 250 g rats required 50 micrograms X kg-1. This model could be used to assess the relative effects of other anticholinergic drugs and as a non-dehydrated heatstroke model.

Animals↗
PubMed1986

Effect of age, weight, and metabolic rate on endurance, hyperthermia, and heatstroke mortality in a small animal model.

Since exercise performance in man is a function of the age, body weight, and metabolic efficiency interrelationship, this investigation was designed to investigate in rats the effects of these variables on endurance, thermoregulation, and heatstroke mortality at a relatively mild environmental temperature (26 degrees C). The results indicate that light rats (250 g) are able to run (11 m X min-1, 6 degrees incline) longer (221 min), have the lowest rate of heat gain (0.019 C degrees X min-1) than the other groups and thereby experience low heatstroke mortality (20%) despite a large proportion of fluid loss (6.1%). Alternatively, heavier and older rats (350 g-12 week, 500 g-16 week, 500 g-30 week) demonstrated significantly reduced run times (108, 67, and 54 min), more rapid accumulation of metabolic heat (0.040, 0.057 and 0.062 degrees C X min-1) and much higher mortalities (50, 69, and 50%) despite lower percentages of fluid loss (5.2, 3.7, or 4.2%). Although the mechanisms responsible for these varying thermoregulatory responses to exercise-induced exhaustion are not fully understood, the present data indicate that the rate of fluid loss, body weight, and age are important variables in the etiology of thermoregulatory failure culminating in heatstroke and death.

Aging↗
PubMed1986

A heat-stressed rat model to determine relative anticholinergic and anticholinesterase drug potency.

We have reported that atropine, the prototype of muscarinic anticholinergic drugs, elicits a dose-dependent increase in core temperature of heat-stressed rats. In the present study, we have quantified the effects of other anticholinergic drugs on increments in core temperature and have derived the following potencies relative to atropine: imipramine 0.004, amitriptyline 0.02, chlorpromazine 0.1, atropine 1, L-hyoscyamine 2, atropine methyl nitrate 4, and scopolamine 16. Additionally, we quantified the efficacy of carbamates to reduce the elevated heating rate of atropinized rats as a measure of anticholinesterase efficiency. The results indicated the following relative potencies: neostigmine 8, physostigmine 2, and pyridostigmine 1. We have concluded that alterations in core temperature responses to exposure to hot environments may be a useful and sensitive bioassay for anticholinergic and anticholinesterase efficacy.

Animals↗
PubMed1986

Dietary manipulation and exercise in the heat: thermoregulatory and metabolic effects in rats.

To determine the effects of dietary manipulation on the metabolic, physical, and physiological responses to exercise in the heat, adult male rats (n 5 16/group) were food deprived for 72 h followed by ad lib consumption of a high protein (HIPROT) or high carbohydrate (HICARB) diet for 96 h. Each dietary regimen was followed immediately by exercise (9.14 m . min-1) in the heat (35.58C) to hyperthermic exhaustion (TCO approximately 43 8C). Animals consuming the HICARB or HIPROT diet had an increased mean TCO prior to the acute heat/exercise protocol when compared with a control (CONT) group with uninterrupted access to a normal rodent diet; the HICARB rats also manifested a decreased endurance when compared with the CONT group. Plasma levels of urea nitrogen, lactate, and potassium were increased following exercise in the heat in all groups, but greatly exacerbated increments in urea nitrogen occurred in the HIPROT group. Following exercise, significant increments occurred in circulating levels of glucose and insulin in the HIPROT and HICARB groups. Plasma triglycerides were decreased by the exercise/heat regimen but increased by both diets. Thus, these dietary manipulations elicited a variety of metabolic responses which did not markedly alter the physiological and physical effects of work in the heat.

Animals↗
PubMed1985

Chronic low-sodium diet in rats: responses to severe heat exposure.

To determine the effects of sodium (Na+) deficiency on the responses to severe heat stress (35.5 degrees C), immature (mean wt 150.4 g) male rats (n = 21) were fed a low-Na+ diet for 71 days. Rates of weight gain and food consumption were significantly (P less than 0.001) reduced in the low-Na+ group, whereas water consumption was unaffected. Prior to heat exposure circulating Na+ levels were unaffected by dietary Na+ restriction, but both circulating potassium (K+) and hematocrit levels were significantly (P less than 0.001) increased. After 24-h exposure to severe heat stress, circulating Na+ levels did manifest a significant (P less than 0.001) decrement in the low-Na+ group. K+ levels increased significantly (P less than 0.01) in the control group after 6 h of heat exposure but remained depressed in comparison with the low-Na+ group after 48 and 72 h. Although plasma renin activity (PRA) was not increased by chronic consumption of the low-Na+ diet or by severe heat exposure in the control group, severe heat stress in the low-Na+ group did elicit significant (P less than 0.005) increments in PRA after 24 h of exposure. Alternatively, plasma aldosterone levels were significantly (P less than 0.001) elevated by both the low-Na+ diet and heat stress. We concluded from these studies that chronic consumption of the low-Na+ diet had severe effects on hematologic, endocrinological, and thermoregulatory variables as well as thermal sensitivity to prolonged and sedentary exposure to severe heat stress.

Aldosterone↗
PubMed1985

Plasma hormonal responses at graded hypohydration levels during exercise-heat stress.

The effects of graded levels of hypohydration (3, 5, and 7% of body weight) on hormonal responses to exercise in the heat were examined in six heat-acclimated male volunteers. On the day following dehydration, subjects performed light (approximately 25% maximal O2 consumption, 1.03 1 X min-1) exercise in a hot (49 degrees C, 20% relative humidity) environment for four consecutive 25-min intervals interspaced by 10-min rests; blood was obtained before exercise and at approximately 10 min before completion of each exercise period. During euhydration, plasma cortisol (PC) levels manifested significant decrements over time (e.g., time 0, 14.2 micrograms X 100 ml-1 vs. time 2, 8.9 micrograms X 100 ml-1), probably related to its diurnal periodicity. However, during hypohydration, levels of PC were increased and correlated with hypohydration intensity (e.g., time 0, 0, 3, 5, and 7% hypohydration, 14.2, 16.5, 19.8, and 36.2 micrograms X 100 ml-1, respectively). Plasma renin activity (PRA) was increased significantly by hypohydration (e.g., time 0, euhydrated vs. 3%, 3.7 vs. 6.2 units) but was unaffected by exercise in the heat. Plasma aldosterone (ALD) levels were generally increased by exercise in the heat (e.g., time 0 vs. time 4, 3% hypohydration, 12.1 vs. 18.7 ng X 100 ml-1). Regression analysis illustrated that graded intensities of hypohydration were correlated with incremented PRA and ALD through 5% hypohydration. Conversely, PC was incrementally elevated through 7% hypohydration.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Food deprivation and exercise in the heat: thermoregulatory and metabolic effects.

To determine the effects of food deprivation on the physical, physiological, and metabolic responses to exercise in the heat, adult, male rats (330-360g, N = 16/group) were food-deprived for 24, 48, or 72 h. They were then exercised (9.14m X min-1) in the heat (35.5 degrees C) to hyperthermic exhaustion (Tco approximately 43 degrees C). Food deprivation had no effects on endurance, but ad lib fed controls manifested significantly (p less than 0.05) increased Tco and Tsk during the latter portion of the treadmill interval. While plasma osmolality was significantly (p less than 0.01) increased in all groups as a result of the heat/exercise contingency, hematocrit ratios were elevated (p less than 0.01) as a result of 48 and 72 h of food deprivation. Food deprivation resulted in severe hypoglycemia following exercise (p less than 0.01), and these decrements were accompanied by marked (p less than 0.01) reductions in circulating insulin levels. Prolonged food deprivation (48 and 72 h) resulted in significant (p less than 0.01) hypertriglyceridemia and hyperlactacidemia subsequent to exercise. Levels of sodium, potassium, urea nitrogen, and creatine phosphokinase were unaffected by the food deprivation intervals. We have concluded from these studies that while several thermoregulatory and metabolic responses to exercise in the heat can be significantly affected by food deprivation, short-term endurance capacity was unaltered.

Animals↗
PubMed1985

Voluntary dehydration and electrolyte losses during prolonged exercise in the heat.

The effects of water temperature (6 degrees, 22 degrees, 46 degrees C) and chlorination on voluntary dehydration (D), sweat electrolyte losses (SEL), and total body electrolyte losses (BEL) were studied in 12 healthy males during 6 h of intermittent treadmill exercise (1.34 m X s-1, 5% grade) in a climatic chamber (40.6 degrees C DB, 25.5 degrees C WB). Body weight (BW), rectal temperature (Tre), mean weighted skin temperature (Tsk), heart rate (HR), plasma osmolality (PO), sweat rate (SR), sweat sodium (Na+), chloride (Cl-), potassium (K+), and magnesium (MG++), urine volume, Na+, and K+ were measured. No differences were found between chlorinated and non-chlorinated treatments except SEL of Mg++. Subjects (Ss) who drank 46 degrees C (-2.1% BW) consumed approximately 50% less water (p less than 0.001), and had D which was 1.050 kg larger (p less than 0.001) than subjects who consumed 6 degrees C (-0.5 %BW). There were no significant between-group PO differences, but Tre and Tsk differed between 46 degrees and 6 degrees C (p less than 0.01), and the HR of 22 degrees and 46 degrees C were both different from 6 degrees C (p less than 0.05). SR of all groups were essentially equal, although differences in total sweat Na+ (p less than 0.02) and Cl- (p less than 0.04) losses were observed between 46 degrees and 6 degrees C. SEL of sweat K+ and Mg++ were not affected by the experimental design. Based on 24 h projections of BEL, it was concluded that K+ depletion is more likely than Na+ depletion because food is often supplemented with sodium chloride.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1984

Community mental health and the elderly: service and training approaches.

There is a growing gap between needed and available mental health services for older adults. This article discusses the training needs, personnel shortages, and lack of effective service programs and proposes some strategies for dealing with the problems. There is a lack of adequate methods for identifying and referring frail elderly persons in need of mental health services. Services that are currently available to the elderly are identified along with factors that may influence their use by older adults and other service personnel. There are shortages of mental health professionals with special training and experience in gerontology and geriatrics, and clinical geropsychologists. An innovative and practical service model that was developed to coordinate and integrate the identification and treatment of frail, community-dwelling elderly is presented. Various aspects of the program that include outreach and case management approaches, the integration of student volunteer activities with those of special volunteer corps within public housing and specially trained paraprofessionals, telephone reassurance programs, and a system of layered supervision are described. Comparisons are made between this Coordinated Agency Resources for Elderly Services (CARES) model and existing service delivery programs. A three-tiered approach to training and coordinating the activities of trained mental health personnel: (a) paraprofessionals and volunteers, (b) middle-level professionals and (c) supervisory professionals within an integrated system is proposed. Specific roles and functions of personnel at each level are described. The summary discusses the potential of the proposed strategies for dealing with the problems created by the shortage of personnel and services. It suggests some time frames within which the strategies could be operationalized.

Aged↗
PubMed1984

Albumin-induced plasma volume expansion: diurnal and temperature effects.

To develop a reliable procedure for the acute expansion of plasma volume (PV), 26 male volunteers were randomly assigned to either a thermoneutral (25 degrees C and 40% relative humidity) or hot-dry (37 degrees C and 25% relative humidity) environment; subsequently each subject was seated for at least 1 h and then infused intravenously with either 100 or 200 ml of a 25% albumin solution or 0.9% saline. On the day before each infusion, PV was estimated by dye dilution using indocyanine green. Net percent change in PV (using hematocrit and hemoglobin values) was calculated at 1, 3, 6, 9, 12, and 24 h postinfusion. The PV of subjects residing in the heat after a 100-ml saline infusion increased significantly over 1-h values at 6, 9, and 12 h postinfusion but not at 24 h. The same trend, although not significant, was apparent at room temperature. The data suggest a slow isooncotic circadian pattern of PV expansion and contraction. The infusion of hyperoncotic albumin produced rapid expansion of plasma volume. With the low dose (25 g) at 1 h postinfusion, the expansion was 379 +/- 102 ml in the heat and 301 +/- 160 ml at room temperature. With the high dose (50 g) at 1 h postinfusion, the expansion was 479 +/- 84 ml in the heat and 427 +/- 147 ml at room temperature. The high dose produced an expansion that persisted for at least 9 h in subjects in either environment. The data suggest a mechanism for the retention of fluid during heat acclimatization and a useful procedure for plasma volume expansion in humans.

Acclimatization↗
PubMed1984

Voluntary dehydration and alliesthesia for water.

The purpose of this experiment was to explore the complex relationship between fluid consumption and consumption factors (thirst, voluntary dehydration, water alliesthesia, palatability, work-rest cycle) during a simulated 14.5-km desert walk (treadmill, 1.34 m X s-1, 5% grade, 40 degrees C dry bulb/26 degrees C wet bulb, and wind speed of approximately 1.2 m X s-1). Twenty-nine subjects were tested (30 min X h-1, 6 h) on each of two nonconsecutive days. The subjects were randomly assigned to one of three groups: tap water (n = 8), iodine-treated tap water (n = 11), or iodine-treated flavored tap water (n = 10). The temperature of the water was 40 degrees C during one trial and 15 degrees C on the other. Mean sweat losses (6 h) varied between 1.4 kg (warm iodine-treated; 232 +/- 44 g X h-1) and 3.0 kg (cool iodine-treated flavored; 509 +/- 50 g X h-1). Warm drinks were consumed at a lower rate than cool drinks (negative and positive alliesthesia). This decreased consumption resulted in the highest percent body weight losses (2.8 and 3.2%). Cooling and flavoring effects on consumption were additive and increased the rate of intake by 120%. The apparent paradox between reduced consumption concomitant with severe dehydration and hyperthermia is attributed to negative alliesthesia for warm water rather than an apparent inadequacy of the thirst mechanism. The reluctance to drink warm iodine-treated water resulted in significant hyperthermia, dehydration, hypovolemia, and, in two cases, heat illness.

Adult↗
PubMed1983

Effects of acute plasma volume expansion on altering exercise-heat performance.

To determine the effect an acute plasma volume expansion has on body temperature responses and exercise performance in the heat, seven unacclimatized male volunteers attempted to complete two 90-min walks (45% of VO2 max) in a hot/dry (45 degrees C/20% rh) environment. The experimental walk was preceded by an infusion of human albumin (50 g in a 200-ml solution) and the control walk was preceded by an infusion of isotonic saline (200 ml). Saline infusion did not alter the plasma volume. The albumin infusion was found to significantly (p less than 0.01) increase plasma volume approximately 13% over control levels. No significant differences were found for performance time, final heart rate or final rectal temperature values between the two walks. In general, significant differences were not found for systolic blood pressure, rectal temperature, mean skin temperature, heat storage, sweat rate, plasma lactate, plasma osmolality, or plasma protein content values between the two walks. However, heart rate responses were found to be significantly lower (p less 0.05; approximately 13 bt x min-1) during the 25-min and 40-min measurements of the experimental walk. These data suggest that plasma volume expansion may be a supportive adaptation to enable lowered heart rate responses but does not improve thermoregulatory function or performance time in the heat.

Adult↗
PubMed1983

Acute albumin-induced plasma volume expansion and exercise in the heat: effects on hormonal responses in men.

To assess the responses of fluid regulatory and stress hormones to acute expansion of plasma volume and exercise in the heat, 50 g of albumin dissolved in 200 ml normal saline or 200 ml saline alone was administered intravenously to 7 adult, male test subjects followed by exercise (40% VO2 max) in the heat (Tdb = 45 degrees C, Twb = 25 degrees C). Blood samples were obtained after sitting in the heat for 1 h, 1 h after completion of infusion which itself required approximately 1.5 h, after standing for 30 min, and 15, 30, 45, and 60 min after commencing exercise. Plasma cortisol levels were generally unaffected by these treatments. Responses of plasma aldosterone levels to postural change and exercise in the heat were attenuated in the albumin trial, and growth hormone levels were unaffected by albumin administration. Angiotensin I levels' were significantly decreased at several sampling intervals during the albumin trial, but unaffected by exercise. We concluded from these studies that plasma volume expansion by intravascular albumin administration had no effect on stress hormone responses during exercise in the heat, while regulatory hormone levels were lower in several instances during the albumin trial.

Adult↗
PubMed1983

Liquid chromatographic separation of antidepressant drugs: I. Tricyclics.

A simple normal-phase (silica), high-performance liquid chromatographic (HPLC) assay of amitriptyline (AMI), doxepin (DOX), imipramine (IMI), nortriptyline (NORT), desmethyldoxepin (DESDOX), desipramine (DESIP), and protriptyline (PRO) in serum with no coelution is described here. Trimipramine and promazine were used as internal standards. Extraction of the 1.0-ml serum samples (collected in plastic) was done with Bond-Elut C18 columns. The compounds of interest were eluted with 10 mM methanolic ammonium acetate. The eluates were evaporated at 56-58 degrees C and reconstituted with 200 microliters of the mobile phase. The mobile phase was absolute ethanol-acetonitrile-tert-butylamine (98:2:0.05, vol/vol/vol). Detection of eluted drugs was at 254 nm at 0.01 absorbance units full scale (AUFS), except for PRO, which was detected at 229 nm at 0.02 AUFS. Absolute recoveries were 87-97%. A 5-micron silica (4.6 X 250 mm) HPLC column was used; results with a 10-micron silica column (3.9 X 300 mm) are also presented. Peak height ratios with trimipramine were linear for each analyte between 25 and 1200 ng/ml. Peak height ratios with promazine as the internal standard were linear for each analyte between 25 and 600 ng/ml. Detection limits under the conditions described were 2 ng/ml for AMI, DOX, and IMI, 4 ng/ml for NORT, DESDOX, and DESIP, and 10 ng/ml for PRO. Coefficients of within-day and day-to-day variation at three concentration levels were less than 9.8% and less than 11.2%, respectively. The hydroxylated metabolites of IMI, DES, NORT, and the cis isomer of DOX are discussed. Steady-state daily dosages and corresponding serum levels are presented for 69 patients. The total assay time was less than 10 min for DESIP and 12 min for PRO. This assay can be used in correlating serum levels with clinical effects, compliancy, and pharmacokinetic studies.

Amitriptyline↗
PubMed1983

Liquid chromatographic separation of antidepressant drugs: II. Amoxapine and maprotiline.

The simultaneous serum analysis of amoxapine (AMOX) and its major metabolite 8-hydroxyamoxapine (8-OH AMOX), and maprotiline (MAP) and its major metabolite desmethylmaprotiline (D-MAP) by high-performance liquid chromatography (HPLC) and ultraviolet detection is described here. AMOX and 8-OH AMOX were detected at 254 nm at 0.01 absorbance units full scale (AUFS). MAP and D-MAP were detected at 214 nm at 0.05 AUFS. Serum (1.0 ml collected in plastic) extraction was by Bond-Elut C18 columns. The compounds of interest were eluted from the columns with 10 mM methanolic ammonium acetate. The eluates are evaporated at 56-58 degrees C and reconstituted with 200 microliter of mobile phase. The mobile phase was absolute ethanol-acetonitrile-tert-butylamine (98:2:0.05, vol/vol), and the flow rate was 2.0 ml/min. Absolute recoveries range from 97 to 100% for all compounds. HPLC was done on a 5-micron (4.6 X 250 mm) silica-packing column (normal phase). Separations on a 10-micron silica column (3.9 X 300 mm) are also discussed. Peak height ratios using trimipramine as the internal standard were linear for each drug between 25 and 1080 ng/ml. AMOX and 8-OH AMOX ratios with promazine as the internal standard were linear between 25 and 1080 ng/ml. Detection limits were 3 ng/ml for AMOX and 8-OH AMOX, 12 ng/ml for D-MAP, and 15 ng/ml for MAP. Coefficients of within-day and day-to-day variation at three concentration levels were less than 10.8% and 10.5%, respectively, for all compounds. Correlations of AMOX, 8-OH AMOX, and MAP sample assays using gas chromatography (or gas chromatography-mass spectrometry) and this method were compared. Steady-state daily dosages and corresponding serum levels are presented for seven patients. AMOX and 8-OH AMOX concentrations for 37 patients are given; these show that the ratios of these compounds are highly variable between patients. MAP and D-MAP concentrations for 30 patients show that D-MAP can be a significant fraction of the circulating drug. Assay time for 8-OH AMOX/AMOX was 6.5 min and less than 13 min for D-MAP/MAP.(ABSTRACT TRUNCATED AT 250 WORDS)

Amoxapine↗