Relationship Between Right Atrial and Mixed Venous Oxygen Saturation and Heart Rate During Exercise in Normal Subjects and Patients with Cardiac Disease WILLIAM J. FRENCH, RICHARD CASABURI, DAVID A. LEWIS, JAMES A. DALY, JOSEPH FLORIO, and GEORGE W. WESLEY From the Department of Medicine, UCLA School of Medicine, Los Angeles, and the Department of Medicine, Division of Cardiology, Harbor-UCLA Medical Center, Torrance, California
FRENCH, W.J., ET AL.: Relationship Between Right Atrial and Mixed Venous Oxygen Saturation and Heart Rate During Exercise in Normal Subjects and Patients with Cardiac Disease. An ideal sensing variable for use in rate responsive pacemakers should measure a physiological parameter that closely correlates with heart rate during various activities in a diverse group of subjects. Nineteen patients, 12 normal and 7 patients with heart disease, were studied to assess the relationship between mixed venous oxygen saturation and heart rate. In patients with heart disease right atrial oxygen saturation and heart rate were also compared. Each subject underwent pulmonary artery catheterization and performed seated cycle ergometer exercise. Gas exchange and heart rate were measured continuously and blood sampled at frequent intervals. Normal patients were studied at rest and during steady-state exercise (mean work rate 149 watts). Patients were studied at rest, steady-state exercise [mean work rate 37 watts), and during incremental exercise (5-10 wattsimin) to tolerance. There were 248 paired right atrial or mixed venous oxygen saturationlheart rate observations obtained. Changes in mixed venous oxygen saturation and heart rate were not substantially altered by fitness or cardiac disease. Rate responsive pacemakers sensing changes in oxygen saturation may be a superior sensing variable for both normal and patients with heart disease. (PACE, Vol. 13, December, Part II 1990) mixed venous oxygen saturation, rate responsive pacemakers
Introduction Rate responsive pacemakers have the disadvantage that to optimize cardiac function the relationship between sensed variable and heart rate response must be determined for each patient.' However, patient fitness and presence of cardiac disease may alter this relationship. An ideal sensing variable should measure a physiological parameter that accurately reflects heart rate response during exercise in those with normal hearts as well as those with severe cardiac diseases.2 In nor-
Address for reprints: William J. French, M.D., Harbor-UCLA Medical Center, 1000 W. Carson Street, Torrance, CA 90509.
PACE, Vol. 13
ma1 subjects, pulmonary artery (i.e., mixed venous] oxygen saturation is related inversely to the level of exercise performance. The decrease in mixed venous oxygen saturation is large between rest and low level exercise, but becomes smaller as the level of exercise increases. Less is known about changes in right atrial and mixed venous oxygen saturation during exercise in patients with heart d i ~ e a s eThe . ~ purpose of this study was to compare changes in mixed venous oxygen saturation and heart rate in normal subjects and in patients with heart disease at a range of different exercise intensities. Also the relationship between right atrial saturation and heart rate was determined in patients with various cardiac diseases during exercise.
December 1990, Part I1
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FRENCH, ET AL.
Clinical Nineteen subjects were studied. There were seven males with clinical manifestations of heart disease. The mean age was 50 years with a range of 36-64 years. The mean left ventricular ejection fraction determined by radionuclide techniques or left ventriculography was 30% with a range of 17%-75%. Patients had coronary artery disease or idiopathic dilated cardiomyopathy. Twelve normal male subjects were younger with a mean age of 25 years and a range of 19-35 years. The normal subjects were asymptomatic and had no known heart disease. All studies were done as outpatient procedures. This study had Human Subjects Approval from the Harbor-UCLA Medical Center.
Methods Pulmonary Artery Catheterization Seven patients underwent percutaneous insertion of either a fiberoptic (Oximetric) or standard thermodilution balloon flotation catheter through a brachial or subclavian vein. The fiberoptic catheter allowed continuous monitoring of pulmonary artery oxygen saturation during exercise. In the first three patients, a brachial artery catheter was placed for continuous monitoring of blood pressure and intermittent blood sampling for measurement of arterial oxygen saturation. Because there was virtually no change in arterial oxygen saturation during exercise in these three patients, subsequent patients had only a pulmonary artery catheter positioned. Right atrial and pulmonary artery pressures were recorded continuously. In the absence of a brachial arterial line, blood pressure cuff measurements were recorded every 2 minutes during rest and exercise. Exercise Protocol Prior to the day of study, all patients and normals underwent a bicycle exercise protocol to maximum tolerance. On the study day normal subjects performed only steady-state exercise, but patients underwent both steady state and incremental exercise t e ~ t i n g . ~ Steady-state exercise testing at moderate levels of exercise was performed. The workload cho-
1810
sen was approximately 80% of the subject’s anaerobic threshold as determined from the prior exercise test. Steady-state testing included 3 minutes at rest, 4 minutes of cycling at 80% of the anaerobic threshold, and 5 minutes of recovery while seated on an electromagnetically-braked cycle ergometer. During steady-state exercise, pulmonary artery blood samples were drawn every 4 seconds for the first 80 seconds of exercise by a computerized anaerobic sampling manifold. Thereafter, pulmonary artery blood samples were drawn manually at frequent intervals during the rest of the exercise period and then every 1 minute during recovery. The incremental exercise test was designed to obtain 6 to 15 minutes of work. Incremental exercise testing involved 3 minutes at rest, 3 minutes of unloaded pedalling, incremental exercise with a gradual increase of workload by 5-10 wattslmin, and a recovery phase of at least 5 minutes. During unloaded cycling pulmonary blood samples were drawn every 4 seconds for the first 80 seconds of exercise and then every 1 minute during incremental exercise. Blood samples were drawn from the right atrial port during rest, unloaded cycling, and then every minute during incremental exercise and recovery. Patients performed incremental exercise to tolerance. All blood samples were placed in an ice slurry until analyzed by CO-Oximetry (Instrumentation Laboratory 282 or 482 [Fisher Medical Div Instrumentation Laboratory, Lexington, MA, USA]]. Noninvasive Measurements Breath-by-breath analysis of expired gas was performed by a computerized system to allow calculation of ventilation, carbon dioxide output, oxygen consumption, end-tidal oxygen and carbon dioxide, oxygen pulse, and anaerobic threshold as previously d e ~ c r i b e d .Heart ~ rate was continuously recorded from three electrocardiographic leads. Twelve-lead electrocardiograms were obtained every 2 minutes during exercise.
Results Fiberoptic Derived Versus CO-Oximeter Measured Oxygen Saturation Overall, fiberoptic derived pulmonary artery or mixed venous oxygen saturation values under-
December 1990, Part I1
PACE, Vol. 1 3
MIXED VENOUS OXYGEN SATURATION
estimated oxygen saturation measured by a COOximeter. Fiberoptic derived oxygen saturation values more closely approximated CO-Oximeter measured oxygen saturation above 55%. However, below 55% the discrepancy between the two values progressively increased. At a CO-Oximeter measured oxygen saturation of 30% the fiberoptic saturation was only about 15% [Fig. 1). Because of this discrepancy, for this study, only CO-Oximeter measured values for oxygen saturation were used for analysis.
Exercise Protocol During steady-state exercise normal subjects performed a mean work rate of 149 watts with a range of 100-200 watts. Patients, however, exercised a mean of only 77 watts with a range of 1560 watts during steady-state exercise. Despite the discrepancy between the absolute work rates, all
subjects performed work of moderate intensity [i.e., below the anaerobic threshold). During incremental exercise patients reached a mean of 74 watts with a range of 20-130 watts. Oxygen Saturation Compared to Head Rate Paired right atrial oxygen saturatiodheart rate or mixed venous oxygen saturationlheart rate measurements were analyzed. There were 84 paired right atrial oxygen saturatiodheart rate measurements obtained in patients during steady state and incremental exercise. Right atrial oxygen saturation ranged from 30%-69°/0. There were 93 paired mixed venous oxygen saturationlheart rate measurements in normal subjects and 71 in patients. Mixed venous oxygen saturation ranged from 30°/o-75% in both groups. Heart rate ranged from 56-162 in normals and between 55-157 beatdmin in patients.
MV02 S a t u r a t i o n
Measured v s . Fiberoptic V a l u e s
70
--
60
--
50 --
HV02 Sat
I / ..
4o
(f iberopticl
0
20
60
40
MY02
eo
100
Sat (measured)
Figure 1. Comparison of pulmonary artery or mixed venous oxygen saturation measured by GO-Oximetry and fiberoptic catheter.
PACE, Vol. 13
December 1990, Part I1
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FRENCH, ET AL.
an average of 6% oxygen saturation with a range of 1Y0-14Y0. This represented a 10% decrease from resting values.
Right Atrial Oxygen Saturation There was more variability in right atrial than mixed venous oxygen saturation measurements during exercise. Essentially, there were two responses of right atrial oxygen saturation with exercise. Two patients had an initial marked decrease in right atrial oxygen saturation with unloaded pedalling during early exercise followed by a slower decrease during the remainder of exercise. This abrupt premature decline in oxygen saturation was similar to that seen in mixed venous oxygen saturation (see below). The other five patients had no steep early decrease, but only a gradual decrease in right atrial oxygen saturation throughout exercise. After 3 minutes of unloaded cycling, right atrial oxygen saturation decreased
Mixed Venous Oxygen Saturation During Incremental Exercise In Patients The mean resting mixed venous oxygen saturation level was only 61% with a range of 56%-68Y0 in seven patients. In the patient studies, during 3 minutes of unloaded pedalling, mixed venous oxygen saturation decreased rapidly an average of 10 oxygen saturation percent (range 7%-17%) which represented a 16% change from resting values. Following this abrupt fall in mixed venous oxygen saturation, there was a further progressive decrease in mixed venous oxygen saturation as work rate increased (Fig. 2).
MV02 DURING INCREMENTAL EXERCISE
t 30
--
25
/ 0
I
I
I
I
I I
I I
I I
I
I
2
4
6
B
10
12
14
16
I
TIME
I
I
I
I
18
20
(mid
Figure 2. Changes in mixed venous (i.e., pulmonary artery) oxygen saturation during incremental exercise.
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December 1990,Part I1
PACE, Vol. 13
MIXED VENOUS OXYGEN SATURATION
180
-
HEART RATE COMPARED TO MV02 (PATIENTS 1-7)
H 160 -E A 140 --
R 120
R A T E
--
100 -80
--
60
--
7"
-
Y = 160 1.17(X) (SEE = 19 bpm)
, 20
-0
I
0
I
,
30
40
50
70
60
80
MIXED VENOUS OXYGEN SATURATION (%) Figure 3. Mixed venous oxygen saturation compared to heart rate response during incremental exercise for all seven patients with heart disease. Except for the patient represented by open circles, the other six patients closely fit the regression line.
HEART RATE COMPARED TO MIXED VENOUS OXYGEN SATURATION
1807
H A T
R
160 --
140-120--
0
100 -I
I
A T
80 --
-
-
**
60.-
I
4
0 20
L
30
u
' -
40
i
50
60
70
80
MIXED VENOUS OXYGEN SATURATION (%) Figure 4. Comparison of mixed venous oxygen saturation and heart rate for both normal subjects and patients. Note the similarity of the regression lines.
PACE, Vol. 13
December 1990,Part I1
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FRENCH, ET AL.
Heart Rate During Exercise Heart rate rose slightly during unloaded pedaling. The mean increase was 16 beatdmin with a range of 9-43 beatdmin. This represented a 23% change. During incremental exercise the mean maximum heart rate was 132 beats/min with a range of 109-154 beatdmin. Comparison of Mixed Venous Oxygen Saturation Measurements and Heart Rate Mean resting mixed venous oxygen saturation in normals was 67% with a range of 60%-75%. Of importance, these values fall in a relatively narrow range. Linear regression produces a standard error of the estimate of only 13 beatdmin. Figure 3 compares mixed venous oxygen saturation and heart rate during incremental exercise in patients with heart disease. Except for one patient, most values closely fit the regression line with the standard error of the estimate only 19 beatdmin. When values for both normal subjects and patients with cardiac disease are superimposed, changes in mixed venous oxygen saturation were similar for both groups and ranged from 30%-75% while heart rate ranged from 60-160 beats/min (Fig. 4). There is no statistically significant difference in the regression lines for normal subjects and patients.
At a given heart rate, patients with cardiac disease are likely to have a smaller increase in oxygen consumption and stroke volume than normal subjects because they reach a given heart rate at a lower work rate. Thus, the relative decrease in mixed venous oxygen saturation during exercise would be similar for both groups. Because of this relatively close correlation between heart rate and mixed venous oxygen saturation and heart rate at rest and during exercise, mixed venous oxygen saturation may be a superior sensing variable for use in pacemaker algorithms in both normal subjects and patients with cardiac disease. The greater variability of right atrial oxygen saturation measurements during exercise may be related to the location of the right atrial catheter port in individual patients. Slight variations in positioning of the right atrial port could result in sampling of blood streaming from the superior or inferior venae cavae or coronary sinus.' Unanswered by this study is whether an oxygen sensing electrode, presumably positioned in the right ventricle, would reflect the more uniform changes measured in mixed venous (i.e., pulmonary artery) oxygen saturation during exercise or those in right atrial oxygen saturation measurements. Further studies are needed to assess this problem.
Discussion This study has demonstrated that the relationship between mixed venous oxygen saturation and heart rate is not substantially altered by fitness or cardiac disease. This may best be explained by considering factors that influence mixed venous oxygen saturation and cardiac output during exercise. In the Fick principle, mixed venous oxygen saturation (MVO,) is related to cardiac output by the following equation: MVO, = Arterial 0, Saturation Oxygen consumption Heart rate x Stroke Volume
Clinical Implications A permanent pacemaker sensing changes in mixed venous oxygen saturation would probably not require a substantially different pacing algorithm for normal subjects and for patients with cardiac disease.
Acknowledgments: The authors wish to thank the Cardiac Catheterization Laboratory technical staff (Mary Chavez, Terrance Doherty, Jim Gibson, and Dorothy Gravett) and the Pulmonary Physiology Laboratory staff for their technical assistance: and Cecelia Hatcher for her secretarial assistance.
References 1. Geddes LA, Fearnot NE, Smith HJ. The exercise-
responsive cardiac pacemaker. IEEE Trans Biomed Eng 1984; BME-31:763-770. 2. Wirtzfeld A, Heinze R, Stanzl K, et al. Regulation
1814
of pacing rate by variations of mixed venous oxygen saturation. PACE 1984; 7:1257-1262. 3. Casaburi R, Daly JA, Hansen JE, et al. Abrupt changes in mixed venous blood gas composition
December 1990, Part I1
PACE, Vol. 13
MIXED VENOUS OXYGEN SATURATION
after the onset of exercise. J Appl Physiol 1989; 67(3):1106-1112. 4. K Wasserman, JE Hansen, DY Sue, et al. (eds.)Principles of Exercise Testing and Interpretation. Philadelphia, Pennsylvania, Lea and Febiger, 1987. 5. Haskell RJ, French WJ. Physiological importance of
PACE, Vol. 13
different atrioventricular intervals to improved exercise performance in patients with dual chamber pacemakers. Br Heart J 1989; 61:46-51. 6. French WJ, Criley JM. Estimation of mixed venous oxygen saturation. Cathet Cardiovasc Diagn 1983; 9~25-31.
December 1990, Part I1
1815
FRENCH, W.J., ET AL.: Relationship Between Right Atrial and Mixed Venous Oxygen Saturation and Heart Rate During Exercise in Normal Subjects and Patients with Cardiac Disease. An ideal sensing variable for use in rate responsive pacemakers should measure a physiological parameter that closely correlates with heart rate during various activities in a diverse group of subjects. Nineteen patients, 12 normal and 7 patients with heart disease, were studied to assess the relationship between mixed venous oxygen saturation and heart rate. In patients with heart disease right atrial oxygen saturation and heart rate were also compared. Each subject underwent pulmonary artery catheterization and performed seated cycle ergometer exercise. Gas exchange and heart rate were measured continuously and blood sampled at frequent intervals. Normal patients were studied at rest and during steady-state exercise (mean work rate 149 watts). Patients were studied at rest, steady-state exercise [mean work rate 37 watts), and during incremental exercise (5-10 wattsimin) to tolerance. There were 248 paired right atrial or mixed venous oxygen saturationlheart rate observations obtained. Changes in mixed venous oxygen saturation and heart rate were not substantially altered by fitness or cardiac disease. Rate responsive pacemakers sensing changes in oxygen saturation may be a superior sensing variable for both normal and patients with heart disease. (PACE, Vol. 13, December, Part II 1990) mixed venous oxygen saturation, rate responsive pacemakers
Introduction Rate responsive pacemakers have the disadvantage that to optimize cardiac function the relationship between sensed variable and heart rate response must be determined for each patient.' However, patient fitness and presence of cardiac disease may alter this relationship. An ideal sensing variable should measure a physiological parameter that accurately reflects heart rate response during exercise in those with normal hearts as well as those with severe cardiac diseases.2 In nor-
Address for reprints: William J. French, M.D., Harbor-UCLA Medical Center, 1000 W. Carson Street, Torrance, CA 90509.
PACE, Vol. 13
ma1 subjects, pulmonary artery (i.e., mixed venous] oxygen saturation is related inversely to the level of exercise performance. The decrease in mixed venous oxygen saturation is large between rest and low level exercise, but becomes smaller as the level of exercise increases. Less is known about changes in right atrial and mixed venous oxygen saturation during exercise in patients with heart d i ~ e a s eThe . ~ purpose of this study was to compare changes in mixed venous oxygen saturation and heart rate in normal subjects and in patients with heart disease at a range of different exercise intensities. Also the relationship between right atrial saturation and heart rate was determined in patients with various cardiac diseases during exercise.
December 1990, Part I1
1809
FRENCH, ET AL.
Clinical Nineteen subjects were studied. There were seven males with clinical manifestations of heart disease. The mean age was 50 years with a range of 36-64 years. The mean left ventricular ejection fraction determined by radionuclide techniques or left ventriculography was 30% with a range of 17%-75%. Patients had coronary artery disease or idiopathic dilated cardiomyopathy. Twelve normal male subjects were younger with a mean age of 25 years and a range of 19-35 years. The normal subjects were asymptomatic and had no known heart disease. All studies were done as outpatient procedures. This study had Human Subjects Approval from the Harbor-UCLA Medical Center.
Methods Pulmonary Artery Catheterization Seven patients underwent percutaneous insertion of either a fiberoptic (Oximetric) or standard thermodilution balloon flotation catheter through a brachial or subclavian vein. The fiberoptic catheter allowed continuous monitoring of pulmonary artery oxygen saturation during exercise. In the first three patients, a brachial artery catheter was placed for continuous monitoring of blood pressure and intermittent blood sampling for measurement of arterial oxygen saturation. Because there was virtually no change in arterial oxygen saturation during exercise in these three patients, subsequent patients had only a pulmonary artery catheter positioned. Right atrial and pulmonary artery pressures were recorded continuously. In the absence of a brachial arterial line, blood pressure cuff measurements were recorded every 2 minutes during rest and exercise. Exercise Protocol Prior to the day of study, all patients and normals underwent a bicycle exercise protocol to maximum tolerance. On the study day normal subjects performed only steady-state exercise, but patients underwent both steady state and incremental exercise t e ~ t i n g . ~ Steady-state exercise testing at moderate levels of exercise was performed. The workload cho-
1810
sen was approximately 80% of the subject’s anaerobic threshold as determined from the prior exercise test. Steady-state testing included 3 minutes at rest, 4 minutes of cycling at 80% of the anaerobic threshold, and 5 minutes of recovery while seated on an electromagnetically-braked cycle ergometer. During steady-state exercise, pulmonary artery blood samples were drawn every 4 seconds for the first 80 seconds of exercise by a computerized anaerobic sampling manifold. Thereafter, pulmonary artery blood samples were drawn manually at frequent intervals during the rest of the exercise period and then every 1 minute during recovery. The incremental exercise test was designed to obtain 6 to 15 minutes of work. Incremental exercise testing involved 3 minutes at rest, 3 minutes of unloaded pedalling, incremental exercise with a gradual increase of workload by 5-10 wattslmin, and a recovery phase of at least 5 minutes. During unloaded cycling pulmonary blood samples were drawn every 4 seconds for the first 80 seconds of exercise and then every 1 minute during incremental exercise. Blood samples were drawn from the right atrial port during rest, unloaded cycling, and then every minute during incremental exercise and recovery. Patients performed incremental exercise to tolerance. All blood samples were placed in an ice slurry until analyzed by CO-Oximetry (Instrumentation Laboratory 282 or 482 [Fisher Medical Div Instrumentation Laboratory, Lexington, MA, USA]]. Noninvasive Measurements Breath-by-breath analysis of expired gas was performed by a computerized system to allow calculation of ventilation, carbon dioxide output, oxygen consumption, end-tidal oxygen and carbon dioxide, oxygen pulse, and anaerobic threshold as previously d e ~ c r i b e d .Heart ~ rate was continuously recorded from three electrocardiographic leads. Twelve-lead electrocardiograms were obtained every 2 minutes during exercise.
Results Fiberoptic Derived Versus CO-Oximeter Measured Oxygen Saturation Overall, fiberoptic derived pulmonary artery or mixed venous oxygen saturation values under-
December 1990, Part I1
PACE, Vol. 1 3
MIXED VENOUS OXYGEN SATURATION
estimated oxygen saturation measured by a COOximeter. Fiberoptic derived oxygen saturation values more closely approximated CO-Oximeter measured oxygen saturation above 55%. However, below 55% the discrepancy between the two values progressively increased. At a CO-Oximeter measured oxygen saturation of 30% the fiberoptic saturation was only about 15% [Fig. 1). Because of this discrepancy, for this study, only CO-Oximeter measured values for oxygen saturation were used for analysis.
Exercise Protocol During steady-state exercise normal subjects performed a mean work rate of 149 watts with a range of 100-200 watts. Patients, however, exercised a mean of only 77 watts with a range of 1560 watts during steady-state exercise. Despite the discrepancy between the absolute work rates, all
subjects performed work of moderate intensity [i.e., below the anaerobic threshold). During incremental exercise patients reached a mean of 74 watts with a range of 20-130 watts. Oxygen Saturation Compared to Head Rate Paired right atrial oxygen saturatiodheart rate or mixed venous oxygen saturationlheart rate measurements were analyzed. There were 84 paired right atrial oxygen saturatiodheart rate measurements obtained in patients during steady state and incremental exercise. Right atrial oxygen saturation ranged from 30%-69°/0. There were 93 paired mixed venous oxygen saturationlheart rate measurements in normal subjects and 71 in patients. Mixed venous oxygen saturation ranged from 30°/o-75% in both groups. Heart rate ranged from 56-162 in normals and between 55-157 beatdmin in patients.
MV02 S a t u r a t i o n
Measured v s . Fiberoptic V a l u e s
70
--
60
--
50 --
HV02 Sat
I / ..
4o
(f iberopticl
0
20
60
40
MY02
eo
100
Sat (measured)
Figure 1. Comparison of pulmonary artery or mixed venous oxygen saturation measured by GO-Oximetry and fiberoptic catheter.
PACE, Vol. 13
December 1990, Part I1
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FRENCH, ET AL.
an average of 6% oxygen saturation with a range of 1Y0-14Y0. This represented a 10% decrease from resting values.
Right Atrial Oxygen Saturation There was more variability in right atrial than mixed venous oxygen saturation measurements during exercise. Essentially, there were two responses of right atrial oxygen saturation with exercise. Two patients had an initial marked decrease in right atrial oxygen saturation with unloaded pedalling during early exercise followed by a slower decrease during the remainder of exercise. This abrupt premature decline in oxygen saturation was similar to that seen in mixed venous oxygen saturation (see below). The other five patients had no steep early decrease, but only a gradual decrease in right atrial oxygen saturation throughout exercise. After 3 minutes of unloaded cycling, right atrial oxygen saturation decreased
Mixed Venous Oxygen Saturation During Incremental Exercise In Patients The mean resting mixed venous oxygen saturation level was only 61% with a range of 56%-68Y0 in seven patients. In the patient studies, during 3 minutes of unloaded pedalling, mixed venous oxygen saturation decreased rapidly an average of 10 oxygen saturation percent (range 7%-17%) which represented a 16% change from resting values. Following this abrupt fall in mixed venous oxygen saturation, there was a further progressive decrease in mixed venous oxygen saturation as work rate increased (Fig. 2).
MV02 DURING INCREMENTAL EXERCISE
t 30
--
25
/ 0
I
I
I
I
I I
I I
I I
I
I
2
4
6
B
10
12
14
16
I
TIME
I
I
I
I
18
20
(mid
Figure 2. Changes in mixed venous (i.e., pulmonary artery) oxygen saturation during incremental exercise.
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PACE, Vol. 13
MIXED VENOUS OXYGEN SATURATION
180
-
HEART RATE COMPARED TO MV02 (PATIENTS 1-7)
H 160 -E A 140 --
R 120
R A T E
--
100 -80
--
60
--
7"
-
Y = 160 1.17(X) (SEE = 19 bpm)
, 20
-0
I
0
I
,
30
40
50
70
60
80
MIXED VENOUS OXYGEN SATURATION (%) Figure 3. Mixed venous oxygen saturation compared to heart rate response during incremental exercise for all seven patients with heart disease. Except for the patient represented by open circles, the other six patients closely fit the regression line.
HEART RATE COMPARED TO MIXED VENOUS OXYGEN SATURATION
1807
H A T
R
160 --
140-120--
0
100 -I
I
A T
80 --
-
-
**
60.-
I
4
0 20
L
30
u
' -
40
i
50
60
70
80
MIXED VENOUS OXYGEN SATURATION (%) Figure 4. Comparison of mixed venous oxygen saturation and heart rate for both normal subjects and patients. Note the similarity of the regression lines.
PACE, Vol. 13
December 1990,Part I1
1813
FRENCH, ET AL.
Heart Rate During Exercise Heart rate rose slightly during unloaded pedaling. The mean increase was 16 beatdmin with a range of 9-43 beatdmin. This represented a 23% change. During incremental exercise the mean maximum heart rate was 132 beats/min with a range of 109-154 beatdmin. Comparison of Mixed Venous Oxygen Saturation Measurements and Heart Rate Mean resting mixed venous oxygen saturation in normals was 67% with a range of 60%-75%. Of importance, these values fall in a relatively narrow range. Linear regression produces a standard error of the estimate of only 13 beatdmin. Figure 3 compares mixed venous oxygen saturation and heart rate during incremental exercise in patients with heart disease. Except for one patient, most values closely fit the regression line with the standard error of the estimate only 19 beatdmin. When values for both normal subjects and patients with cardiac disease are superimposed, changes in mixed venous oxygen saturation were similar for both groups and ranged from 30%-75% while heart rate ranged from 60-160 beats/min (Fig. 4). There is no statistically significant difference in the regression lines for normal subjects and patients.
At a given heart rate, patients with cardiac disease are likely to have a smaller increase in oxygen consumption and stroke volume than normal subjects because they reach a given heart rate at a lower work rate. Thus, the relative decrease in mixed venous oxygen saturation during exercise would be similar for both groups. Because of this relatively close correlation between heart rate and mixed venous oxygen saturation and heart rate at rest and during exercise, mixed venous oxygen saturation may be a superior sensing variable for use in pacemaker algorithms in both normal subjects and patients with cardiac disease. The greater variability of right atrial oxygen saturation measurements during exercise may be related to the location of the right atrial catheter port in individual patients. Slight variations in positioning of the right atrial port could result in sampling of blood streaming from the superior or inferior venae cavae or coronary sinus.' Unanswered by this study is whether an oxygen sensing electrode, presumably positioned in the right ventricle, would reflect the more uniform changes measured in mixed venous (i.e., pulmonary artery) oxygen saturation during exercise or those in right atrial oxygen saturation measurements. Further studies are needed to assess this problem.
Discussion This study has demonstrated that the relationship between mixed venous oxygen saturation and heart rate is not substantially altered by fitness or cardiac disease. This may best be explained by considering factors that influence mixed venous oxygen saturation and cardiac output during exercise. In the Fick principle, mixed venous oxygen saturation (MVO,) is related to cardiac output by the following equation: MVO, = Arterial 0, Saturation Oxygen consumption Heart rate x Stroke Volume
Clinical Implications A permanent pacemaker sensing changes in mixed venous oxygen saturation would probably not require a substantially different pacing algorithm for normal subjects and for patients with cardiac disease.
Acknowledgments: The authors wish to thank the Cardiac Catheterization Laboratory technical staff (Mary Chavez, Terrance Doherty, Jim Gibson, and Dorothy Gravett) and the Pulmonary Physiology Laboratory staff for their technical assistance: and Cecelia Hatcher for her secretarial assistance.
References 1. Geddes LA, Fearnot NE, Smith HJ. The exercise-
responsive cardiac pacemaker. IEEE Trans Biomed Eng 1984; BME-31:763-770. 2. Wirtzfeld A, Heinze R, Stanzl K, et al. Regulation
1814
of pacing rate by variations of mixed venous oxygen saturation. PACE 1984; 7:1257-1262. 3. Casaburi R, Daly JA, Hansen JE, et al. Abrupt changes in mixed venous blood gas composition
December 1990, Part I1
PACE, Vol. 13
MIXED VENOUS OXYGEN SATURATION
after the onset of exercise. J Appl Physiol 1989; 67(3):1106-1112. 4. K Wasserman, JE Hansen, DY Sue, et al. (eds.)Principles of Exercise Testing and Interpretation. Philadelphia, Pennsylvania, Lea and Febiger, 1987. 5. Haskell RJ, French WJ. Physiological importance of
PACE, Vol. 13
different atrioventricular intervals to improved exercise performance in patients with dual chamber pacemakers. Br Heart J 1989; 61:46-51. 6. French WJ, Criley JM. Estimation of mixed venous oxygen saturation. Cathet Cardiovasc Diagn 1983; 9~25-31.
December 1990, Part I1
1815
