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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.

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.

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.

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.

The changes in pulse rate elicited by a Valsalva maneuver, a maximal inspiration and a passive head-up tilt, have been measured in patients within a few hours of limb injury before definitive treatment and in control subjects. The injuries were of minor or moderate severity. In all those tested in the Valsalva maneuver, the pulse rate increased during phase 2 and decreased during phase 4 of the response, and both changes were directly related to the initial pulse rate. In controls the increase in pulse rate during phase 2 was greater when the maneuver was performed at 40 mm Hg than at 20 mm Hg, but after injury this difference was not seen and the increases at 20 mmHg and at 40 mm Hg were the same as in controls at 20 mm Hg. The bradycardia during phase 4 was less in injured patients than in controls. The responses returned to normal during recovery. The increase in pulse rate during a maximal inspiration was not affected by injury. When the controls were given a head-up tilt the pulse rate increased, the rise depending on the angle of the tilt. A proportion of the injured patients, which increased with the severity of the injury, did not show this response, for the pulse rate decreased at the higher angles of tilt.

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.

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.

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.