Coronary blood flow was measured by the radioactive xenon (133Xe) washout technique in 13 subjects: 6 controls, 5 patients with coronary artery disease and 2 patients who had undergone aortocoronary saphenous vein bypass grafts. The method did not discriminate between normal subjects and patients with coronary artery disease, but may be useful to the study of blood flow in coronary bypass grafts. In 2 patients changes in coronary flow were associated with a change in the patient's clinical status.S. Afr. Med. J., 48, 175 (1974)

Bakst, A.

Carswell, S.P.

Gotsman, M.S.

Houlder, A.E.

Lewis, B.S.

English

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2 February 1974 S.A. MEDlCAL JOUR.'AL 175Coronary Blood Flow Measured by theXenon-133 Washout TechniqueB. S. LEWIS, A. BAKST, S. P. CARSWELL, A. E. HOULDER, M. S. GOTSMASUMMARYCoronary blood flow was measured by the radioactivexenon ('"Xe) washout technique in 13 subjects: 6 controls,5 patients with coronary artery disease and 2 patientswho had undergone aortocoronary saphenous vein bypassgrafts. The method did not discriminate between normalsubjects and patients with coronary artery disease, butmay be useful to the study of blood flow in coronary by-pass grafts. In 2 patients changes in coronary flow wereassociated with a change in the patient's clinical status.S. Air. Med. J., 48, 175 (1974).Myocardial ischaemia occurs when myocardial oxygendemand exceeds the available supply. Myocardial oxygenconsumption is related to heart rate, ventricular ejectiontime, myocardial contractility and systolic tension in theventricle.'" Oxygen supply depends on arterial oxygencontent and coronary blood flow-these, in turn, arerelated to velocity of aortic blood flow, the duration ofdiastole, the aorta-left ventricular pressure gradient andthe length and diameter of the coronary arteries.There are several methods for measurement of coronaryblood flow in man:" Tracer techniques are effective ifthe coronary circulation is isolated from other segmentsof the vascular bed and this can be achieved by selectiveinjection of radioactive xenon ('''Xe) into the coronaryarteries. The gas is taken up by viable myocardium andthe \\'ashoUI curve is a function of coronary blood flow.the volume of myocardium in which the gas is distributedand the blood-tissue partition coefficient of xenon.' Thegas is eliminated from the lungs so that recirculation isunimportant.We have measured coronary blood flow in 13 patientsusing the 133Xe washout technique to a~sess the value ofthe method and to study the relationship between theextent and distribution of coronary artery narrowing andobstruction and coronary blood flow.PATIENTS AND METHODSThirteen patients were studied. The patients were dividedinto 3 groups.Cardiac Unit, Wentworth Hospital and University of Natal,DurbanB. S. LEWIS, M.B. B.CH.A. BAKST, M.B. B.CH.S. P. CARSWELL, B.Se.A. E. HOULDER, M.Se.M. S. GOTSMAN. M.D., F.R.C.P.Date received: 23 August 1973.Group I-normal coronary arteries: Six patients had aclinical history suggestive of angina pectoris, but coronaryangiography showed that the coronary arteries were nor-mal. One patient had hypertrophic (non-obstructive) car-diomyopathy, the others had no haemodynamic abnor-mality.Group 2--coronary artery disease: Selective coronaryangiography showed a proximal obstruction of 70% ormore involving one or more major coronary artery(ies)in 5 patients.Group 3--coronary artery vein bypass grafts. Two pa-tients with coronary artery disease (CAD) bad undergonethe operation of aortocoronary saphenous vein bypassgrafting 3 and 5 months before this study.No patient was receiving coronary vasodilator drugsor drugs which act on the autonomic nervous systemat the time of study, although selective injection ofcontrast medium used for cine angiocardiography alterscoronary blood flow.""Premedication consisted of 10 mg diazepam and 50 mgpethidine. Routine left heart catheteri ation was performedthrough a percutaneous puncture of the femoral artery.Pressures were recorded by means of a Statham P23 Dbbonded strain gauge and an Electronics-for-MedicineDR-16 photographic recorder with electronic analoguedifferentiating circuit with minimal phase lag or distortion.The mid-chest level was used as the zero reference forpressure measurements.Left ventriculography was performed in the right anterioroblique (RAO) position by using a slow injection of 50 ml76~o Urografin. Selective left and right coronary angio-graphy was performed by means of the J udkins techniquewith cine filming at 32 frames per second on Gevapan 36film in multiple oblique views. A Philips 15-cm imageintensifier and Arriflex 35-mm camera were used.'o,llCoronary blood flow was measured in each arteryafter the corresponding coronary arteriogram had beenmade. Fifteen measurements were made in duplicate.A solution of 0,5-1 mCi "'Xe dissolved in 2 ml normalsaline was injected into each coronary artery; 5 ml flushingsolution was used and the catheter promptly withdrawnfrom the coronary ostium. The myocardial clearancecurve of ""'Xe was recorded with a collimated scintillationdetector with rate meter and a direct-writing recorder. Thecurves were digitised manually and analysed as an ex-ponential function by means of a Wang 700 series pro-grammable calculator and plotter-printer. Myocardial bloodflow was calculated"''''U for each coronary artery from theformulae of Ross et at.':176 S.-A. MEDIESE TYDSKRIF 2 Februarie 1974Measurements of coronary blood flow were comparedwith the clinical status of the patient and the correspondingcoronary arteriogram (Table I). Resting coronary bloodflow varied in normal subjects (LCA = 43,8 ± 13,2 mllmin/100 g; RCA = 45,8 ± 22,5 ml/min/100 g). There wasnot a significant difference in patients with coronaryartery disease (LCA = 65,1 ± 25,4 mI/min/lOO g, NS:RCA = 44,5 ± 10,2 ml/min/100 g, NS) and this confinnedprevious reports."" A large coronary flow was observedin I patient with isolated subtotal (90%) disease of theleft anterior descending coronary artery. Measurements ofblood flow in coronary vein grafts were also similar tothose previously reported (30.3 - 76,0 ml/min/100 g)"kQi (t)where QikFApVQi (0) e- k 'FV.Ak (A. 100)FlOO = ml/min/ 100 gpquantity of indicator,rate constant,flow,partition coefficient of xenon,specific gravity of myocardium,volume of myocardium.RESULTSThere was no correlation between abnormal coronaryanatomy and coronary blood flow except in I patient whohad had a triple aortocoronary saphenous vein bypassgraft operation. In him, angiography showed large graftsto the left anterior descending and circumflex coronaryarteries with good distal perfusion: the flow measurementswere 74,0 ml/min/ IOOg and 76,0 ml/min/100 g myocardiumrespectively. The graft to the distal segment of the rightcoronary artery supplied a small area of the diaphragmaticsurface of the heart and there was slow clearance ofangiographic contrast medium from this graft: coronaryblood flow was 47,1 ml/min/lOO g.The flow measurements were not reproducible in allpatients. In 5 estimations duplicate flow measurementswere clearly different: this finding may have been due to atechnical fault or to a change in the patient's myocardialoxygen supply and clinical status. Two patients showeda significant reduction in coronary blood flow during thesecond measurement in the same coronary artery: it isinteresting that this was accompanied by angina pectorisin each patient and (reversible) ventricular fibrillationoccurred during the immediately succeeding (contralateral)coronary angiogram.DISCUSSIONResting coronary blood flow per 100 g of viable myo-cardium is similar in normal subjects and in patients withcoronary disease and myocardial hypertrophy, althoughTABLE I. CORONARY ARTERIOGRAPHIC AND CORONARY FLOW DATACoronary arteriographyCl, obstruction)* xCoronary blood flow Cml/min/l00 g)co Ql*Ql -= RCAco 0 E LCA Grahscc Cl. :JQl X Cl (J) <l: 0 ~Cl Ql C ;>, U <l: (5 2 Mean 2 Mean LAD Circumflex<l: Cl) <l: 0 er: -lGroup 1. Control subjects1 59 F 32,5 37,0 34,72 50 F 60,6 77,9 69,2 29,4 54,8 42,13 55 F 59,4 59,4 49,1 49,14 49 F 20,4 20,4 24,6 39,0 31,85 39 M 57,6 78,0 67,86 78 M 30,3 38,1 34,2 34,8 39,7 37,2Mean -+- 1 SO 45,8 43,8-+- 22,5 -+-13,2Group 2. Coronary artery disease7 60 M 3 1 90 90 31,7 31,7 39,6 39,68 43 M 3 1 100 100 35,3 43,5 39,4 63,4 57,1 60,19 62 M 3 1 90 71,5 38,5 55,0 145,4 68,8 107,110 45 M 3 2a 80 100 100 38,8 45,1 41,9 60,6 71,1 65,811 42 M 3 1 80 95 100 61,6 48,0 54,8 52,9 52,9Mean -+- 1 SO 44,S-+- 65,1-+-10,2 25,4Group 3. Post-aortocoronary vein bypass grafts12 58 M 2a 2b 60 100 100 26,9 26,9 72,2 72,2 47,1 74,0 76,013 67 M 2a 1 40 100 80 54,8 42,5 48,7 33,5 30,3Mean 26,9 60,5 47,1 53,8 53;2.' New York Heart Association grading at time of study)O2 February i974 S.A. MEDICAL JOURNAL 177there is an abnormal response to exercise and to coronaryvasodilators in patien ts with coronary artery disease.'.S,"."·" Pacing-induced angina may cause a considerableincrease in coronary flow; the increase may be due toincreased flow in the normal adjacent non-ischaemic areaas a compensatory mechanism or following the liberationof vasodilator substances from ischaemic tissue." Theconcept of 'coronary steal' has also been suggested,"''''''where vasodilatation of the resistance vessels in the non-ischaemic area in response to certain vasodilators shuntsblood away from the ischaemic zone.The measured rate of disappearance of '''Xe is afunction of coronary blood flow, the volume of myo-cardium and the partition coefficient of xenon; if coronaryflow and myocardial volume are decreased proportionately,there is no change in the rate of disappearance and theapparently normal flow may be due to lack of perfusionof a fibrous or cold area of myocardium.' The '''Xemethod, made with a single praecordial counter, is oftenincapable of detecting areas of reduced blood flow.We have observed that clinical symptoms may beaccompanied by changes in the 133Xe washout curve andthat angiographically visible abnormalities in perfusionare usually confirmed by coronary blood flow measure-ment. The method is probably insensitive where there aresmall changes in regional coronary flow, and the problemof inhomogeneous perfusion is the most likely explanationfor conflicting results.'·'" We have been disappointed bythe insensitivity of the 133Xe washout technique in assessingregional abnormalities of myocardial perfusion, althoughit may be useful to study the effect of acute interventions(e.g. exercise or drugs) on myocardial blood flow"'· orfor the serial study of aortocoronary saphenous veinbypass grafts. It does not measure coronary blood flowin absolute terms of ml/min.Fibrotic areas of myocardium with reduced perfusioncan be demonstrated by regional scintiscanning"'" or bymacro-autoradiography in the animal laboratory.'" More·over, macro-autoradiography has shown that radioactivityis located primarily in the myocardium during the earlyportion of the xenon washout curve and later in epicardialfat. More sophisticated methods of measuring regionalabnormalities of perfusion, such as the injection of ·'K.require more extensive investigation and verification."This study was supported by grants from the South AfricanMedical Research Council and the Anglo Amer:can Corpora-tion of South Africa.REFERENCESI. Sarnoff, S. 1 , Braunwald, E., Welch, G H., Case, R. B.. Stainsby,W. N. and Macrnz, R. (1958). Amer. 1. Physiol., 192, 14~.2. Braunwald, E. (1971): Amer. l. Cardiol., 27, 416. .3. Sonnenblick, E. H. and Skelton, C. L. (1971): Mod. Cone. Card,ov.DlS., 40, 9.4. Bing, R. J., Hammon, M. M., Handelsman, J. C.. Powers, S. R.,Spencer, F. C., Eckenhoff, J. E., Goodale, W. T., Hafkenschiel,J. H. and Kety, S. S. (1949): Amer. Heart J., 38, 1.5. Rowe, G. G. (1959): Ibid., 58, 268.6. Ross, R. S., Ueda, K., Lichtlen, P. R. and Rees, 1. R. (1964):CircuJat. Res., 15, 28.7. Ross, R. S. and Friesinger, G. C. (1965): Circulation, 32, 630.8. Knoebel, S. B., McHenry, P. L., Stein, L. and Sonel, A. 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Heart J., 33, 173.22. EtHer, D. B., Sheldon, W. C., Turner, 1. C. and Groves, L. K.(1967): Surgery, 61, 41.23. Fam, W. M. and McGregor, M. (1968): Circulat. Res., 22. 649.24. KJocke, F. J. and Wittenberg, S. M. (1969): Amer. J. Cardiol., 24,72.25. Cannon, P. J., Dell, R. B. and Dwyer, E. M. jun. (1972): J. Clin.Invest., 51, 964.26. Idem (1972): Ibid., 51, 978.27. Bonte, F. J., Parkey, R. W., Stokely, E. M., Lewis, S. W., Horwitz,L. D. and Curry, G. C. (1973): Semin. Nucl. Med., 3, 153.28. Shaw, D. J., Pitt, A. and Friesinger, G. C. (1971): Cardiovasc. Res.,6, 268.29. Botti, R. E., MacIntyre, W. J. and Pritchard, W. H. (1973): Circu-lation. 47, 486.30. New York Heart Association (1964): Diseases of (he Hear( mulBlood Vessels, 6th ed., pp. 110 et seq. New York: Little, Brown.

Coronary blood flow measured by the Xenon-133 washout technique

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Coronary blood flow measured by the Xenon-133 washout technique

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