BrHeart3' 1994;71:177-181 Lack of cardioprotective efficacy of allopurinol in coronary artery surgery D P Taggart, V Young, J Hooper, M Kemp, R Walesby, P Magee, J E Wright Department of Cardiothoracic Surgery D P Taggart V Young R Walesby P Magee J E Wright Department of Biochemistry, London Chest Hospital, London J Hooper M Kemp Correspondence to: D P Taggart MD (Hons) FRCS, Department of Cardiothoracic Surgery, London Chest Hospital, Bonner Rd, London E2. Accepted for publication 21 September 1993 Abstract Objective-To examine the cardioprotec- tive efficacy of allopurinol in patients undergoing elective coronary artery surgery. Design-Prospective randomised trial. Setting-London teaching hospital. Patients-Twenty patients with at least moderately good left ventricular function undergoing elective coronary artery surgery and requiring at least two bypass grafts. Interventions-Patients were random- ised to receive allopurinol (1200 mg in two divided doses) or to act as controls. Main outcome measure-The primary determinant of the efficacy of myocardial protection was serial measurement (pre- operatively and subsequently at one, six, 24, and 72 hours after the end of cardio- pulmonary bypass) of cardiac troponin T (cTnT) a highly sensitive and specific marker of myocardial damage. Addi- tional evidence was provided by serial measurement of the MB-isoenzyme of creatine kinase (CK-MB) and myoglobin, ECG changes, and clinical outcome. Results-There was no significant differ- ence in age, ejection fraction, number of grafts, bypass times, or cross clamp times between the two groups. In both groups there was a highly significant (p < 0-01) rise in cTnT, CK-MB, and myoglobin. Peak concentrations were reached between one (CK-MB and myo- globin) and six hours (cTnT) after the end of cardiopulmonary bypass. At 72 hours cTnT concentrations were six times higher than baseline concentra- tions whereas CK-MB and myoglobin were approximately double baseline con- centrations. There was no significant dif- ference in cTnT, CK-MB, or myoglobin between the allopurinol and control groups at any time. There was no diag- nostic ECG evidence of perioperative infarction in any patient. Conclusion-Unlike previous reports this study did not show that allopurinol had a cardioprotective effect in patients with good left ventricular function undergoing elective coronary artery surgery. (Br HeartrJ 1994;71:177-181) Pretreatment with allopurinol in experimen- tally induced ischaemia may reduce infarct size and the incidence of arrhythmias and may improve myocardial function.1-' More recently allopurinol has been reported to reduce the mortality4 and morbidity of car- 5 6 diac surgery. Both experimentally and clinically the beneficial action of allopurinol has been attributed to its ability to interfere with the production or actioms of oxygen derived free radicals. Free radicals, generated by the oxygenated reperfusion of ischaemic tissues, possess an unpaired electron and are highly reactive molecules capable of damaging bio- logical structures. There is now a consider- able body of experimental and clinical evidence to incriminate free radicals in myocardial dysfunction ("stunning") associ- ated with reperfusion after an ischaemic inter- val.7-12 Only recently, however, has conclusive evidence of their generation during cardiac surgery been presented."l-"3 In experimentally induced ischaemia the most important effect of allopurinol (or its primary active metabolite oxypurinol) is the inhibition of xanthine oxidase. In mammalian hearts, however, there is little xanthine oxi- dase activity'4 and the main sources of free radicals are probably the mitochondria, acti- vated neutrophils, and the arachidonic acid cascade."3 It has been postulated that the pro- tective mechanism of allopurinol or oxypuri- nol in the mammalian heart may be due directly to its free radical scavenging proper- ties'5; whatever the mechanism allopurinol has been reported to significantly improve the results of cardiac surgery."5 To investigate clinically the proposed cardioprotective efficacy of allopurinol we randomised 20 patients undergoing elective coronary artery surgery to receive allopurinol (1200 mg in two divided doses) or to act as controls. Evidence for any cardiac protective effect of allopurinol was assessed by clinical course, electrocardiographic changes, and serial measurement of cardiac troponin T (cTnT), the MB-isoenzyme of creatine kinase (CK-MB), and myoglobin. Methods The study was approved by the Hospital Ethics Committee and all patients gave writ- ten informed consent. We studied 20 men undergoing elective coronary surgery. To keep the group as homogeneous as possible the following patients were excluded: those already taking allopurnnol: those aged over 70 or those 177 on October 30, 2021 by guest. Protected by copyright. http://heart.bmj.com/ Br Heart J: first published as 10.1136/hrt.71.2.177 on 1 February 1994. Downloaded from
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BrHeart3' 1994;71:177-181
Lack of cardioprotective efficacy of allopurinol incoronary artery surgery
D P Taggart, V Young, J Hooper, M Kemp, R Walesby, P Magee, J E Wright
Department ofCardiothoracicSurgeryD P TaggartV YoungR WalesbyP MageeJ E WrightDepartment ofBiochemistry, LondonChest Hospital,LondonJ HooperM KempCorrespondence to:D P TaggartMD (Hons)FRCS, Department ofCardiothoracic Surgery,London Chest Hospital,Bonner Rd, London E2.
Accepted for publication21 September 1993
AbstractObjective-To examine the cardioprotec-tive efficacy of allopurinol in patientsundergoing elective coronary arterysurgery.Design-Prospective randomised trial.Setting-London teaching hospital.Patients-Twenty patients with at leastmoderately good left ventricular functionundergoing elective coronary arterysurgery and requiring at least two bypassgrafts.Interventions-Patients were random-ised to receive allopurinol (1200 mg intwo divided doses) or to act as controls.Main outcome measure-The primarydeterminant of the efficacy ofmyocardialprotection was serial measurement (pre-operatively and subsequently at one, six,24, and 72 hours after the end of cardio-pulmonary bypass) of cardiac troponin T(cTnT) a highly sensitive and specificmarker of myocardial damage. Addi-tional evidence was provided by serialmeasurement of the MB-isoenzyme ofcreatine kinase (CK-MB) and myoglobin,ECG changes, and clinical outcome.Results-There was no significant differ-ence in age, ejection fraction, number ofgrafts, bypass times, or cross clamptimes between the two groups. In bothgroups there was a highly significant(p < 0-01) rise in cTnT, CK-MB, andmyoglobin. Peak concentrations werereached between one (CK-MB and myo-globin) and six hours (cTnT) after theend of cardiopulmonary bypass. At 72hours cTnT concentrations were sixtimes higher than baseline concentra-tions whereas CK-MB and myoglobinwere approximately double baseline con-centrations. There was no significant dif-ference in cTnT, CK-MB, or myoglobinbetween the allopurinol and controlgroups at any time. There was no diag-nostic ECG evidence of perioperativeinfarction in any patient.Conclusion-Unlike previous reports thisstudy did not show that allopurinol had acardioprotective effect in patients withgood left ventricular function undergoingelective coronary artery surgery.
(Br HeartrJ 1994;71:177-181)
Pretreatment with allopurinol in experimen-tally induced ischaemia may reduce infarct
size and the incidence of arrhythmias andmay improve myocardial function.1-' Morerecently allopurinol has been reported toreduce the mortality4 and morbidity of car-
56diac surgery.Both experimentally and clinically the
beneficial action of allopurinol has beenattributed to its ability to interfere with theproduction or actioms of oxygen derived freeradicals. Free radicals, generated by theoxygenated reperfusion of ischaemic tissues,possess an unpaired electron and are highlyreactive molecules capable of damaging bio-logical structures. There is now a consider-able body of experimental and clinicalevidence to incriminate free radicals inmyocardial dysfunction ("stunning") associ-ated with reperfusion after an ischaemic inter-val.7-12 Only recently, however, has conclusiveevidence of their generation during cardiacsurgery been presented."l-"3
In experimentally induced ischaemia themost important effect of allopurinol (or itsprimary active metabolite oxypurinol) is theinhibition of xanthine oxidase. In mammalianhearts, however, there is little xanthine oxi-dase activity'4 and the main sources of freeradicals are probably the mitochondria, acti-vated neutrophils, and the arachidonic acidcascade."3 It has been postulated that the pro-tective mechanism of allopurinol or oxypuri-nol in the mammalian heart may be duedirectly to its free radical scavenging proper-ties'5; whatever the mechanism allopurinolhas been reported to significantly improve theresults of cardiac surgery."5To investigate clinically the proposed
cardioprotective efficacy of allopurinol werandomised 20 patients undergoing electivecoronary artery surgery to receive allopurinol(1200 mg in two divided doses) or to act ascontrols. Evidence for any cardiac protectiveeffect of allopurinol was assessed by clinicalcourse, electrocardiographic changes, andserial measurement of cardiac troponin T(cTnT), the MB-isoenzyme of creatine kinase(CK-MB), and myoglobin.
MethodsThe study was approved by the HospitalEthics Committee and all patients gave writ-ten informed consent.We studied 20 men undergoing elective
coronary surgery. To keep the group ashomogeneous as possible the followingpatients were excluded: those already takingallopurnnol: those aged over 70 or those
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Table Clinical requiring emergency surgery; those with ejec-characteristics ofpatients tion fractions estimated to be less than 30%;
Allo- and those requiring endarterectomy or com-Control purinol bined procedures: those with renal impair-(n=10) (n10) ment (metabolism of allopurinol impaired).
Age (yr) 60 60Ejection
fraction(%) 56 49
Grafts (n) 2-8 3 0Use of
internalmammaryartery 10 9
Cardio-pulmonarybypasstime (min) 63 70
Ischaemictime (min) 33 34
There was no significantdifferences between groups.
Figure 1 cTnTconcentration (mean(SEM)) in allopurinoland control groups.
I-CM
0.0
RANDOMISATIONPatients were randomised to allopurinol or notreatment by a computer generated pro-gramme.
DRUG TREATMENTPatients allocated to allopurinol (1200 mg)received the drug in two divided doses (600mg the evening before and 600 mg at 0600on the morning of operation).
SURGERYCardiopulmonary bypass was performed withnon-pulsatile flow at 2x4 1/M2 of body surfacearea/minute with the body temperatureallowed to drift to 340C. The coronary anas-tomoses were performed with alternatingbrief periods (about 10 minutes) of aorticcross clamp and fibrillation for the distalanastomosis and reperfusion during theproximal anastomosis.
BLOOD SAMPLESBlood samples for measurement of CK-MB,myoglobin, and troponin T were obtainedpreoperatively and subsequently at one, six,24, and 72 hours after the end of cardiopul-monary bypass. Samples were collected intotubes containing lithium heparin and centri-fuged within 30 minutes. The plasma wasseparated from the cells, and stored at- 200C until analysed.
BIOCHEMICAL ANALYSEScTnT was measured by an enzyme linkedimmunoadsorbent assay technique (ELISA
Troponin T Kit, Boehringer Mannheim,Lewes, UK). The coefficient of variationbetween assays was 4-3% at troponin T con-centrations of 4-8 ,ug/l and 12-9% at concen-trations of 0-2 ,ug/l. CK-MB was measured bymicroparticle enzyme immunoassay with theAbbott IMX CK-MB kit and an Abbott IMXanalyser (Abbott Diagnostics Division,Maidenhead, UK). Myoglobin was assayedby a double antibody radioimmunoassay(Myoglobin RIA Test Kit, Biogenesis,Bournemouth, UK).
ELECTROCARDIOGRAPHIC DIAGNOSIS OFMYOCARDIAL INFARCTIONSerial electrocardiograms were performed atone, six, 12, 24, and 72 hours after surgery. Anew persistent Q wave (>0.04 ms) or loss of>25% of R waves in at least two leads wereconsidered indicative of perioperative infarc-tion. Minor ST-T wave changes and changesin conduction were not, by themselves, con-sidered diagnostic of myocardial infarction.
STATISTICAL ANALYSESData from patients are presented as mean(SD). Biochemical data are presented asmedian (SEM) to allow comparison with pre-viously published data. Serial changes withinand between the allopurinol and controlgroups were compared with the Wilcoxonrank sum test.
ResultsThe study comprised 20 men undergoingelective coronary artery surgery randomisedto receive allopurinol or no drug treatment.There were no significant differences in age,ejection fraction, number of grafts, bypasstimes, or cross clamp times between the twogroups (table).
There was a highly significant increase incTnT concentration one hour after the end ofcardiopulmonary bypass (fig 1). By contrastwith CK-MB and myoglobin, cTnT peakconcentrations were not reached until sixhours after cardiopulmonary bypass and were16 times higher than baseline concentrations.At 24 hours cTnT concentrations were sixtimes the baseline concentrations in bothgroups with little further change by 72 hours.There was no signficant difference betweenthe groups.
In both groups there was a highly signifi-cant (p < 0.01) rise in the CK-MB isoenzymeconcentration throughout the postoperativeperiod with peak concentrations between oneand six hours after the end of cardiopul-monary bypass (fig 2). CK-MB remainedraised at 24 hours but had returned towardsbaseline concentrations by 72 hours. Therewas no significant difference between thegroups.
In both groups there was a highly signifi-cant rise (p < 0 01) in myoglobin with peaksbetween 1 and 6 hours after the end ofcardiopulmonary bypass (fig 3). Myoglobinconcentrations remained significantly raisedat 24 hours and had returned towards, but
2-0 r
1-5 -
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Lack of cardioprotective efficacy of allopurinol in coronary artery surgery
Figure 2 CK-MBconcentration (mean(SEM)) in allopurinoland control groups.
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Figure 3 Concentrationofmyoglobin (mean(SEM)) in allopurinaland control groups.
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surgery creatine kinase and lactate dehydro-genase are released from both cardiac andnon-cardiac tissues,'819 and non-specific STsegment and T wave changes are commonelectrocardiographic findings. The MB isoen-zyme of creatine kinase, although more car-diospecific than creatine kinase, is not entirelycardiospecific and can originate from skeletalmuscle during cardiac operations.'8-20Myoglobin rises first and is the earliest indica-tor of myocardial injury.20 Although itimproves the accuracy of quantifying myocar-dial damage after cardiac operations it is alsoreleased from skeletal muscle.T cTnT is a cardiospecific protein derived
from the tropomyosin binding protein of thetroponin regulatory complex (subunits I, C,and T) on the thin filament of the myocardialcontractile apparatus.2' Because cTnT existsas a unique isoform distinct from the skeletalmuscle isoform22 it can specifically identifymyocardial damage in various clinical set-tings.23-28 Katus et al compared circulatingcTnT and CK-MB isoenzyme in 56 patientsundergoing cardiac surgery and 34 controlpatients undergoing non-cardiac surgery.cTnT was raised in all patients undergoingcardiac surgery and the most persistent riseswere in the five patients with Q waveinfarcts.2' cTnT was not raised in any of thecontrol patients whereas CK-MB was raisedin 25%.
30 Our trial showed no significant differencein any of the biochemical indices of myocar-dial damage between the allopurinol and con-trol groups. Mair et al reported that cTnT
30 concentrations of <2-5 ,ug/l rule out clinicallyrelevant myocardial injury.25 The peakconcentration of cTnT in both our groups
o I I was approximately 1V jug/l, similar to that-36 -24 -12 0 12 24 36 48 60 72 previously reported in patients undergoing
uneventful cardiac surgery and less than onefifth the value found in patients with periop-erative infarction.22 The peak concentrationof the CK-MB isoenzyme in both our groups
e still about double, baseline concentra- was < 30 jug/l, similar to that previouslyIs by 72 hQurs. There was no significant reported in patients undergoing uneventful:rence between the groups. cardiac surgery and less than one third theerial electrocardiograms in the post- value found in patients with acute myocardialrative period only showed occasional infarction.2023 The peak concentration ofor ST-T wave changes and no Q wave myoglobin in both groups was <400 ug/l,rcts. All patients had an uneventful recov- similar to the concentration previouslyand were discharged home on the seventh reported in patients undergoing uneventfulighth day after operation. cardiac surgery and less than one eighth the
value found in patients with acute myocardialinfarction.20
,cussion These results, together with the lack of anyore discussing the results of this trial it is electrocardiographic evidence of Q waveropriate to comment on the methods for infarction imply that none of our patients sus-ssing postoperative myocardial damage. tained major myocardial injury. Nevertheless,Aeasurement of cardiac performance is the as the half life of troponin T is two hours,2't method of measuring myocardial injury six hours for CK-MB,29 and eight hours for
it is difficult in clinical practice.'6 myoglobin30 the continuing release of cTnT,isequently, conventional assessment of CK-MB, and myoglobin at 24 to 72 hours)cardial damage is based on serial changes may imply ongoing minor myocardial injurycardiac enzymes and the electrocardio- and be consistent with the minor ST-T wavem. Although these techniques can detect changes often found. Katus et al have shownconfirm major myocardial damage'7 they that cTnT occurs in myocytes both within aof limited use in quantifying more subtle small cytosolic pool and a larger structurallyIs of myocardial injury. During cardiac bound fraction." It is possible that die six
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hour peak in cTnT is due to leakage oftroponin from the cytosolic pool, indicatingreversible cellular damage whereas thecontinuing increase in cTnT concentrationsbeyond 24 hours probably reflects ongoingrelease from disintegration of contractilemyofibrils.23 26 31
Our failure to detect any cardioprotectiveeffect of allopurinol contrasts with previouslypublished reports" although we used a simi-lar dose regimen -and studied comparablepatients in terms of age and ejection fractionto those described in these studies.Allopurinol is absorbed rapidly from theupper gastrointestinal tract and 60% is con-verted to its primary active metabolite oxy-purinol, which has a half life of 18-30 hourscompared with 1 25 hours for allopurinol.10Consequently a once daily dose achieves atherapeutic effect.
In a randomised trial of 169 patientsundergoing elective coronary artery surgeryJohnson et al reported a reduction in mortal-ity from 18% in the placebo group to 4% inthe allopu-rnol group.4 The mortality in thecontrol group, however, (elective patientswith a mean age of 61 years and a mean ejec-tion fraction of 47%) seemed particularlyhigh. In a randomised (but non-blinded)study of 90 patients undergoing coronaryrevascularisation Rashid et al reported nodifference in mortality but a significant reduc-tion in arrhythmias, infarction, and require-ment for inotrope or an intra-aortic balloonpump in the allopurinol group.5 Again, how-ever, the need for inotropes or an intra-aorticballoon pump in 38% of the control group(mean age 63 years, most with an ejectionfraction >50%) seemed excessively high. In anon-randomised study of 90 patients under-going cardiac surgery Tabayashi et al reporteda significant reduction in cardiac enzymerelease with a high dose of allopurinol.6 Thediffering nature of the cardiac operations intheir allopurinol and control groups, how-ever, confused interpretation of the results.
Das et al have reported that allopurinol andoxypurinol are direct scavengers of free radi-cals.'5 This explains their beneficial effects inmammalian cardiac ischaemia even in theabsence of xanthine oxidase. Our failure toshow any beneficial action of allopurinolcould be due to an insufficient dose of allo-purinol (although it was similar to that usedin other clinical studies) or the possibility thatfree radicals are not important determinantsof myocardial injury in cardiac surgery.
There is still no consensus on the optimaltechnique of myocardial protection duringcardiac surgery. Cold crystalloid cardioplegiais the most widely used but many surgeonsstill use non-cardioplegic techniques for coro-nary revascularisation with excellent clinicalresults.32-'4 Our cTnT results suggest that theintermittent ischaemic arrest techniqueresults in only minor myocardial damage,comparable with that in which cardioplegiawas used for myocardial protection.2425
In summary our study did not show anycardioprotective effect of allopurinol in
patients with good left ventricular functionundergoing elective coronary artery surgery.Whether allopurinol may be of benefit inolder and sicker patients with unstable anginaor poor left ventricular function is unknown.
1 Chambers DJ, Braimbridge MV, Hearse DJ. Free radicalsand cardioplegia: allopurinol and oxypurinol reducemyocardial injury following ischemic arrest. Ann ThoracSurg 1987;44:291-7.
2 Stewart JR, Crute SL, Loughlin V, Hess ML, GreenfieldU. Prevention of free radical-induced myocardial reper-fusion injury with allopurinol. J Thorac Cardiovasc Surg1985;90:68-72.
3 Akizuki S, Yoshida S, Chambers DE, et al. Infarct sizelimitation by the xanthine oxidase inhibitor, allopurinol,in closed-chest dogs with small infarcts. Cardiovasc Res1985;19:686-92.
4 Johnson WD, Kayser KL, Brenowitz JB, Saedi SF. Arandomized controlled trial of allopurinol in coronarybypass surgery. Am HeartJ 1991;121:20-4.
5 Rashid MA, William-Olsson G. Influence of allopurinolon cardiac complications in open heart operations. AnnThorac Surg 1991;52:127-30.
6 Tabayashi K, Suzuki Y, Nagamine S, Ito Y, Sekino Y,M Mohri H. A clinical trial of allopurinol (Zyloric) formyocardial protection. J Thorac Cardiovasc Surg 1991;101:713-8.
8 Bolli R. Oxygen-derived free radicals and postischemicmyocardial dysfunction ("stunned myocardium"). J AmColl Cardiol 1988;12:239-46.
9 Menasche P, Piwnica A. Free radicals and myocardialprotection: a surgical viewpoint. Ann Thorac Surg 1989;47:939-45.
10 Opie LH. Reperfusion injury and its pharmacologic modi-fication. Circulation 1989;80:1049-62.
11 Cavarocchi NC, England MD, Schaff HV, et al. Oxygenfree radical generation during cardiopulmonary bypass:correlation with complement activation. Circulation1986;74 (suppl 3): 130-3.
12 Ferrari R, Alfieri 0, Curello S, et al. Occurrence of oxida-tive stress during reperfusion of the human heart.Circulation 1990081:201-1 1.
13 Bolli R, Jeroudi MO, Patel BS, et al. Marked reduction offree radical generation and contractile dysfunction byantioxidant therapy begun at the time of reperfusion.Evidence that myocardial "stunning" is a manifestationof reperfusion injury. Circ Res 1989;65:607-22.
14 Eddy U, Stewart JR, Jones HP, Engerson TD, McCordJM, Downey JM. Free radical-producing enzyme, xan-thine oxidase, is undetectable in human hearts. Am YPhysiol 1987;253:H709-1 1.
15 Das DK, Engeiman RM, Clement R, et al. Role of xan-thine oxidase inhibitor as free radical scavenger: a novelmechanism of action of allopurinol and oxypurinol inmyocardial salvage. Biochem Biophys Res Commun 1987;148:314-8.
16 Sell TL, Purut CM, Silva R, Jones RH. Recovery ofmyocardial function during coronary artery bypass graft-ing. Intraoperative assessment by pressure volumeloops. Y Thorac Cardiovasc Surg 199 1;101:681-7.
18 Chan KM, Ladenson JH, Pierce GF, Jaffe AS. Increasedcreatine kinase MB in the absence of acute myocardialinfarction. Clin Chem 1986;32:2044-51.
19 Lee ME, Sethna DH, Conklin RN, Shell WE, MatloffJM, Gray RJ. CK-MB release following coronary arterybypass grafting in the absence of myocardial infarction.Ann Thorax Surg 1983;35:277-9.
20 Seguin J, Saussine M, Ferriere M, et al. Comparison ofmyoglobin and creatine kinase MB levels in the evalua-tion of myocardial injury after cardiac operation.Y Thorac Cardiovasc Surg 1988;95:294-7.
21 Gerhardt W, Katus H, Ravkilde J, et al. S-troponin T insuspected ischemic myocardial injury compared withmass and catalytic concentrations of s-creatine kinaseisoenzyme MB. Clin Chem 1991;37.1405-11.
22 Wilkinson JM, Grand RJ. Comparison of amino acidsequence of troponin T from different striated muscles.Nature 1987;271:31-5.
23 Katus HA, Schoeppenthau M, Tanzeem A, et al. Non-invasive assessment of perioperative myocardial celldamage by circulating cardiac troponin T. Br Heart J199 1;65:259-64.
24 Mair J, Wieser CH, Seibt I, et al. Troponin T to diagnosemyocardial infarction in bypass surgery. Lancet 1991;337:434-5.
25 Mair P, Mair J, Koller J, Wieser C, Armer-Dworzak E,Puschendorf B. Cardiac troponin T in the diagnosis ofheart contusion. Lancet 1991;338:693.
26 Hamm CW, Ravkilde J, Gerhardt W, et al. The prognosticvalue of serum troponin T in unstable angina. N Engl JMed 1992;327:146-50.
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Lack of cardioprotective efficacy of allopurinol in coronary areey surgety
27 Zimmermann R, Bald S, Dengler TJ, et al. Troponin Tafter heart transplantation. Br HeartJ 1993;69:395-8.
28 Donnelly R, Hillis WS. Cardiac troponin T. Lancet 1993;341:410-1.
29 Friedel R, Diederichs F, Ludena J. Release and turnoverof intracellular enzymes. In: Schmidt E, Schmidt FW,Trautschold E, et al eds. Advances in clinical enzymology.Basel: Karger, 1979:70-105.
30 Tomaso CL, Salzeider K, Arif M, Klutz W. Serial myo-globin vs CPK analysis as an indicator of uncomplicatedmyocardial infarction size and its use in assessing earlyinfarct extension. Am HeartI 1980;99:149-54.
31 Katus HA, Remppis A, Scheffold T, Diederich KW,Kuebler W. Intracellular compartmentation of cardiactroponin T and its release kinetics in patients with
reperfused and nonreperfused myocardial infarction.AmI Cardiol 1991;67:1360-7.
32 Flameng W, Van der Vusse GJ, de Meyere R, et al.Interniuttent aortic cross-clamping versus St Thomas'Hospital Cardioplegia in extensive aorto-coronarybypass grafting. A randomized clinical study. J ThoracCardiovasc Surg 1984;88:164-73.
34 Bonchek LI, Burlingame MW, Vazales BE, Lundy EF,Gassmann CJ. Applicability of noncardioplegic coronarybypass to high-risk patients. Selection of patients, tech-nique and clinical experience in 3000 patients. J ThoracCardiovasc Surg 1992;103:230-7.
Does X equal endothelial dysfuinIn people with angiographically normal coro-nary arteries, angina caused by myocardialischaemia (syndrome X) is probably the resultof miicrovascular dysfnfiction. The finger ofsuspicion has been pointed at the endothe-lium but without convincing evidence untilnow (abstract). Egashira and colleagues, how-ever, have now shown that the response ofcoronary blood flow to acetylcholine (anendothelium-dependent vasodilator) in thecoronary microcirculation of these patients isimpaired. So is endothelial dysfunction thecause of the angina and the end of the story?The physiological role of endothelium-
dependent dilatation in the microcirculationis not well understood. Impairment of endo-
thelium-dependent dilatation of the coronarymicrovasculature has been demonstrated inpatients with hypercholesterolaemia, hyper-tension, and heart failure. It does not appar-ently cause chest pain in these patients. Theimplications of the current study by Egashiraet al are either that coronary microvascularendothelial dysfunction is somehow morepronounced in microvascular angina or thatsome other factor must be abnormal for chestpain to develop.The challenge to understand this syndrome
remains. This new finding is important, butprobably not alone equal to X.
CHRIS J H JONES
ABSTRACTS IN CARDIOLOGY
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