Synaptogenesis in monkey somatosensory cortex.

The time course and rate of synaptogenesis were studied in the somatosensory cortex (Brodmann's areas 1 and 3b) of 27 rhesus monkeys ranging in age from embryonic day 41 to 20 years. Two to four vertical probes, each consisting of a series of overlapping electron micrographs and extending from the pial surface to the interface of the cortex with the white matter, were made from sections cut across the postcentral gyrus in the region of the upper limb representation. We found that the density of synapses per unit volume of cortex as well as per unit volume of neuropil increases steadily throughout the late fetal ages and early infancy. A density of 70/100 microns 3 of neuropil was reached by the second postnatal month; thereafter, between 1 and 3 years a slightly lower density of 50-60/100 microns 3 was maintained. At around puberty, the decrease in concentration of synapses appears to be accelerated. Thus, the average synaptic density of a group of 10 adult animals composed of monkeys over 4 years of age was 30-40 synapses per 100 microns 3 of neuropil. This value is significantly lower than that of the group of 11 infant and juvenile animals below 4 years of age. Since synaptic density per unit volume of neuropil is not affected by changes in other parameters of cortical growth, these numbers reflect an actual overproduction of synapses in infancy followed by their elimination during adolescence. The decline in the number of synapses is due primarily to elimination of asymmetrical junctions located on dendritic spines while symmetrical synapses on dendritic shafts and cell bodies remained relatively constant during postnatal life. The course of synapse formation recorded in the present study coincides with the course of overproduction and elimination of neurotransmitter receptors (Lidow et al., 1991) and the developmental schedule of synaptogenesis in other neocortical areas (Rakic et al., 1986). The timing of synaptogenesis and synaptic elimination in the postcentral gyrus may account for the maturation and plasticity of various aspects of somatosensory function during post-natal life.     

Synaptogenesis in layer I of the human cerebral cortex in the first half of gestation

The formation of synapses is among the most important steps in neuronal differentiation and the establishment of neuronal circuits. To establish baseline data about the time of onset, density and the course of synaptic formation in different regions of the human cerebral cortex before birth, synaptogenesis in layer I was examined by electron microscopy in fetuses ranging in age from 6 to 24 gestational weeks. Synapses were first observed in the primordial plexiform layer (marginal zone) in both the lateral and medial cerebral walls between the 6th and 7th gestational week, before the formation of the cortical plate. The density of synapses increased rapidly after the formation of the cortical plate, increasing by 37% between 12 and 14 weeks. Synaptogenesis proceeded at the same rate in the lateral and occipital cortex during this period. Further, with one exception, the insular region, synaptic density was comparable in prospective areas of prefrontal, motor, visual, temporal and cingulate cortex in a group of fetuses at midgestation (20 weeks). The results are consistent with a synchronous course of synaptogenesis of the neocortex.      

Ultrastructural variations of synapses in the normal human cerebral cortex]

The numerous synapses in the normal human brain cortex display various aspects. The authors have also observed some electronic type synapses which are more numerous around the pericaryons. The cortical synapses are classed according to their synaptic vesicle richness : synapses with very few vesicles, synapses very rich in vesicles and synapses with a middling vesicular density. With the help of observations on these aspects and on variations of the synaptic cleft and that of the postsynaptic density, the authors advance an hypothesis on synaptic plasticity, the synaptic structures going from a simple intercellular contact (probably non functional) to a completly formed synapse and vice versa.     

Synaptic distinction of laminar-specific prefrontal-temporal pathways in primates

Prefrontal pathways exert diverse effects in widespread cortical areas, issuing projections both to the middle layers and to layer I, which are anatomically and functionally distinct. Here we addressed the still unanswered question of whether cortical pathways that terminate in different layers are distinct at the synaptic level. We addressed this issue using as a model system the robust and functionally significant pathways from prefrontal areas 10 and 32 to superior temporal areas in rhesus monkeys. Boutons from prefrontal axons synapsing in the middle layers of superior temporal cortex were significantly larger than boutons synapsing in layer I. Most synapses were on spines in both layers, which are found on dendrites of excitatory neurons. The less prevalent synapses on smooth dendrites, characteristic of inhibitory interneurons, were more common in the middle cortical layers than in layer I. Bouton volume was linearly related to vesicular and mitochondrial content in both layers, though a subset of small boutons, found mostly in layer I, contained no mitochondria. The systematic laminar-specific presynaptic differences in stable cortical synapses in adult primates were independent of their origin in the functionally distinct prefrontal areas 10 and 32, or their destination in architectonically distinct superior temporal areas. This synaptic distinction suggests differences in efficacy of synaptic transmission and metabolic demands in laminar-specific pathways that may be selectively recruited in behavior.     

EFFECTS OF THIOPENTONE ON MEDIAN NERVE SOMATOSENSORY EVOKED POTENTIALS

We have studied the effects of an i.v. bolus of thiopentone4 mg kg^–1 on the median nerve somatosensory evoked potentials(SSEP) in 15 unpremedicated patients. The latency and amplitudeof the SSEP response over the second cervical vertebra (SC)and sensory cortex (P₁₅, N₂₀, P₂₅) were recorded before andfor 12 min after injection. Data were analysed at 0, 4, 8 and12 min for time-related alterations. Cortical amplitude wasvariable, with a tendency to decrease (P < 0.03). There wasa statistically significant but clinically insignificant transientincrease in latency of the cortical N₂₀ (P < 0.008), andinterwave conduction times of SC to P₁₅ (P < 0.007) and SCto P₂₅ (P < 0.039). The relation of these results to theproposed mechanism of thiopentone action at synapses is discussed. Presented in part at the Annual Meeting of the InternationalAnesthesia Research Society in Las Vegas, Nevada, March 1986.     

Differential short-term synaptic plasticity and transmission of complex spike trains: to depress or to facilitate?

Experimental studies have revealed conspicuous short-term facilitation and depression that are expressed differentially at distinct classes of cortical synapses. To explore computational implications of synaptic dynamics, we investigated transmission of complex spike trains through a stochastic model of cortical synapse endowed with short-term facilitation and vesicle depletion. Inputs to the synapse model were either real spike train data recorded from the visual and prefrontal cortices of behaving monkeys, or were generated numerically with prescribed temporal statistics. We tested the hypothesis that short-term facilitation could enable synapses to filter out single spikes and favor bursts of action potentials. We found that the ratio between release probabilities for a burst spike and an isolated spike grows monotonically with increasing number of spikes per burst, and with increasing interval between isolated spikes. Burst detection is optimal when the facilitation time constant matches the average burst duration. Using fractal-like spike patterns characterized by long-term power-law temporal correlations and similar to those seen in sensory neurons, we found that facilitation increases correlation at short time scales. In contrast, depression leads to a dramatic reduction in temporal correlations at all time scales, and to a flat ('whitened') power spectrum, thereby decorrelating natural input signals.     

Functional maturation of excitatory synapses in layer 3 pyramidal neurons during postnatal development of the primate prefrontal cortex

In the primate dorsolateral prefrontal cortex (DLPFC), the density of excitatory synapses decreases by 40-50% during adolescence. Although such substantial circuit refinement might underlie the adolescence-related maturation of working memory performance, its functional significance remains poorly understood. The consequences of synaptic pruning may depend on the properties of the eliminated synapses. Are the synapses eliminated during adolescence functionally immature, as is the case during early brain development? Or do maturation-independent features tag synapses for pruning? We examined excitatory synaptic function in monkey DLPFC during postnatal development by studying properties that reflect synapse maturation in rat cortex. In 3-month-old (early postnatal) monkeys, excitatory inputs to layer 3 pyramidal neurons had immature properties, including higher release probability, lower alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)/N-methyl-D-aspartate (NMDA) ratio, and longer duration of NMDA-mediated synaptic currents, associated with greater sensitivity to the NMDA receptor subunit B (NR2B) subunit-selective antagonist ifenprodil. In contrast, excitatory synaptic inputs in neurons from preadolescent (15 months old) and adult (42 or 84 months old) monkeys had similar functional properties. We therefore conclude that the contribution of functionally immature synapses decreases significantly before adolescence begins. Thus, remodeling of excitatory connectivity in the DLPFC during adolescence may occur in the absence of widespread maturational changes in synaptic strength.     

Transitory Corpus Callosum Axons Projecting throughout Developing Rat Visual Cortex Revealed by Dil

Anatomical tracing was used to determine the extent and distributionof CC axons in mammalian visual cortex. Postnatal developmentof rat CC was studied by in vitro callosal labeling with thelipophilic carbocyanine dye Dil in 59 rats. Solid Dil crystalswere placed in the midsagittal region of the CC in aldehyde-fixedbrain slabs. Coronal sections through visual cortex were photographedand reconstructed to show the overall distribution of Dil-labeledcallosal projections as well as the locations of individualcallosal axons and their presumed synaptic boutons. During postnatal weeks 1 and 2, CC axons were found to projectto layer I throughout the entire mediolateral extent of areas17, 18a, and 18b. Numerous varicosities on callosal axons arelocated en passant and at axon terminals in layer I. Duringpostnatal week 3 the tangential density of callosal projectionswas significantly reduced, so that fewer callosal axons extendedto layer I throughout areas 17, 18a, and 18b than in youngerpostnatal rats. However, at this age some CC axons could stillbe found extending to layer I throughout the mediolateral extentof areas 17, 18a, and 18b. By postnatal week 4 the tangentialdistribution of callosal projections was greatly restricted;most callosal axons projecting to layer I were located at theborders of the visual cortical areas. Nevertheless, there werestill callosal axons projecting into cortex and terminatingin supragranular and infragranular layers in areas 17, 18a,and 18b; this was most pronounced in area 18a. Thus, in the rat there are many elaborately formed transitoryCC axons projecting throughout visual cortex for several weekspostnatal. These projections extend to layer I and have varicositiesin all cortical layers. With increasing age, fewer axons extendedto layer I; subsequently most axons not at cytoarchitectonicborders fail to extend to layer I. If some of the varicositieson the transitory rat callosal axons were to form synapses,there would be extensive opportunities for the CC to provideinput to all layers of visual cortical areas while corticalmicrocircuitry is being established. The same type of studyin the cat has shown similar results during early postnataldevelopment. Cat CC axons project to all parts of primary andassociation visual cortical areas; even in regions found tobe acallosal in the adult, the neonatal callosal axons extendthrough all layers of cortex to reach layer I (Elberger, 1993).The parallel results for rat and cat suggest a common mammalianpattern for CC development.     

Pressure-controlled ventilation improves oxygenation during laparoscopic obesity surgery compared with volume-controlled ventilation

Background: We compared pressure and volume-controlled ventilation (PCVand VCV) in morbidly obese patients undergoing laparoscopicgastric banding surgery. Methods: Thirty-six patients, BMI>35 kg m^–2, no major obstructiveor restrictive respiratory disorder, and Pa_CO2<6.0 kPa, wererandomized to receive either VCV or PCV during the surgery.Ventilation settings followed two distinct algorithms aimingto maintain end-tidal CO₂ (E'_CO2) between 4.40 and 4.66 kPaand plateau pressure (P_plateau) as low as possible. Primaryoutcome variable was peroperative P_plateau. Secondary outcomeswere Pa_O2 (FI_O2 at 0.6 in each group) and Pa_CO2 during surgeryand 2 h after extubation. Pressure, flow, and volume time curveswere recorded. Results: There were no significant differences in patient characteristicsand co-morbidity in the two groups. Mean pH, Pa_O2, Sa_O2, andthe Pa_O2/FI_O2 ratio were higher in the PCV group, whereas Pa_CO2and the E'_CO2–Pa_CO2 gradient were lower (all P<0.05).Ventilation variables, including plateau and mean airway pressures,anaesthesia-related variables, and postoperative cardiovascularvariables, blood gases, and morphine requirements after theoperation were similar. Conclusions: The changes in oxygenation can only be explained by an improvementin the lungs ventilation/perfusion ratio. The decelerating inspiratoryflow used in PCV generates higher instantaneous flow peaks andmay allow a better alveolar recruitment. PCV improves oxygenationwithout any side-effects.     

Tetraethylammonium-Induced Synaptic Plasticity in Rat Neocortex

Recordings were obtained from neurons in layer II/III of slicesof rat frontal cortex maintained in vitro. We investigated whetherbrief application of the potassium channel blocker tetraethylammonium(TEA), which induces a novel form of synaptic plasticity inthe CA1 region of the hippocampus referred to as LTP_k evokessimilar responses in neocortex. Consistent with previous findings,TEA produced a persistent enhancement of excitatory transmission,which was independent of NMDA receptor activation but requiredthe activation of nifedipine-sensitive voltage-dependent Ca²⁺channels (VDCC), presumably the L-type. We also observed a persistentenhancement of presumptive Cl^–-dependent GABA_A receptor-mediatedtransmission. Enhancement of excitatory and inhibitory synaptictransmission did not require activation of synapses with electricalstimulation during TEA application. The enhancement of excitatory,but not inhibitory synaptic transmission, was blocked when theCa²⁺ chelator 1,2-bis(2-aminophenoxy)-ethane N,N,N',N'-tetraaceticacid (BAPTA) was included in the recording electrode. Undervoltage clamp conditions that minimized the activation of L-typechannels robust enhancement of both excitatory and inhibitorytransmission was still observed. No enhancement of excitatorysynaptic transmission was observed in the presence of NiCl₂,a putative T-type channel blocker. The possible involvementof kinase activation was studied by including the non-specificand competitive kinase inhibitor (±)-1-(5-isoquinolinesulfonyl)-2-methylpiperazinedihydrochloride (H-7) in the patch pipette. H-7 retarded thetime course and reduced the magnitude of the enhancement ofexcitatory transmission. These results suggest that TEA-inducedenhancement of excitatory transmission in the neocortex requiresentry of Ca²⁺ into the postsynaptic neuron via VDCCs and possiblythe activation of a kinase.     

Correlation of bispectral index with end-tidal sevoflurane concentration and age in infants and children

Background. The bispectral index (BIS) has been evaluated asa tool for measuring depth of anaesthesia, but the use of BISin a paediatric population is still controversial. This studywas designed to evaluate the correlation of BIS with end-tidalsevoflurane concentration and age in infants and children. Methods. Eighty-one patients undergoing elective urology surgerywere allocated into three age groups; 6 months to 2 yr (n=28),3–7 yr (n=33), and 8–12 yr (n=20). Sevoflurane wasadministered to achieve steady-state end-tidal sevoflurane concentrations(ET_sevo) of 2.0, 3.0, and 4.0%; these were achieved consecutivelyeither from the lowest or from the highest concentration. TheBIS (version XP) was monitored continuously. Results. In all three groups, BIS decreased significantly whenET_sevo increased from 2.0 to 3.0% but there was a paradoxicalincrease in BIS values when ET_sevo increased from 3.0 to 4.0%.The non-linear regression analysis showed a significant correlationbetween BIS and age at each ET_sevo. The younger patients showedthe higher BIS values. Conclusions. In children aged 6 months to 12 yr, the BIS increasedparadoxically as ET_sevo increased from 3.0 to 4.0%. BIS valuesshowed a wide variation in the same ET_sevo and the age itselfwas considered to be a factor affecting the BIS values.     

COMPARISON OF VENTILATION AND GAS EXCHANGE IN ANAESTHETIZED INFANTS AND CHILDREN DURING SPONTANEOUS AND ARTIFICIAL VENTILATION

Measurements of minute and alveolar ventilation (VE and VA),respiratory frequency, end-tidal carbon dioxide concentration(E'CO₂), deadspace (VD) and carbon dioxide output (VCO₂) weremade in 22 anaesthetized infants and young children during spontaneous(SV) and intermittent positive pressure ventilation (IPPV).In the children who had been given an opioid premedication,E'CO₂ concentrations were significantly greater during SV thanthe predetermined value set for IPPV. In infants premedicatedwith atropine alone, E'CO₂ during SV was only slightly greaterthan during IPPV, and VA was not changed. A mean tidal volume(VT) of 9.8 ± 2.5 ml kg^–1, and a mean VE of between225 and 250 ml min kg^–1, were required to produce (E'CO₂)4.5% during IPPV. Despite a decrease in respiratory frequency,VD/VT and VD per minute were both decreased by IPPV in infants.VCO₂ was unchanged in both groups. The decrease in wasted ventilationseen during IPPV in infants supports its use in clinical practice. ^*Department of Anaesthesia, St. Georges Hospital, BlackshawRoad, London SW17. ^**Department of Anaesthesia, University Hospital, S-221 85,Lund, Sweden.     

Ultrasonographic detection of thickened joint capsules and tendons as marker of dialysis-related amyloidosis: a cross-sectional and longitudinal study

Dialysis-related amyloidosis is characterized by a ß₂-microglobulin(ß₂M) infiltration of joint synovia, tendons and capsules.We report a cross-sectional ultrasonographic evaluation of supraspinatustendon and femoral neck capsule thickness in 49 patients onlong-term haemodialysis. Ultrasonographic evaluation was repeated21±4 (SD) months later in 16 patients. Normal valuesfor the supraspinatus tendon and femoral neck capsule were definedin a group of control subjects without history or signs of jointdisease. Among the 49 patients, aged 21–86 (median 59) years, dialysedfor 1–228 (median 97) months, 33 had at least one abnormaljoint. The prevalence of patients with at least one and at leasttwo abnormal joints, the number of abnormal joints per patient,and the thickness of the supraspinatus tendon and femoral neckcapsule increased significantly with dialysis duration (P<0.001 for all parameters considered). By multiple linear regressionanalysis, mean thickness of the supraspinatus tendon was positivelyrelated to both dialysis duration (P< 0.0001) and age (P= 0.036) independently. All (n=11) patients with radiological and/or histological evidenceof dialysis-related amyloidosis at the time of ultrasonographyhad thickened supraspinatus tendon and/or femoral neck capsule;which were also thickened in an additional 22 patients withoutradiological evidence of dialysis-related amyloidosis. Threedied within 5–10 months of the ultrasonographic investigation: post-mortem examination of the periarticular tissue confirmedthat the detected thickening was due in all three to ß₂Mamyloid infiltration. Sixteen patients underwent a second ultrasonographic evaluation21±4 months later. In nine patients on dialysis for <60months at the time of the first evaluation, mean femoral neckcapsule thickness increased significantly (7.0±0.8 to8.2±2.3mm, P = 0.017) whereas mean supraspinatus tendonthickness increment was not significant (6.6±0.4 to 7±0.8mm, P=0.23). In the seven other subjects dialysed for <60months, neither the supraspinatus tendon nor femoral neck capsulethickness changed. We suggest that ultrasonographic measurement of supraspinatustendon and femoral neck capsule thickness is a useful, non-invasivetool to detect and monitor dialysis-related amyloidosis.     

SEPARATE EFFECTS OF HALOTHANE AND CARBON DIOXIDE ON RESPIRATORY DURATION IN VAGOTOMIZED CATS

The independent effects of halothane and carbon dioxide on centralmechanisms regulating respiratory frequency were investigatedin 12 vagotomized, artificially ventilated cats. Changes inrespiratory pattern analysed from the phrenic neurogram revealedthat increasing Pa_CO2 at a constant depth of halothane anaesthesiacaused a progressive increase in TE with various changes inT1, whereas increasing the depth of halothane anaesthesia ata constant Pa_CO2 caused a progressive decrease in TE with variouschanges in T1. These results suggest that the effect of carbondioxide on central mechanisms regulating respiratory durationis exactly the opposite of that produced by halothane and thatrespiratory frequency is modified by both the depth of halothaneanaesthesia and Pa_CO2.     

CORRELATION OF ALVEOLAR PCO2 ESTIMATED BY INFRA-RED ANALYSIS AND ARTERIAL PCO2 IN THE HUMAN NEONATE AND THE RABBIT

The performance of an infra-red analyser (Beckman LB-2) in samplingalveolar gas at ventilatory frequencies and volumes occuringin the human neonate has been examined. The optimum samplingflow rate was found to be 300 ml/min; at this flow the 90% responsetime of the analyser-catheter system was 140 ms. Correlationof estimated alveolar P2 and arterial PCO₂ was performed inthe rabbit which has a ventilatory rate and tidal volume similarto those of the human neonate. There was a good correlationbetween maximum end-expired PCO₂ (PÉCO₂) and arterialPCO₂ over a wide range of ventilatory rates (10–100 b.p.m.);maximum PÉCO₂ was a better index than mean PÉCO₂or alveolar plateau PÉCO₂     

The effects of aging on layer 1 of primary visual cortex in the rhesus monkey

The effect of age on layer 1 in primary visual cortex was determined in 19 rhesus monkeys of various ages. Twelve of the monkeys had been behaviorally tested. With age layer 1 becomes thinner and the glial limiting membrane becomes thicker. In the neuropil of layer 1 many of the dendrites in old monkeys appear to be degenerating and, as a consequence, electron micrographs from old monkeys display fewer dendritic and spine profiles per unit area than in young monkeys. As determined using both the disector and size-frequency methods, there is also a concomitant decrease in the numerical density of synapses with age. Although there is a significant correlation between the thinning of layer 1 in area 17 and age, there is no significant correlation between either the thinning of layer 1 or its loss of synapses and any of the behavioral measures of memory function obtained from the 12 behaviorally tested monkeys. Similar morphological changes with age occur in layer 1 of prefrontal cortex of these same monkeys, but in area 46 both the thinning of layer 1 and the loss of synapses show a significant correlation with behavioral measures of memory function. These differences between layer 1 in these two cortical areas presumably relate to the fact that prefrontal cortex has a greater role in subserving cognition than does primary visual cortex.     

Pharmacokinetics of levobupivacaine 0.25% following caudal administration in children under 2 years of age

Background. Levobupivacaine, the S(–)enantiomer of racemicbupivacaine is less cardiotoxic than racemic bupivacaine andthe R(+)enantiomer dexbupivacaine, while retaining similar localanaesthetic properties and potency to racemic bupivacaine. Thepharmacokinetic profiles of the two bupivacaine enantiomersdiffers and that of racemic bupivacaine may be age dependent.We examined the pharmacokinetics of levobupivacaine after itssingle shot caudal epidural administration in children. Methods. An open-label phase 2 study was undertaken to examinethe pharmacokinetics of levobupivacaine 0.25% 2 mg kg^–1in 49 children aged less than 2 yr, after single shot caudalepidural administration. Plasma concentrations were determinedat intervals up to 60 min after caudal injection. Results. Time to peak plasma concentration (T_max) ranged between5 and 60 min (median 30 min) and was reached later in childrenaged less than 3 months (P<0.005). Peak plasma concentration(C_max) ranged between 0.41 and 2.12 µg ml^–1 (median0.80, mean (SD) 0.91 (0.40) µg ml^–1). Conclusion. After the caudal epidural administration of levobupivacaine2 mg kg^–1 in children less than 2 yr of age, C_max waswithin the accepted safe range for racemic bupivacaine. T_maxvaried and occurred later in some children, particularly thoseaged less than 3 months. Sampling in future pharmacokineticstudies in this age group should extend beyond 60 min. Br J Anaesth 2004; 92: 218–22     

Changes in bone mineral content during long-term CAPD. Indication of a sex-dependent bone mineral loss

Change in bone mineral content (BMC) was evaluated in a longitudinaltrial comprising 12 women and 11 men with chronic renal diseasetreated with CAPD and 1-alpha-OH-D3 for 2 years. The patientsserved as their own controls. No patients were treated withsteroids. Median age was 54 and 60 years for women and men respectively.No significant difference in 1-alpha-OH-D3 dosage or serum 1,25(OH)₂D3was found between the genders in the study period. Bone mineral content at the distal radius deteriorated significantlyin the females with a median decrease of 12% over 2 years, i.e.approximately 6% per year (P<0.001 and 95% confidence limits8–20%). No significant change was noted in the males.There was no correlation between age and BMC change. Serum total alkaline phosphatase decreased nonsignificantlyin both sexes. Total serum calcium increased significantly (P<0.05)and serum phosphate decreased significantly (P<0.05) in thewomen. Serum albumin and body weight decreased significantlyin the males (P<0.01 and P<0.05) while no change was seenin the females. The demonstrated decrease in BMC in the female patients of approximately6% per year exceeds the commonly observed loss of 1–2%per year in healthy women when measured with the same technique.Tentatively, the severe mineral loss in the women could indicatea sex-hormone-related disturbance in bone metabolism of uraemicfemales.     

INFLUENCE OF AGE ON ATELECTASIS FORMATION AND GAS EXCHANGE IMPAIRMENT DURING GENERAL ANAESTHESIA

We have studied the effects of anaesthesia on atelectasis formationand gas exchange in 45 patients of both sexes, smokers and non-smokers,aged 23–69 yr. None of the patients showed clinical signsof pulmonary disease, and preoperative spirometry was normal.In the awake patient, partial pressure of arterial oxygen (Pa_O2)decreased with increasing age (P < 0.001) and the alveolar—arterialoxygen partial pressure difference (PA_O2 – Pa_O2) increasedwith age (P < 0.001). Shunt, assessed by the multiple inertgas elimination technique, was small (mean 0.5%) and uninfluencedby age. However, there was an increasing dispersion (log SDQ) of ventilation/perfusion ratios (VA/Q) and increasing perfusionof regions of low VA/Q (VA/Q <0.1) with increasing age (P< 0.001 and P < 0.05, respectively). No patient displayedany atelectasis as assessed by computed x-ray tomography ofthe chest. During inhalation anaesthesia (halothane or enflurane)with mechanical ventilation, 39 of 45 patients developed atelectasisand shunt. There was a strong correlation between the atelectaticarea and the magnitude of shunt (r = 0.81, P < 0.001). Atelectasisand shunt did not increase significantly with age, whereas logSD Q and perfusion of regions with low VA/Q ratios did (r =0.55, P < 0.001 and r = 0.35, P < 0.05, respectively).Awake, the major determinant of Pa_O2 was perfusion of regionsof low V;A/Q ratios, which increased with age, During anaesthesiashunt influenced Pa_O2 most low Va/Q being a secondary factorwhich, however, was increasingly important with increasing age,thus explaining the well-known age-dependent deterioration ofarterial oxygenation during anaesthesia.     

ANALYSIS OF POSSIBLE FACTORS INFLUENCING Pao2 AND (PAo2--Pao2) IN PATIENTS AWAITING OPERATION

Data on arterial oxygen tension (Pa_o²) and alveolar—arterialPo₂ difference (PA_o²—Pa_o²) have been obtained from 337patients awaiting elective surgery. Statistical analysis ofthese data has assessed both the individual and the combinedinfluence of various factors on Pa_o² and (PA_o²—Pa_o²).The factors of importance in relation to Pa_o² include age, smokinghabits, body build and PA_o². In relation to (PA_o²—Pa_o²)the significant factors include age, Pa_CO2, weight and smokinghabits.