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Biomedical subjects

R A Little

Publications and source records attributed to R A Little.

At least 55 records · Page 3Linked to original sources
PubMed1993

Regional cerebral blood flow and carbon dioxide reactivity after noncerebral injury in the rat.

A loss of cerebral autoregulation and vascular reactivity to CO2 has been reported after a direct head injury; however, little has been published concerning the effect of CO2 after peripheral injury. In the present study, the effects of extracranial injury (bilateral hindlimb ischaemia followed by reperfusion) were studied on regional cerebral blood flow in the hypothalamus and cortex and on the changes in these blood flows induced by altering PaCO2 in the conscious rat. After release of the tourniquets, when fluid was being lost from the circulation into the postischaemic hindlimbs, there was a decrease in regional cerebral blood flow (rCBF). Administration of CO2 at this time markedly increased rCBF. There was no evidence that cerebrovascular responsiveness to hypercapnia was impaired after peripheral injury in the rat.

Animals↗
PubMed1992

Resuscitation fluids and oxygen transport in haemorrhagic shock.

This study examined the cardiovascular and oxygen transport/consumption relationships in haemorrhagic shock and resuscitation using Human Albumin and Gelatin solutions in a porcine haemorrhagic shock model. Immature pigs (17-25 kg) were anaesthetised and ventilated with nitrous oxide, oxygen and isoflurane. Aortic pressure monitoring and monitoring of pulmonary pressures and cardiac output via a Swan-Ganz catheter were instituted. A controlled haemorrhage of 40% of blood volume at 1% blood volume per minute was followed 30 minutes later by resuscitation with 60% of blood volume of 4.5% Human Albumin (Immuno) or 4% Modified Fluid Gelatin (Gelofusine). Haemorrhage caused marked decreases in (CI), mean arterial pressure and oxygen delivery (DO2). Oxygen consumption (V02) remained unchanged. Resuscitation with Albumin and Gelatin raised CI to values 60% to 70% above control though only Albumin restored DO2. Deterioration was more rapid in the Gelatin group due to the estimated half a life of 3 hours in this model. Oxygen extraction was 10% higher in the Gelatin group 2 hours after resuscitation. The role of oxygen radicals in haemorrhagic shock is discussed.

Albumins↗
PubMed1992

Measured energy expenditure and plasma substrate and hormonal changes after severe head injury.

The influence of head trauma on the pattern of response to injury has been studied. Metabolic and hormonal data from brain injured patients over 20 days following injury were compared with an existing data base from non-head-injured patients and control subjects. The results demonstrated elevated concentrations of plasma glucose, lactate, non-esterified fatty acids (NEFA), cortisol, glucagon and insulin above that of control values in both groups after injury. Head injury as a separate factor did not affect the concentrations of any of these plasma substrates and hormones independently of its contribution to the Injury Severity Score (ISS). However, plasma catecholamine concentrations were higher in the head injured initially and at 7 days after injury. All head-injured patients showed an increase in metabolic rate (above predicted values) at some stage after injury. It should be noted, however, that there were some features of head injury (and its treatment) such as paralysis, ventilation and fasting which were not matched in the non-head-injured group. It was concluded that the metabolic changes occurring after head injury are similar to those occurring after extracranial injury and that therapeutic intervention has a major effect on the level of energy expenditure seen in these patients.

Adolescent↗
PubMed1992

Substrate oxidation and the contribution of protein oxidation to energy expenditure after severe head injury.

The 'flow' phase response to head injury is characterized by hypermetabolism and catabolism of lean body mass. In order to measure the contribution of protein oxidation (CPO) to resting metabolic expenditure (RME), 11 severely head injured patients (AIS 5) were studied. All patients had 24 h urine collections for at least 10 days after injury and RME was determined at intervals by indirect calorimetry. No patient received exogenous steroids. Peak urinary nitrogen excretion was 11.63 +/- 1.28 g/m2/day occurring between days 6 and 9 after injury. Fat oxidation was the greatest component of the RME at all times after head injury and the CPO to RME was 26.4 +/- 2.9 per cent during days 1-2, 31.8 +/- 3.3 per cent during days 3-5, 28.6 +/- 3.4 per cent during days 6-9 and 23.3 +/- 3.8 per cent during days 10-20 after injury. These figures are higher than those previously reported for burns, musculoskeletal injury or sepsis. The mechanism for the increased CPO is unclear. It may be related to such conditions of management as paralysis and fasting, but more likely it is an idiosyncratic feature of the metabolic response to head injury.

Craniocerebral Trauma↗
PubMed1992

Lower limb ischaemia and reperfusion alters gut permeability.

The gut may be important in the aetiology of multiple organ failure (MOF) by amplifying of the inflammatory response to trauma. We investigated the effects of the reperfusion of ischaemic lower limbs on gut permeability. Male Wistar rats (n = 30) were randomised to (group 1) controls; (group 2) 3 h bilateral hind-limb ischaemia alone; or 3 h ischaemia followed by (group 3) 15 min reperfusion or (group 4) 2 h reperfusion. Gut permeability and plasma endotoxin were measured prior to tourniquet application, immediately before tourniquet release, and following reperfusion. To evaluate the effect of the hypotension that follows tourniquet release, (group 5) sodium nitroprusside was infused in further controls to maintain mean arterial pressure (MAP) at 75 mmHg for 2 h. Horseradish peroxidase was instilled into the isolated ileo-caecal loop 15 min before the animals were killed to measure permeability of horseradish peroxidase through mucosal intercellular tight junctions by electron microscopy. Mean arterial pressure increased from 105 +/- 5 mmHg to 136 +/- 4 mmHg on tourniquet application and fell to 79 +/- 7 mmHg following reperfusion (p less than 0.05). In group 1 (controls), group 2 (ischaemia alone animals) and group 5 (ischaemia and nitroprusside) one animal out of six demonstrated permeability to horseradish peroxidase. Following reperfusion, horseradish peroxidase permeability had not developed by 15 min (group 3) but was present in all animals by 2h (group 4) (p = 0.015 Fisher's exact test). Plasma endotoxin increased from 21.8 +/- 2.0 pg ml-1 to 30.7 +/- 2.6 pg ml-1 following 2 h reperfusion (p less than 0.05 Scheffe F-test).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Cutaneous heat loss shortly after burn injury in children.

1. Total heat loss and its components have been studied in cool (20 degrees C) and warm (30 degrees C) environments in 30 healthy children and 21 children who had been burned (10-17% body surface area) 0.5-29 h previously. 2. In healthy naked children at 20 degrees C, the partition of total heat loss was: radiation, 64%; convection, 32%; evaporation, 4%. On transfer to the warm, total heat loss was reduced by approximately 50%, with disproportionate reductions in the contributions from radiation and convection being offset, to some extent, by an increase in evaporative heat loss. 3. In patients during the first 5.5h after injury, the magnitude and pattern of heat loss at 20 degrees C and 30 degrees C were similar to those in control subjects and were unaffected by bandaging. 4. Ten to twenty-nine hours after injury, when the patients were bandaged and body temperature and heat content were significantly higher than in control subjects, radiant and convective heat losses were increased, but as evaporative heat loss tended to be reduced; total heat loss in the warm was unchanged. However, at this time at 20 degrees C, total heat loss was reduced compared with healthy children at the same ambient temperature. 5. The findings of unchanged or reduced total heat loss and reduced evaporative heat loss in injured patients are interpreted as inappropriate responses to an increased body temperature and heat content in children after burn injury.

Body Temperature Regulation↗
PubMed1992

Salbutamol, a beta 2-adrenoceptor agonist, increases skeletal muscle strength in young men.

1. beta 2-Adrenoceptor agonists have been shown to increase rapidly lean body mass and reverse muscle wasting in several animal models of human illness. However, no published information is available for humans. In the present study, we investigated the effects of a slow-release preparation of salbutamol or a placebo on skeletal muscle functional capacity in 12 healthy men. The strength of different muscle groups was measured on two occasions before and after 14 and 21 days of treatment. 2. No significant changes in muscle strength were observed with placebo during the trial. In contrast, the strength of both quadriceps muscles increased significantly (12 +/- 3%) after 14 days on salbutamol, and remained elevated at 21 days. Whereas the strength of the hamstring muscles of the dominant leg significantly increased after 21 days on salbutamol (22 +/- 6%), the strength of the non-dominant hamstring muscles returned to baseline values. 3. There was no significant change in the grip strength of either hand in these subjects during the trial. The maximal static inspiratory mouth pressure increased significantly (7 +/- 2%) after 14 days on salbutamol, and increased further after 21 days (15 +/- 4%); the expiratory mouth pressure remained constant. No significant changes in body weight, skinfold thickness, lean body mass or limb circumferences were measured in either group. 4. These data demonstrate that short-term administration of salbutamol increases voluntary muscle strength in man. However, the magnitude and duration of this effect vary between muscle groups. This study implies that the beta 2-adrenoceptor agonists may be of therapeutic potential in altering skeletal muscle function in humans.

Adult↗
PubMed1992

Testing arterial baroreflex function in acutely unwell patients.

Cardiovascular function is deranged in acute illnesses but specific details of this pathophysiological phenomenon are poorly understood. With advances in intensive care it is now necessary to define these changes. Existing tests of cardiovascular reflex function are ill-suited to the study of acutely unwell patients. The arterial baroreflex is the principal cardiovascular homeostatic reflex. We have modified the neck suction test of baroreflex function such that it can be performed in 30 min using portable equipment. The protocol was validated on control subjects. Testing of injured patients showed that this test and protocol could be used sequentially, beginning within 2 h of injury, to demonstrate acute changes in baroreflex function and to follow these changes through the disease process. Patient tolerance of the test was excellent. Subsequently, further modification developed an even shorter protocol whereby similar information could be obtained within 15 min. The cardiac response to deep respiration can be measured with minimal patient upset or compliance and is ideal for repetitive testing in critically ill patients. This is not a specific test of baroreflex function but responses to it show interesting parallels with changes in baroreflex function which merit further study.

Acute Disease↗
PubMed1992

Plasma catecholamine responses in acute severe asthma.

Twenty patients presenting to an A&E department with acute severe asthma were studied. Despite clinically severe airway obstruction few had raised catecholamine levels. However several patients with impending respiratory arrest had markedly elevated catecholamine levels, and relationships are demonstrated between these levels and other measures of disease severity.

Acute Disease↗
PubMed1992

Thermogenic and hormonal responses to amino acid infusion in septic humans.

Metabolic effects of a commercially available amino acid infusate were investigated in five preoperative patients with abdominal sepsis and five healthy subjects. Oxygen consumption (VO2) was measured continuously during the 3-h study, and blood samples were taken regularly for hormone and metabolite analyses. During 1 h of preinfusion measurements, VO2 was 15% higher (P less than 0.05) in the septic patients. Preinfusion plasma cortisol, glucagon, and catecholamines were also significantly elevated in the septic group. The amino acid solution (9 g nitrogen; 950 kJ; 227 kcal) was infused into each subject through their central venous catheter during the 2nd and 3rd h of the study. VO2 increased similarly in both groups by approximately 21% during the infusion (P less than 0.05), whereas respiratory quotient increased significantly in only the controls (P less than 0.05). Plasma insulin and glucagon concentrations rose significantly in both groups during the infusion, despite little change in glucose levels. Plasma norepinephrine increased in both groups, although the response was significant in only the control subjects. In summary, the amino acid infusate stimulated metabolic rate similarly in the septic and nonseptic subjects.

Amino Acids↗
PubMed1992

Anabolic effects of clenbuterol on skeletal muscle are mediated by beta 2-adrenoceptor activation.

The potent anabolic effects of the beta 2-adrenoceptor agonist clenbuterol on skeletal muscle have been reported to be independent of actions on beta-adrenoceptors. In the present study clenbuterol, presented to rats in the diet (4 mg/kg), caused significant increases in gastrocnemius muscle mass, protein, and RNA content and a decrease in epididymal fat pad mass. These effects were not mimicked by oral administration of the beta 2-adrenoceptor agonist salbutamol even at high dose (52 mg/kg diet), and the effects of clenbuterol were not inhibited by addition of DL-propranolol (200 mg/kg diet). However, the selective beta 2-antagonist ICI-118,551 (200 mg/kg diet) reversed the anabolic effects of clenbuterol, and a high dose of DL-propranolol (1,000 mg/kg diet) also inhibited these actions of clenbuterol. Furthermore, continuous infusion of salbutamol (1.15 mg.kg body wt-1.day-1) via miniosmotic pumps did cause significant increases in muscle mass, protein, and RNA content. These results indicate that the anabolic effects of clenbuterol are dependent on interaction with the beta 2-adrenoceptor. However, a long duration of action appears to be required to induce the anabolic effects of beta 2-agonists.

Albuterol↗
PubMed1992

Metabolic and febrile responses to typhoid vaccine in humans: effect of beta-adrenergic blockade.

Fever and activation of acute phase responses were induced in human volunteers by intramuscular injection of typhoid vaccine. Vaccine injection caused a rapid (within 1 h) and sustained rise in metabolic rate (peak response 16%, 6-8 h), followed by later increases in white blood cell count (3-4 h), skin temperature (4-5 h), oral temperature (5-6 h), heart rate (6-8 h), and plasma cortisol (5-8 h). A peak fever [1.2 +/- 0.2 degree C (SE) rise] was recorded 12 h after vaccine injection. The involvement of the sympathetic nervous system in the development of these responses was investigated by the oral administration of propranolol before (80 mg) and 3 h after (40 mg) vaccine injection. Propranolol prevented the increases in metabolic rate, heart rate, and skin temperature but did not inhibit the rise in oral temperature or white cell count after vaccine administration. These data indicate that the sympathetic nervous system is responsible for the rise in energy expenditure associated with fever in humans. However, the rise in body temperature can develop in the absence of this increase in metabolic rate possibly by changes in heat loss.

Acute-Phase Reaction↗
PubMed1991

Dose-response relationships for the effects of insulin on glucose and fat metabolism in injured patients and control subjects.

1. Twenty-four patients were studied at around 7 days after musculoskeletal injuries in order to define the nature of the impairment of sensitivity to insulin. Insulin was infused at 6, 35, 200 or 1200 m-units min-1 m-2 for 2 h and the plasma glucose concentration was 'clamped' at 5 mmol/l. Forearm (uninjured) glucose extraction and blood flow were measured, and whole-body substrate oxidation and energy production rates were assessed by indirect calorimetry. The patients were compared with normal control subjects. 2. Plasma insulin concentrations during infusion were similar in patients and control subjects, showing a similar metabolic clearance of insulin. At each infusion rate, the rate of glucose infusion needed to maintain euglycaemia was less in the patients than in the control subjects. The dose-response curve for whole-body glucose infusion rate against plasma insulin concentration showed diminished sensitivity and diminished maximal response in the patients. A similar pattern was seen for forearm glucose uptake, with a marked impairment of both sensitivity to insulin and maximal responsiveness. 3. The resting metabolic rate was increased in the patients compared with the control subjects, but failed to respond to insulin infusion, so that final metabolic rates were similar in patients and control subjects. At the higher insulin infusion rates, the final rate of whole-body oxidation of carbohydrate was significantly less in the patients than in the control subjects, and that of fat was significantly greater.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Lipid infusion increases oxygen consumption similarly in septic and nonseptic patients.

This investigation compared the metabolic effects of lipid infusion in five septic and five nonseptic patients. Oxygen consumption was determined by indirect calorimetry over 1 h of rest and during 2 h when Intralipid (20%) was infused [166 mL/h; 23 kJ/min (5.5 kcal/min)]. Septic patients had a resting metabolic rate 17% higher than that of their nonseptic control subjects and a significant (P less than 0.05) rise (13%) in oxygen uptake was measured in both groups of subjects during the 2-h infusion of lipid. Preinfusion respiratory quotient (RQ) was 7% higher in the septic patients (P less than 0.05), and during the infusion period RQ decreased similarly (approximately 6%; P less than 0.05) in both groups. Plasma catecholamines were elevated in the septic patients preinfusion and the concentrations remained unaltered during the infusion. Norepinephrine rose significantly in the nonseptic group with the lipid infusion. The results show that sepsis has little or no influence on the characteristic rise in metabolic rate that occurs with intravenous lipid.

Adult↗
PubMed1991

The effect of nociceptive stimulation on the changes in hemodynamics and oxygen transport induced by hemorrhage in anesthetized pigs.

The effects of somatic nociceptive afferent stimulation on aspects of cardiac function and oxygen transport were examined in a model of hemorrhage in anesthetized pigs. The brachial nerves were stimulated (BNS) alternately to obtain a rise in heart rate of 18% and in mean arterial pressure of 17%. This stimulation was started 75 minutes before the start of hemorrhage and maintained throughout and after the withdrawal of blood. The animals were bled at a rate of 0.75 ml/min.kg until a total of 30 ml/kg had been removed. At the end of hemorrhage the reductions in cardiac index (CI), stroke volume (SV), and left ventricular stroke work (LVSW) were greater in the BNS group compared with controls. The nociceptive stimulation also elicited greater reductions in oxygen delivery (DO2I) and oxygen consumption (VO2) and a greater rise in the arterial plasma lactate concentration. Thus it seems that nociceptive stimulation exacerbates the changes in systemic oxygen transport and cardiac function induced by hemorrhage.

Animals↗
PubMed1991

Brown adipose tissue activity and oxygen consumption after scald injury in the rat.

Scald injury (30% surface scald) in the rat caused rapid (1-3 h) and transient decreases in oxygen consumption (VO2 20%), colonic temperature (1.1 degree C), and brown adipose tissue (BAT) thermogenic activity (22%). Three days after injury, VO2 was slightly increased in injured rats, and sympathetically mediated heat production (assessed from the inhibitory effect of a beta-adrenergic antagonist on VO2) was significantly greater than than for controls. At this time, BAT activity (in vitro mitochondrial GDP binding) was 35% higher in injured than control rats. Food intake was inhibited for only 24 h in injured animals, but weight gain was suppressed for at least 3 days. The data indicate that sympathetic modification of BAT thermogenesis may contribute to the changes in metabolic rate and body weight gain after scald injury in the rat.

Adipose Tissue, Brown↗