Characterising recovery following abdominal aortic aneurysm repair using cardiopulmonary exercise testing and patient reported outcome measures.

PURPOSE: Surgery is associated with a post-operative stress response, changes in cardiopulmonary reserve, and metabolic demand. Here recovery after abdominal aortic aneurysm repair is investigated using cardiopulmonary exercise testing and patient-reported questionnaires. MATERIALS AND METHODS: Patients undergoing open (n = 21) or endovascular (n = 21) repair undertook cardiopulmonary exercise tests, activity, and health score questionnaires pre-operatively and, 8 and 16 weeks, post-operatively. Oxygen uptake and ventilatory parameters were measured, and routine blood tests were undertaken. RESULTS: Recovery was characterised by falls in anaerobic threshold, peak oxygen uptake, and oxygen pulse at 8 weeks which appeared to be associated with operative severity; the fall in peak oxygen uptake was greater following open vs. endovascular repair (3.5 vs. 1.6 ml.kg-1.min-1) and anaerobic threshold showed a similar tendency (3.1 vs. 1.7 ml.kg-1.min-1). In the smaller number of patients re-tested these changes resolved by 16 weeks. Reported health and activity did not change. CONCLUSIONS: Aortic repair is associated with falls in the anaerobic threshold, peak oxygen uptake, and oxygen pulse of a magnitude that reflects operative severity and appears to resolve by 16 weeks. Thus, post-operatively patients may be at higher risk of further metabolic insult e.g. infection. This further characterises physiological recovery from aortic surgery and may assist in defining post-operative shielding time.IMPLICATIONS FOR REHABILITATIONAbdominal aortic aneurysm repair is a life-saving operation, the outcome from which is influenced by pre-operative cardiopulmonary reserve; individuals with poor reserve being at greater risk of peri-operative complications and death. However, for this operation, the physiological impact of surgery has not been studied.In a relatively small sample, this study suggests that AAA repair is associated with a significant decline in cardiopulmonary reserve when measured 8 weeks post-operatively and appears to recover by 16 weeks. Moreover, the impact may be greater in endovascular vs. open repair.

Efficacy of the subcostal transversus abdominis plane block in laparoscopic cholecystectomy: Comparison with conventional port-site infiltration.

BACKGROUND: Pain experienced following laparoscopic cholecystectomy is largely contributed by the anterior abdominal wall incisions. This study investigated whether subcostal transversus abdominis (STA) block was superior to traditional port-site infiltration of local anesthetic in reducing postoperative pain, opioid consumption, and time for recovery. MATERIALS AND METHODS: Forty-three patients presenting for day case laparoscopic cholecystectomy were randomly allocated to receive either an ultrasound-guided STA block (n = 21) or port-site infiltration of local anesthetic (n = 22). Visual analog pain scores were measured at 1 and 4 h postoperatively to assess pain severity, and opioid requirement was measured in recovery and up to 8 h postoperatively. The time to discharge from recovery was recorded. RESULTS: STA block resulted in a significant reduction in serial visual pain analog score values and significantly reduced the fentanyl requirement in recovery by >35% compared to the group that received local port-site infiltration (median 0.9 vs. 1.5 µcg/kg). Furthermore, STA block was associated with nearly a 50% reduction in overall 8-h equivalent morphine consumption (median 10 mg vs. 19 mg). In addition, STA block significantly reduced median time to discharge from recovery from 110 to 65 min. CONCLUSION: The results suggest that STA block provides superior postoperative analgesia and reduces opioid requirement following laparoscopic cholecystectomy. It may also improve theater efficiency by reducing time to discharge from the recovery unit.

Hypothermic responses to infection are inhibited by alpha2-adrenoceptor agonists with possible clinical implications.

BACKGROUND: alpha(2)-Adrenoceptor agonists are currently used as primary sedative agents in high dependency patients who are at high risk of sepsis. Clinical surveillance of such patients relies in part on their ability to mount appropriate responses to infection, in particular thermal responses. Thermoregulatory responses to infection are well studied in the rat and in this species, and humans, infection can induce febrile, hypothermic, or mixed hypothermic and febrile responses. The involvement of noradrenergic systems in thermal responses to infection prompted the hypothesis that ligands that act on adrenoceptors may interfere with the normal thermal responses to infection. METHODS: In this study on rats, the effect of infusion of the selective alpha(2)-agonist, mivazerol, on hypothermic and plasma corticosterone responses induced by bacterial lipopolysaccharide (LPS) was investigated. RESULTS: Clinically effective doses of mivazerol (4.8 and 10 microg kg(-1) h(-1)) had no effect on body temperature alone. However, mivazerol significantly inhibited the typical thermoregulatory response to bacterial LPS in a dose-dependent manner. This effect was mimicked by the selective alpha(2)-agonist, UK14304-18 (6 microg kg(-1) h(-1)), and antagonized by the alpha(2)-antagonist, RX811059A (7 microg kg(-1) h(-1)). The alpha(2)-ligands had no effect on basal or LPS-induced corticosterone levels. CONCLUSIONS: These data suggest that early thermoregulatory responses to infection can be selectively antagonized by ligands that activate alpha(2)-adrenoreceptors. High dependency patients receiving alpha(2)-adrenoceptor agonists may not be capable of mounting a normal thermal response to infecting organisms and clinical monitoring using core temperature to detect infection may therefore be unreliable in these vulnerable patients.

Identifying sources of dissolved organic carbon on the River Swale, Yorkshire

A dissolved organic carbon (DOC) sampling study was carried out on the River Swale in Yorkshire as part of the NERC LOIS programme. Loads of DOC were calculated from the river and its tributaries. For the River Swale calculated loads varied between 1900 and 9000 kg/day and for the tributaries between 1 and 8500 kg/day. No relationship was found between the amount of organic carbon in the soil of the catchments and the DOC loads, perhaps because of the preceding dry summer. DOC loads were also estimated for sewage point sources and ranged between 7 and 287 kg/day. Some of the catchments draining to the River Swale respond with high DOC loads during high flow conditions, others do not. Some catchments are dominated by sewage point sources during low flows and diffuse sources during high flows. A mass balance for DOC on the River Swale was calculated, however, loads from inputs did not balance with outputs because of a lack of data and errors inherent in some of the approaches used. Despite this, results indicate in-stream losses of approximately 20%. A highly detailed measurement study of a stretch of river is recommended to identify all the sources and sinks of DOC, the relative size of their contribution and how they respond in differing conditions.

Modulation of synaptic transmission in the rat ventral septal area by the pharmacological activation of metabotropic glutamate receptors.

The ventral septal area (VSA) is considered to be critically involved in the control of the height and duration of fever. The major excitatory input to this region of the brain is glutamatergic, and the aim of this study was to investigate possible modulation of this synapse by metabotropic glutamate (mGlu) receptors. Whole-cell patch recordings were made from individual VSA neurons voltage-clamped at -60 mV. Activation of either group I or group II mGlu receptors (by bath application of 3,5-dihydroxyphenylglycine (DHPG) or (2S,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)glycine (DCG-IV), respectively) produced a long-lasting depression of synaptic transmission which in both cases was insensitive to the N-methyl-D-aspartate (NMDA) receptor antagonist D-2-amino-5-phosphonopentanoate (D-AP5). In contrast, application of (S)-2-amino-4-phosphonobutyric acid (L-AP4), a group III mGlu receptor agonist, had a biphasic effect on synaptic transmission in the VSA, first eliciting a transient depression of transmission during drug application, followed by a marked and sustained potentiation of synaptic transmission upon drug washout. The response elicited by L-AP4 was dependent on NMDA receptor activation, as in the presence of D-AP5 the potentiation was replaced by an underlying long-term depression (LTD) of transmission. These data provide the first evidence that metabotropic glutamate receptor agonists can induce both NMDA receptor-dependent and -independent modulation of synaptic transmission in the VSA.

TNF alpha mimics the endocrine but not the thermoregulatory responses of bacterial lipopolysaccharide (LPS): correlation with FOS-expression in the brain.

Thermoregulatory and plasma corticosterone responses to peripheral LPS and TNF alpha were compared and correlated with brain FOS protein expression. TNF alpha mimicked the corticosterone response evoked by LPS and the increase in FOS expression in the hypothalamic PVN. TNF alpha also mimicked LPS-activation of central noradrenergic and adrenergic neurones. TNF alpha did not induce a hypothermia which might reflect its failure to activate the vasopressin neurones of the BNST.

Bacterial lipopolysaccharide-induced changes in FOS protein expression in the rat brain: correlation with thermoregulatory changes and plasma corticosterone.

In the present study the regions of the brain showing an increase in the number of FOS protein stained cells 180 min following intravenous saline or bacterial lipopolysaccharide (LPS) treatment were investigated and correlated with changes in body temperature and plasma corticosterone levels. Particular attention was given to the possible involvement of the circumventricular organs and regions of the brainstem containing central noradrenergic neurones. LPS at doses of 0.35, 3.5 and 50 micrograms caused highly significant increases in FOS protein expression in the organum vasculosum of lamina terminalis, the area postrema and the subfornical organ compared with saline controls. Marked increases in bacterial lipopolysaccharide-induced FOS protein expression were observed in the ventrolateral medulla, the nucleus of the solitary tract and the locus coeruleus which contain the A1, A2 and A6 noradrenergic neurones respectively. The changes in body temperature induced by LPS were found to be dependent upon the dose of LPS administered; the lowest dose employed (0.35 micrograms) induced an immediate and sustained fever, 3.5 micrograms LPS caused a biphasic response consisting of a hypothermic response followed by a febrile response, whereas 50 micrograms LPS induced a hypothermic response which then normalised by 160 min post-injection. Intravenous saline injection had no significant effect on body temperature. The occurance of LPS-induced hypothermia was coincident with increased FOS expression in the bed nucleus of stria terminalis, which houses vasopressinergic neurones involved in antipyresis, whereas in animals showing an LPS-induced febrile response there was no significant difference in the number of FOS stained cells in the bed nucleus of stria terminalis compared with saline treated animals. LPS also caused marked increases in FOS protein expression in the parvocellular regions of the paraventricular nucleus (pPVN) of the hypothalamus, the central nucleus of the amygdala and the ventral septal area. Plasma corticosterone was unaffected by the lowest dose of LPS (0.35 micrograms), however the higher doses employed (3.5 and 50 micrograms) caused significant increases in plasma corticosterone which correlated with the increases in the number of FOS stained cells in the pPVN. The results of the present study suggest that, in addition to the organum vasculosum of lamina terminalis, the area postrema and subfornical organ may be important in the responses to antigenic challenge that are mediated by the central nervous system. They also add support to the possible involvement of the bed nucleus of stria terminalis in LPS-induced hypothermia and of the involvement of the of the major noradrenergic cell groups (A1, A2 & A6) and a number of hypothalamic and extrahypothalamic forebrain regions in the interaction of immune and central nervous systems.

[Arg8]vasotocin excites neurones in the dorsal vagal complex in vitro: evidence for an action through novel class(es) of CNS receptors.

Using extracellular recordings from brainstem slices in vitro, it was demonstrated that a high proportion (38/56) of neurones in the dorsal vagal complex of dioestrus, virgin female rats exhibit an excitatory response to [Arg8]-vasotocin (AVT). Pharmacological characterization suggests that these responses cannot be entirely explained by interaction with either of the currently known classes of central receptors for oxytocin (OT) and vasopressin (V1a). Comparison of the responses with those to the OT receptor-specific agonist [Thr4,Gly7]-OT (TGOT), showed that not all neurones that responded to TGOT also responded to AVT (3/27). Furthermore, while the effects of 10(-7) M TGOT could be blocked either by the broad-spectrum antagonist d(CH2)5[d-Tyr(OEt)2,Val4,Cit8]-vasopressin or by the selective OT receptor antagonist d(CH2)5[Tyr(Me)2,Thr4,Orn8,Tyr-NH2(9)]-vasotocin, these peptides did not completely block the responses to AVT, indicating that AVT is unlikely to act through the central OT receptor. The responses to AVT and [Arg8]-vasopressin (AVP) indicated the presence of at least 2 classes of receptor with which these agonists could act. Of 42 neurones tested with both AVP and AVT, none responded to AVP in the absence of a response to AVT, while 7/42 responded to AVT without a response to AVP. This might be explained by AVP acting through only the V1 receptor, while AVT acts through both the V1 and its own novel class of receptor. This was substantiated by the fact that two OT/V1 receptor antagonists, d(CH2)5[d-Tyr(OEt)2,Val4,Cit8]-VP and d(CH2)5[Tyr(Me)2,Tyr-NH2(9)]-AVP, were unable to block completely all the responses to AVT at a dose which suppressed responses to both AVP and TGOT.(ABSTRACT TRUNCATED AT 250 WORDS)

Electrophysiological actions of oxytocin in the dorsal vagal complex of the female rat in vitro: changing responsiveness during the oestrous cycle and after steroid treatment.

The effect of the oxytocin-specific agonist Thr4,Gly7-oxytocin (TGOT) was tested on neurones in tissue slices of the dorsal vagal complex, obtained from virgin female rats at different stages of the oestrous cycle. The proportion of neurones excited by TGOT (0.1 microM) was independent of the day of the cycle, but both the basal activity and magnitude of response induced by TGOT were significantly reduced on the day of oestrus by comparison with dioestrus. This was due to a small but significant shift in the dose-response relationship. The magnitude of the excitation of neurones obtained from animals at proestrus did not differ significantly from either oestrus or dioestrus, but lay between the two. Ovariectomy 6 days prior to recording reduced the proportion of responsive neurones (35% vs. 69% at dioestrus), but had only a small effect on the amplitude of the averaged responses. Daily injection of 10 micrograms oestradiol benzoate had no additional effect on the proportion of responsive neurones (40%), but caused a marked suppression of the amplitude of the response at all doses (change in firing rate caused by 0.1 microM: 1.68 +/- 0.27 Hz vs. 2.69 +/- 0.39 Hz). In contrast, injections of 5 mg progesterone caused a small increase in the amplitude of the response. The data show that ovarian steroids have a marked effect on oxytocin-sensitive neurones of the dorsal vagal complex, causing dynamic changes in responsiveness over the oestrous cycle. This is discussed with respect to the effects of ovarian steroids on central oxytocin receptors and the possible involvement in regulating autonomic functions.

Role of dialysable solutes in the mediation of uremic encephalopathy in the rat.

This study addresses mechanisms of the clinical, encephalopathic uremic illness and its suppression by dialysis. Renoprival rats were treated with peritoneal dialysis (8 exchanges per day, 30 min dwell), or untreated (attrition group), and their EEG's were automatically sampled overnight and subjected to power spectrum analysis as an index of encephalopathy. As in man the background rhythm of the quantified EEG (Q.EEG) in the attrition group slowed with time as extracellular fluid composition became increasingly abnormal; these changes were normalized by therapeutic dialysis (TD) using standard, commercial dialysate. However, Q.EEG slowing was only partially normalized by solute-specific dialysis using "mock uremic dialysate" (M-UD), prepared from laboratory chemicals to equal plasma concentrations in preterminal uremic rats of urea, creatinine, potassium, phosphorus, calcium, magnesium, bicarbonate, sodium, and chloride. When only phosphate was added to TD, the Q.EEG slowed to the same level achieved after M-UD. We conclude that uremic encephalopathy in this model is produced by an unknown neurotoxin and augmented by one or more of the M-UD solutes, phosphate being a likely candidate. To localize the encephalopathic effect, regional brain glucose uptake was estimated in 20 discrete brain areas. Significance of reduced uptake in three areas is discussed.

Separate and combined effects of morphine and amphetamine on quantitative electroencephalogram and regional cerebral glucose uptake in a rat model.

The effects of morphine (5 mg/kg) and amphetamine (5 mg/kg) were examined on relative regional cerebral glucose uptake (RrCGlu), surveyed in 20 brain areas in the rat. No relationship was found between drug effects on the cortical RrCGlu and the quantitative electroencephalogram (QEEG) measured from frontal and occipitoparietal cortices. Discriminant function analysis revealed that the two drugs produced identifiably different QEEG changes and that the combination engendered an unique metastate that most closely resembled amphetamine's effect with no morphine characteristics. The two drugs evoked qualitatively similar RrCGlu changes at most sites surveyed, with certain exceptions which are discussed. Both increased RrCGlu at the substantia nigra. Morphine, but not amphetamine, increased RrCGlu at the periaquaeductal gray. Since amphetamine is known to potentiate morphine analgesia and to ameliorate many of the opiate's depressant effects, the finding that the combination evokes cortical QEEG changes that more closely resemble amphetamine may have implications for understanding the increased psychotoxicity of chronic combined abuse.

Comparison of the effects of central and peripheral aluminum administration on regional 2-deoxy-D-glucose incorporation in the rat brain.

Intracerebroventricular (ICV) Injection of aluminum tartrate (ALT 205.7 mcg) in the rat induces a progressive encephalopathy characterized by neurobehavioral derangements, by the slowing of the background rhythm of the quantitative electroencephalogram and by learning and memory deficits. The condition, lethal within about 35 days, is associated with a reduced ability of cerebral synaptosomes to incorporate radiolabeled 2-Deoxy-D-glucose (2DG) in vitro. The present study surveyed and compared the in vivo regional cerebral glucose uptake (rCGlu) capacity of rats injected with ALT 7 or 14 days previously either by the ICV or intraperitoneal (120 mg/Kg) routes. ICV injection produces transient rCGlu depression in caudate-putamen, geniculate bodies and periaquaeductal gray, resolving by day 14. Thalamic nuclei exhibit depressed rCGlu by the 7th day undergoing further depression by day 14. The rCGlu of occipitoparietal cortices, normal at day 7, was increased by day 14. In contrast, peripheral aluminum administration produced transient rCGlu depression in olfactory bulbs, frontal and occipitoparietal cortices, nucleus accumbens and cerebellum, and transiently increased rCGlu in the geniculate nuclei. These effects, present by day 7, had resolved by day 14 when rCGlu had increased in the previously normal pontine nuclei and decreased in the previously normal hippocampus. Neither treatment changed rCGlu in the septal nuclei, globus pallidus, amygdala, olfactory cortex, substantia nigra, superior or inferior colliculi or the medullary nuclei. The pattern of anomalies in cerebral 2DG incorporation most probably indexes the deranged glucoregulatory and metabolic demands of these brain areas in the aluminum intoxicated state.