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Biomedical subjects

R A Little

Publications and source records attributed to R A Little.

At least 91 records · Page 5Linked to original sources

Changes in body composition, brown adipose tissue activity and thermogenic capacity in BN/BiRij rats undergoing senescence.

Metabolic rate, thermogenesis, brown adipose tissue (BAT) activity, and body composition were followed in ageing rats (female BN/BiRij) at 3 to 35.5 months of age. Colonic temperatures were similar in rats at 3 to 23 months of age (37.1-37.6 degrees C), but significantly reduced (36.3 degrees C) in those aged 36 months. Resting oxygen consumption (VO2), corrected for body size, was comparable in all groups, but the thermogenic response to noradrenaline was significantly reduced with age. BAT mass was unaffected by age, but brown fat protein content, specific mitochondrial cytochrome oxidase activity, and thermogenic activity (assessed from mitochondrial purine nucleotide binding) all declined markedly with age. Carcass analysis revealed a fall in body protein in very old (35.5 month) rats, but body fat content increased up to 23 months of age and thereafter declined.

Adipose Tissue, Brown↗

Energy metabolism during chronic endotoxin infusion in the rat, with special reference to free fatty acid turnover.

We have studied various aspects of whole-body energy metabolism during chronic endotoxin infusion in the rat. In particular, we studied free fatty acid kinetics using bolus injections of 14C-palmitate. The general response to 7 days of chronic endotoxin infusion could be divided into an initial 3- to 4-day period of illness with loss of appetite, followed by rapid recovery. Using saline-infused, pair-fed controls, the following observations were made throughout the 7-day period of endotoxin infusion: 1) Plasma free fatty acids, glycerol and 3-hydroxybutyrate concentrations were reduced; 2) plasma glucose concentrations were elevated; 3) free fatty acid production rates were unaffected; 4) metabolic clearance of free fatty acids was unaffected on day 1 but was significantly greater on days 3 and 7; 5) haematocrits and plasma volumes were elevated. The results suggest that the observed changes in circulating free fatty acid concentrations are more likely to be a consequence of haemodynamic alterations than of metabolic alterations.

3-Hydroxybutyric Acid↗

Effects of chronic endotoxaemia on oxygen consumption at different ambient temperatures in the unanaesthetised rat.

Oxygen consumption has been measured at different ambient temperatures at intervals during the intravenous infusion of endotoxin (1 mg/kg.day-1) from a subcutaneously implanted osmotic minipump in unanaesthetised rats. On day 1 of the infusion oxygen consumption was elevated at ambient temperatures of 10, 28, and 31 degrees C but not at 20 degrees C, compared with pair-fed saline-infused controls. There was a significant negative correlation between oxygen consumption on days 1 and 3 and environmental temperature (10, 20, and 28 degrees C) in both groups, but the regression line describing the relation in endotoxin-infused rats was displaced above that for the saline-infused control without a change in slope. The "minimal observed" oxygen consumption, which is taken as an estimate of basal metabolic rate, was elevated by the infusion of endotoxin. The endotoxin-induced increase in "minimal observed" oxygen consumption was removed by indomethacin (5 mg/kg.sc) on day 1 of the infusion but was ineffective on days 3 and 7.

Animals↗

Factors affecting the plasma insulin concentration shortly after accidental injury in man.

There are conflicting reports on plasma insulin concentrations in the acutely injured. Plasma insulin and glucose concentrations have been measured in 504 patients within 8 h of injury, and related to the severity of injury as assessed by the injury severity score (ISS). As in previous surveys of injured patients, an extremely wide range of insulin concentrations was found (2-141 mU/l). Most of the variability occurred at lower severities of injury. In very severely injured patients (ISS greater than or equal to 30), insulin concentrations were uniformly suppressed (less than 20 mU/l), especially in relation to the hyperglycaemia in these patients. Two small subgroups, patients dying within 3 h of injury and known psychiatric patients on psycho-active drugs, differed from the general pattern in displaying elevated insulin concentrations despite very severe injuries. The results bear out the idea that insulin secretion is usually acutely suppressed by adrenaline after severe injury; after less severe injuries, however, the response is much less uniform.

Accidents↗

The disposal of intravenous glucose studied using glucose and insulin clamp techniques in sepsis and trauma in man.

Whole body glucose uptake and oxidation during a hyperglycemic clamp have been shown to be depressed in hypermetabolic septic patients compared to control subjects despite similar plasma insulin concentrations. Forearm glucose uptake was similarly impaired. Metabolic rate was not increased further by the glucose infusion in the patients although a 20% rise was elicited in the controls. This resistance to the effects of insulin was also clearly demonstrated in trauma patients using the euglycemic clamp technique. The maximal rate of glucose disposal after injury was half that found in controls and the pattern of response was consistent with the insulin resistance being a post-receptor defect.

Glucose↗

An effect of injury on thermoregulation in man.

The effect of trauma on human thermoregulation has been studied using a behavioural test and the vascular response to cold exposure. It was confirmed, in controls, that a pleasurable temperature for the hand (Thand) depended on core temperature (Tc) to which it was negatively related. Shortly after moderately severe fractures in a leg this relationship was lost and in the patients the slope of this regression line was not significantly different from zero and they usually chose a Thand towards the upper end of the normal range irrespective of Tc. This effect was not imitated in controls by removing 500 ml blood but Thand was increased by occluding the circulation to one leg. Naloxone did not alter Thand in controls but when given in a suitable dose it reduced the rise in Thand during a short period of limb ischaemia. Immersing one hand and forearm in water at 17 degrees C reduced the blood flow through the contralateral forearm and hand. The reduction in flow was positively related to the initial rate of flow in both controls and injured but the slope of the regression line was significantly less after injury. It is concluded that thermoregulation is affected by trauma in man.

Adolescent↗

Plasma catecholamines in the acute phase of the response to myocardial infarction.

Plasma catecholamine (adrenaline, noradrenaline and dopamine) concentrations have been measured in 48 patients within 6 hours of the onset of symptoms of an acute myocardial infarction. The concentrations of all three catecholamines were elevated, and there were positive correlations between plasma noradrenaline concentrations and the severity of infarct as assessed by the coronary prognostic index and serum LDH levels. Plasma glucose, free fatty acid, lactate and cortisol levels were elevated while insulin levels were reduced. The site of infarction did not influence the pattern of hormonal and metabolic responses although heart rate was significantly lower in the inferior than in the anterior infarct group. Seven patients went into ventricular fibrillation shortly (less than 1.8 h) after blood sampling. Plasma catecholamine concentrations were markedly elevated in these patients with levels similar to those previously reported after cardiac arrest.

Adult↗

Plasma catecholamines in patients with acute myocardial infarction and in cardiac arrest.

Plasma catecholamine concentrations in cardiac arrest (ventricular fibrillation and asystole) are significantly higher than after myocardial infarction. The levels reached are well above those normally required to stimulate cardiac activity. Possible reasons for the failure of the myocardium to respond to the catecholamines are discussed and the rationale for giving more catecholamines is questioned.

Adult↗

The relationship of plasma catecholamines to acute metabolic and hormonal responses to injury in man.

Plasma catecholamine concentrations in 40 patients shortly after accidental injury rose progressively with increasing severity of injury. Norepinephrine and epinephrine concentrations were unrelated other than by a common rise with severity; dopamine was closely related norepinephrine and not independently related to injury severity. Plasma glucose concentrations rose after injury; however, this was related only to the plasma epinephrine concentration and not independently to injury severity. Plasma lactate concentrations, in contrast, showed components related both to severity of injury and independently to norepinephrine and epinephrine concentrations. Plasma insulin concentrations were uniformly low, especially with respect to the hyperglycemia, in patients with high plasma epinephrine concentrations. Plasma concentrations of free fatty acids and of cortisol were unrelated to plasma catecholamine concentrations, as were pulse rate and blood pressure. These relationships confirm the expected role of the sympathoadrenal system in the metabolic changes following injury in man.

Adolescent↗

Metabolic control in non-septic patients with musculoskeletal injuries.

Changes in gaseous exchange, plasma substrates and hormones and excretion of nitrogen were followed in 13 non-septic male patients, all of whom had sustained at least 1 fracture of a long bone. Results were compared with normal subjects given glucose to produce a range of substrate and hormone concentrations. Over the 3 weeks following injury, oxidation of fat decreased from high levels whilst oxidation of carbohydrate rose. This reflected to some extent changes in availability of substrate, but early after injury oxidation of fat was higher than expected for the concentration of free fatty acids in plasma and later oxidation of carbohydrate was increased relative to concentrations of glucose and insulin. Concentrations of insulin in plasma were high for the prevailing concentrations of glucose, and peak urinary excretion of nitrogen coincided with maximum levels of insulin. It was concluded that in the injured patient there are changes at the level of utilization and oxidation of plasma substrates as well as in their availability, and that there is marked unresponsiveness of protein metabolism to the normal anabolic effect of insulin.

Adolescent↗

Components of injury (haemorrhage and tissue ischaemia) affecting cardiovascular reflexes in man and rat.

The effects of two components of tissue injury, namely fluid loss from the circulation and tissue ischaemia, on cardiovascular reflex activity have been studied. Moderate blood loss (10-20% blood volume) in the unanaesthetized rat increased the slope of the regression line relating heart period to mean arterial blood pressure and usually displaced it to the left (i.e. towards a relative bradycardia). A blood donation of 500 ml (approximately 10% blood volume) increased the Valsalva ratio in conscious man without a change in resting pulse rate. However, a 15 min period of unilateral limb ischaemia in man reduced the Valsalva ratio. The pattern of change in the pulse rat response to the Valsalva manoeuvre produced by limb ischaemia closely resembles that found previously after limb injury in man. There was no evidence that the endogenous opioids were involved in the interaction between limb ischaemia and cardiovascular reflex activity in man.

Adult↗