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Biomedical subjects

R A Little

Publications and source records attributed to R A Little.

At least 37 records · Page 2Linked to original sources
PubMed1997

Morphine blocks the bradycardia associated with severe hemorrhage in the anesthetized rat.

Progressive hemorrhage in the absence of tissue injury produces a biphasic response: an initial tachycardia, vasoconstriction and maintenance of arterial blood pressure by the baroreflex, followed by bradycardia, vasodilatation and hypotension due to the activation of a second 'depressor' reflex. The present study has investigated the effect of morphine (a mu-opioid receptor agonist) on the cardiac chronotropic response to a progressive hemorrhage at 2% total estimated blood volume (BV) min(-1) in the anesthetized rat. In control rats (20 microl saline intracerebroventricularly, i.c.v.) heart period initially decreased significantly (P < 0.05) by a maximum of 5.4 +/- 0.8 ms from a baseline of 147.3 +/- 2.2 ms after a blood loss of 8.3 +/- 1.5% BV, and then increased significantly by a maximum of 43.0 +/- 5.5 ms above the baseline after the loss of 34.5 +/- 1.6% BV. Blood pressure was initially maintained and then fell during the hemorrhage. The increase in heart period was prevented by treatment with morphine (10 microg i.c.v.), and the fall in blood pressure delayed significantly. These effects of morphine were prevented by pretreatment with naloxone (20 microg i.c.v.). Intravenous (i.v.) administration of morphine (10 microg) had no effect on the response to hemorrhage. However, a clinically relevant dose of 0.5 mg x kg(-1) morphine (i.v.) abolished the bradycardia and delayed the fall in blood pressure associated with hemorrhage. These results indicate that morphine, acting on central nervous opioid receptors, can abolish the bradycardia and delay the hypotension associated with progressive hemorrhage, a pattern of response reminiscent of the effects of musculo-skeletal injury on the response to blood loss.

Anesthesia↗
PubMed1997

Reticuloendothelial function after hemorrhage and hypothermia.

The effects of hypothermia and hemorrhage, alone and together, on reticuloendothelial system function have been studied in male BALB/c mice anesthetized with isoflurane. Whole body phagocytic activity was assessed at a deep body temperature (Tc) between 30 and 37 degrees C by measuring the clearance rate (K) of intravenously injected 51Cr-labeled sheep red blood cells (SRBC). There was a positive linear relationship between K and Tc. At a Tc of 30 degrees C splenic uptake of 51Cr-SRBC was reduced to approximately 50% of that at 37 degrees C, whilst liver and lung uptake were unaffected by the change in Tc. The hypothermia-induced reduction in K was rapidly reversed by rewarming to normothermia. A hemorrhage of 40% of measured blood volume followed after 30 min by return of the shed blood had no effect on K provided Tc was maintained at 37 degrees C. If Tc was allowed to fall to 30 degrees C during the hemorrhage, K was reduced to the same extent as in control hypothermic animals. There was also a tendency for uptake by liver, as well as spleen, to be reduced. These studies indicate that it is important to pay attention to core temperature when studying the effects of hemorrhage on aspects of reticuloendothelial function, at least in a small-animal model.

Animals↗
PubMed1997

Phagocytic reticuloendothelial function after hemorrhage and resuscitation: modulation by different fluids.

Although the efficacy of colloid resuscitation fluids in restoring cardiovascular status in hemorrhagic shock is accepted, the effect they have on the activity of the reticuloendothelial system (RES) is less clear. As interaction with the RES may be important in determining susceptibility to infections after resuscitation the effects of three such fluids, hydroxyethyl starch, Haemaccel, and fresh autologous blood on RES function after a 40% hemorrhage have been investigated in BALB/C mice. The mice, anesthetized with isoflurane, were bled over a 10 min period, left hypovolemic for 30 min, and then resuscitated with their shed blood or the same volume of asanguineous fluid. Normothermia was maintained throughout the experiments. Whole body phagocytic activity was assessed at 1, 6, 24, 48, and 72 h after the end of hemorrhage by measuring the clearance rate (K) of intravenously injected 51Cr-labeled sheep red blood cells. No significant change in K was found at any time in animals resuscitated with shed blood. However, significant increases in K were found 48 h after resuscitation with Haemaccel. Hepatic uptake of sheep red blood cells was significantly increased at 48 and 72 h in Haemaccel-resuscitated animals compared with hydroxyethyl starch or shed blood resuscitation, whereas spleen uptake decreased at 72 h. Lung uptake was not affected at any time with any fluid. The same volume of Haemaccel had no significant effect either on K or on organ uptake when given to normovolemic animals. The changes in organ uptake after hemorrhage and resuscitation with Haemaccel were partially prevented if animals were resuscitated with Haemaccel plus autologous red cells.

Animals↗
PubMed1997

Differences in eicosanoid and cytokine production between injury/hemorrhage and bacteremic shock in the pig.

Plasma concentrations of the eicosanoids leukotriene (LT)B4, LTC4D4E4, thromboxane (TX)A2 and prostaglandin (PG)I2, and tumor necrosis factor (TNF) were measured during acute bacteremic shock and injury/hemorrhage in two porcine models. As TXA2 and PGI2 are rapidly metabolized, we measured their stable metabolites TXB2 and 6-keto-PGF1 alpha. Bacteremic shock was induced by a graded infusion of Aeromonas hydrophila over 4 h. Injury/hemorrhage was produced by a 30 min, 30% total blood volume hemorrhage followed by a 30 min shock period and then reinfusion of shed blood. Nociceptive afferent nerve stimulation was applied to the brachial plexi to mimic the cardiovascular responses to tissue injury. There was no increase in eicosanoid or TNF levels in the injury/hemorrhage model. In sepsis there was an early peak in TNF (at 60 min) followed by peaks in LTB4 and LTC4D4E4 at 180 min. Both TXB2 and 6-keto-PGF1 alpha showed large increases at the end of the study but there was no evidence that they had reached a peak. These results suggest that the very early inflammatory response in bacteremic shock and injury/hemorrhagic shock may be quite different. This may have implications for any therapies aimed at reducing the incidence of multiple organ failure after either of these physiological insults.

Animals↗
PubMed1997

Thermogenic, hormonal and metabolic effects of intravenous glucose infusion in human sepsis.

BACKGROUND: Sepsis is associated with alterations in glucose metabolism and the effect of intravenous feeding on energy expenditure is unclear. Many studies of glucose metabolism in humans with sepsis have employed techniques that are not relevant to the practice of intravenous feeding. METHODS: The thermogenic, hormonal and metabolic effects of glucose were evaluated in a prospective experimental study of septic (n = 6) and non-septic (n = 6) subjects, by administering glucose intravenously under conditions and at a rate similar to those used in total parenteral nutrition. RESULTS: Patients with sepsis had a higher fasting metabolic rate than control subjects (P < 0.001) and a lower fasting respiratory quotient (P < 0.03). The thermic effect of glucose in both groups was small and not statistically significant (median 3.2 and 0.4 per cent in septic and non-septic subjects respectively, P > 0.1). Patients with sepsis had an attenuated plasma insulin response to glucose administration compared with control subjects (P < 0.001) and less marked suppression of plasma fatty acid and glycerol concentrations (P < 0.001). Glucose administration was not associated with significant changes in plasma catecholamine concentrations in either group of patients. CONCLUSION: Intravenous infusion of glucose at clinically relevant rates is associated with a negligible thermogenic response, with no activation of the sympathetic nervous system.

Adult↗
PubMed1996

Nociceptive somatic nerve stimulation and skeletal muscle injury modify systemic hemodynamics and oxygen transport and utilization after resuscitation from hemorrhage.

OBJECTIVE: To examine if either nociceptive somatic nerve stimulation or skeletal muscle injury modified systemic hemodynamics and oxygen transport and utilization after resuscitation from hemorrhage in anesthetized pigs. DESIGN: Prospective, randomized, controlled laboratory study. SETTING: Animal laboratory. SUBJECTS: Twenty isoflurane-anesthetized and mechanically ventilated large white pigs. INTERVENTIONS: Three groups of animals were instrumented with femoral arterial and thermodilution pulmonary artery catheters. One group of animals had bilateral brachial nerve electric stimulation before hemorrhage (brachial nerve stimulation + hemorrhage, n = 7). The second group of animals had bilateral hindlimbs skeletal muscle injury induced by firing a captive-bolt handgun with standard charges before hemorrhage (skeletal muscle injury + hemorrhage, n = 6). The third group had neither insult before hemorrhage (control, n = 7). Controlled bleeding was initiated to reduce the cardiac index and systemic oxygen delivery (Do2) by 50% in all animals. Animals were then left for 30 mins before resuscitation. All animals were resuscitated with 4.5% human serum albumin at 45 mL/kg and observed for 2 hrs. MEASUREMENTS AND MAIN RESULTS: Plasma volume, systemic hemodynamics, and oxygen transport variables were measured and calculated after resuscitation. Similar increases of plasma volume and supranormal cardiac index were observed in all groups immediately after resuscitation. The branchial nerve stimulation and hemorrhage group maintained higher heart rate, cardiac index, Do2, and oxygen consumption (Vo2) than the hemorrhage group. In contrast, the skeletal muscle injury and hemorrhage group had lower systemic mean arterial pressure and vascular resistance, and a tendency for decrease in Vo2, than the hemorrhage group, although heart rate, cardiac index, and Do2 were similar in both groups. Hemorrhage increased the arterial plasma lactate concentration, which was later normalized in all groups 60 mins after resuscitation. CONCLUSIONS: Neither nociceptive brachial nerve stimulation nor skeletal muscle injury attenuated the increase in plasma volume, cardiac index, or the repayment of systemic oxygen debt after resuscitation from hemorrhage. Brachial nerve stimulation was associated with augmented cardiac index, systemic Do2, and increased Vo2 requirements related to increased sympathetic nervous system activation. Skeletal muscle injury produced early systemic arterial hypotension and vasodilation, and a decrease in Vo2 that was suggestive of pathologic supply dependency on systemic Do2.

Animals↗
PubMed1996

The use and misuse of meta-analysis.

OBJECTIVE: To demonstrate how the results of a meta-analysis can confuse rather than clarify therapeutic dilemmas if clinical heterogeneity among trials is ignored. Then to further discuss the qualities emergency physicians should expect from published meta-analyses if they are to affect clinical practice. SUBJECTS AND METHODS: The data and results were examined from 23 randomised controlled trials of selective decontamination of the digestive tract (SDD), which have been combined in a previous meta-analysis. These were reviewed to take account of clinical heterogeneity, particularly with regard to severity of patient illness. RESULTS: Severity of patient illness predicts degree of reduction in mortality with SDD in a regression analysis: log odds ratio (OR) of death with SDD = -0.0074 - (0.0035 x control group mortality rate), P = 0.017. This is also true when trials are stratified into more and less severely ill patients: pooled OR (a) for CMR > 41% = 0.69 (0.54 to 0.89), with (b) CMR < 3% = 1.02 (0.86 to 1.21). This difference was not suggested by the original meta-analysis result. CONCLUSIONS: Failure to take account of clinical heterogeneity between trials can mean a meta-analysis result ignores important differences in the effect of a treatment on different groups of patients. The discussion indicates how emergency physicians might guard against basing clinical practice on misleading meta-analysis results.

Anti-Bacterial Agents↗
PubMed1995

Effects of afferent neural stimulation on critical oxygen delivery: a hemodynamic explanation.

Injury and activation of somatic afferent nerve fibers may alter critical oxygen delivery (DO2C), the point at which oxygen consumption becomes dependent upon delivery, and hence reduce tolerance to hypovolemia. The present study investigated the mechanism of this. Anesthetized mongrel dogs were divided into two groups: control (n = 6) and those subject to brachial nerve stimulation (BNS; n = 5). Whole body oxygen delivery (DO2I) and consumption were initially similar in both groups. DO2I was reduced by cardiac tamponade to determine DO2C. DO2C was significantly higher in BNS compared with control (11.5: 11.0-16.7 vs. 7.5: 6.9-9.5 ml.min-1.kg-1; median: Q1 - Q3), whereas critical oxygen extraction ratios were lower (54.8: 39.7-61.2 vs. 78.3: 53.5-92.4%). At approximately DO2C, normalized femoral blood flow was lower than renal flow in control (renal-femoral difference 17.4: 8.7-40.0%) but not in BNS (-7.8: -14.8 to +11.8%). These results indicate that activation of somatic afferent nerve fibers elevates DO2C. This could be due to an impairment in peripheral oxygen extraction as a consequence of a redistribution of blood flow away from metabolically active vital organs toward relatively inactive skeletal muscle.

Afferent Pathways↗
PubMed1994

Change in bioelectrical impedance following laparoscopic and open abdominal surgery.

The effect of surgery, and in particular, the relative effects of open and laparoscopic abdominal surgery on whole body bioelectrical impedance (BI) has been investigated. Repeated measurements of BI were performed over a 60 h period in 12 patients undergoing laparoscopic surgery (group A) and in 12 patients undergoing elective open abdominal surgery for benign conditions (group B). Control measurements were performed upon 4 healthy adult subjects over the same time period. Attempts were made to relate postoperative changes in BI in group A and group B to changes in net postoperative fluid balance. The postoperative disturbance in BI was significantly greater in group B than group A (P < 0.001 Mann-Whitney-U test) and differed significantly from the minor fluctuations of BI observed in the control group (P < 0.001 Mann-Whitney-U test). The fluctuations in BI observed after laparoscopic surgery were not significantly greater than those seen in the control group (P = 0.1 Mann- Whitney U test). Changes in BI in both group A and B did not correlate with changes in net postoperative fluid balance, which suggests that the effect of surgery upon BI was related to changes of body water distribution rather than changes in total body water volume.

Journal Article↗
PubMed1994

Ethanol augments the baroreflex-inhibitory effects of sciatic nerve stimulation in the anaesthetized dog.

Electrical stimulation of somatic afferent fibres in the sciatic nerve has been used as a model of injury in the anaesthetized dog. Stimulation of the sciatic nerve (during reflexly induced periods of apnoea to obviate any respiratory effects of sciatic stimulation) led to a simultaneous increase in arterial blood pressure and heart rate and a decrease in baroreflex sensitivity. Infusion of ethanol sufficient to produce clinically relevant plasma ethanol levels (100-200 mg %) had no consistent effects on baroreflex sensitivity, but enhanced the pressor response and significantly augmented the inhibitory effects of sciatic stimulation on the baroreflex. Since ethanol is commonly associated with injury in man, such changes in the response to 'injury' may modify the patients' cardiovascular response to the injury and complicate diagnosis.

Animals↗
PubMed1994

Acute changes in oxygen consumption and body temperature after burn injury.

This study describes the pattern of oxygen consumption (VO2), rectal temperature (Tr), and acral skin temperature (Tac) in sleeping and resting (awake) burned children nursed in a thermoneutral environment. Measurements of respiratory gas exchange (VO2 and carbon dioxide production (VCO2)) were made using an open circuit, flow through system of indirect calorimetry. Tr and Tac were monitored continuously. Sixteen patients were studied during the first 18 hours after being burned. Three phases of change in VO2, Tr, and Tac are described. The first was a stable period and there was little change from admission values. The second (7-10 hours after burn) was a phase of rapid heat storage. It started with a fall in Tac. Peak values of Tr (38.8-41.1, median 40.0 degrees C) and VO2 (8.5-11.8 ml/min/kg) occurred either in phase 2 or in the later phase 3. At its peak VO2 was 12-61% above values in phase 1. In phase 3, Tac returned towards admission values but Tr and VO2 were variable. These changes suggest that both an increase in metabolic heat production as well as heat conservation at the extremities may be involved in the generation of early fever after a burn.

Body Temperature↗
PubMed1994

Thermogenic, hormonal, and metabolic effects of a TPN mixture. Influence of glucose and amino acids.

The thermogenic, hormonal, and metabolic effects of intravenous nutrition were examined by administering a complete total parenteral nutrition (TPN) mixture to 11 subjects, and the relative contributions of the glucose and amino acid components of the mixture were evaluated by administering these nutrients separately (n = 7 and n = 6, respectively). The complete TPN mixture caused a 22.9% rise in resting energy expenditure (REE), which significantly exceeded that associated with glucose (10.4% P < 0.02). The rise in REE produced by the amino acids (11.5%) did not differ significantly from that associated with administration of the TPN or glucose. The rise in REE associated with the TPN was almost exactly equal to the sum of the rises associated with the separate components of the mixture (22.9% and 22.0%, respectively), indicating that glucose and amino acids contributed equally to the thermogenic effect of the TPN mixture. In contrast, although the amino acid component of the TPN mixture was associated with small but significant reductions in plasma free fatty acid and glycerol concentration and with small increases in plasma insulin concentration, the effects of the complete TPN mixture were significantly greater and attributable to the glucose component.

Adult↗
PubMed1993

Effect of dietary fish oil supplementation on fever and cytokine production in human volunteers.

The effect of dietary fish oil supplementation on acute phase responses to intramuscular injection of typhoid vaccine, and in vitro cytokine production, was investigated in human volunteers. Half of the subjects supplemented their normal diet with 4.5 g/day of fish oil for 6-8 weeks. Injection of typhoid vaccine in unsupplemented subjects caused an increase in white cell count, resting heart rate, metabolic rate, oxygen consumption, and oral temperature. Fish oil supplementation inhibited the tachycardia and attenuated the maximal increases in oral temperature and metabolic rate following typhoid vaccine. However, interpretation of these latter results were complicated by similarly attenuated responses in saline-injected subjects. The in vitro production of interleukin-1 and interleukin-6 from whole blood was suppressed by fish oil supplementation, however, production of tumor necrosis factor alpha was not significantly altered. Fish oil supplementation may therefore provide a non-pharmacological approach of attenuating several of the responses associated with injury and infection and this may be related to reduced cytokine (IL-1 and IL-6) production.

Journal Article↗
PubMed1993

Clenbuterol, a beta 2-adrenergic agonist, reverses muscle wasting due to scald injury in the rat.

The effects of clenbuterol, a beta 2-adrenergic agonist, on body weight, tissue masses, and protein and RNA contents were studied following scald injury (30 per cent TBSA) in the rat. While the masses of heart, liver and epididymal fat pads remained unaffected, significant reductions in gastrocnemius, plantaris and soleus muscle masses (approximately 11 per cent; P < 0.01) were observed following injury, none of which were mimicked by pair-feeding or could be attributed to dehydration. This muscle wasting was accompanied by significant reductions in protein and/or RNA content. Oral administration of clenbuterol (4 mg/kg diet) had no anabolic effects, either in the scalded animals or their pair-fed controls. While clenbuterol (12 mg/kg diet) did not affect the masses of heart and fat pads, increases in the wet weights (approximately 20 per cent), RNA (approximately 30 per cent) and protein content (approximately 20 per cent) of the gastrocnemius and plantaris muscles were observed in all animals; the magnitude of these effects was greater (P < 0.05) in the scalded animals than in their pair-fed controls. Clenbuterol had no effect on body weight but increased (P < 0.001) carcass water content. These data indicate that there is a selective mobilization of muscle protein and sparing of fat in the early phase following burn injury, and that beta 2-adrenergic agonists, such as clenbuterol, may be of therapeutic value in inhibiting or reversing muscle atrophy associated with thermal injury.

Animals↗
PubMed1993

A comparison of the effects of skeletal muscle injury and somatic afferent nerve stimulation on the response to hemorrhage in anesthetized pigs.

The effect of skeletal muscle injury (SMI) on cardiovascular and O2 transport responses to hemorrhage (HS) were examined in anesthetized pigs. Bilateral hindlimb muscle was injured 75 minutes before HS was started at a rate of 0.75 mL/min.kg until a total of 30 mL/kg (40% estimated total blood volume) had been removed. The reductions in cardiac index (CI), left ventricular stroke work, and oxygen delivery (Do2) and the increase in plasma lactate concentration following HS were exacerbated by SMI such that although oxygen consumption was maintained after HS it fell after SMI + HS. The deleterious effect of SMI on the response to HS was greater than that recorded previously following somatic brachial nerve stimulation (BNS). Thus, in order to achieve a given reduction in CI and Do2 or a rise in Shock Index (heart rate divided by systolic blood pressure) to approximately 3, a blood loss of 40% was needed after HS; this was reduced to 36% by the addition of BNS, whereas a loss of only 29% was needed when SMI was introduced. The mechanism of the deleterious effect of SMI is unclear although a change in the distribution of regional blood flow and a rise in the critical oxygen delivery may be implicated.

Anesthesia↗
PubMed1993

The neuropeptide CRF is involved in the modulation of the baroreflex during hindlimb ischaemia in the anaesthetized rat.

1. The effects of bilateral hindlimb ischaemia (BHLI), and of administration of the neuropeptide corticotrophin-releasing factor (CRF), were tested on cardiovascular variables in propofol-anaesthetized Sprague-Dawley rats. In addition, the effects of antagonizing endogenous CRF on the cardiovascular response to BHLI was investigated. 2. BHLI produced significant increases in mean arterial pressure and heart rate. Baroreflex sensitivity was reduced in all animals tested both 10 and 30 min after the induction of ischemia and this was accompanied by changes which are consistent with an underlying baroreflex resetting. 3. Intracerebroventricular (I.C.V.) administration of CRF (1.5 nmol) produced significant increases in heart rate but not mean arterial pressure. CRF also produced significant reductions in baroreflex sensitivity 10 and 30 min after administration, but there was no consistent evidence of baroreflex resetting. These effects of CRF could be prevented by pretreatment with the synthetic CRF antagonist, alpha-helical CRF(9-41) (alpha hCRF, 6.5 nmol, I.C.V.), which itself had no effect on these cardiovascular variables. 4. Pretreatment with alpha hCRF (6.5 nmol, I.C.V.) prevented the reduction in baroreflex sensitivity observed 10 min after the induction of BHLI, but had no consistent effect on the pressor or tachycardiac responses to BHLI and allowed a clear expression of BHLI-induced baroreflex resetting. alpha-Helical CRF(9-41) had no effect on the reduction in baroreflex sensitivity after 30 min of BHLI. 5. We conclude that corticotrophin-releasing factor mediates, at least in part, the early reduction in baroreflex sensitivity observed during hindlimb ischaemia in the rat.

Anesthesia↗
PubMed1993

Plasma NE concentrations do not accurately reflect sympathetic nervous system activity in human sepsis.

Plasma norepinephrine concentrations ([NE]) when raised in patients with sepsis are thought to indicate increased activity of the sympathetic nervous system (SNS). However, increased SNS activity may occur without a concomitant rise in plasma [NE]. Measurement of NE kinetics (clearance and spillover) is a more accurate and direct assessment of SNS activity. In the present study plasma [NE] and NE kinetics were measured in six patients with intra-abdominal sepsis (septic) using tritiated NE infused to achieve a plateau plasma concentration. The measurements were repeated in the same patients after they had recovered (nonseptic). NE clearance and spillover were both significantly higher (P < 0.05) in the septic compared with the nonseptic state. However, there was no statistically significant difference in plasma [NE] between the two conditions. Plasma [NE] indicates no alteration in SNS activity during the septic state, whereas NE kinetics indicate increased activity of the SNS during sepsis. The results suggest that plasma [NE] is a poor indicator of SNS activity during septic illness.

Adult↗