a new system for ambulatorypulmonary artery pressure...

Br Heart J 1992;68:230-5

TECHNOLOGY

A new system for ambulatory pulmonary arterypressure recording

J Simon R Gibbs, Donald MacLachlan, Kim M Fox

AbstractObjective-To develop a complete

system for the measurement, recording,and analysis of ambulatory pulmonaryartery pressure.Design-The new system consists of

a pulmonary artery catheter, anambulatory recorder, and a desktopcomputer. Pulmonary artery pressure ismeasured by a micromanometer tippedcatheter with an in vivo calibrationsystem to allow correction for zero drift.This catheter is plugged into a smallbattery powered recorder. The recorderhas two input channels, one for pressureand one for an event marker. Thepressure wave is sampled 32 times/s,processed by an in built computer,compressed, and stored in semi-conductor memory. On completion of arecording, data is transferred from theambulatory recorder through a serialdata link to an Acorn Archimedes desk-top computer on which further dataprocessing, statistical analysis, graphics,and printouts can be obtained.Results-The system has been used in

18 patients, with technically successfulrecording in 14, less than 15 minutes ofdata loss in three, and 12 hours of dataloss in one.Conclusions-A new system for

ambulatory pulmonary artery monitor-ing has been developed and usedclinically with success. It may providenew perspectives on the pathophysiologyof disease as it applies to everyday life.

(Br Heart J 1992;68:230-5)

The pulmonary circulation is somewhat in-accessible for haemodynamic measurements,but this should not belittle its importance inthe pathophysiology of cardiovascular andpulmonary disease. As pulmonary arterypressure undergoes large changes with altera-tions in posture and activity, ambulatoryrecordings provide more information thansingle measurements made in a catheterlaboratory.Ambulatory pulmonary artery pressure has

been used to investigate pathophysiologicalaspects of heart failure, 13 coronary artery

disease,' and pulmonary hypertension.7 Itmay be used to study the effects of medical andsurgical treatments. Because pulmonary arterydiastolic pressure is a good estimate of leftventricular end diastolic pressure in theabsence of mitral valve disease or raisedpulmonary vascular resistance,89 this tech-nique may be used to assess left ventricularfunction in ambulant patients.' 01' Ambulatorymonitoring of the pulmonary artery has beenused in a few cases both in our own studiesand by others to guide clinical decisions.'2The application of ambulatory monitoring

of pulmonary artery pressure has been limitedbecause of the lack of a suitable catheter forlong-term pressure recording and a datarecording and analysis system specialised forpulmonary artery pressure. To make thistechnique practical we have developed acomplete system for measurement and record-ing of ambulatory pulmonary artery pressure.

Patients and methodsDESCRIPTION OF NEW SYSTEMThe new system consists of a pulmonary arterycatheter, an ambulatory recorder, and a desk-top computer.

CatheterPulmonary artery pressure is measured by a 7FNIH catheter (Type 7F/B, Gaeltec Ltd, UK)designed for making continuous long termrecordings. The catheter is intended formultiple use and is sterilised either in activatedglutaradlehyde (Cidex, Surgikos Ltd, UK) forat least 10 hours, or ethylene oxide.A pressure transducer is located at the tip of

the catheter thus making the tip its own zeroreference point and overcoming the difficulty oflevelling an external transducer with thecatheter tip. As zero drift is an unpredictableproperty of micromanometer tipped cathetersduring prolonged recordings, the specialfeature of this catheter is that it is fitted with anin vivo calibration system to allow correctionfor zero drift.'3 The calibration is simpleto perform: it takes 10 to 15 s and can beperformed by medical or nursing staff.During normal recording the back of the

pressure transducer is in contiguity withatmospheric pressure through a luer fitting onthe end ofthe catheter outside the patient (fig 1).

Department ofCardiology, RoyalBrompton NationalHeart and LungHospital, SydneyStreet, LondonJ S R GibbsD MacLachlanK M FoxGaeltec LtdDunvegan, Isle ofSkye, Inverness-shireD MacLachlanCorrespondence to:Dr J S R Gibbs,Royal Brompton NationalHeart and Lung Hospital,Sydney Street,London SW3 6NP.Accepted for publication18 February 1992

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A new system for ambulatory pulmonary artery pressure recording

Figure I Pulmonaryartery catheter showing aI ml syringe attached tothe external luer fitting asrequiredfor calibration.The stainless steel tiphouses the transducer.

The catheter is calibrated during recording byinjecting 0 4 ml air from a 1 ml syringe into theluer fitting. This causes a pressure ofabout 124mm Hg to be applied not only to the back ofthepressure transducer, but also to a second lumenwhich connects with the opposite side of thetransducer and causes the elastomer coveringthe transducer at the tip of the catheter to belifted off its surface. The high and equalpressure that now exists either side of thetransducer restores it to its zero state. Duringcalibration, pulmonary artery pressure istransiently interrupted by a calibration line(fig 2). When the syringe is removed from theluer lock, pulmonary artery pressure recordingrestarts automatically.

Because zero drift tends to be largest duringthe early part of the recording,'3 we calibratethe catheter every 10 minutes for the first twohours, every 20 minutes for the next six hours,and one to two hourly thereafter.

Ambulatory RecorderThe catheter is plugged into a battery poweredambulatory recorder (Type 7MPR, GaeltecLtd, UK) which is carried by the patient on ashoulder strap. The dimensions are 188 x 137x 67 mm and it weighs 850 g including its foursize AA batteries that provide sufficient powerfor 24 hours of recording.The recorder (fig 3) has three buttons that are

used for setting it up at the beginning ofrecording and one of which is used as an event

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Figure 2 Pulmonary artery pressure recording showing transient interruption by areference calibration.

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Figure 3 The new ambulatory recorder. Note the threefunction buttons and the liquid crystal display on thefront of the box, and the socketfor the serial link to thedesktop computer on the side.

button during recording. A liquid crystalscreen displays the clock time and the amountofmemory used. A socket on the side ofthe boxis used to connect it to the desktop computerthrough a serial link and the catheter connec-tion socket is at the rear of the box.

Figure 4 shows a schematic diagram of theambulatory recorder. Pulmonary arterypressure can be recorded in the range -30mm Hg to 223 mm Hg. The analogue pressuresignal from the catheter is received by theanalogue input board, amplified, filtered to limitthe highest frequency to 16 Hz to preventaliasing, and sampled 32 times/s. This data isprocessed to reduce the amount of data that hasto be stored and then held in a semiconductormemory. This data reduction is important toenable long recordings to be made. Sufficientmemory is provided for roughly 12 hours ofrecording. The memory used for storage ofdata has a back up power source separate fromthe main batteries, so that these can be changedwithout loss of data.The desktop computer can be connected to

the ambulatory recorder through the seriallink, which for patient safety is opticallyisolated. This link is used for three purposes.Firstly, it is used to download recorded datafor analysis and storage on magnetic disk.Secondly, it allows the desktop computer to beused to interrogate the recorder and alter itsrecording parameters before and duringrecording. Thirdly, it allows the desktopcomputer to display pulmonary artery pressurein real time. This real time display, which doesnot undergo any data compression, can besaved on disk and compared later with thecompressed data stored in the recorder.We used an Archimedes desktop computer

(Acorn Computers, UK) which is multitaskingand particularly suited to this type of applica-tion. A minimum of two megabytes of randomaccess memory and a 20 megabyte hard disk arerequired.The reference pressure port includes an

industrial standard pressure transducer and isused for calibration purposes.

Calibration of Ambulatory RecorderThe ambulatory recorder is calibrated with the

catheter immediately before catheterisation.The catheter is connected to the recorder and

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Gibbs, MacLachlan, Fox

Figure 4 Schematic diagram of the ambulatory recording system. EPROM,electronically programmable read only memory; EEPROM, electronically erasable andprogrammable read only memory.

set to zero, the catheter output being stored inmemory. Negative pressure is then appliedsimultaneously to the catheter transducerthrough the external luer fitting and to therecorder's own reference standard. When thereference transducer measures a pressure of- 100 mm Hg, the catheter output is stored.The system is then ready to use.

Compression of Pressure DataData compression presents a particularproblem because of the irregular nature ofpulmonary artery pressure waves during largeamounts of respiratory variation. One con-

sequence of this is that the diastolic pressure ofone wave may exceed the systolic pressure ofthe next.

Figure 5 shows pressure waves composed ofequally spaced samples marked by crosses. Thenumber of samples stored may be reduced byusing only those marked by circles. If thecircles are linked by straight lines, themaximum deviation of the other points fromthe lines is very small. The algorithm that wehave used identifies such data points. Theimportant features of this algorithm are that allrecorded points lie on the original curve, andthat it tends to select points of inflection so thaterrors in the subsequent calculation of systolicand diastolic pressure are less than 1 mm Hg.The amount of data stored is further reducedby dynamically varying the number of pointsrecorded with the amplitude of the pressurewave. Over 24 hours this algorithm willtypically store between 800 000 and 1 milliondata points.As the amount of irregularity of the pulmon-

ary artery pressure waveforms varies betweenpatients, we have validated this algorithm forindividual patients by comparing real timerecordings made from non-compressed dataover the serial link, with the same recordcompressed within the recorder and replayedlater.

Data Analysis and PresentationWith a menu driven programme on the desktopcomputer, pressure recordings can be analysed,printed, and stored on hard or floppy disks.

Firstly, pressure recordings are corrected forzero drift. This requires the operator tovalidate recorded data visually and identifycatheter calibrations. The computer will thenautomatically recalculate the whole recordingby linear interpolation between calibrations.Secondly, heart rate is automatically derived bymeasuring the distance between pressure wavepeaks. Thirdly, event markers, which appear asshort vertical lines on the screen display of thepulmonary artery pressure, can be annotatedwith comments concerning posture andactivity from a diary kept during the recordingperiod.

Presentation graphics allow the display ofany period of recording from 15 seconds to 48hours with a summary of the average systolic,diastolic, and mean pulmonary artery pressureas well as heart rate during the specified period.The value of individual data points can beobtained with the aid of a screen cursor.

Patient StudiesWe have performed ambulatory recordingswith the new pulmonary artery catheter in 36patients of whom the ambulatory recorder andanalysis system described here was used in 18.The age range was 16-68 years and recordingshave been made from 10 to 48 hours in dura-tion. Twenty four patients with chronic heartfailure, 10 with pulmonary hypertension, andone with breathlessness of unknown aetiologywere investigated.

Patients were not given premedication. Thecatheter was inserted into a subclavian orinternal jugular vein through an 8F sheathunder local anaesthesia, and positioned in theproximal right or left pulmonary artery underfluoroscopy. The sheath was then withdrawnfrom the vein and the catheter sutured to theskin and covered with a sterile dressing. Allcatheterisations were performed by one of us(JSRG). All patients went about unrestrictedactivities within the confines ofthe hospital andunderwent symptom limited exercise testingduring the period of recording.An ambulatory electrocardiogram was per-

formed simultaneously with two bipolar leads,an anterior lead CM5, and an inferior lead.Recordings on to magnetic tape were made by a

Figure 5 Schematic representation of the datacompression algorithm. See text for explanation.

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Figure 6 Comparison of compressed (top panel) and non-compressed (middle panel)pulmonary artery pressure recording showing good agreement between systolic anddiastolic values when the traces are superimposed (bottom panel).

frequency modulated dual channel recorder(Oxford Medilog II) to detect arrhythmias.The results of these studies were scrutinised

for complications related to catheterisation andtechnical problems related to the catheter andrecording system. Recordings were consideredtechnically satisfactory if no data loss wascaused by the catheter or ambulatory recorderduring the intended recording period(minimum 24 h). The results of the studies onpatients with heart failure have been publishedelsewhere.23

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Figure 7 An example of display of a region of interest. The horizontal axis represents32 min. Heart rate is displayed in the top panel and pulmonary artery pressure in thelower panel. Pulmonary artery pressure is shaded: the upper border is systolic pressureand the lower border is diastolic pressure. Event markers indicating the beginning andend of exercise appear as short vertical lines at the top of the figure. Pulmonary arterypressure rises with exercise andfalls rapidly after the end of exercise.

ResultsVALIDATION OF DATA COMPRESSION ALGORITHMFigure 6 shows the result of comparing arecording of non-compressed data with com-pressed data. This typical excerpt from arecording includes a catheter calibration.Despite data compression the pulmonaryartery waveform, shown in the middle panel, isstill clearly recognisable. When the non-compressed trace (top panel) is superimposed(bottom panel) on the compressed trace there isa good match and the maximum error betweenthe two traces is < 1 mm Hg. This good matchwas confirmed in multiple comparisons indifferent patients.

PATIENT STUDIESNo complications were encountered because ofcatheterisation. In particular, no pneumo-thoraces, inadvertent arterial punctures, orlocal or systemic sepsis occurred. There was noclinical evidence of pulmonary embolism orinfarction. Some patients had a mild ache at thesite of catheter insertion, but this was alwaysrelieved by paracetamol and did not restricttheir activities. One patient had the catheterremoved after 10 hours because of discomfort.Continuous recording ofthe electrocardiogramshowed no sustained disturbance of rhythmduring recording ofpulmonary artery pressure.

Seven catheters were used in the 36 patients.The maximum recording time for a singlecatheter was 240 hours. Catheters were dis-carded if there way any evidence of damage tothe shaft or the tip.Ofthe 18 patients assessed with the complete

system, recordings were technically satisfac-tory in 14. Data loss occurred because ofdisconnection of the catheter from the leadconnecting it to the recorder in two patientscausing data loss of <5 minutes; inadvertentcalibration of the recorder after downloadingdata after 12 hours of recording in one patientresulted in subsequent data loss; and loss ofbattery power in one patient caused the loss of15 minutes of data. None ofthese causes of dataloss can be blamed on the recording systemitself. As catheter tip impaction in a pulmonaryarteriole causes distortion or loss of thepulmonary artery pressure wave, it can beconcluded that no such impaction occurred.During exercise tests the pulmonary arterypressure waveform remained undistorted.

Figure 7 shows how a particular region ofinterest, in this example a treadmill exercisetest performed by our patient with unexplainedbreathlessness, can be displayed. The rise inpressure occurred at the beginning of exerciseand there is a rapid fall when exercise stops.Figure 8 shows a 48 hour recording in a patientwith chronic heart failure. This patient wasinvestigated as part of a single blind study inwhich he received placebo during the first halfof the recording and xamoterol during thesecond half. The time the patient was in bed atnight is indicated by the horizontal lines. Notehow the nocturnal pressure rise on placebo wasabolished while the patient was takingxamoterol.

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Figure 8 A 48 hour recording of ambulatory pulmonary artery pressure in a patientwith chronic heart failure. Heart rate is displayed in the top panel andpulmonary arterypressure in the lower panel. Pulmonary artery pressure is shaded: the upper border issystolic pressure, the lower border is diastolic pressure, and the measured mean is shownas a white line in between. The patient was given placebo during the first 24 hours andxamoterol during the second 24 hours. The horizontal lines indicate the time spent by thepatient in bed at night.

DiscussionPULMONARY ARTERY PRESSURE MEASUREMENTReliable assessment of pulmonary arterypressure requires catheterisation. It was thepartnership of Cournand and Richards andtheir coworkers who, experimenting first on

animals and then on humans, perfected rightheart catheterisation and used it to sampleblood and measure cardiac output.'"6 The firstrecorded pressure tracings in the pulmonaryartery of humans were taken in 1944 and thusopened a new era for the study of the pulmon-ary circulation in health and disease."

Catheterisation of the pulmonary artery andthe measurement of the oxygen saturation inblood taken from the pulmonary capillary"wedge" position was achieved by Dexter et aland Hellems et al while they were investigatingcongenital heart disease.'"20 The close relationbetween the pressure measured in the "wedge"position, the pulmonary venous and left atrialpressure, and the pulmonary artery diastolicpressure was also reported." 1221 It was only ashort time before catheterisation was used toinvestigate physiological problems and to guidemedical treatment.2"24 The value of measuringpulmonary artery pressure in acutely illpatients was recognised,25 26 and a simplemethod for catheterising the pulmonaryarteries without the need for fluoroscopy was

described in 1970.27 Fluid filled balloon flotationcatheters have since remained the standardmethod for measurement of pressure in thepulmonary artery for research on haemo-dynamics. Whereas these catheters provide thesimplest method of bedside monitoring, thedifficulty oflevelling an external pressure trans-ducer with the catheter tip during totallyunrestricted activities is impractical

Gibbs, MacLachlan, Fox

AMBULATORY PULMONARY ARTERY PRESSUREMEASUREMENTDifferent methods of ambulatory pulmonaryartery monitoring have been reported by fourother groups. Three of these have usedmicromanometer tipped catheters,' 28 29 butonly one has attempted to measure zero drift,and published data on their technique islimited.29 The two methods that have notmeasured zero drift, including one publishedby our own laboratory,28 have not been pursuedfurther.The fourth group have reported a method in

which pressure was measured for 10 to 25 hourswith a 5F Goodale Lubin catheter with one endhole and two side holes.30 The external pressuretransducer was calibrated once near the begin-ning and once near the end of each study. Thecatheter was linked to a portable transducer-perfusion unit. The investigators experienceddifficulties with the catheter clotting despiteadministration ofheparin at a rate of20 000 IUa day. Twenty per cent of the recordings wereaffected by artefacts that presumably originatedfrom the fluid filled catheter.

Various recording systems have beenemployed. The originators of the techniqueused a digital recorder that averaged systolicand diastolic pressure over consecutive 30second intervals.' The system was unable torecord pressure waves and neither visualvalidation of the recorded data nor beat to beatchanges in pressure could be measured. Twogroups favoured a miniature tape recorder.One used their own custom written computerprogramme to digitise and analyse the data,303'and the other an optical writer to playback thedata for visual analysis.28 Our own experienceof visual analysis is that it is immensely timeconsuming.

All of these systems were developed byresearch workers for their own use. Without acommercially available system ambulatory pul-monary artery pressure recording has beenunable to find general application.The principal application of long-term con-

tinuous monitoring of ambulatory pulmonaryartery pressure is as a research tool to inves-tigate the natural history and pathophysiologyof cardiovascular and pulmonary disease. Itmay be used to investigate diurnal variation,and the effects of daily activities and specificinterventions, such as exercise tests, coldpressor tests, and drug administration, onpulmonary artery pressure. We have recentlyused ambulatory recordings for spectralanalysis.32

THE NEW SYSTEMThe purpose of developing a new systemfor monitoring ambulatory pulmonary arterypressure was to make this technique generallyavailable while overcoming the technical dif-ficulties that have dogged previous inves-tigators. Pressure measurement is accurate anddata analysis rapid. Patients do not requireanticoagulation.The limitations of the technique are those of

all invasive investigations, but in particularoperators should have previous experience of

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right heart catheterisation and not simply theinsertion of flotation catheters. Care should betaken not to advance the catheter too far intothe pulmonary artery to a position from whichit could migrate and become wedged. Likemost invasive investigations the patientsrequire careful monitoring as catheter calibra-tions should be performed frequently. With theneed for more calibrations early in the record-ing we perform our catheterisations in themorning. Despite the frequent need for cali-brations during recording, the brevity of thisprocedure hardly interferes with the dailyactivities ofpatients. During recording a doctorneed only be in attendance during specificmanoeuvres such as exercise tests. Althoughour patients were limited to the confines of thehospital, we do not believe that this is strictlynecessary. For the forseeable future we shallcontinue to investigate patients on an inpatientbasis. The ambulatory recorder has enoughmemory for about 12 hours of recording.Although it might be more convenient to store24 hours of data, 24 hour recordings will not fiton to a single floppy disc for data storage, and itis assumed that investigators will want toarchive their data.

In conclusion, a new system for measure-ment of ambulatory pulmonary artery press-ure, recording and analysis has been developedwith a micromanometer tipped catheter, anambulatory digital recorder, and a desk topcomputer. A data compression algorithmdesigned to contend with large fluctuations inpulmonary artery pressure has been validated.Measurement of ambulatory pulmonary arterypressure is safe and well tolerated. It mayprovide new perspectives on the patho-physiology of disease as it applies to everydaylife.

1 Gibbs JSR, Cunningham AD, Shapiro LM, Park A, Poole-Wilson PA, Fox KM. Diurnal variation of pulmonaryartery pressure in chronic heart failure. Br Heart J1989;62:30-5.

2 Gibbs JSR, Keegan J, Wright C, Fox KM, Poole-WilsonPA. Pulmonary artery pressure changes during exerciseand daily activities in chronic heart failure. J Am CollCardiol 1990;15:52-61.

3 Gibbs JSR, Ferrari R, Keegan J, et al. The influence of rightheart catheterisation on pulmonary artery pressure inchronic heart failure: relationship to neuroendocrinechanges. Int J Cardiol 1991;33:365-76.

4 Levy RD, Shapiro LM, Wright C, Mockus L, Fox KM.Haemodynamic response to myocardial ischaemia duringunrestricted activity, exercise testing and atrial pacingassessed by ambulatory pulmonary artery pressure moni-toring. Br Heart J 1986;56:12-8.

5 Levy RD, Shapiro LM, Wright C, Mockus L, Fox KM. Thehaemodynamic response to myocardial ischaemia inambulant patients with variant angina. Br Heart J 1986;56:518-25.

6 Levy RD, Shapiro LM, Wright C, Mockus L, Fox KM. Thehaemodynamic significance of asymptomatic patients withST segment depression assessed by ambulatory pulmo-nary artery monitoring. Br Heart J 1986;56:526-31.

7 Richards AM, Ikram H, Crozier IG, Nicholls MG, Jans S.Ambulatory pulmonary arterial pressure in primary pul-monary hypertension: variability, relation to systemicarterial pressure, and plasma catecholamines. Br Heart J1990;63: 103-8.

8 Falicov RE, Resnekov L. Relationship of the pulmonary

artery end-diastolic pressure to the left ventricular end-diastolic pressure and mean filling pressures in patientswith and without left ventricular dysfunction. Circulation1970;42:65-73.

9 Jenkins BS, Bradley RD, Branthwaite MA. Evaluation ofpulmonary arterial end-diastolic pressure as an indirectestimate of left atrial mean pressure. Circulation 1970;42:75-8.

10 Levy RD, Shapiro LM, Wright C, Mockus L, Fox KM.Syndrome X: the haemodynamic response to ST segmentdepression. Br Heart J 1986;56:353-7.

11 Levy RD, Cunningham AD, Shapiro LM, Wright C,Mockus L, Fox KM. Diurnal variation in left ventricularfunction: a study of patients with myocardial ischaemia,syndrome X, and ofnormal controls. Br Heart J 1987;57:148-53.

12 Nathan AW, Perry SG, Cochrane T, Banim SO, SpurrellRA, Camm AJ. Ambulatory monitoring of pulmonaryartery pressure. A preliminary clinical evaluation. BrHeart J 1983;49:33-7.

13 Gibbs JSR, Cunningham D, Sparrow J, Poole-Wilson PA,Fox KM. Unpredictable zero drift of intravascularmicromanometer-tipped catheters during long-term pul-monary artery pressure recording: implications for cath-eter design. Cardiovasc Res 1989;23:152-8.

14 Cournand AF, Ranges HS. Catheterization of the rightauricle in man. Proc Soc Exp Biol Med 1941;46:462-6.

15 Richards DW. Cardiac output by the catheterization tech-nique in various clinical conditions. Federation Proceed-ings 1945;4:215-20.

16 Cournand AF, Riley RL, Breed ES, Baldwin EF, RichardsDW. Measurement of cardiac output in man using thetechnique of catheterization of the right auricle. J ClinInvest 1945;24:106-16.

17 Cournand A, Bloomfield RA, Lauson HD. Double lumencatheter for intravenous and intracardiac blood samplingand pressure recording. Proc Soc Exp Biol Med 1945;60:73-5.

18 Dexter L, Burwell CS, Haynes FW, Seibel RE. Oxygencontent of pulmonary "capillary" blood in unanesthetizedhuman beings. J Clin Invest 1946;25:913.

19 Dexter L, Haynes FW, Burwell CS, Eppinger EC, SagersonRP, Evans JM. Studies of congenital heart disease. II. Thepressure and oxygen content of blood in the right auricle,right ventricle, and pulmonary artery in control patients,with observations on oxygen saturation and source ofpulmonary "capillary" blood. J Clin Invest 1947;26:554-60.

20 Hellems HK, Haynes FW, Dexter L. Pulmonary capillarypressure in men. J Appl Physiol 1949;2:24-9.

21 Werko L, Varnauskas E, Eliasch H, LagerlofH, Senning A,Thommasson B. Further evidence that the pulmonarycapillary venous pressure pulse in man reflects cyclicpressure changes in the left atrium. Circ Res 1953;1:337-44.

22 Lenegre J, Maurice P. Premiers recherches sur la pressionventriculaire droite. Bulletins et Memoires de la SocieteMedicale des Hopitaux de Paris 1944;80:239-40.

23 McMichael J, Sharpey-Schafer EP. Cardiac output in manby a direct Fickmethod: effects of posture, venous pressurechange, atropine, and adrenaline. Br Heart J 1944;6:33-40.

24 Stead EA Jnr, Warren JV. Cardiac output in man: analysis ofmechanisms varying cardiac output based on recentclinical studies. Arch Intern Med 1947;80:237-48.

25 Bradley RD. Diagnostic right heart catheterisation withminiature catheters in severely ill patients. Lancet 1964;2:941-2.

26 Fife WP, Lee BS. Construction and use of self-guiding rightheart and pulmonary artery catheter. J Appl Physiol 1965;20:148-9.

27 Swan HJC, Ganz W, Forrester J, Marcus H, Diamond G,Chonette D. Catheterization of the heart in man with useof a flow-directed balloon-tipped catheter. N Engl J Med1970;283:447-51.

28 Levy RD, Cunningham AD, Shapiro LM, Wright C,Mockus L, Fox KM. Continuous ambulatory pulmonaryartery pressure monitoring. A new method using a trans-ducer tipped catheter and a simple recording system. BrHeart J 1986;55:336-43.

29 Brigden GS, Cashman P, Lahiri A, Raftery EB. Ambulatoryhaemodynamic monitoring: validation and assessment of24 h patterns in patients with coronary artery disease[abstract). Eur Heart J 1990;11(suppl):285.

30 Ikram H, Richards AM, Hamilton EJ, Nicholls MG.Continuous recording of pulmonary artery pressure inunrestricted subjects. Br Heart J 1984;51:421-6.

31 Richards AM, Ikram H, Nicholls MG, Espiner EA,Hamilton EJ, Richards RD. Ambulatory pulmonaryarterial pressures in humans: relationship to arterialpressure and hormones. Am J Physiol 1986;251:H1I1-8.

32 Gibbs JSR, Sanderson W, Smith LDR, Sparrow J, Poole-Wilson PA, Fox KM. Instability of circulatory regulationin chronic heart failure: evidence from low frequencyoscillations of pulmonary artery pressure [abstract]. EurHeart 1991;12(suppl):119.

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