Haemodynamic to isometric exercise (handgrip) in patients ...exercise evokeda lesser increase in...

British HeartJournal, I973, 35, 422-432.

Haemodynamic responses to isometric exercise(handgrip) in patients with heart disease'

Michael L. Fisher, Donald 0. Nutter, William Jacobs, and Robert C. SchlantFrom the Division of Cardiology, Department of Medicine, Emory University School of Medicineand the Grady Memorial Hospital, Atlanta, Georgia, U.S.A.

The haemodynamic responses to isometric handgrip exercise in 72 patients with heart disease were studiedduring cardiac catheterization. The results confirm observations in normal man, showing that isometric exerciseimposes a sudden and significant stress on the cardiovascular system. During isometric handgrip exercise(255% of maximum voluntary contraction for 5 minutes or 75%0 for one minute), the heart rate increased byan average of I7 beats a minute (20%), mean systemic pressure increased by 22 mmHg (23%), and the cardiacindex increased by 470 ml (i8%), with inconsistent changes in total systemic resistance. Isometric handgripexercise had little effect on left ventricular end-diastolic pressure in patients with normalLVfunction or mitralstenosis whereas in patients with abnormal LV function the average end-diastolic pressure increased by 7-ImmHg (from I8-2 to 25 3 mmHg). In patients with normal L Vfunction isometric handgrip exercise had littleeffect on mean pulmonary arterial pressure but in patients with mitral stenosis or abnormal LV function mean

pulmonary artery pressure rose by 8 o mmHg (2I%) and 6 8 mmHg (26%), respectively. Isometric handgripexercise evoked a lesser increase in heart rate and cardiac output than did submaximal dynamic (treadmill)exercise but resulted in a more potent systemic pressor response. Isometric handgrip exercise was not accom-

panied by complications in this study and appears to be a simple manoeuvre for cardiac stress testing.

Isometric (static) exercise is performed as part ofmany daily activities. Studies in healthy young sub-jects have shown that a potent cardiovascular reflexadjustment rapidly occurs during sustained staticexercise (Tuttle and Horvath, I957; Lind et al.,I964; Donald et al., I967; Lind and McNicol,I967a; Freyschuss, I970). Compared to dynamicexercise, the reflex increase in heart rate and cardiacoutput is modest whereas a conspicuous increaseoccurs in mean systemic blood pressure. Lind andMcNicol (I967a) have shown that the magnitude ofhaemodynamic changes occurring during staticexercise seems to depend upon the relative strengthof contraction, i.e. the proportion of maximal effortemployed, and on the duration of contraction.Within wide limits the cardiovascular reflex isindependent of the mass of contracting muscle (Lindand McNicol, I967b). Reports from our laboratoryand from other investigators have described similarcirculatory responses to isometric handgrip exercisein patients with heart disease (Fisher, Nutter, and

Received 2I August 1972.1 This study was supported by U.S. Public Health ServiceGrants.

Schlant, I971; Helfant, deVilla, and Meister, I97I;Kivowitz et al., I97I; Krayenbuehl et al., I972;Mullins et al., I970). These studies also suggest thatisometric stress testing can provoke evidence of de-creased left ventricular compliance or dysfunction.In addition, we have used isometric handgrip stresstesting at the bedside and during noninvasive cardiacgraphic recording to evoke or accentuate indirectphysical evidence of cardiac dysfunction in patientswith left ventricular myocardial disease (Siegel et al.,I972).The present report is a qualitative and quantita-

tive assessment of the haemodynamic responseselicited by isometric handgrip exercise in patientswith a variety of cardiac diseases studied duringcardiac catheterization. The responses to isometricexercise are compared with those obtained duringgraded treadmill (dynamic) exercise in a number ofsubjects. These data demonstrate the degree ofcirculatory stress imposed on the cardiac patient byisometric exercise. Analysis of our findings alongwith those reported by Helfant et al. (I97I),Kivowitz et al. (I97i), and Krayenbuehl et al. (I972)indicate the potential values of isometric handgripexercise as a noninvasive cardiac stress test.

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Haemodynamics during isometric exercise 423

TABLE I Functional status of patients tested with isometric handgrip exercise

Group NYHA* functional class Maximal treadmill exercise duration

No. I II III-IV No. Minutes

I: Normal left ventricular function 14 I4 I-0 I21III: Mitral stenosis I2 - 5 7 9 5-8

III: Abnormal left ventricular functionMyocardial disease I5 - 5 10 I0 7 3Volume overload 14 I 3 I0 10 7-0Miscellaneous I7 2 II 4 II 6-9Total group III 46 3 I9 24 31 71I

* NYHA, New York Heart Association.

Subjects and methodsSeventy-two patients undergoing routine diagnostic car-diac catheterization were studied. All patients gave in-formed consent for the performance of cardiac catheter-ization and isometric stress testing. Fifty of these patientshad objective determination of exercise performanceusing a modified Bruce maximal treadmill exercise test(Bruce et al., I963). Sixty patients were arbitrarilyclassified as having normal or abnormal left ventricularfunction. The criteria used for this classification were:clinical assessment including NYHA functional class;treadmill exercise tolerance; resting cardiac index; andleft cineventriculography for the assessment of ven-tricular size, contraction pattern, and, when possible,the measurement of end-diastolic volume and ejectionfraction. Left ventricular end-diastolic pressure was notincluded in these criteria because it was one of the majorvariables to be observed during isometric exercise. Thepatient classification with a distribution of NYHA func-tional class and exercise tolerance is shown in Table i.

The I4 subjects in whom all of the above criteria werenormal (group I) included 5 subjects with no demon-strable cardiac disease and 3 each with mild pulmonarystenosis, small interventricular septal defect (less thanI 5 to I o shunt), and interatrial septal defect. Twelvepatients with predominant or isolated mitral stenosis(group II) were classified separately because of the in-herent difficulty in assessing left ventricular functionwith this lesion. The remaining 46 subjects in whomone or more of these criteria were abnormal (group III)included I5 patients with left ventricular disease (9 withcoronary atherosclerotic disease and 6 with nonobstruc-tive cardiomyopathy), 14 with volume loading due tovalvular regurgitation (9 with aortic regurgitation, 4 withmitral regurgitation, and i with combined aortic andmitral regurgitation), and I7 patients with miscellaneouslesions, including 6 patients with mixed stenotic andregurgitant valvular lesions and 3 with hypertrophicobstructive cardiomyopathy (idiopathic hypertrophicsubaortic stenosis).

Cardiac catheterizationThe patients were studied in a fasted state and withoutpremedication. Patients who had been receiving digitalis

and/or diuretics received their usual medications on theday before study. A single patient with obstructivecardiomyopathy was receiving propranolol and none ofthe patients was receiving antiarrhythmic agents. Diag-nostic right and left heart catheterization at rest wascompleted before handgrip testing. In the io patientsstudied primarily to evaluate coronary artery anatomy,parenteral atropine sulphate and sublingual nitrogly-cerin were given before multiple selective coronaryartery injections. A minimum of 30 minutes recoverywas allowed between the final coronary injection andhandgrip exercise testing. Other angiographic studieswere performed after the exercise. Intracardiac and vas-cular pressures were recorded through saline-filledcatheters using Statham 23Db strain gauges and aphotographic recorder (Electronics for Medicine, ModelDR-i2). Cardiac outputs were measured by indicatordilution (Cardiogreen dye) or the Fick technique usingstandard procedures. Monoplane ventricular volumesand ejection fraction were calculated from left cine-ventriculograms by the method of Kennedy, Trenholme,and Kasser (1970).

Isometric handgrip testingDuring preparatory phases of the catheterization pro-cedure the patients' maximal voluntary handgrip con-traction was determined with a calibrated spring-typedynamometer. The arm, usually the left, not employedfor catheter placement was used for handgrip testing.After control recordings of intracardiac pressures andelectrocardiogram were obtained, the patient was askedto sustain either 25 per cent maximal voluntary handgripcontraction for five minutes (46 tests) or 75 per cent forone minute (57 tests). Thirty-one patients performedboth 25 and 75 per cent maximal tests with at least I0minutes of recovery time allowed between contractions.The patients were encouraged to maintain normal res-piration and were observed in order to detect the per-formance of a simultaneous Valsalva manoeuvre. Cardiacoutput was measured during the third to fifth minutesof 25 per cent maximal voluntary contraction tests.Control determination of cardiac output was performedimmediately before the 25 per cent test. Peak haemo-dynamic responses were measured for both 25 and 75per cent tests.



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424 Fisher, Nutter, Jacobs, and Schlant

TABLE 2 Heart rate and pressure responses to isometric handgrip exercise

Group Heart rate Mean pulmonary arterial pressure Systemic systolic pressure

No. Rest IHE A No. Rest IHE A No. Rest IHE A

I: Normals I4 82 I07 + 25t I4 I7.I 19-7 + 2.6t I4 I24 I50 + 26t(±i5) (±24) (±4-o) (±5-2) (±22) (±30)

II: Mitral stenosis I2 88 96 +8t 6 37-5 45 5 + 80ot 12 120 I34 + 4t(±20) (±20) (I3-8) (± I6-7) (±20) (±26)

III: AbnormalLVfunctionMyocardial i5 85 98 + I3t 8 31.9 39.2 +7 3t I5 1I5 I36 +2It

disease (± I2) (± I4) (± I6-9) (±+ I77) (±i6) (±20)Volume I4 82 99 +17t I3 25-5 31.5 + 6-ot I4 I30 I49 + i9t

overload (±8) (±iI) (±+4-9) (±s5-2) (±29) (±28)Miscellaneous I7 80 Ioo +20t I3 22.3 29.7 +7 4t 17 I40 i68 +28t

(±20) (±23) (±8-7) (±1"-9) (±34) (±37)Total group III 46 82 99 +I7t 34 25-8 32.6 +6-8t 46 I29 I52 +23t

(±I5) (±I7) (±13-5) (±14-7) (±29) (±32)

Total patients 72 83 100 + 17t 54 24-8 30°7 +5 9t 72 I22 I45 +23t

IHE =Maximal value during isometric handgrip exercise; values in parentheses are one standard deviation.t P<o05.

TABLE 3 Clinical and haemodynamic data from patients with abnormal LVfunction and normal restingLV end-diastolic pressure (Group IIIA)

Response to IHE Cardiac diagnosis Age NYHA Treadmill Cardiac(yr) functional duration* index

class (min) (I.1minIm2)

Abnormal (raised LV i: Cardiomyopathy (non-obstructive) 3I II I0-3 4-I0end-diastolic pressure)

2: Rheumatic heart disease (aortic regurg., mild mitral 53 III 9 ° I.77stenosis)

3: Rheumatic heart disease (aortic and mitral regurg., 34 III 8-o i-6omitral stenosis)

4: Rheumatic heart disease (mitral regurg.) 58 III I-02

Normal (little or no 5: Rheumatic heart disease (mitral regurg., stenosis) 21 II 3'50change in LV end- 6: Rheumatic heart disease (aortic regurg., mild mitral 29 II 7-8 4-43diastolic pressure) stenosis)

7: Rheumatic heart disease (mitral regurg., and stenosis) 63 III 3-0 21I2

8: Post-repair gunshot wound of LV 37 II 90° I.97

9 Traumatic mitral regurgitation 40 II 90° 2.64I0: Idiopathic aortic regurgitation 25 I g-o 2-40iI: Coronary atherosclerotic heart disease (angina) 48 III 6-o 2.5I

12: Coronary atherosclerotic heart disease (angina) 40 III 5-8 2.3I

I3: Essential hypertension and interatrial septal defect 67 III - 2VI0

IHE= Isometric handgrip exercise.* Maximal exercise duration score.EDV= end-diastolic volume index (ml/m2).EF= ejection fraction.



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LV end-diastolic pressure

No. Rest IHE /

5 9-0 8-2 -o-8(±6-5) (±7-2)

12 9-8 9-9 +01I(±4-5) (±5-8)

13 20-8 30-9 + IO-it(±1+0-3) (± I3 4)

I0 I9-I 25.7 +66t(±12-6) (±I44)

I3 I4.8 19-5 +417t(±8-4 (±io-8)

36 I8-2 25.3 +7-It(± I0-4) (± I3 4)

53 15.4 20-2 +4-8t

LV end-diastolic Left cineventriculographypressure (mmHg)

Chamber size Contraction patternRest IHE

4 35 Enlarged(EDV I62)

8 I9 Enlarged(EDV 172)

7 I7 Enlarged(EDV I04)

II i8 Enlarged(EDV 135)

7 5 Normal8 7 Normal

10 II Enlarged(EDV I02)

3 5 Normal

7 I0 Normal9 I I Normal10 II Normal

(EDV 65)I2 II Normal

(EDV go)8 I0 Normal

Hypokinetic (EF 0-37)


Normal (EF o067)

Normal (EF 0-58)

NormalNormal


Localized akineticarea

NormalNormalNormal (EF 0o75)

Normal (EF 0o59)

Normal

Treadmill exercise testingDynamic exercise testing was performed on a treadmillusing three-minute stages of progressive, graded activityand the total exercise time (Treadmill Duration Score)was recorded. Scalar Frank lead orthogonal electro-cardiograms were continuously recorded. Arterial bloodpressure was recorded by sphygmomanometry immedi-ately at the conclusion of each stage, and oxygen con-sumption was determined during the final minute ofeach stage using a Douglas bag and Beckman 02 andinfrared CO2 analysers.

ResultsThe patients were in general able to sustain a 25per cent maximal test for five minutes but somecould sustain only a 50-60 per cent maximal volun-tary contraction for one minute during the attempted75 per cent test. The isometric contraction did notinterfere with continuous haemodynamic monitor-ing. Occasional premature ventricular contractionswere noted, but no other dysrhythmias or complica-tions occurred during or immediately after isometrichandgrip exercise.

Peak haemodynamic responses were generallyseen at or near the completion of the exercise test.Maximal heart rate, mean pulmonary arterial pres-sure, and systemic systolic arterial pressure re-sponses during isometric exercising were similar forboth 25 per cent (5 min) and 75 per cent maximalvoluntary contraction (i min) testing. Peak heartrate increased by I4 beats a minute during 25 percent maximal voluntary contraction (mean responsefrom 84-98 beats a minute) and by i8 beats a minuteduring 75 per cent maximal voluntary contraction(85-I02). Mean pulmonary artery pressure increasedby 5-9 mmHg (24-9-30-8 mmHg) and by 7-3mmHg (25 2-32.6); and systolic arterial pressureincreased by 24 mmHg (I25-I49) and by 26 mmHg(I23-I49) during 25 and 75 per cent maximal con-traction, respectively. The isometric contractionexercise values for all of these variables differedsignificantly from control when tested with a pairedt test. The haemodynamic results are therefore ex-pressed as pooled values from both levels of testing.Only the data from a 75 per cent maximal voluntarycontraction were selected in those patients perform-ing both 25 and 75 per cent maximal contractiontests. Systemic arterial pressure is expressed as sys-tolic pressure because aortic pressures were notsimultaneously recorded in patients in whom leftventricular systolic and diastolic pressures werebeing recorded. In contrast to dynamic exercise,during which diastolic pressure remains relativelyunchanged, the 22 patients in whom aortic pressureswere measured during isometric handgrip exercisedemonstrated equivalent increases in systolic, dias-



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MITRALSTENOSISMIRLABNORMAL LV FUNCTION

ALVEDP (12 J|LVEDP )12

40-

30-

20-

-* ~~~~~~~~~~~~~~~~P(.0O1

R IHE R IHE R IHE R IHE

FIG. Individual responses of left ventricular end-diastolic pressure (LVEDP) to isometrichandgrip are shown for patients with normal and abnormal left ventricular function (see text fordefinitions) and with mitral stenosis. The two patients groups on the right-hand side had abnormalleft ventricular function and are divided according to the presence of normal ( <1r2 mmHg) or

abnormal ( >12 mmHg) LVED pressures at rest. R = resting control LVEDP; IHE= maximalLVEDP value during isometric handgrip exercise. The heavy horizontal bars represent the meanchange in LVEDP for each group and the heavy vertical bars represent ± one standarddeviation.

tolic, and mean aortic pressure. Mean aortic pressureincreased by 22 mmHg (96 to i i8 mmHg) in thesepatients.The resting and maximum values during isometric

handgrip exercise for heart rate, mean pulmonaryartery pressure, systolic arterial pressure, and LVend-diastolic pressure are given for the variouspatient groups in Table 2. Resting values for heartrate and systolic arterial pressure were the same fornormal and abnormal groups. Isometric handgrip

exercise resulted in significant increases of thesevariables in all groups. Mean heart rate increasedby 31 per cent in normals, by 2I per cent in patientswith abnormal left ventricular function, and by 9

per cent in patients with mitral stenosis. In themitral stenosis group, 2 patients with chronic atrialfibrillation showed 25 and 33 per cent increases inventricular rate during isometric handgrip exercise,whereas a single patient with atrial flutter did notincrease ventricular rate. Systolic arterial pressure

TABLE 4 Clinical and haemodynamic data from patients in groups I and II with raised resting LVend-diastolic pressure

Group Cardiac diagnosis Age NYHA Treadmill Cardiac(yr) functional duration index

class (min)

I: Normal LV func- Atypical chest pain with normal coronary arteriography 39 I I3-5 3-19tion Small interventricular septal defect i6 I 15-7 2-58

II: Mitral stenosis Rheumatic heart disease (mitral stenosis, mild aortic 28 III 3.66regurg.)

Rheumatic heart disease (mitral stenosis, mild mitral 6o III 3-2 2-60regurg.)

Rheumatic heart disease (mitral stenosis, mild aortic 23 III 6-2 2o00regurg.)

NORMAL LVFUNCTION

LVEDF

mmHg



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similarly showed a 2I per cent rise in normals, anI8 per cent rise in patients with abnormal left ven-tricular function, and a I2 per cent rise in mitralstenosis. The mean pulmonary arterial pressure atrest was raised in all abnormal groups and was high-est in patients with mitral stenosis. A small but sig-nificant increase in pulmonary arterial pressure(IS5%) occurred in normal subjects. All abnormalgroups showed larger and roughly equivalent rises inpulmonary artery pressure (26%) with isometrichandgrip exercise. The average LV end-diastolicpressure at rest in 5 subjects with normal cardiacfunction and in patients with predominent mitralstenosis was normal. In these groups end-diastolicpressure did not significantly increase during iso-metric handgrip exercise. In patients with abnormalleft ventricular function the average LV end-dias-tolic pressure was raised at rest and showed a sig-nificant increase during isometric handgrip exercise.The behaviour of LV end-diastolic pressure inindividual patients during exercise is graphicallyillustrated in the Figure. Here patients classified ashaving abnormal LV function (group III) are sub-divided on the basis of the resting LV end-diastolicpressure in order to show the several patterns ofresponse seen during isometric handgrip exercise.The patients in group IIIA (normal resting LVend-diastolic pressure) showed 2 distinct patternsof response (Table 3): 4 patients showed obviousincreases in LV end-diastolic pressure to clearlyabnormal levels during isometric handgrip exercise,whereas 9 patients showed little or no change inend-diastolic pressure. Patients in group IIIB (ab-normal resting LV end-diastolic pressure) had rela-tively consistent increases in these pressures duringhandgrip. Unexpectedly, two of the patients whofulfilled all of our criteria for normal LV function(group I) had a raised LV end-diastolic pressure as

LV end-diastolic pressure Left cineventriculography

Rest IHE Chamber size Contraction pattern

17 I9 Normal NormalI5 I0 Normal Normal

20 19 Normal Hypokinetic

I4 I3 Normal Normal

I 5 I 8 Normal Hypokinetic

an isolated, unexplained abnormality. Three pa-tients with predominant mitral stenosis (group II)also had a raised resting LV end-diastolic pressure.The clinical and haemodynamic features of these 5patients are summarized in Table 4.The effects of isometric handgrip exercise on

stroke volume, cardiac output, cardiac index, andtotal peripheral and pulmonary resistances areshown in Table S. The S normal subjects in whomcardiac output determinations were recorded duringisometric handgrip exercise did not include the twopatients with abnormal resting LV end-diastolicpressure. In this normal group the average restingstroke volume and cardiac output were higher andtotal systemic and pulmonary resistance lower thanin patients with mitral stenosis or abnormal leftventricular function. In all patient groups isometrichandgrip exercise had an inconsistent effect onstroke volume, cardiac output, and total resistances.This variability was noted in data derived from bothindicator dilution and Fick methods. In the 5 nor-mal subjects stroke volume increased in 3 and car-diac output increased in 4; while in 23 abnormalsstroke volume increased in I2 and cardiac outputincreased in I9. In 7 patients in the mitral stenosisgroup, cardiac output increased in 6 while strokevolume increased in 4. In 5 normal subjects totalperipheral resistance rose in 3 and fell in 2 whiletotal pulmonary resistance rose in 4 and fell in one.In the I9 abnormal subjects total peripheral resist-ance rose in I2 and fell in 7 patients, while pulmon-ary resistance rose in 7, fell in II, and remainedunchanged in 2. The average response in all sub-jects studied was a small increase in stroke volume(5%), a modest but significant increase in cardiacoutput (I8%) (due mainly to the increased heartrate), and essentially no change in total peripheralresistance or total pulmonary resistance.The effect of isometric handgrip exercise upon

the mean mitral diastolic pressure gradient wasdetermined in IO patients with mitral stenosis. Themean diastolic gradient was I4'3 mmHg at rest andincreased to I7-6 mmHg (23%, P<o.oi) duringisometric handgrip exercise.

Isometric and treadmill testingTable 6 presents the mean product of systolic pres-sure and heart rate(HP.SP) duringsubmaximal tread-mill exercise for 50 patients and during isometrichandgrip exercise for all 72 patients. Oxygen con-sumption and the duration of treadmill exercise is in-dicated for two levels oftreadmill activity. There wasa significant difference in the duration of treadmillexercise, maximal oxygen consumption, and HRSPindex between the normal and abnormal groupsduring maximal treadmill exercise. When the same



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TABLE S Cardiac output and vascular resistance responses to isometric handgrip exercise

Patient group Stroke volume Cardiac output Cardiac index

No. Rest IHE A No. Rest IHE A No. Rest IHE A

I: Normals 5 69 79 +I0 5 6-65 8-34 +i69 5 3-33 4.I3 +o-8o(± I5) (±38) (± I-76) (±3-8I) (±PI3) (± I-97)

II: Mitral stenosis 7 56 62 +6 7 4-36 5-26 +0-90* 7 2-76 3-35 +0-59*(±i8) (±22) (± I-09) (±I-58) (±0+7o) (± i-i8)

III: Abnormal LV 23 59 59 0 23 4-52 5.i8 +o-66* 23 2-50 2-88 + 0-38*function (±33) (±3') (±i-66) (±2-08) (±o089) (± I-15)

Total patients 35 59 62 +3 35 4-80 5.66 +o-86* 35 2-67 3.I4 +0.47*

* P<o os.

TABLE 6 Isometric handgrip exercise and treadmill exercise

Group IHE Treadmill - stage II Treadmillduration

HRSP index (x IO3) HRSP index (x Io3) qO2 (min)

No. Rest Peak A No. Rest Peak Aexercise exercise

I: Normals I4 I0-4 i6-i +5 7 6 9-4 22-2 + I2-8 I5.9 6-oII: Mitral stenosis I2 I0*4 13.0 +2-6 5 I2-2 214 +9-2 I6-i 6-o

III: AbnormalLVfunctionMyocardial disease I5 IO,I I3.7 +3-6 7 10-5 22-2 + II-7 15-0 6-oVolume overload I4 I0-2 14.3 +4.I 6 9-9 24.3 + I4-4 I5 8 6-oMiscellaneous I7 II*I I6.3 +5-2 8 I0-0 I9-5 +9-5 I6.7 6-oTotal group III 46 io-6 I5-I +4-5 2I IO-I 2I-8 + II-7 I5-8 6-o

Total patients 72 IO-I I4-5 +4 4 32 I0-3 2I-8 + II-5 I5-9 6-o

HR-SP index=(heart rate) (systemic systolic pressure); qO2=maximal oxygen consumption (ml/kg/min).

level of moderate treadmill exercise (stage II, 6minutes) is compared, however, there was no differ-ence between the normal or abnormal groups interms of oxygen consumption or HR-SP index.There was also little difference in the HR-SP indexof normal and abnormal groups at rest and duringisometric exercise, though the HR-SP index in mit-ral stenosis patients was somewhat less than in otherpatients during both types of exercise. The averageHRSP index increase for all patients during iso-metric handgrip exercise (4 4 x i03) was, however,much less than that observed during a moderatelevel of treadmill exercise (II .5 x Io3).

DiscussionThe reflex circulatory adjustments previously de-scribed with isometric (static) exercise in normalsubjects were readily elicited in the present investi-gation during isometric handgrip exercise in patients

with both normal and abnormal left ventricularfunction. In both normal and abnormal patientgroups isometric handgrip resulted in significantincreases of heart rate and systemic arterial pressure.The patients with normal LV function had thelargest responses in rate and systemic pressure,similar in magnitude to those reported in normalyoung subjects (Tuttle and Horvath, I957; Lind etal., i964; Freyschuss, I970) and in the normalpatient group described by Helfant et al. (I97I).Two levels of static exercise (75% maximal volun-

tary contraction held for one minute and 25%held for five minutes) were chosen for study because:(a) contractions greater than I5 per cent maximalvoluntary contraction are known to cause progres-sive haemodynamic changes to the point of fatigue(Donald et al., i967); (b) the chosen durationsapproximate the points of fatigue; (c) cardiac outputdeterminations could be performed during the five-minute 25 per cent maximal voluntary contraction



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Total systemic resistance Total pulmonary resistance

No. Rest IHE A No. Rest IHE A

5 I7-6 I7.8 +0-2 5 2 4 2-5 +01I(±6-8) (± II-8) (±0+4) (±0+9)

2 I8-6 23-6 +5-0 4 I2-1 I2-8 +0-7

I9 22.4 23I +°07 2I 7T5 7.6 +O-I(±8-9) (±8-8) (±5-5) (±5-3)

26 2I-2 22-2 + I-0 30 7-3 7.5 +0-2

Treadmill - maximumTreadmill

HR-SP index (x ro3) qO2 duration

No. Rest Exercise A

I0 91I 30-2 +2I-I 30.6 I21I9 III 20-4 +9-3 I6-8 5-8

I0 I0-7 25.2 + I4.5 17-4 7.3I0 I0-0 231I + I3-1 I8-4 7-0II I0-0 23.6 + I4-4 I7.0 6-93I 10-2 24-0 + I3 7 I7.6 7.I

50 I0-2 24.6 + I4-4 I9-8 7.8

tests; and (d) possible qualitative or quantitativedifferences in the haemodynamic responses couldbe observed. Haemodynamic changes developedmuch more slowly during 25 per cent maximalvoluntary contraction tests, but the average peakheart rate and blood pressure responses were similarto the peak responses during 75 per cent contractiontests. These findings are compatible with studiesin normal subjects which have shown that the rateof development of haemodynamic changes dependson the relative strength of contraction (% maximal

voluntary contraction) and that similar peak bloodpressure responses may occur when contractions ofvarying intensity are held to fatigue (Lind andMcNicol, I967b).

All I4 patients in the normal group responded toisometric handgrip exercise in a consistent manner,but several patients in the abnormal groups showedlittle or no increase in rate or systemic pressure.These poor responses may be due to several factors:

(a) the failure of the patient to co-operate in per-forming a true maximal voluntary contraction couldlead to the subsequent performance of a contractionthat represented a very low percentage of the truemaximal contraction strength; (b) though only afew of these subjects received atropine premedica-tion, many were taking digitalis and/or diuretics,which might alter the isometric cardiovascularreflex; (c) some component(s) of the reflex may bedepressed in the presence of cardiac failure. Thelatter two explanations appear more reasonablesince Lind and McNicol (I967b) showed thatmodest increases in rate and pressure occur with aslittle as io per cent maximal voluntary contractionstatic exercise in normal subjects. There was noapparent correlation between the absolute magni-tude of the handgrip contraction and the haemo-dynamic responses either in this study or in normalsubjects (Freyschuss, 1970). Review of recent re-ports (Helfant et al., 197I; Kivowitz et al., I971)confirms our observation that some patients withheart disease fail to increase heart rate or bloodpressure during isometric exercise.

Patients with predominant or isolated mitralstenosis responded to exercise in a distinctive man-ner. The heart rate and blood pressure responseswere attenuated during both isometric handgripexercise and dynamic exercise (see Table 6). Thus,in patients with mitral stenosis left ventricular stressis limited during handgrip exercise. It does cause amodest increase in the mitral diastolic gradient.The small increase in stroke volume and the in-

crease in heart rate during 25 per cent maximalvoluntary contraction isometric testing produced amodest increase in cardiac output in all patientgroups. This suggests that both heart rate and aug-mented cardiac sympathetic activity play a role inincreasing the cardiac output. Studies by Freyschuss(I970) suggest that the increased heart rate is re-lated to a withdrawal of vagal inhibition. Earlierstudies in normal subjects also showed an increasein cardiac output due to an increase in heart ratewith little change in stroke volume (Donald et al.,I967; MacDonald et al., I966). The patients withheart disease reported in this study, and those re-ported by Helfant et al. (I97i) and Kivowitz et al.(I97I) also demonstrate inconsistent changes incardiac output and stroke volume. Individual re-sponses in cardiac output observed in these studiesshould be interpreted cautiously since isometricexercise greater than I5 per cent maximal voluntarycontraction causes non-steady state haemodynamics,limiting the validity of cardiac output calculation byeither Fick or indicator dilution techniques. Thismay explain the observed variation in the directionand magnitude of stroke volume and cardiac output



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changes despite reasonably consistent increases inheart rate.Lind et al. (I964) and MacDonald et al. (I966)

showed that in normal young subjects calculatedtotal peripheral resistance is relatively unaffectedduring isometric handgrip exercise. Some investi-gations of the isometric cardiovascular reflexmechanism have suggested that the increase in sys-temic arterial pressure is in part due to increasedalpha-adrenergic activity in addition to the increasein cardiac output (Freychuss, 1970). In our patientswith heart disease the changes in total systemic andpulmonary resistance were quite variable. Furtherdata on handgrip exercise-induced changes in sys-temic resistance are reported by Kivowitz et al.(I97I) and can be calculated from systolic pressureand cardiac output data reported by Helfant et al.(I97I). Compared to our patients, the averagechange (increase) in systemic resistance was greater,but these patients also showed considerable indi-vidual variation in the magnitude and direction ofchange. The individual variability in resistance cal-culations may in part be due to the problem ofaccurately measuring cardiac output. Several factorsappear to contribute to the pressor response ob-served during isometric handgrip exercise, and inthis context Lind and McNicol (I967b) have pro-posed that any available mechanism will be em-ployed to increase the perfusion pressure and bloodflow to a muscle group undergoing sustained con-traction. It is probable that arterial resistance is in-creased in many vascular beds, including the con-tracting muscles, inactive muscles, and skin, whileresistance is decreased in other vascular beds, as yetpoorly defined.An abnormal LV end-diastolic pressure may re-

present either raised end-diastolic volume, decreasedmyocardial compliance, or a combination of thesefactors. When these conditions are present an in-crease in aortic pressure usually evokes or accentu-ates the abnormal increase in LV end-diastolic pres-sure (Ross and Braunwald, I964; Linhart et al.,I969).

Isometric haemodynamic exercise causes little orno change in LV end-diastolic pressure in normalsubjects. Direct LV end-diastolic pressure measure-ments were available in only 5 of the 14 patients whofulfilled our criteria for normal LV function, and inthis group average LV end-diastolic pressure wasunchanged during isometric handgrip exercise. Pul-monary artery mean and diastolic pressures recordedin all normal subjects increased only slightly, con-firming that left ventricular filling pressure is mini-mally affected during isometric handgrip exercise.In addition, the 9 normal subjects reported by Hel-fant et al. (197I) had an average increase in LV

end-diastolic pressure of only 2 mmHg during iso-metric handgrip pressure. Krayenbuehl et al. (I972)also reported a 2 mmHg average increase in end-diastolic pressure in I3 patients described as havinglittle or no left ventricular loading. Furthermore,these 13 patients had evidence of increased contrac-tility during exercise. Of interest are the end-dias-tolic pressure responses seen during isometric hand-grip exercise in our 2 patients who had a raisedresting end-diastolic pressure as an isolated, un-explained abnormality (Table 4, group I). LV end-diastolic pressure increased only 2 mmHg in one ofthese patients and decreased to normal in the otherpatient, suggesting that LV function was normalor only minimally impaired.

In patients with mitral stenosis LV end-diastolicpressure did not change significantly though theirleft atrial and pulmonary arterial pressures increased.The 3 patients with mitral stenosis with raised rest-ing LV end-diastolic pressure (shown in group IIof the Figure and Table 4) presumably had LVdysfunction or abnormal compliance, possible dueto healed rheumatic myocarditis or other unknownfactors, since the degree of associated valvular re-gurgitation was minor. Even in these 3 patients,isometric handgrip exercise did not significantlyincrease LV end-diastolic pressure.

Patients classified as having abnormal left ven-tricular function (group III) significantly increasedboth LV end-diastolic and pulmonary arterial pres-sures during handgrip. In these patients the increasein the latter during isometric handgrip exerciseappears to result primarily from an increase in leftatrial pressure, though minor changes may alsooccur as a result of increased pulmonary blood flow.Patients classified as having abnormal LV function,but with normal resting LV end-diastolic pressure(group IIIA in the Figure and Table 3) showed twopatterns of response to isometric exercise. Fourpatients (I-4) increased LV end-diastolic pressureto distinctly abnormal levels, while 9 patients (5-I3)showed little or no change. The type of responseappears to correlate best with the LV angiographicfindings (Table 3). Two patients (3 and 4) withabnormal LV end-diastolic pressures during iso-metric handgrip exercise had normal ejection frac-tions from enlarged left ventricles; however, eachof these patients also had severe valvular regurgita-tion which should be exaggerated by the increasedafterload during handgrip. There were 2 patients(7 and 8) with normal left ventricular end-diastolicpressures at rest and during isometric handgripexercise, who had abnormal ventricular contractionpatterns. Case 7 had significant mitral stenosis whichappears to limit LV stress during exercise. Case 8showed a vigorous and normal LV contraction pat-



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tern except for the localized area of previous surgicalrepair. Patients with abnormal LV function and anabnormal resting LV end-diastolic pressure (groupIIIB in Figure) significantly increased end-diastolicpressure during handgrip. Three of these patientswere exceptions to this rule: in one, the systemicpressure failed to rise during exercise and the othertwo had clinical and ventriculography data suggest-ing left ventricular infarction (one) and hypertrophy(one), but did not have cardiac failure or ventriculardysfunction. In these patients the abnormal restingend-diastolic pressure may be explained on the basisof a decrease in ventricular compliance though thefailure further to increase LV end-diastolic pressureduring a systemic pressor stress remains un-explained.The LV end-diastolic pressure responses de-

scribed above are quite comparable to the responsesreported by Helfant et al. (197I), Kivowitz et al.(I97i), and Krayenbuehl et al. (1972). Of particularinterest, among the 74 patients described by thesethree groups, there were 5 patients in whom LVend-diastolic pressure was normal at rest but in-creased to distinctly abnormal levels during hand-grip exercise. This type of response, also seen in 4of our patients, suggests that the exercise may be auseful stress test during cardiac catheterization, par-ticularly in patients with suspected ventricular dys-function in whom resting LV end-diastolic pressureis normal or borderline raised.

It, therefore, appears that if one excludes patientswith significant mitral stenosis, an abnormal LVend-diastolic pressure can be elicited or accentu-ated by isometric handgrip in patients with dys-function or decreased compliance of the left ven-tricle. A significant increase in LV end-diastolicpressure during isometric handgrip exercise seemedto correlate best with angiographic evidence of ven-tricular dysfunction. These direct haemodynamicdata and similar findings from other investigators(Helfant et al., I97I; Kivowitz et al., I971; Krayen-buehl et al., 1972; Mullins et al., I970) support thework from our laboratory showing that isometrichandgrip exercise can selectively provoke or accen-tuate gallop sounds and abnormal apical diastolicpulsations in patients with left ventricular disease(Siegel et al., I972). Our studies have shown that theexercise can easily be performed at the bedside orin the graphics laboratory as a stress test for thedetection of ventricular dysfunction.The haemodynamic data from this study clearly

show that the heart rate, cardiac output, and HR-SPindex responses to submaximal isometric handgripexercise are smaller than the increase in these vari-ables during submaximal dynamic (treadmill) exer-cise. We have also previously shown the same rela-

tion when the HRSP index is calculated duringmaximal treadmill exercise and during a maximalvoluntary isometric contraction (Siegel et al., 1972).The application of isometric handgrip exercise forcardiac stress testing does have the advantage ofproducing a conspicuous increase in both systolicand diastolic systemic pressure. Furthermore, iso-metric handgrip exercise can be performed in a re-producible, graded manner in the supine patientwhile permitting the continuous recording of physi-cal, phonocardiographic, and haemodynamic data.Peak responses can be readily elicited in one minuteusing a 75 per cent maximal voluntary contractiontest.

Significant arrhythmias or other complicationswere not encountered during the performance ofthese I03 handgrip tests in 72 patients, many ofwhom had cardiac failure and myocardial disease.Since the induction of angina pectoris and ventricu-lar arrhythmias has been reported during isometrichandgrip exercises (Siegel et al., I972; Matthews etal., 1971), certain precautions are necessary for itssafe application. The electrocardiogram should becontinuously monitored and isometric handgripexercises terminated if angina pectoris or rhythmdisturbances develop. The nature of the haemo-dynamic responses elicited during isometric hand-grip exercises suggests that this exercise testing orthe spontaneous performance of significant iso-metric stress is best avoided in patients with recentmyocardial infarction, severe systemic hypertension,significant cerebral vascular disease, or recurrentcardiac dysrhythmias.

The authors wish to express gratitude for the treadmillexercise testing performed in The Cardiac FunctionLaboratory under the supervision of Dr. Charles A.Gilbert, and for the technical assistance provided in theCardiac Catheterization Laboratory by Miss CarolynMears, Mrs. Dorothy Brewer, R.N., and Mrs. HarrietteMatthews.

ReferencesBruce, R. A., Blackmon, J. R., Jones, J. W., and Strait, G.

(I963). Exercise testing in adult normal subjects and car-diac patients. Pediatrics, 32, 742.

Donald, K. W., Lind, A. R., McNicol, G. W., Humphreys,P. W., Taylor, S. H., and Staunton, H. P. (I967). Cardio-vascular responses to sustained (static) contractions.Circulation Research, 20, SuppI. I, 15.

Fisher, M., Nutter, D., and Schlant, R. (I97i). Hemodynamicevaluation of isometric exercise testing in cardiac patients(abstract). Circulation, 44, Suppl. II, 50.

Freyschuss, U. (I970). Cardiovascular adjustment to somato-motor activation. Acta Physiologica Scandinavica, 79,Suppl. 342, I-63.

Helfant, R. H., deVilla, M. A., and Meister, S. G. (I97I).Effect of sustained isometric handgrip exercise on leftventricular performance. Circulation, 44, 982.



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Kennedy, J. W., Trenholme, S. E., and Kasser, I. S. (I970).Left ventricular volume and mass from single-plane cine-angiocardiogram. A comparison of anteroposterior andright anterior oblique methods. American Heart J7ournal,8o, 343.

Kivowitz, C., Parmley, W. W., Donoso, R., Marcus, H.,Ganz, W., and Swan, H. J. C. (I97I). Effects of isometricexercise on cardiac performance: the grip test. Circulation,44, 994.

Krayenbuehl, H. P., Rutishauser, W., Schoenbech, M., andAmende, I. (1972). Evaluation of left ventricular functionfrom isovolumic pressure measurements during isometricexercise. American3Journal of Cardiology, 29, 323.

Lind, A. R., and McNicol, G. W. (I967a). Circulatory re-sponses to sustained hand-grip contractions performedduring other exercise, both rhythmic and static. Journal ofPhysiology, 192, 595.

Lind, A. R., and McNicol, G. W. (I967b). Muscular factorswhich determine the cardiovascular response to sustainedand rhythmic exercise. Canadian Medical AssociationJournal, 96, 706.

Lind, A. R., Taylor, S. H., Humphreys, P. W., Kennelly,B. M., and Donald, K. W. (I964). Circulatory effects ofsustained voluntary muscle contraction. Clinical Science,27, 229.

Linhart, J. W., Hildner, F. J., Barold, S. S., and Samet, P.(I969). Myocardial function in patients with coronaryartery disease. American Journal of Cardiology, 23, 379.

MacDonald, H. R., Sapru, R. P., Taylor, S. H., and Donald,K. W. (I966). The effect of intravenous propranolol onthe systemic circulatory response to sustained handgrip.American Journal of Cardiology, I8, 333.

Matthews, 0. A., Atkins, J. M., Houston, J. D., Blomqvist,G., and Mullins, C. B. (I97i). Arrhythmias induced byisometric exercise (handgrip) (abstract). Clinical Research,19, 23.

Mullins, C. B., Leshin, S. J., Mierzwiak, D. S., Matthews,0. A., and Blomqvist, G. (I970). Sustained forearm con-traction (hand-grip) as a stress test for evaluation of leftventricular function (abstract). Clinical Research, I8, 322.

Ross, J., Jr., and Braunwald, E. (I964). The study of left ven-tricular function in man by increasing resistance to ven-tricular ejection with angiotensin. Circulation, 29, 739.

Siegel, W., Gilbert, C. A., Nutter, D. 0., Schlant, R. C., andHurst, J. W. (I972). The use of isometric handgrip for theindirect assessment of left ventricular function in patientswith coronary atherosclerotic heart disease. AmericanJ7ournal of Cardiology, 30, 48.

Tuttle, W. W., and Horvath, S. M. (I957). Comparison ofeffects of static and dynamic work on blood pressure andheart rate. Journal of Applied Physiology, 10, 294.

Requests for reprints to Dr. Donald 0. Nutter, EmoryUniversity School of Medicine, Thomas K. GlennMemorial Building, 69 Butler Street, S.E., Atlanta,Georgia 30303, U.S.A.



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