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Biomedical subjects

R A Little

Publications and source records attributed to R A Little.

At least 73 records · Page 4Linked to original sources
PubMed1990

Changes in cardiovascular homeostasis after injury are mediated by tissue damage and not haemorrhage.

During treatment of the injured patient it is assumed that the cardiovascular responses follow recognized physiological principles. Studies in humans have shown that injury causes a profound suppression of arterial baroreflex function which alters the normal relationship between heart rate and blood pressure and casts doubt on this assumption. To investigate the mechanism of baroreflex suppression, we have studied the effects of the two major components of injury, blood loss and tissue damage, on baroreflex function in healthy volunteers. Baroreflex function was assessed using suction stimulation of the carotid sinus. The loss of 500 ml blood had no effect on baroreflex sensitivity. A human laboratory model of tissue injury reduced the ability of the baroreflex to compensate for a rise in blood pressure (P less than 0.05, Wilcoxon signed rank test). We conclude that tissue damage, rather than hypovolaemia, appears to mediate the effect of injury on baroreflex function in the injured. Blockade of neural signals from damaged tissue may have a role in the treatment of injury.

Adolescent↗
PubMed1990

Effects of the beta 2-adrenoceptor agonist, clenbuterol, on muscle atrophy due to food deprivation in the rat.

The effects of a beta 2-adrenoceptor agonist, clenbuterol, on body weight and protein metabolism of gastrocnemius muscle, heart, and liver were studied in rats subjected to 50% food restriction or fasting. Food restriction by 50% for 7 days caused a complete cessation of growth and reductions in the mass, protein, and RNA content of muscle, heart, and liver. The ratio of RNA to protein content was also suppressed in muscle and heart, but not in liver. Fasting for 3 days caused loss of body weight (BW), reductions in the mass, protein, and RNA content, and the ratio of RNA to protein of gastrocnemius muscle, heart, and liver. Oral administration of clenbuterol (approximately 0.6 mg/kg BW/d) to food-restricted animals did not affect BW, but did increase in the mass, protein, and RNA content, and the ratio of RNA to protein of gastrocnemius muscle. The protein content of heart was also increased. Twice-daily injections of clenbuterol (2 mg/kg body weight/d) to fasting animals had no effect on BW or the mass or protein content of gastrocnemius muscle or liver, but both parameters were stimulated in heart. The results indicate that the anabolic action of clenbuterol are maintained when substrate availability is reduced by food restriction, but this effect is lost during severe protein and energy deficit (fasting).

Adrenergic beta-Agonists↗
PubMed1990

Dietary intake and changes in body weight in burned children.

Two groups of children were studied. In the first group serial measurements of body weight were made during the child's stay in hospital. In 11 patients, aged 7 months to 13 years, admitted with 10-58 per cent burns, the maximum weight loss was between 6 and 13 per cent of admission weight. Patients had not regained their admission weight at discharge (8-77 days after injury). In the youngest patients, the discharge weight corresponded with the maximum recorded weight loss. In five of the 11 patients dietary intake was calculated by weighing the foods in meals. This was done on average twice per week. Energy and protein intake was below that recommended for children with burns and often lower than that recommended for healthy children. In the second group of 10 patients, 6 months to 7 years had elapsed since the burn. These children were outpatients attending the Burns Aftercare Clinic. Six of the children were at a lower weight centile position when compared to the position at the time of the accident. The children had not 'caught up' to their original centile position.

Adolescent↗
PubMed1990

An effect of trauma on human cardiovascular control: baroreflex suppression.

Survival from injury depends on the interaction between the patient's own homeostatic responses and treatment given. The function of the principal homeostatic reflex of the cardiovascular system, the arterial baroreflex, was studied in 22 healthy controls and in 21 moderately injured patients (ISS range, 9 to 17; median, 9) using suction stimulation of the carotid sinus baroreceptors. When compared to controls, marked baroreflex suppression was evident 3 hours after injury (p less than 0.05), at 3 days after injury (p less than 0.001), and even 15 days after injury (p less than 0.05, all Wilcoxon rank sum test). Partial recovery of baroreflex function occurred between 3 and 15 days after injury (p less than 0.005, all Wilcoxon signed rank test) and was complete by 5 months after injury. The suppression of baroreflex activity was accompanied by a "fixed" rise in heart rate and a rise in systolic blood pressure. This study has shown that moderate injury results in a profound and prolonged suppression of baroreflex function. Further advances in the resuscitation and critical care of the injured may need to take account of such derangements of cardiovascular physiology.

Adolescent↗
PubMed1990

The involvement of the midbrain periaqueductal grey in the cardiovascular response to injury in the conscious and anaesthetized rat.

Cell bodies within the periaqueductal grey (PAG) of the midbrain of the propofol-anaesthetized rat were stimulated using the excitotoxin kainic acid. This resulted in a rise in arterial blood pressure and a tachycardia, together with a reduction in the sensitivity and a rightward resetting of the baroreflex. These changes mimicked the cardiovascular effect of bilateral hindlimb ischaemia in the rat. Further experiments in conscious rats indicated that electrolytic lesions in the PAG prevented the reduction in baroreflex sensitivity induced by limb ischaemia, but did not abolish the rightward resetting of the reflex or the pressor response and tachycardia when compared with sham-lesioned controls. It is postulated that the PAG, a site of importance both in the integration of the defence reaction and the processing of afferent nociceptive information, may form part of a pathway involved in the reduction of the sensitivity of the baroreflex following injury. This pathway is suggested to be separate from a second, as yet undefined, pathway mediating the baroreflex resetting and pressor responses associated with injury.

Anesthesia, Local↗
PubMed1990

Glucose metabolism in children during the first day after burn injury.

Plasma and blood metabolites were measured in 31 children over the first day after burn injury. In 14 of them blood glucose peaked, rising within 1-4h to 10-20 mmol/l and then falling, by 4-8 h, to 5-10 mmol/l. Usually the peak value preceded treatment and the fall occurred during infusion of dextrose-saline. Peak incidence was independent of burn severity. There was no evidence of similar peaks in children or adults with other injuries, or in 8 adults with burn injuries; through high glucose levels have been reported in children with head injuries. Lactate, non-esterified fatty acids, insulin, cortisol, epinephrine and norepinephrine were also measured. Values in the first 4 h were similar to those reported in adults with other injuries, except for lactate, which rose less in the children. Unexpectedly, the hyperglycemia in the children with burns was poorly related to epinephrine concentration at all times to 24h. Insulin resistance probably developed within the first hour or two; but from 8 h did not seem to depend on synergism between epinephrine and cortisol.

Adolescent↗
PubMed1990

Anabolic beta-2-agonist clenbuterol fails to modify muscle atrophy due to femur fracture.

Unilateral femur fracture in rats resulted in a significant reduction in body weight gain and food intake. The former was reversed by addition of the beta 2-adrenoceptor agonist clenbuterol to the diet (4 mg/kg) but food intake was unaffected. Neither resting oxygen consumption (VO2) nor brown adipose tissue GDP binding (measured on day 4) was affected either by femur fracture or by administration of clenbuterol. Femur fracture caused reductions in the mass, protein, and RNA content of gastrocnemius muscle from the fractured leg but not from the intact leg. Clenbuterol did not modify the reduction in the mass or protein content of muscle from the fractured leg, but stimulated these parameters in the intact leg and in heart. The ratio of RNA to protein was enhanced by clenbuterol in gastrocnemius muscle from both legs and heart. These data confirm the anabolic effect of clenbuterol in intact limb muscle but suggest that this agent is unable to prevent muscle atrophy at the site of femur fracture in the rat.

Adipose Tissue, Brown↗
PubMed1990

Dopamine beta-hydroxylase inhibition reveals a selective influence of endotoxin on catecholamine content of rat tissues.

Endotoxin is known to affect sympathetic nervous system (SNS) activity. However, it is unknown whether selective activation occurs in different tissues. The present work assessed SNS activity in several tissues of endotoxin-treated rats by measuring the accumulation of dopamine following dopamine beta-hydroxylase inhibition with disulfiram. Twenty-four hours following endotoxin injection (1 mg/kg), body weight and food intake were significantly reduced. The weight of spleen and liver was significantly greater in endotoxin-injected rats compared to either control animals or rats pair-fed the same quantity of food ingested by the endotoxin-treated rats. Norepinephrine (NE) content of heart, liver, and brown adipose tissue (BAT) was significantly lower in endotoxin-injected animals, but it was unchanged in spleen and gastrocnemius muscle. Endotoxin caused a significant elevation in the dopamine content of heart, liver, BAT, and gastrocnemius muscle, whereas it had no effect on spleen. The results suggest that SNS activity is increased in heart, liver, BAT, and gastrocnemius muscle 26 h after endotoxin injection.

Adipose Tissue, Brown↗
PubMed1989

Muscle wasting associated with endotoxemia in the rat: modification by the beta 2-adrenoceptor agonist clenbuterol.

A single injection of endotoxin (1 mg/kg, sc) in rats caused significant fever, body weight loss and reduction in gastrocnemius muscle mass, none of which was mimicked by pair-feeding. Infusion of endotoxin via osmotic minipump over five days caused transient fever and suppression of growth. Recovery of body weight was significantly enhanced by the administration of the beta 2-adrenoceptor agonist clenbuterol (added to the diet at 4 mg/kg). In a separate experiment, injections of endotoxin (day 0 and day 2) caused significant reductions in body weight gain (42%), mass (9%) and protein content (13%) of gastrocnemius muscle over 3 days. Addition of clenbuterol to the diet reversed all of these effects but did not alter food intake or the febrile response to endotoxin. Clenbuterol caused large (20%) increases in the ratio of RNA to protein in muscle indicating that it may have stimulated protein synthesis. beta 2-adrenoceptor agonists may therefore be of value in preventing or inhibiting muscle atrophy associated with infection or injury.

Animals↗
PubMed1989

Bacterial infection (Legionella pneumophila) stimulates fever, metabolic rate and brown adipose tissue activity in the guinea pig.

The objective of this study was to assess whether bacterial infection stimulates oxygen consumption and brown adipose tissue (BAT) activity. Guinea pigs infected with Legionella pneumophila showed marked fever and a significant (33%) increase in resting oxygen consumption (VO2), 24h after infection. At this time, food intake and body weight were normal and the in vitro thermogenic activity of BAT taken from infected animals was elevated by 64% above that of control guinea pigs. VO2 and BAT activity fell to control values by 48h as infected animals became moribund and over this period food intake was markedly reduced.

Adipose Tissue↗
PubMed1989

A comparison of some thermoregulatory responses in healthy children and in children with burn injury.

1. Changes in body heat content in five normal adults, in 30 healthy children and in 24 children who had suffered burn injury 1-5 h previously, have been studied in cool (20 degrees C) and warm (30 degrees C) environments. 2. On moving from a cool to a warm environment, the heat content rose in both normal adults and healthy children, but the increase was significantly larger in the children. 3. Much larger changes occurred in the burned children in whom the heat content rose to a new plateau within about 8 h of the accident. 4. The changes after burn injury were unrelated to the bandaging of the burn and were little affected by the environmental temperature.

Adult↗
PubMed1989

Thermic effect of parenteral nutrition in septic and nonseptic individuals.

This study compared the metabolic responses to parenteral nutrition in five septic and six nonseptic individuals. Oxygen uptake (VO2) was measured for 1 h preinfusion and during the first 2 h of parenteral nutrition infusion. While baseline VO2 was 19% higher in the septic compared with nonseptic patients (p less than 0.01), both groups responded similarly to nutrition: VO2 increased 25% and 27% above baseline in the nonseptic and septic groups, respectively (NS between groups). Respiratory quotient increased 9% in the nonseptic (p less than 0.01) and 5% in the septic (p less than 0.05) patients during infusion. Plasma glucose and insulin increased identically in both groups. Cortisol was consistently higher in the septic patients whereas glucagon decreased similarly in both groups with feeding. Norepinephrine increased 25% in response to the nutrition and remained elevated in the nonseptic group. The results illustrate the effect nutrient-induced thermogenesis may have in the energy balance of parenterally fed patients.

Adult↗
PubMed1989

Attenuation of the acute cardiovascular responses to haemorrhage by tissue injury in the conscious rat.

A moderate haemorrhage of 0.75 +/- 0.09 ml (100 g body weight)-1 (11.1 +/- 1.3% of estimated blood volume) in the conscious rat produces a tachycardia, possibly mediated by the baroreflex, which serves to maintain mean arterial blood pressure. A severe haemorrhage of 1.20 +/- 0.06 ml (100 g)-1 (greater than or equal to 19.5 +/- 1.5% of estimated blood volume) produces a bradycardia and marked hypotension. The bradycardia is reflex in nature and is due to an increased vagal efferent activity to the heart. This bradycardia is markedly attenuated in animals treated neonatally with capsaicin to render them deficient in C fibres, suggesting that peripheral C fibres (possibly cardiac C fibre afferents, Oberg & Thorén, 1972) are of importance in the bradycardic response to a severe haemorrhage. Concomitant tissue injury produced by bilateral hindlimb ischaemia in a group of animals with normal C fibre afferents markedly attenuates or abolishes the bradycardia and reduces the fall in mean arterial blood pressure produced by severe haemorrhage, although the tachycardia seen with smaller haemorrhages is affected to a much lesser degree. It is concluded that tissue injury can modify the cardiovascular response to a severe haemorrhage, possibly by interacting with the reflex effects of stimulating cardiac C fibre afferents.

Animals↗
PubMed1989

Comparison of the effects of several endotoxin preparations on body temperature and metabolic rate in the rat.

The effects of several bacterial endotoxins on body temperature and resting oxygen consumption (VO2) were compared in normal rats. Low doses (0.05 mg/kg, i.m.) of 0127:B8 phenol-extracted endotoxin caused significant increases in both parameters. Maximal febrile responses (+1.6 degrees C) occurred at a dose of 0.05 mg/kg, but higher doses produced smaller effects. The maximal increase in VO2 (17%) occurred at doses of 0.5-1.0 mg/kg. A TCA extract of the same strain of endotoxin elicited a similar pattern of responses but was less potent than the phenol extract, whereas another endotoxin 026:B6 (TCA extract) was much less potent. The data illustrate the importance of constructing dose-response curves when comparing different endotoxins and indicate that in the rat, oxygen consumption provides a useful index of the response to pyrogens.

Animals↗
PubMed1989

Energy balance and brown adipose tissue thermogenesis during chronic endotoxemia in rats.

The effects of continuously administered endotoxin on 7-day energy balance were investigated in male rats. Three groups of rats were implanted with osmotic pumps; two groups received saline-filled pumps, whereas the third received endotoxin. One of the saline groups was pair fed to match the food intake of the endotoxemic rats. After 7 days, body energy and protein and fat contents of rats were determined together with the energy content of food and feces. Endotoxin infusion not only induced fever, but it also suppressed appetite and significantly decreased body weight gain. Metabolizable energy intake was reduced by approximately 20% in infected rats. Although protein and fat gains were lowest in the endotoxin group, there appeared to be a selective loss of protein when considered as percent of body weight. Percent body fat was unaltered between the groups. Energy expenditure considered in absolute (kJ) or body weight-independent (kJ/kg0.67) terms yielded similar patterns of results; expenditure (kJ) was 10 and 20% (P less than 0.05, P less than 0.01) lower in the endotoxemic and pair-fed rats, respectively, compared with controls. Hence, compared with pair-fed rats, endotoxin-infused animals had a 10% rise in their expenditure. Brown adipose tissue thermogenesis was assessed by mitochondrial binding of guanosine 5'-diphosphate, and results showed that binding was greatest in endotoxemic rats and lowest in the pair-fed animals. The present results suggest that in this endotoxemic model appetite suppression exacerbates changes in energy balance. However, the reduction in body weight gain is also dependent on a decrease in metabolic efficiency and an increase in total energy expenditure.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue, Brown↗
PubMed1988

Acetaminophen (paracetamol) in the management of burned children with fever.

Acetaminophen (paracetamol 12 mg/kg p.o.) was administered on a total of 33 occasions to 12 children (13-36 months of age) during the first 60 h after burn injury covering 10-44 per cent of the body surface area (BSA). The drug was effective in lowering rectal temperature on most (80 per cent) occasions; failure to elicit a response was not restricted to particular patients or patterns of injury. There was no evidence of tachyphylaxis to the antipyretic effects of acetaminophen. The pattern of change in the rectal and toe temperature after acetaminophen suggested that it may be acting by either increasing heat loss or by lowering heat production, both of which are consistent with a reduction in thermoregulatory setpoint mediated by inhibition of prostaglandin synthetase.

Acetaminophen↗