Comparison of metabolic, ventilatory, and neurohumoral responses during light forearm isometric exercise and isotonic exercise in congestive heart failure

Comparison of Metabolic, Ventilatory, and Neurohumoral Responses During Light Forearm Isometric Exercise and Isotonic Exercise in Congestive Heart Failure Guy

A. MacGowan, Susan Loftus,

MB, MRCPI, Srinivas Murali, RN, and Barry F. Uretsky, MD

MD,

Maximal treadmill exercise responses were compared with light forearm isometric exercise responses in patients with chronic, stable heart failure (n = 14, and normal sedentary controls (n = 11). isometric exercise was performed to exhaustion with 25% of maximal voluntary contraction. Gas-exchange analysis was used to determine oxygen consumption (VO ), carbon dioxide production (VCO,), and minute vent&ion (VE) during exercise. Significant correlations were observed in normal controls, but not in patients with heart failure, between peak isotonic exercise and peak isometric exercise for VO, (r = 0.75, p = 0.001) and VCO, isoton(r = 0.67, p <0.03), and between submaximal ic exercise (SO% of peak) and peak isometric exercise for VO, (r = 0.75, p = 0.007), VCO, (r = 0.67, p = 0.02), and VE (r = 0.71, p = 0.01). At 90 seconds after isometric exercise in both groups, significant correlations

(p eO.05) were observed with peak isotonic exercise for VE (r = 0.62 normals, and r = 0.63 heart failure). Plasma nor inephrine increased significantly (p 4.01) after To th isotonic and isometric exercise in patients with heart failure, although peak values were greater with isotonic than with isometric exercise (p = 0.01). Plasma atrial natriuretic peptide and renin activity did not change with either isotonic or isometric exercise. In conclusion, maximal isotonic exercise responses are not predictive of peak isometric VO or VCO, in Patients with heart failure. However, VE a uring maximal isotonic exercise predicts postisometric exercise ventilation in both normals and patients with heart failure; this ma determine the extent of dysp nea that Patients wi x heart failure experience with isometric activities of daily living. (Am J Cardiol 1996;77z390-396)

he evaluation of patients with compensated congesT tive heart failure frequently necessitates exercise testing, as rest symptoms may be absent or minimal, and

ied. Twelve of these patients had idiopathic dilated cardiomyopathy, and 2 had ischemic cardiomyopathy. Ejection fraction (+ SD) determined by radionuclide angiography in patients with heart failure was 24 + 10%. Patients with significant respiratory disease, as determined by physical examination, chest roentgenography, or pulmonary function tests, were excluded. Eleven normal sedentary control subjects (3 women and 8 men, mean age 31 f 7 years) were also studied. All subjects gave signed, informed consent for the study, and this study was approved by the institutional committee on human research. Exercise tests: Maximal isotonic exercise tests were performed by using the Modified Naughton protocol for patients with heart failure.* The Bruce protocol was used for normal subjects. * Heart rate, blood pressure, and a 12-lead electrocardiogram were monitored continuously during the exercise tests. Breath-by-breath gas exchange analysis was obtained by a zirconia cell oxygen gas analyzer, and an infrared carbon dioxide gas analyzer (Medical Graphics Corporation, St. Paul, Minnesota). Ventilation was determined using a disposable, prevent pneumotach (Medical Graphics Corporation). All subjects fasted for 2 hours before the exercise test. Isometric exercise tests were performed using a calibrated hand dynamometer in both normal subjects and patients with heart failure. Maximal voluntary contraction was determined 30 minutes before the beginning of the study. The isometric tests were performed to exhaus-

resting hemodynamics may not be accurate determinants of the severity of the disease.’ Maximal isotonic trcadmill or bicycle exercise may not, however, reflect fully the daily activities of patients at home, since they would be expected to undergo isometric exercise as well when performing routine tasks. Despite this, isometric exercise testing is not routinely used during the evaluation of patients with heart failure, and it is not known whether assessing maximal isotonic exercise capacity can be used to prescribe daily activities that are isometric in nature. The purpose of this study was to compare metabolic, ventilatory, and neurohumoral responses to both maximal isotonic exercise and maximal light forearm isometric exercise in a group of patients with heart failure. METHODS Patients: Fourteen patients (I woman and 13 men, mean age + SD 48 f 10 years) with New York Heart Association class II or III heart failure, without clinical evidence of pulmonary or peripheral edema, were studFrom the Division OF Cnrdlology, Universky of Pittsburgh School of Medicine. Pittsburgh. Pennsylvania. Monuscript received Ju y 1 1 , 1995; revised mowscriot received October 10, 1995, and occep.ed October 12 Address (or reprin’s: Srinivos Muroll, MD, SS54, Scoife Hall, Unive:slty of Pittsburg5 Medical Certer, 300 lothrop Street, Pittbburgh, Pew7sylvorin 152 1 :?

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tion using 25% of maximal voluntary contraction. Heart rate, blood pressure, 1Zlead electrocardiogram, and breath-by-breath gas exchange data were collected continuously as for isotonic exercise tests. After isometric exercise tests, data were collected for 90 seconds into the postexercise period. All isometric tests were performed in the sitting position, with the shoulder adducted, and the elbow flexed 90” with forearm and wrist in a neutral position. Patients were randomly assigned to perform either the isometric or the isotonic exercise study first, and there was a l-hour rest period between the 2 tests. From the breath-by-breath gas exchange data, oxygen consumption (VO ), carbon dioxide production (VCO,), and minute vent14 ation (VE) were analyzed. Oxygen pulse was calculated by dividing VO, by heart rate. For patients with heart failure, plasma levels of norepinephrine, plasma renin activity, and atrial natriuretic peptide were determined at baseline and after isotonic and isometric exercise tests. Blood samples were drawn through an 18-gauge needle, which was inserted 30 mm-

utes before drawing the resting sample. Cannulas were placed in the arm not used for isometric testing. Assays were performed using methods previously described.“-” Statistical analysis: Repeated measures analysis of variance was used with adjusted paired t tests between individual time points to determine the significance of changes over time. Paired t tests were used to determine the significance of differences between isometric and isotonic tests for paired data. Unpaired t tests were used to compare differences between the congestive heart failure and control groups. Linear regression analysis was used to determine correlation between data derived from isometric and isotonic exercise tests. All results are given as mean + SD, and a p value co.05 was considered significant. RESULTS Isotonic exercise tests (Tables I to III): The gas exchange

variables, VO,, VCO,, VE, were significantly greater at peak isotonic exercise in normal subjects than in patients with heart failure (all p 50.01). The only variable not to

Normals:

CHF: Peak

Isotonic

n

x

FIGURE 1. Top pane/s, linear regression analysis of oxygen consumption (VO,,pnl/k /min); middle panels, ca son dioxide production (VCO,; ml/min); and bottom pane/s, minute ventikAon (VE; L/min) at peak isotanic treadmill exercise with peak isometric light forearm exercise for 14 patients with congestive heart failure (CHF) and 11 normal sub+cts.

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TABLE I Heart Rate, Systolic Blood Pressure, mal Subjects and Patients With Heart Failure

and

Diastolic

Blood

Pressure

Rest HR (beats/min)

Exercise Isotonic Normal CHF Isometric Normal CHF

SBP hi

SBP

DBP [mm Hg)

(bea$min)

i 23

78 * 6 80* 10

186* 145

11 f 27’

187*24 147i33+

71*12 8Ozt15

82* 92*

16 15

115 114*

* 13 18

77 78

91 108

* 17 i 13’

144*21 136 i 28

87* 92 i

f 6 i 7

tp <0.005, normal versus CHF; ‘p ~0.05, normal versus CHF. DBP - diastolic blood pressure; HR = heart rate; SBP - systolic

and

Oxygen

Pulse

at Rest,

Peak

Exercise,

Rest

i Exercise Isotonic Normal CHF Isometric Normal CHF *p ~0.05, normal CHF - congestive

Carbon Exercise

and

Seconds

After

Exercise

in Nar-

90

blood

DBP

SBP (bea$min)

(mm ktl

10 11

lmm

41

-

-

-

75i 13 96 * 14+

128 126

* 15 i 26

86 87

i 8 +. 11

pressure.

Seconds

After

Exercise

in Normal

Subjects

and

Patients

Post

02 Pulse (VOJheart rate; ml/beat)

VO, (ml/kg/min)

4*1

3*1

38

3*1

3*1

17*6*

* 8

10*4+

3il 3*1

3*1 3*1

6i2 5*1

5i2 4*

16

02 Pulse (VOz/heart rate; ml/beat)

VOZ (ml/kg/min)

* 4

1’

-

-

3*1 3il

3*1 3*1

versus CHF; +p
Dioxide Production, in Normal Subjects

Ventilation, and the Ventilatory Equivalent and Patients With Hear+ Failure

Rest vco, (ml/min)

VE (L/min)

i 75 + 77

10*3 12 * 3

42 46

Isometric Normal CHF

228 241

ct 36 i 67

9*2 11 *2

43 * 6 46* 10

VCO,

vco, (ml/min)

VE/VCO,

252 268

versus CHF. heart failure;

for Carbon

Dioxide

at Rest,

Peak

Exercise,

Peak

Isotonic Normal CHF

‘p
90

Peak

02 Pulse (V&/heart rate; ml/beat)

Exercise

DBP (mm Hg)

(mm Hgl

llB*7 114

Consumption

and

Post

*9 * 18*

TAME II Oxygen With Heart Failure

Aher

Exercise,

81 98

vews CHF; heart foilure;

onds

Peak

Peak

(mm

‘p
TAME Ill

at Rest,

= carbon

i 7 f 8

dioxide

4,505 2,063 536 439 production;

i 1123 zt 823* * 188 i 136

CONGESTIVE

VE/VCO,

f 31 i 20’

18 *7 16 i 4

VE = minute ventilation;

change significantly from rest to peak exercise during isotonic exercise in either group was diastolic blood pressure in patients with heart failure (80 + 10 to 80 + 15 mm Hg, p = NS), although diastolic blood pressure in normal subjects decreased from rest to peak exercise (78 + 6 to 71 + 12 mm Hg, p ~0.05). Isometric exercise tests (Tables I to III): Patients with heart failure performed the isometric tests to the same intensity as normal subjects; maximal voluntary contraction was 43.4 + 14.3 kg in patients with heart failure, and 53.6 -t 14.5 kg in normal subjects (p = NS). Patients with heart failure also performed isometric exercise tests for similar durations as normal subjects; exercise duration 384 + 122 seconds in patients with heart failure, and 330 + 130 seconds in normal subjects (p = NS). VO, at peak exercise was not significantly different between the 2 groups: patients with heart failure, 5 k 1

90

Sec-

Post

VE (L/min) 121 65

and

27 33

VE (L/min)

-

-

i 3 f 7f

34 f 5 38* 10 VE/VCO,

vco, (ml/min)

= ventilatory

236 301

i 77 * 106

equivalent

VE/VCO, -

lOi 2 13 *4* for carbon

44i 45*

13 10

dioxide.

ml/kg/min; normal subjects, 6 + 2 ml/kg/min (p = 0.08). However, there was a significantly greater heart rate response in the patients with heart failure at peak exercise (patients with heart failure, 108 f 13 beats/min; normal subjects, 91 f 17 beats/min, p = O.Ol), so that oxygen pulse (VO,/heart rate; ml/beat) was significantly greater at peak exercise in normal subjects (5 f 2 vs 4 f 1, p ~0.05). The absence of a significant heart rate response in the norrmal subjects was the only variable that did not significantly change in either group with isometric exercise testing. In the postexercise period, VE was signiEcantly greater in patients with heart failure than in normal subjects (13 + 4 vs 10 f 2 Wmin, p = 0.01). linear regression analysis: Correlations between peak isometric and either peak isotonic exercise variables (Figure 1) or isotonic exercise variables at 50% of peak HEART

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TABLE IV

Plasma Atrial

Natiuretic ANP

Exercise

Rest

Isotonic Isometric

164 * 154 192 zt 158

‘p
Peptide,

Renin Activity,

and Norepinephrine

(rig/ml)

PM Peak

295 207

* 9.2

14.6

i 8.8

32.3 17.0

‘median 24.9; range I 15.9; tp = 0.01, PRA = plasma renin activity.

(Figure 2) are drawn. Significant correlations were observed for VO,, VCO,, and VE (for 50% peak isotonic exercise only) among normal subjects but not in patients with heart failure. Correlation betweenpeak isotonic exercise and variables at 90 secondsafter isometric exercise (Figure 3) was significant for VE in both normal subjects and patients with heart failure. NeurohomKnres: Plasma norepinephrine increased significantly from rest to peak exercise for both isotonic and isometric exercise in patients with heart failure

Normals:

vco2

ve Peak

zt 36.3 f 14.4 isotonic

vews

Ieotonic

Imnnetlic

vco2

50%

Ieotonic

50%

3,370 851

zt 2,958 * 353t

exercise.

Cardiovascular responsesto light forearm isometric exercise are difierent in normal subjects when com-

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hometric IDotonic

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50%

Heart Failure

NEipg/mll’ Peak7

13.7

in Patients With

h/ml/h)

Rest

zt 260 zt 171

peak, both types of exercise; peptide; NE = norepinephrine;

at Rest and Peak Exercise

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FIGURE 2. Top pane/s, tinear regression analysis of consumption (VO * LyFrnin); middle pan&, carbon dioxide production (VCO,; ml/min); and hottom As, minute ventilation iYE * L/min) ot 50%. peak is&& treadmill exercise with peak isometric light forearm exercise for 14 patients witfl congestive heart failure (CHF) and 11 normal subjects.

pared to patients with heart faih.tre.6 In normal subjects, as isometric exercise increases >15% of maximal voluntary contraction, there is a progressive reduction in blood flow to the exercising muscle as the increase in intramuscular pressure compresses arterial blood vessels.7 Systolic blood pressure increases to maintain muscle perfusion. As isometric exercise exceeds 70% of maximal voluntary contraction, there is complete obstruction of arterial flow,s so that energy requirements are met by anaerobic metabolism.9 The difference between normal subjects and patients with heart failure appears to be that impairment in arterial blood flow occurs at a much lower intensity of isometric exercise. It has been shown that in patients with heart failure performing isometric exercise to 25% of maximal voluntary contraction, in contrast to normals, the cardiac index does not increase,6 but lactic acid levels increase in the exercising forearm.*” Although there are significant correlations between peak isometric exercise and peak isotonic exercise for VO, and VCO, in normal subjects (Figures 1 and 2), no significant correlations were observed in patients with heart failure. This is probably because in normal subjects, both forms of exercise result in an increase in cardiac index.‘O However, in patients with heart failure, the absence of such correlations is probably due to the fact that isometric exercise produces little or no increase in cardiac index.“’ Thus, peak isotonic VO, and VCO, arc predictive of peak isometric VO, and VCO, in subjects with normal cardiac function only. During isometric exercise in patients with heart failurc, lactic acid is produced, which is released into the circulation after exercise, resulting in carbon dioxide production to buffer the acidosis, which in turn stimulates ventilation. This response, as shown by Reddy et al,‘” is not seen in normal subjects, which explains the significantly greater ventilation at 90 seconds after isometric exercise in patients with heart failure. It has been suggested that the increase in ventilation after isometric exercise may be a factor in the exertional dyspnea that patients with heart failure often experience after daily tasks that are isometric in nature.‘a Ventilation at peak isotonic exercise in patients with heart failure dots not correlate with ventilation at peak isometric exercise, but does at 90 seconds after isometric exercise (Figure 3). This suggests that lactic acidosis plays a role in the postisometric exercise hyperventilation, as lactic acidosis is known to stimulate ventilation at peak isotonic exercise.rr The duration of isometric exercise was similar in both groups, and the differences in indexes derived from gas exchange analysis were small between normal subjects and patients with heart failure. Thus, these data do not support the USCof isometric exercise as an alternative to isotonic exercise testing, or the use of isotonic exercise testing to predict isometric activities in patients with heart failure. However, although there was no significant difference in peak isometric exercise VO, between the 2 groups, by taking into account the higher heart rate response in patients with heart failure, the oxygen pulse (VO,keart rate) was significantly reduced. By analyzing oxygen pulse and postcxerCONGESTIVE

cise ventilation, with the addition of venous lactate lcvels as described by Reddy et al,“’ it may be possible to assess patients with heart failure with isometric exercise testing. Further studies are required to examine other intensities of forearm isometric exercise, and to determine reproducibility, to establish the role of this potentially useful clinical application. Our finding of a signilicant increase in plasma norepinephrinc levels during isometric exercise (which is smaller than the increase during isotonic exercise) in patients with heart failure, and the absence of a significant increase in plasma renin activity, support the previously described observations of Elkayam et al.6 This is consistent with the hypothesis that vagal withdrawal and sympathetic nerve stimulation are involved in the early c:lrculatory response to isometric exercise.‘*,t)

Normals: Peak Isotonic ,

VE vs Post Isometric

175

VE I

e CL

s!

Post

Isometric

i

VE

CHF: Peak Isotonic

VE vs Post Isometric

VE

60-

40-

1=0.63 pa.02

0

(D

s! Post

s Isometric

R

ti

VE

FIGURE 3. linear regression analysis of minute vedi~tion (VE; L/min) at peak isotonic treadmill exercise with 90 seconds pastisomdric (I’ ht forearm) exercise in 14 ‘eles with cangestive hwrt fan7 we (CHF) and in 11 narma F” sub$cis.

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EXERCiSE IN HEAR1 FAltURF

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1. Franciosa JA. Ziesche S, Wilen M. Functional capacity of patients with chronic left vennicular failure:. Relationship of bicycle exercise performance IO clinical and hemodynamic characterization. Am J Med lY79;67:4m66. 2. Wa..serman K, Hansen JE, Sue DY, Whipp BJ. Principles of Exercise Testing and Interpretation. Philadelphia: lea & l-cbiger, 198658-71. 3. Urehky BF, Verbalir. JG, Murali S. Betschti AR, Kolesar JA, Reddy PS. Control of atrial natriuretic peptide wcretion in patients with ~evcrc congestive heart failure. J C/in ~ndorrinol Merah 1990;71:14&151. 4. Davis GC. Kissinger P. Shoup R. Strategies for determination of semm or plasma owcpinephrine by~venrph~liquidchromatofr~hy.A~/Chem lY81;53:15~15Y. 5. Haber E, Koemer J, Page LB, Kliman BM. Purwde A. Application of a radioimmonoassay for angiotensin I to phyciological measurement of plasma renin activity in normal sub@&. J C/in Mcmb l%Y:2Y: 1349- 1355. 6. Elkayam U, Roth A, W&r L. Hsueh W, Nanna M, Freidenberger L, Chatdramtna PAN, Rahimtoola SH. Isometric exerciu: in patients with chronic advanced heart failure: hemodynamic and neurohumoral evaluation. Cinulutirm lY85;72: 915-98 I.

7. Longhurst JC. Stebbins CL. The isometric athlete. Car&d Clin 1992; 10128 I-294. 8. Humphreys PW. Lind AR. Thr blood flow through active and inactive muscles of the forearm during sustained hand-tip contractions. / Physiol /Imaim) 1963:166:12C-131. 9. Edwards RJIT. Wiles CM. Energy exchange in human skeletal muscle during isomeaic contmction. Circ Kes 1981;48:11 l-117. 10. Reddy HK. Weber KT. Janicki JS. McElroy PA. Hemodynamic, ventilatory and metabolic effects of light isometric exercise in patients with chronic hurt failure. J Am Coil Cur&l lY88:12:353-358. 1 I. Wassemnn K. Determinants and detection of anaerobic threshold and consequenccs of exercising above it. Cirdurion 1987;76(suppI Vl):Vl-29-VI-39. 12. MacDonald HR. Sapm RP, ‘Taylor SH, Donald KW. Effect of intravenous propranolol on the systemic circulatory response to sustained handgrip. Am J Cur&d lY66;18:333-343. 13. Haskel WL, Savin WM, Schroeder JS, Alderman EA. lngles NB, Daughters CT. Stinson EB. Cardiovascular responses to handgrip exercise in patients following cardiac transplantation. Circ Rev lY81;48(suppl I):]-156,-l-161.

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