Quantification patients - Thoraxsimultaneous shunt measurement in subjects breathing 100% oxygen while they rested. Themicrosphere technique wasadaptedto measurethe right to left shunt

Thorax 1992;47:790-796

Quantification of right to left shunt at rest andduring exercise in patients with pulmonaryarteriovenous malformations

Moira K B Whyte, AM Peters, J M B Hughes, B L Henderson, G J Bellingan,J E Jackson, E R Chilvers

AbstractBackground Current treatment ofpatients with pulmonary arteriovenousmalformations requires serial embolisa-tions by means of steel coils or balloons.Measurement of right to left shunt is themost specific index of response to treat-ment. A new method of measuring shunthas been developed that is less invasivethan traditional methods.Methods Right to left pulmonary shunt(expressed as percentage of cardiac out-put) was measured at rest in 19 patientswith pulmonary arteriovenous malfor-mations and six normal subjects by usingintravenously injected albumin micro-spheres labelled with technetium-99m.The technique was compared with asimultaneous shunt measurement insubjects breathing 100% oxygen whilethey rested. The microsphere techniquewas adapted to measure the right to leftshunt during exercise in 12 patients andfive normal subjects with a new method ofquantification.Results The mean (SD) shunt at rest asmeasured by the microsphere methodwas 23-2% (15-6%) in the patients and2-7% (1-2%) in the normal subjects. Whenthese values were compared with those ofthe 100% oxygen method the difference inmean values was 1% and the limits ofagreement between the two methods-32% to + 45%. The microspheremethod is less invasive (arterial blood gassampling is not required), quicker, andmore comfortable for patients than the100% oxygen method. In five ofthe normalsubjects the mean (SD) "'Tc micro-sphere shunt increased from 2-9% (1-3%)at rest to 5-1% (2-9%) during exercise. Inthe 12 patients studied during exercise theshunt increased from 33-7% (12-7%) atrest to 41-7% (13-3%) during exercise ineight but decreased from 22-6% (2-4%) atrest to 17-6% (2-2%) during exercise infour. Arterial desaturation during exer-cise correlated with change in the size ofthe right to left shunt during exercise(r= + 0-80).Conclusions The microsphere methodallows measurement of right to left shuntat rest and during exercise. Serialmeasurements at rest provide a simple,safe assessment of the physiological res-ponse to embolisation in patients with

pulmonary arteriovenous malforma-tions.

(Thorax 1992;47:790-796)

Major advances have been made in the treat-ment of pulmonary arteriovenous malforma-tions in the last decade, based on percutaneoustranscatheter embolisation with steel coils' orballoons,2' with a greatly reduced need forsurgical resection. This, combined with in-creasing recognition of the high incidence ofneurological sequelae from paradoxical embol-isation,2A has meant that early intervention isrecommended for most patients.56The classical triad of physical signs of pul-

monary arteriovenous malformations consistsof cyanosis, clubbing, and an overlying bruitand one or more of these is present in aboutthree quarters of patients with pulmonaryarteriovenous malformation.7 Arterial oxygentension was reduced in more than 80% of casesstudied by Dines et al.4 All 15 patients in ourprevious series had a resting arterial oxygensaturation (Sao2) below 95% when it wasmeasured supine, further desaturation occur-ring in the standing position and with exercise.8The diagnosis of pulmonary arteriovenousmalformations and assessment of shunt size areimportant both in the initial evaluation ofpatients and in monitoring the effects of treat-ment. Extra-alveolar shunt is usually measuredby the classical 100% oxygen breathingmethod.9 We have recently described a methodusing technetium-99m albumin microspheres,7-25 gum in diameter, to quantify right to leftshunt at rest.' As particles greater than 8 ,um indiameter are normally trapped in the pul-monary capillary bed, passage of larger par-ticles into the systemic circulation represents aright to left shunt.

Chilvers et al8 commented on the increase inarterial oxygen desaturation that occurs withexercise in patients with pulmonary arterioven-ous malformations, despite good exercisecapacity in many cases. The mechanism of theprogressive hypoxaemia during exercise is notunderstood. Possible explanations include (1)an increase in the right to left shunt; (2)increased tissue oxygen extraction, leading tothe addition of very desaturated mixed venousblood to the systemic arterial blood via thearteriovenous malformation; (3) increasingventilation-perfusion (V/() mismatch.This paper reports measurement of shunt by

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Department ofMedicine (RespiratoryDivision)M K B WhyteJ M B HughesG J BellinganE R ChilversDepartment ofDiagnostic RadiologyA M PetersB L HendersonJ E JacksonRoyal PostgraduateMedical School,HammersmithHospital, LondonW12 ONNReprint requests to:Dr Moira WhyteAccepted 26 March 1992

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Quantification of right to left shunt at rest and during exercise in patients with pulmonary arteriovenous malformations

the microsphere method and by the 100%oxygen method in 19 patients with pulmonaryarteriovenous malformations and in six normalsubjects at rest. In addition, we have adaptedthe 9'Tc microsphere method to measure

shunt size during exercise. The results in 12patients and five normal subjects are presentedbelow.

MethodsMEASUREMENT OF RIGHT TO LEFT SHUNT AT RESTWe studied 19 patients (10 female; age 13-66,mean 44 years) with pulmonary arteriovenousmalformations on pulmonary angiography.Thirty six measurements of right to left shuntwere obtained, serial measurements being per-

formed in some patients. Clinical details aregiven in table 1. No patient had hepatic or renalimpairment according to routine biochemicalinvestigations. Fourteen of the 19 patients hadhereditary haemorrhagic telangiectasia. Ninepatients had had a previous thoracotomy, withligation ofpulmonary arteriovenous malforma-tions in three and partial or total lobectomy insix. Six normal volunteers were also studied(one female; age 28-52, mean 36 years). Ethicalpermission was obtained from the local ethicscommittee and the patients and normal volun-teers gave informed consent.Measurement of right to left shunt at rest was

performed by two independent methods: the100% oxygen method and the technetium-99mlabelled albumin microsphere method.

100% oxygen methodShunt was measured in the supine posture,with the patient breathing 100% oxygen from a

Douglas bag, via a mouthpiece, two way valve,and noseclip to ensure delivery of 100%oxygen. The patient was asked to make every

tenth breath as deep as possible to accelerate

nitrogen washout. Arterial oxygen saturation(Sao2) was measured by pulse oximeter(Ohmeda Biox 3700) during the procedure.When the subject had breathed 100% oxygenfor 20 minutes an arterial blood sample wastaken, cooled on ice, and analysed rapidly forarterial oxygen tension (Pao2). As the right toleft shunt may be increased at high lungvolumes," blood was drawn during and for fiveseconds after the patient had paused at func-tional residual capacity. The right to left shuntwas calculated from the Pao2 and Sao2 valuesobtained while the subject breathed 100%oxygen and the haemoglobin concentration (ing/dl) by using the classical equation.89

Technetium-99m albumin microsphere methodMicrospheres were injected immediately afterarterial blood gas sampling. While the patientremained supine, breathing 100% oxygen, 110MBq of technetium-99m microspheres 7-25um, 0-4 X 106 particles/mg; TCK-5-S, CIS,Sorin Biomedica, Saluggia, Italy) were injectedvia an antecubital vein, again with the patient atfunctional residual capacity. After five minutesimages were obtained of the upper abdomen(posterior and lateral views) and lungs (pos-terior views). An International General Elec-tric 400A gamma camera was used, fitted with a

parallel hole, general purpose, low energy

collimator and on line to a computer (MedicalData Systems A2). Thus total counts were

obtained from regions of interest over the right-kidney and the right and left lungs. The depthof the right kidney was determined from thenumber of pixels between the skin marker andthe centre of the kidney on the right lateralimage. Total lung radioactivity was taken to bethe sum of the counts, in the posterior view, inthe regions of interest over the right and leftlungs. The total injected microsphere radioac-

Table 1 Clinical details, presence or absence of hereditary haemorrhagic telangiectasia (HHT) and arterial oxygensaturation (Saoj) in erect and supine postures in all 26 patients with pulmonary arteriovenous malformations

Sao2Patient HaemoglobinNo Age (y) Sex HHT Presentation (g/dl) Erect Supine1* 27 F + Dyspnoea, cyanosis 18 4 80 842* 13 F + Epistaxis, cyanosis 18-1 65 763* 40 M + Dyspnoea, epistaxis 17-6 74 854* 26 M - Abnormal chest radiograph 19-5 82 905* 25 M + Abnormal chest radiograph 19.1 88 916 47 F + Epistaxis 12-3 84 897 48 F + Dyspnoea, epistaxis 13-4 90 948 63 F + Transient ischaemic attacks 18-1 79 879 42 M - Dyspnoea, polycythaemia 16-8 82 8810 34 M + Epistaxis, migraine 15-5 93 9511 56 M + Epistaxis 15 9 88 9312 57 F + Epistaxis 8-1 91 9113 42 F - Abnormal chest radiograph 13-8 95 9614 51 M - Transient ischaemic attacks 15-7 87 9215 36 M - Transient ischaemic attacks 17-3 96 9816 29 F + Epilepsy, epistaxis 13-4 70 7917 57 F + Epistaxis 11-8 96 9618 35 M - Cyanosis 16 6 94 9419 16 F + Epistaxis 15 4 97 9720* 59 F + Transient ischaemic attacks 13-3 74 8821* 66 M - Dyspnoea, cyanosis 14-0 65 8722* 52 F + Cerebral abscess 16-0 80 9123* 40 F - Transient ischaemic attacks 13-7 86 9024* 20 F - Dyspnoea 17 5 73 8525* 31 F + Cyanosis 16-1 93 9526* 51 F + Abnormal chest radiograph 16-9 93 96

*Had right to left shunt measurements at rest and on exercise.

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Whyte, Peters, Hughes, Henderson, Bellingan, Jackson, Chilvers

Figure 1 A-Posteriorimage taken two minutesafter injection of 99"Tcmicrospheres at rest,showing uptake in bothlungs (RL and LL) andsystemic uptake in theright kidney (RK), leftkidney (LK), and spleen(S). B-Posterior imagefrom the same patient,after injection of ""Tcmicrospheres duringexercise. Note the decreasein uptake by the kidneyscompared with the uptakeduring rest and theincreased perfusion of thelung apices.

L l

S

tivity was measured by counting the syringethat contained the dose, before and after injec-tion, on a 3 cm thick perspex block resting onthe face of the collimated gamma camera.According to the time at which each image wasobtained, corrections were made for the decayof 9"mTc (half life 360 minutes).Measurement of the shunt was performed in

two ways:Kidney :dose method The right kidney wasused in preference to the left because splenicuptake ofmicrospheres may be considerable (fig1 A) whereas the liver, receiving more thanthree quarters of its blood supply from theportal vein and little from the hepatic artery,shows very little uptake. Counts in the region ofinterest of the right kidney were corrected forattenuation, an attenuation coefficient obtainedfrom previous phantom studies being used andexpressed as a percentage of the injected dose.The right kidney was assumed to receive 10%of the systemic cardiac output at rest (on thebasis of previous radionuclide studies of renalblood flow).'2 13 Thus

shunt fractionright kidney counts x 10 x attenuation constant

microsphere counts injected

Kidney:lung method The following equationwas used:

right kidney counts x 10shunt fraction (right kidney counts x 10) + total lung counts

No corrections were made for attentuationwhen this method was applied.

MEASUREMENT OF RIGHT TO LEFT SHUNT DURING

EXERCISE

Right to left shunt was measured during exer-cise in 12 patients (eight female; age 13-66,mean 37 years) with pulmonary arteriovenous

malformations (table 1, Patients 1-5 and 20-26)on 19 occasions and in five normal subjects (onefemale; age 28-52, mean 34 years).

METHODIncremental exercise testing was performed inthe seated, erect posture, with a cycleergometer. Patients rested for one hour andthen exercised at 50% of their previouslydetermined maximum workload for five min-utes. Heart rate (from an electrocardiographmonitor) and SaO2 were recorded at the end ofeach minute. At the end of five minutes, withthe patient continuing to cycle, 110 MBq of99mTc microspheres were injected via a 19GButterfly cannula, previously inserted into aforearm vein. Imaging of the upper abdomenand both lungs was performed as soon aspossible, as described above. On the next day abackground count was obtained from thegamma camera, followed by measurement ofresting shunt, as above, with the patient seated.The equations used to calculate shunt flow at

rest cannot be used for shunt flow duringexercise. The redistribution of pulmonaryblood flow, mainly to the lung apices, duringexercise means that total lung counts must beobtained for both lungs. There is also markedredistribution of systemic blood flow on exer-cise, so the assumption that each kidneyreceives 10% of the cardiac output is no longervalid (fig IB).The change in shunt flow can be related to the

change in lung activity with exercise, however,as lung counts reflect the proportion of cardiacoutput that is not shunted. Lung counts areobtained at rest and during exercise, per MBqof injected dose, and the ratio lung counts

(exercise): lung counts (rest) is expressed as afraction, f.

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793Quantification of right to left shunt at rest and during exercise in patients with pulmonary arteriovenous malformations

Thus:1- shunt(exercise)_____ _ _ _ _ _ _ _ _ = f.

1- shunt(rest)Therefore

shunt(exercise) = 1 -f.[1 - shunt (rest)]All shunt values are expressed as fractions. Ifshunt(rest) is measured as before and the fvalue measured as the ratio in lung countsbetween exercise and rest, shunt(exercise) canbe derived. An f value less than 1 will reflectreduced lung counts during exercise and thusan increase in shunt flow, whereas an f valuegreater than 1 will indicate a reduction in rightto left shunt with exercise.

STATISTICAL METHODSShunt measurements by the microsphere and100% oxygen methods were compared by themethod for assessing agreement between twomeasurements as described by Bland and Alt-man."' Data were logarithmically transformedbecause the differences between the two meth-ods increased as the shunt size increased.

Shunt sizes, f values, and arterial oxygensaturation were compared at rest and duringexercise within subjects by paired t tests andbetween groups during exercise by unpaired ttests.

ResultsSHUNT MEASUREMENT AT RESTThe patients had a mean (SD) shunt of 22-2(13 4%) at rest according to the 100% oxygenmethod, 23-2% (15-6%) according to the kid-ney:dose microsphere method, and 23-8%(17 1%) according to the kidney:lung micros-phere method. The right to left shunts obtainedby the 100% oxygen method are comparedwith those obtained by the kidney:dose micros-phere method and kidney:lung microspheremethod in the 19 patients studied at rest in fig 2.The difference between mean values for thekidney:dose and 100% oxygen methods was10%, and the 95% limits of agreement bet-ween the two methods were - 32% to +45%(fig 3A). The difference between mean valuesobtained by the kidney:lung and the 100%oxygen methods was 1 0%, and the 95% limitsof agreement between the two methods were-37% to +57% (fig 3B).In the six normal subjects the mean (SD)

shunt (kidney:lung) was 2-7% (1 2%). Theupper 95% confidence limit of 5 1% may beused to define the upper limit of normal resultsobtained by the microsphere method.

SHUNT MEASUREMENT DURING EXERCISEIn five normal subjects (table 2) the mean (SD)value of f was 0 98 (0 04), with mean shuntvalues of 2-9% (1-3%) at rest and 5 1% (2 9%)during exercise. The mean work load was 102(range 75-120) watts. No subject showedarterial oxygen desaturation with exercise.Of the 12 patients studied during exercise,

eight (all patients in table 3 and patients 21 and26 in table 4) increased their shunts from amean of 33-7% (12 7%) at rest to 41 7%(13 3%) during exercise; the remaining fourpatients decreased their shunt from a mean of

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Figure 2 A-Anatomical right to left shunt as measuredby 99"Tc microspheres (kidney :dose) plotted against shuntmeasured by the 100% oxygen breathing method(n = 36) (line of identity shown). B-Anatomical rightto left shunt as measured by 99"Tc microspheres(kidney:lung) plotted against shunt measured by the100% oxygen breathing method (n = 32) (line ofidentity shown). C-Anatomical right to left shunt asmeasured by 99"Tc microspheres; kidney:dose methodplotted against kidney:lung method (n = 32) (line ofidentity shown).

22-6% (2-2%) at rest to 17-6% (2-4%) duringexercise. Change in oxygen saturation withexercise correlated with f values (r = + 0 80;fig 4).The 12 patients were classified according to

whether the residual right to left shunt afterembolisation ofmost or all of the arteriovenousmalformations with a feeding vessel greaterthan 3 mm in diameter was 10% and over orbelow 10% (a large residual shunt suggests thecontinuing presence of diffuse, smallarteriovenous malformations). Patients with aresidual shunt greater than 10% (table 3)increased their right to left shunt on exercisefrom a mean (SD) of 37 5% (10-5%) at rest to46 5% (10-4%) during exercise (p < 0 001,n = 1 1). Patients with a residual shunt of lessthan 10% (table 4) showed a slight fall in rightto left shunt from 22-1% (7-2%) at rest to20-7% (10-1 %) during exercise (p = 0 54, n =

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A Mean + 2 SD

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7). There were significant differences betweenthe two groups for the f value (p = 0 025) andexercise desaturation (p = 0 009).

* Discussion.. MICROSPHERE MEASUREMENT OF SHUNT

Measurement of right to left shunt withradiolabelled particles was first described in

Mean - 2 SD 1969'5 and quantification was attempted byGates in 1974.16 The microsphere method

30 40 50 described here improves quantification by)0% oxygen) measuring systemic activity from the right

kidney only (to avoid problems with splenicMean + 2 SD activity overlying the left kidney) and also by

allowing for tissue attenuation. More import-. * ant, agreement between the 99"Tc microsphere

shunt and the 100% oxygen breathing shunt is. Mean good (figs 2A-C), even though the former

measures an anatomical shunt and the latter a.Mean - 2 SD functional (physiological) shunt. The micros-

phere method is less invasive (arterial blood gas

l0% sampling is not required), quicker, and less30 40 50 uncomfortable for the subject than the oxygen00% oxygen) method. The radiation dose received is

t of difference (log) relatively small (0-5 mS).between - i c mwcrospnere snunt (Rwaney:aose) ana100% oxygen shunt against the reference technique(100% oxygen breathing). B-Bland-Altman plot ofdifference (log) between " Tc microsphere shunt(kidney:lung) and 100% oxygen shunt against thereference technique.

Table 2 f value / lung counts (exercise) /lungcounts(rest) / and right to left shunt (n9Tcmicrospheres) at rest and during exercise in five normalsubjects

Right to left shunt (%)Normalsubjects f value Rest Exercise

1 094 1 3 722 094 1 8 773 1 03 30 064 098 4 1 695 1 00 43 43

Mean 0-98 2-9 5-1SD 004 1-3 29SE 0-02 06 1-35

MICROSPHERE SHUNT MEASUREMENTS AT RESTThe mean (SD) shunt in normal subjects was

2-7% (1-2%) with the kidney:lung microspheremethod. 100% oxygen shunt measurementswere not performed on our normal volunteers.Measurements of the very small right to leftshunt in normal subjects are unlikely to be as

accurate with the classical 100% oxygen

breathing method9 because they requiremeasurement of high partial pressures ofoxygen. Moreover, the retention of small quan-tities of alveolar nitrogen trapped behindclosed bronchioles may raise the right to leftshunt by 1-5%, especially in elderly subjectsand even when deep breathing is used.'7 Theanatomic right to left shunt (from Thebesianand bronchial veins draining to the left ven-

tricle) appears to be independent of age, accor-

ding to measurements obtained during exercisewhen subjects were breathing 100% oxygen.'8The values for right to left shunt obtained by

Table 3 Workload, right to left shunt, arterial oxygen saturation (Sao2), kidney:dose radioactive count ratio at rest and during exercise (Ex) andresidual shunt after embolisation of all macroscopic pulmonary arteriovenous malformations in patients with residual shunts of 10% or more

Shunt (%) SaO2(%) Kidney: dosePatient ResidualNo Study Work (w) fvalue Rest Ex Rest -Ex At Rest Ex shunt ('o)

1 1 45 0 84 44 53 78-70 -8 44 412 45 073 42 57 78-69 -9 42 413 45 0-89 43 41 80-75 -5 33 23 29

2 1 30 0-92 47 51 64-59 -5 47 452 30 0-88 48 54 77-72 -5 48 29 48

3 1 75 0-74 35 52 78-70 -8 35 192 75 0-95 24 28 78-75 -3 24 13 25

5 1 75 0 87 17 28 87-83 -4 17 11 1520* 1 30 091 18 25 77-71 -6 18 7 NA24 1 45 1 21 50 39 72-69 -3 50 25

2 45 0-78 41 54 72-61 -11 41 343 45 080 31 45 86-81 -5 31 12 31

Mean 505 087 375 465 -62 375 266 296SD 168 0 13 105 104 25 105 124 120SE 51 004 3-2 3 1 08 32 37 54

*Data from patient 20 were excluded from statistical analysis as residual shunt was not available (NA).tA represents the difference between Sao, at rest and during exercise.

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Quantification of right to left shunt at rest and during exercise in patients with pulmonary arteriovenous malformations

Figure 4 Arterial oxygendesaturation (SaO,(rest)-SaO,(exercise))during exercise plottedagainst thef value L lungcounts(exercise) -lungcounts(rest) /.f < 1-0implies an increase in rightto left shunt andf > 1-0 adecrease in shunt withexercise.

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Harris et al."8 represented 1-55-1-88 (0-5-1-1)% of cardiac output, so 4-08% (mean + 2SD) may be regarded as the upper limit ofnormal for the right to left shunt duringexercise. This agrees well with the right to leftshunt in young normal subjects at rest'7 of0-6% (1-74%) and our own values of 2-7%(1-2%) obtained with radiolabelled micro-spheres at rest.There was a close correlation between the

microsphere and reference methods formeasurement of right to left shunt (fig 2).Limits of agreement obtained for the kid-ney:dose method show that if a microsphereshunt of 10% is obtained there is 95% con-

fidence that the shunt measured by the 100%oxygen method would lie in the range 7-14%.For a 20% shunt the limits would be 14-28%.Theoretically the reliability would be greaterfor sequential studies in the same subject as anyvariation due to the attenuation coefficientshould be minimal.

MICROSPHERE SHUNT MEASUREMENTS DURINGEXERCISEThe mean right to left shunt in the five normalsubjects was 2-9% (1-3%) at rest, rising to5-1% (2-9%) with exercise. The microsphereshunt rises with exercise, probably becausevasodilation of the pulmonary capillary bedallows an increased fraction of microspheres topass through the capillaries although thesevessels allow normal gas exchange. The normalsubjects did not desaturate with exercise,which is further evidence that effective gas

exchange was occurring.In the 12 patients with pulmonary

arteriovenous malformations in whom right to

left shunt was measured at rest and duringexercise an inverse correlation was foundbetween the degree of arterial desaturationwith exercise and the f value-that is, thosewho had greater desaturation had smaller fvalues, reflecting increased right to left shuntwith exercise. Measurements of right to leftshunt while subjects were breathing 100%oxygen would have required arterial cannula-tion and were not made during exercise. Thegood correlation between the extent of arterialoxygen desaturation during exercise and thechange in right to left shunt from rest toexercise (fig 4) is encouraging, however.Interestingly, the kidney:dose ratio invariablydeclined with exercise, irrespective of whetherthe relative shunt was increasing or decreasing(tables 3 and 4). This reflects the smallerproportion of the cardiac output that is dis-tributed to the kidneys during exercise thanduring rest.

Patients who were left with a residual shuntof 10% or more after embolisation of allpulmonary arteriovenous malformations withmacroscopic feeding vessels (table 3) increasedtheir right to left shunt with exercise frommean (SD) 37-5% (10-5%) at rest to 46-5%(10-4%) (p < 0-001, n = 11). In contrast,patients who were later shown not to havediffuse pulmonary arteriovenous malforma-tions, with no residual shunt (table 4), showed a

slight fall in right to left shunt with exercise,from 22-1% (7 2%) at rest to 20-7% (10 1%).These results imply differences in the waydifferent sizes of arteriovenous malformationbehave during exercise. The feeding vesselsassociated with small, diffuse arteriovenousmalformations may be more compliant thantheir neighbouring normal vessels and distendrelatively more when pulmonary arterial pres-sure rises with exercise, causing a relative andabsolute increase in right to left shunt flow withexercise. In contrast, larger feeding vesselsassociated with the bigger arteriovenous mal-formations may have a limited capacity todilate, so that absolute shunt flow is unchangedduring exercise or may decrease as a proportionof the increased cardiac output with exercise.Why do the patients with larger arterioven-

ous malformations show further arterialdesaturation during exercise of 2-9% (SD2-0%) when they have not increased their rightto left shunt? We postulate that this is due to

Table 4 Workload, right to left shunt, arterial oxygen saturation (Sao 2), kidney:dose radioactive count ratio at rest and during exercise (Ex), andresidual shunt after embolisation of all macroscopic pulmonary arteriovenous malformations in patients with residual shunts of less than 10%

Shunt (o%) SaO2 (O%) Kidney:dosePatient ResidualNo Study Work (w) f value Rest Ex Rest - Ex A Rest Ex shunt (%)

4 1 75 1-14 26 16 95-92 -3 26 13 421 1 45 0-85 33 43 81-74 -7 33 20 522 1 30 1-04 22 19 83-80 -3 22 13

2 30 1-10 23 15 89-88 -1 23 12 923 1 60 1-03 20 17 88-86 -2 20 10 525 1 60 1-01 22 21 93-91 -2 22 5 226 1 45 0-95 9 14 93-91 -2 9 2 2

Mean 49-3 1-02 22-1 20-7 -2-9 24-3 12-2 4-5SD 16-7 0-10 7-2 10-1 2-0 47 49 2-6SE 6-3 0-04 2-7 3-8 0-7 1-9 2-0 1-1

A represents the difference between Sao2 at rest and during exercise.

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recirculation of increasingly hypoxic mixedvenous blood through the arteriovenous mal-formations. Patients with residual shunts of10% or more after embolisation, who arepresumed to have diffuse arteriovenous malfor-mations, showed arterial desaturation of 6-2%(2 5%) with exercise (table 3). These results,combined with those in table 4, suggest thathalf of their arterial desaturation is due to anincrease in their right to left shunt percentageand half is due to the increased desaturation ofmixed venous blood.This paper focuses on measurements of

intrapulmonary right to left shunt in patientswith pulmonary arteriovenous malformationsand the mechanisms of arterial desaturationduring exercise. For clinical practice we haveshown that measurements of right to left shuntwith radiolabelled microspheres are a con-venient, accurate, and specific way of quanti-fying the physiological effect of pulmonaryarteriovenous malformations and monitoringthe effects of treatment by coil embolisation.

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6 Hartnell GG, Allison DJ. Management of pulmonaryarteriovenous malformations. Br J Hosp Med 1988;39:197-202.

7 Dines DE, Arms RA, Bernatz PE, Gomes MR. Pulmonaryarteriovenous fistulas. Mayo Clin Proc 1974;49:460-5.

8 Chilvers ER, Whyte MKB, Jackson JE, Allison DJ, HughesJMB. Effectofpercutaneous transcatheter embolization onpulmonary function, right to left shunt and arterialoxygenation in patients with pulmonary arteriovenousmalformations. Am Rev Respir Dis 1990;142:420-5.

9 Berggren SM. The oxygen deficit ofarterial blood caused bynon-ventilating parts of the lung. Acta Physiol Scand1942;4(suppl II): 1-92.

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Quantification patients - Thoraxsimultaneous shunt measurement in subjects breathing 100% oxygen while they rested. Themicrosphere technique wasadaptedto measurethe right to left shunt