increased arteriovenous oxygen difference after...

Increased Arteriovenous Oxygen DifferenceAfter Physical Training in Coronary

Heart DiseaseBy JEAN-MARIE R. DETRY, M.D., MICHEL RousSEAU, M.D.,

GENEVIEVE VANDENBROUCKE, M.S., FuSAKo KusuMi, M.S.,LUCIEN A. BRASSEUR, M.D., AND ROBERT A. BRUCE, M.D.

SUMMARYA preliminary study of 12 male patients (mean age, 47.8 years) with coronary

heart disease (six with angina pectoris and six with prior myocardial infarction butwithout angina) was conducted according to a common protocol in Seattle, Washing-ton, and Louvain, Belgium. Maximal oxygen intake (V02 max) and hemodynamic studiesat rest and at two or three levels of submaximal exercise in the upright position wereobtained before and after a 3-month physical training program that involved threesessions of 45 min/week. "V02 max" increased 22.5% (P < 0.0001) with physical train-ing. Changes in maximal heart rate occurred in the patients with angina (+8.4%) butnot in those without angina (+0.8%). At rest and at each submaximal exercise, heartrate, mean blood pressure, and cardiac output decreased after training, whereas strokevolume was unchanged and arterio-mixed venous oxygen (A-Vo0) difference increased.The pressure-rate product and the left ventricular work decreased after training. Theclassic posttraining bradyeardia was compensated not by a higher stroke volume but byan increased A-Vo,0 difference which resulted from both a higher arterial oxygen contentand an increased peripheral oxygen extraction. The latter was more apparent whenexercises of the same relative intensity were compared.

Thus, benefits with physical training in coronary patients result at submaximal ex-

ercise level from enhanced arterial oxygen content and peripheral extraction andsecondarily from lower hemodynamic stress on ischemic myocardium. Increased max-

imal A-V02 difference probably explains most of the increase in "VO9 max" with physicaltraining in coronary patients not limited by angina pectoris.

Additional Indexing WordsMaximal oxygen intakeArterial oxygen content

Cardiac outputPeripheral oxygen extraction

Pressure-rate product

PHYSICAL training is now recommendedin the rehabilitation of ambulatory pa-

tients with coronary heart disease as there is

From the Department of Medicine (Cardiology),University of Washington, Seattle, Washington, andDepartment of Medicine (Cardio-Pulmonary Labora-tory), University of Louvain, Saint-Pierre UniversityHospital, 3000 Louvain, Belgium.

Supported in part by grants from the ScientificCouncil for Cardiac Rehabilitation, InternationalSociety of Cardiology; the Fonds Belge de laRecherche Scientifique Medicale; the National Center

Circulation, Volume XLIV, July 1971

increasing evidence of its beneficial effects.Heart rate at rest and at any given submaxi-

for Health Services (HS00092); the National HeartInstitute (09773); and the National Heart and LungInstitute (HE05281).

Dr. Detry is a Public Health Service InternationalPostdoctoral Research Fellow (F05 TW 1487-01) andPoncin Scholar of the Seattle First National Banks.

Address for reprints: Dr. Detry, Division ofCardiology, University Hospital, University of Wash-ington, Seattle, Washington 98105.

Received December 10, 1970; revision accepted forpublication March 29, 1971.

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ARTERIOVENOUS OXYGEN DIFFERENCE

mal work load is usually decreased afterphysical training. This lower heart rate has tobe compensated by either a larger strokevolume or a wider arteriovenous oxygen (A-V02) difference. Which of these mechanisms iseffective in coronary heart disease is uncertainsince A-V02 difference has been reported asincreased' or unchanged2 3 after physicaltraining.An international cooperative study was

planned, under the auspices of the ScientificCouncil on Cardiac Rehabilitation, Interna-tional Society of Cardiology, to clarify effectsof physical training on coronary patients. Thestudy was designed to determine the changesin maximal oxygen intake ("VYo. max") withphysical training and to measure the hemody-namic changes by the direct Fick principle atrest and at several submaximal exercise levels.Initial results from two participating centers(Louvain, Belgium, and Seattle, Washington)are presented at this time.

MaterialTwelve male patients (ranging in age from 34

to 68 years, with a mean age of 47.8 years) withcoronary heart disease had "Vo2 max" determina-tions and hemodynamic studies before and 3months after the onset of a physical trainingprogram (table 1). Six of these patients hadtypical exercise angina pectoris, and six otherswithout angina had previous acute myocardialinfarction. Two of the angina patients (no. 1 and3, table 1) were taking beta-blocking agents, butthe doses remained unchanged during thecomplete study. Patients with hypertensive dis-ease (resting blood pressure 160/90 mm Hg),clinically manifest heart failure, or ventricularaneurysm were excluded from the study. Nonereceived digitalis. Informed consent after appro-priate explanations was obtained from eachsubject before he entered the study.

MethodsA common protocol was used in Louvain and

Seattle except for minor differences in theprocedures which will be mentioned. Eachpatient had a clinical examination, resting 12-leadECG, and upright chest X-ray for appraisal ofheart volume.

Maximal Oxygen Intake"VO' max" was measured in a single test of

progressive exercise. A multistage treadmill testCirculation, Volume XLIV, July 1971

was used in Seattle,4 5 while a multistage bicycleexercise test (with an initial work load of 10 wand successive increments of 10 w every minute)was performed in Louvain.6 Exercise was contin-ued until the patient reached a self-determinedlimit of maximally tolerable fatigue, dyspnea, legweakness, or angina pectoris. The "Vo2 max" wasmeasured several days before the hemodynamicstudies in Louvain (pre- and posttraining) and inSeattle (pretraining study); in Seattle theposttraining "VO2 max" was measured 3-4 hrafter the hemodynamic study in order to reducethe patient's time lost from gainful employment.

Heart rate and ECG were monitored from abipolar ECG lead (Seattle) or from precordial V4,V5, or V6 (Louvain); S-T-segment depression wasnever a reason for stopping exertion. No test hadto be interrupted for a significant arrhythmia.Continuous magnetic tape recordings of thebipolar lead and Frank leads (X, Y, Z) wereobtained in Seattle and later analyzed bycomputer averaging technique.7 Maximal heartrate was measured during the last 30 sec of thetest.

One-minute samples of expired air werecollected through a low resistance open circuitduring the last 3 to 4 min of the test. Oxygencontent of expired air samples was measured witha paramagnetic oxygen analyzer (Beckman orServomex), and volume was measured with a dryGasmeter (Parkinson and Cowan or AmericanMeter Co.). Maximal oxygen intake (STPD) wasexpressed in ml 02/kg X min.

Hemodynamic StudiesA polyvinyl catheter (0.9 mm inner diameter,

1.3 mm outer diameter) was introduced percuta-neously into the basilic vein and floated into thepulmonary artery. A Teflon catheter-needle wasinserted into the brachial or radial artery of thesame arm (Seattle), and in Louvain a polyethyl-ene radiopaque catheter was introduced into thebrachial artery by the Seldinger technique andadvanced into the ascending aorta. The catheterswere connected to a Statham P23 Db transducer;zero level was the fourth intercostal space in thesitting position. The ECG was monitored asduring maximal oxygen uptake determination.The patients sat on a bicycle ergometer-

Fleisch (Louvain) or Monark (Seattle) -wherethe resting measurements were made. Twoexercise periods of 7-min duration each wereseparated by a 30-min rest period; the twowork loads corresponded to 45% and 75% of thepretraining "V02 max." In some cases (Seattle) athird work load at 90 + 5% of "VO, max" wasperformed during 4 to 5 min after a second 30-min rest period. The pedaling rate was 40 rpm inLouvain and 50 rpm in Seattle.

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The cardiac output was measured in duplicateby the Fick principle during the last 2 min ofeach rest or exercise period. Expiratory gaseswere collected and analyzed as for the Vo. max

determination. Blood samples were drawn simul-taneously from the pulmonary artery and periph-eral artery, and the oxygen content was deter-mined by the Van Slyke technique. The heart ratewas counted from a continuous ECG paperrecording. The mean pressures were obtained byelectrical integration. The ECG (bipolar andFrank leads) was recorded on magnetic tapeduring the hemodynamic determination (Seattle)for subsequent computer analysis.

All patients were conditioned to the experimen-

tal procedures by performing each work load forpreliminary measurements of oxygen intake beforethe hemodynamic study.

In Louvain, the posttraining hemodynamicstudy was similar to the pretraining study. InSeattle the work loads utilized before trainingwere repeated in the same way but, after 7 min ofexercise and hemodynamic measurements, somepatients were asked to continue exercise for 5 to 6min longer at a slightly higher work load. Cardiacoutput and pressure determinations were thenrepeated during the last 2 min of this higherwork load. This minor modification in the protocolwas intended to provide additional data aftertraining without prolonging the total duration ofthe study excessively.The following indices were calculated:(a) Pressure-rate product, in units = HR X

BP/ 100, where HR = heart rate and BP =

mean arterial blood pressure.

(b) Peripheral vascular resistance, in units =BP/Q, where Q = cardiac output.(c) Pulmonary vascular resistance, in unitsPA/Q, where PA = mean pulmonary arterialpressure.

(d) Left ventricular work, in units = BP x Q.(e) Left ventricular stroke work, in units =BP x SV, vhere SV = stroke volume.

Physical Training Program

In both centers, the patients met three times aweek for 45-min training sessions under medicalsupervision. In Seattle, the training was underdirection of the professional staff of the Cardio-Pulmonary Research Institute (CAPRI), usingthe facilities of the Downtown Seattle YMCAgymnasium. The training consisted of six gradedlevels of walking, jogging, and running, and 12calisthenics scaled from five to 15 repetitionsaccording to the capacity of each patient. InLouvain, the training done at the UniversityHospital included walking, calisthenics, jogging,rowing, and bicycling at five graded levels alsoscaled to the capacity of each patient.

Intensity of physical training was adjusted toeach individual capacity taking into accountinitial "VTO, max," heart rate during training, andsubjective reactions and feelings of each patient.The training was largely submaximal, withoutattempt to precipitate angina pectoris; when thelatter occurred, the patients used nitroglycerin forrelief of pain and resumed training.

Table 2

Effect of Physical Traininig on Maximal PerfornmancesNo. of Before Afterpatients Parameter physical training* physical training* Differencet cchangeP+

With angina pectoris6 V°2 max 18.59 - 3.31 24.28 - 5.14 + 5.68 - 1.27 +30.6 <0.01

HR 131.6 - 11.1 142.6 - 21.6 +11 - 5.4 + 8 NS44.7 - 13.0 60.4 - 19.3 +15.7 - 4.2 +35.1 <0.02

Without angina pectoris6 Vo2 max 27.34- 4.99 32.15- 4.63 + 4.81 - 0.84 +17.7 <0.005

HRI 174.5 - 10.1 176 - 6.6 + 1.5 - 3.4 + 0.8 NSVE 70.7 - 20.0 80.9 - 23.2 +10.2 - 4.1 +14.4 NS

All patients12 V02 max 23.0 - 6.1 28.2 - 6.2 ± 5.2 - 0.74 +22.6 <0.0001

HR 153.1 - 24.5 159.4 - 23.2 + 6.2 - 3.35 + 4 NSVE 57.7 - 21.0 70.6 - 23.0 +12.9 - 2.9 +22.4 <0.001

Abbreviations: V0. max = maximal oxvgen intake (ml/kg/min); HR = heart rate (beats /mill); VE = ventilation(liters/min).*Mean values - standard deviation.tMean values - standard error.tSignificance of difference calcuilated by paired t-test.

Circulation, Volume XLIV. July 1971

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Statistical MethodsSignificances of differences were analyzed by

means of the paired t-test; unpaired data weredisregarded for the calculation of means.

ResultsMaximal Oxygen Intake

After physical training (table 2), "'Vo2 max"was increased by 22.6% (P < 0.0001), maximalventilation by 22.4% (P < 0.001), and maximalheart rate by 4% (NS). The increase in "V02max" was greater in patients with anginapectoris (+30.6%) who had lower pretrainingvalues than in patients with healed myocardialinfarction but no angina (+17.7%). Similarly,maximal heart rate was increased by 8% inangina patients, while the change was only0.8% in patients without angina. There were nosignificant changes in heart volume.

All patients felt subjectively improved afterthe 3-month training program, and twopatients limited by angina pectoris beforetraining were free of angina at any level ofexertion after the physical training period.

Hemodynamic Data

Table 3 summarizes the hemodynamic dataat rest and at exercise levels corresponding to45% and 75% of the pretraining "VO2 max."Data at the third exercise level (correspond-ing to 90% of the pretraining "VO2 max")obtained before and after training in only twocases were not considered separately but wereincluded for the general calculations and inthe figures.At rest and at the two submaximal exercise

levels, ventilation, heart rate, cardiac output,mean arterial pressure, and pressure-rateproduct were all significantly decreased whilearterio-mixed venous oxygen (A-V02) differ-ence, arterial oxygen content, and oxygenpulse were significantly increased. Strokevolume, mean pulmonary artery pressure, andleft ventricular stroke work were unchanged.Left ventricular work was significantly de-creased during exercise. Minor changes oc-curred in peripheral vascular resistance and inpulmonary vascular resistance.The individual data for heart rate, A-V02

difference, cardiac output, and pressure-rateCirculation, Volume XLIV, July 1971

product are presented in figures 1 to 4.Hemodynamic changes noted at rest and atsubmaximal level after physical training inpatients with angina pectoris were not signifi-cantly different from those in patients withoutangina.The increased A-V02 difference at a given

submaximal level was explained primarilyby increased arterial oxygen (table 3,fig. 5) content. However, peripheral oxy-gen extraction was also increased since theextraction coefficient (A-Vo2 difference divid-ed by arterial oxygen content x 100) aftertraining rose from 30.8 to 32.3% at rest (NS),from 46.8 to 49.5% at the low exercise level(NS), and from 56.3 to 59.3% at the higherexercise level (P < 0.01); this increase washighly significant (P < 0.001) when all restingand exercise data were pooled.

DiscussionThe major hemodynamic finding was a

decreased cardiac output at rest and atsubmaximal exercise levels after physicaltraining. This lower cardiac output wasattended by an increased A-V02 difference, anunchanged stroke volume, and lower heart

HEART RATEAFTER

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Effects of physical training on heart rate (beats/min)at rest and during submaximal exercise.

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Table 3

Hemodynamnic Data

Vo0 VE Vo2 max HR CaO2 CV02 A-Vo2(ml min) (liters/min) (%) (beats/min) (ml/100 ml) (ml 100 ml) (ml 100 ml)

At restBefore* 287 - 39 8.2 - 1.2 17.6 - 3.9 80 - 11 18.6 - 0.7 12.90 - 1.3 3.7 0.9After* 272 - 42 7.9 - 1.4 13.7 - 3.1 68 - 9 19.2 - 1.2 13.00 - 1.1 6.1 0.9Differencet -13 7.9 -0.4 - 0.38 -3.9 - 0.6 -11 - 2.9 +0.6 - 0.17 +0.1 - 0.19 +0.4 i 0.24ii 12 12 12 12 11 11 11Pt NS NS <0.0001 <0.00) < 0.005 NS NS

Exercise level IBefore 793 - 221 20.7 - 6.4 435 - 6 103 - 18 19.0 - 0.8 10.3 - 1.2 8.7 - 0.8After 749 - 193 17.4 - 4.4 33 - 6 88 - 13 19.7 - 1.3 10.2 - 1.1 9.35 0.7Difference -44 26.0 -3.3 - 0.92 -9.6 - 1.3 -14 - 2.9 +0.8 - 0.24 -0.1 - 0.29 +0.8 - 0.26

o 11 11 11 11 10 10 10P Ns <0.01 <0.0001 <0.001 <0.02 S <0.02

Exercise level IIBefore 1293 - 443 41.7 - 20.2 73.4 - 7 131 - 24 19.2 - 0.8 8.5 1.3 10.3 - 1.2After 1272 - 426 33').9 - 16.9 61.6 - 9 116 - 24 20.0 - 1.4 8.3 - 1.1 11.4 - 1.3D)ifference -22 - 13.1 -35.7 - 1.3 -13.7 = 1.9 -13 1.6 +0.8 - 0.27 -0.2 - 0.21 +0.9 - 0.24n1 12 12 12 12 11 11 11p N7S <0.005 <0.0001 <0.0001 <0.02 INs <0.0035

All dataBefore 834 - 327 25.3 - 19.3 48.3 - 26.4 107 - 31 19.0 - 0.8 10.4 - 2.2 8.3 - 2.3After 813 - 326 22.0 - 16.3 39.4 - 23.1 93 - 28 19.7 - 1.3 10.3 - 2.3 9.3 - 2.6D)ifference -21 - 10.1 -3.2 - 0.71 -9.1 - 1.0 -13 - 1.4 +0.7 - 0.12 -0.1 - 0.13 +0.8 - 0.014

cchange 2.3 - 12.7%( -18.8c- -13.1 %` +3.8e -1 c +9.4C-37 37 37 37 034 34 34

P <0.03 <0.0001 <0.0001 <0.0001 <0.0001 NS <0.0001

Abbreviations: CaO2 = arterial oxygen content; CvO2 = mixed venous blood oxygen content; A-Vo2 - arterio-mixedvenous oxygen differenice; CO = cardiac output; SV = stroke volume; LVW = left ventricular work: others = see table 1.

*Meai1 value - standard deviation.tMeani value - standard error.

tSignificance of difference calculated by paired t-test.

rate and blood pressure. Consequently thepressure-rate product and the left ventricularwork at submaximal exercise were also lowxerafter physical training.These changes are similar to those observed

by Varnauskas et al. in six coronary patientsafter 1 month of physical training,1 but verydifferent from those reported in two otherstudies, 2 which have shown an unchangedsubmaximal cardiac output with an increasedstroke volume after physical training. Reviewvof these reports revealed no apparent differ-ence either in the selection of the patients orin intensity of the physical training programthat could explain such divergent results. Thesupine position used by Frick and Katila2 fortheir hemodynamic measurements is of impor-

tance, however, because of different hemody-namic adjustments in this posture.

All the studies on the effects of physicaltraining agree on one point, namely thatresting and submaximal heart rates are lowerafter physical conditioning.'1 --14 Conse-quently, for any level of submaximal energyexpenditure there must be a compensatoryincrease in stroke volume and/or A-V,.)difference to balance the decrease in heartrate. In normal young or middle-aged sub-jects, both adaptive mechanisms may beoperative since the submaximal stroke volumehas been reported increased8s 12. 14 or un-changed'.'-". 1:1

Unlike healthy subjects, patients with coro-nary heart disease compensate their lowk,er

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Mean arterial Mean pulmonaryCO SV pressure pressure 02 pulse Pressure-rate product LVW

(liters/min) (ml/beat) (mm Hg) (mm Hg) (ml/beat) (mm Hg/min) (units)

At rest3.2 1.1 66=- 14 102 - 11 11 - 3 3.68 - 0.76 81 - 15 530 - 1374.6 1.0 66 14 93 13 11 2 4.09 - 0.81 64 - 15 428 - 132

-0.6 i 0.22 +0.7 - 3.1 -9 - 3.5 - 0.9 +0.35 - 0.15 -16 - 3.9 -100 - 5311 11 12 10 12 12 11

<0.02 NS <0.0 NS < 0.05 < 0.002 NS

Exercise level I9.1 -2.0 88=110 113 - 8 18 5 7.73 1.5 116 - 23 1028 - 2377.9 -2.1 89 - 14 107 - 8 19 4 8.46 1.5 94 - 18 845 - 231

-1.2 - 0.34 +0.6 - 2.1 -6 1.7 +0.6 i 1.3 +0.73 0.22 -21 - 4.0 -178 - 4310 10 11 9 11 11 10

<0.01 NS <0.01 NS <0.01 <0.000.5 <0.005

Exercise level II12.1 - 2.8 93 - 13 127 - 16 25 - 7 9.88 - 2.05 166 - 44 1537 -43411.0 3.1 9.5 - 14 118 16 24 - 8 10.97 - 2.04 137 - 43 1298 - 469-1.1 - 0.14 +2.1 - 1.8 -9 2.1 - - 1.3 +1.11 - 0.16 -29 - 3.4 -238 - 42

11 11 12 11 12 12 11<0.0001 NS <0.005 NS <0.0001 <0.0001 <0(.0005

All data9.1 - 3.6 83 - 17 115 - 16 19 - 8 7.79 - 3.12 123 - 51 1046 - 5358.1 - 3.6 84-118 106-117 19=18 8.74 - 3.47 99 - 46 859 - 504

-0.9 - 0.13 +1 - 1.3 - 8 1.4 - 0.7 +0.90 - 0.12 -23 - 2.3 -186 - 23- 1 1 + 1.2 7.X + 11 -19.5,, -17.9%

34 34 37 32 37 37 34<0.0001 NS <0.0001 NS <0.0001 <0.0001 <0.0001

posttraining heart rate by an increased A-V+,,difference rather than by an increased strokevolume. At the same submaximal level afterphysical training, this greater A-V(., differenceresulted mainly from a 3.3 to 4.2% increase inarterial oxygen content. It was not possible todetermine from these data whether this higherarterial oxygen content resulted from a higherarterial saturation, a higher hemoglobin con-tent, or both. A higher hemoglobin contentwith a higher arterial oxygen capacity hasbeen reported after physical training.'Whether physical training might cause an

increase in stroke volume in some patients withrelatively minor coronary arterial lesions as itdoes in normal middle-aged subjects14 is notclear. This hypothesis could explain some ofthe divergent results in the literature, but it isimpossible to verify since neither coronaryarteriography nor left ventriculography wasutilized.' :Circulation, Volumne XLIV, July 1971

A lower cardiac output at submaximalenergy expenditure raises the question of howit is distributed. Since splanchnic and renalblood flow at a submaximal level are higher intrained than in untrained subjects,15 16 themuscle blood flow for the same submaximalexertion probably is lower after physicaltraining. A lower muscle blood flow afterphysical training has indeed been reported innormal young subjects17 and in patients withcoronary heart disease.'8

Physical training induced a 22.6% increase in

"V()., max" and a 4% increase in maximal heartrate. These changes are less marked than the39.2% increase in "Yo,, max" and the 7%increase in maximal heart rate after 3 monthsof training reported by Kasch and Boyer.'9 Asin healthy sedentary middle-aged men,20 themagnitude of improvement was inverselyrelated to the initial level of physical fitness

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A-V02 DIFFERENCE CARDIAC OUTPUT

AFTER

18-

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Figure 2

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0*0

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0s

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4 6 8 10 12 14 16 18L/mi n

Figure 3

Effects of physical training on cardiac output (liters!ni,i) at rest anid during submaximal exercise.

PRESSURE-RATE PRODUCT

(Detry J.M., Bruce R.: Unpublished observa-tions). The increase in maximal heart ratewas confined to the patients with anginapectoris (+8%) and was not present in thepatients without angina.The data collected at the level of maximal

exercise have to be interpreted with caution.Indeed, the "VTo, max" measured in the anginapatients is a pain-limited one and, therefore,does not have the same physiologic meaningas a true Vo9 max measured in a normalsubject. Presumably the improvement notedafter training in angina patients results mainlyfrom their lower heart rate and blood pressureand, therefore, lower myocardial oxygenrequirements during exercise. This couldexplain why, after physical training, they areable to perform more external work and,therefore, consume more oxygen before theyare stopped by the anginal pain. Since thearterial blood pressure and the ejection timewere not measured during maximal exercise, itis impossible to determine whether the anginapatients were able to meet higher myocardialoxygen requirements21 after physical condi-

AFTER

250 [ No Angina * p <.00011Angina 0 p .00011 p

0

0

BEFORE

50 100 150 200 250Figure 4

Effects of physical training on pressure-rate product(heart rate X mean arterial blood pressure: mm Hg X1O-2/min) at rest and during submaximal exercise.The lower pressure-rate product after physical train-ing results from both lower heart rate and lower mean

arterial blood pressure.

tioning. Although the latter is suggested bytheir higher maximal heart rate, the ECGevidence of myocardial ischemia is often

Circulation, Volume XLIV, JulIe 1971

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ARTERIAL AND VENOUS MIXED

mIloom

9221

20-

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l~~~~~~~~~

18

16

14

12 F

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8po Before Training

* After Training6

4

250 500 750V02 mVmin1000 1250

Figure 5

Influence of physical training on resting and sub-maximal values of arterial and mixed venous bloodoxygen content. The intensity of the exercise is ex-

pressed in absolute values (V02 ml/min).

greater at maximal exercise after physicaltraining.22As suggested by the values of maximal heart

rate, the "'V02 max" measured before and aftertraining in coronary patients not limited byangina probably are close approximations to

the true V02 max. If the latter is true, then a

17.7% increase in this value requires explana-tion. Unfortunately, we did not measure

hemodynamic data at maximal exercise levelin this study. The only explanation we can

currently offer is that the increase in ''O,,Circulation, Volume XLIV, July 1971

max" probably resulted from an expanded A-VO2 difference, since neither the maximal heartrate nor the submaximal stroke volume23 wassignificantly altered by physical conditioning.

In conclusion, the major effect of physicaltraining in ambulatory patients with coronaryheart disease was a significant decrease ofheart rate and cardiac output at rest and atsubmaximal levels of exercise. Unchangedsubmaximal oxygen uptake was maintained byan increase in A-V02 difference associated witha higher arterial oxygen content and no changein mixed venous oxygen content. In contrastto responses of normal subjects, the strokevolume of these patients was not increasedby training. At submaximal levels of exer-cise, lower heart rate and arterial bloodpressure resulted in reduction of the pressure-rate product and, accordingly, of myocardialoxygen requirements. Possibly, the coronaryblood supply, although still restricted bycoronary heart disease, more closely approxi-mated myocardial metabolic demands. Sinceventilation also decreased, awareness of dysp-nea was often diminished as well.

AcknowledgmentsThe authors wish to acknowledge the collaboration

of H. Pyfer, M.D., Director of the Cardio-PulmonaryResearch Institute and of the staff of the DowntownSeattle YMCA; the technical assistance of T.Berckmans, G. Gerets, V. Hofer, B.S., R. Lommez, P.Luyckx, A. Marriott, K. Nilson, W. Nullens, C.Peeters, J. P. Pepermans, G. Pettet, L.P.N., E. Steen,R.N., V. Veriter, and C. Wyss; and the helpfulcomments and criticism of L. B. Rowell, Ph.D.

References1. VARNAUSKAS E, BERGMAN H, HouK P,

BJORNTORP P: Haemodynamic effects ofphysical training in coronary patients. Lancet2: 8-12, 1966

2. FRICK MH, KATILA M: Hemodynamic conse-quences of physical training after myocardialinfaretion. Circulation 37: 192-202, 1968

3. CLAUSEN JP, LARSEN OA, TRAP-JENSEN J:Physical training in the management ofcoronary artery disease. Circulation 40: 143-154, 1969

4. DOAN AE, PETERSON DR, BLACKNION JR, BRUCERA: Myocardial ischemia after maximal exer-cise in healthy men. A method for detectingpotential coronary heart disease. Amer Heart J69: 11-21, 1965

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5. BRUCE RA, KusuMI F: Aerobic costs and capacitywith a multistage treadmill test of exerciseperformance. In preparation

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Circulation Volume XLIV, July 1971

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JEAN-MARIE R. DETRY, MICHEL ROUSSEAU, GENEVIEVECoronary Heart Disease

Increased Arteriovenous Oxygen Difference After Physical Training in

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