Am J Physiol Heart Circ Physiol 288: H1179-H1185, 2005.
First published October 21, 2004; doi:10.1152/ajpheart.00045.2004
0363-6135/05 $8.00
Pronounced HR variability after exercise in inferior ischemia: evidence that the cardioinhibitory vagal reflex is invoked by exercise-induced inferior ischemia
Nobuhiro Tahara,1
Hiroshi Takaki,2
Atsushi Taguchi,1
Kazuhiro Suyama,1
Takashi Kurita,1
Wataru Shimizu,1
Shunichi Miyazaki,1
Toru Kawada,2 and
Kenji Sunagawa2
1Division of Cardiology, Department of Medicine, National Cardiovascular Center, and 2Department of Cardiovascular Dynamics, National Cardiovascular Center Research Institute, Osaka, Japan
Submitted 22 January 2004
; accepted in final form 19 October 2004
 |
ABSTRACT
|
|---|
Potent cardioinhibitory vagal reflex resulting in bradycardia and hypotension has been observed under particular conditions of transmural inferior ischemia and its reperfusion, such as those observed with acute infarction. However, whether exercise-induced ischemia with ST depressions that is subendocardial and that might be recurrently experienced in daily activities can evoke this reflex remains unknown. In patients with exercise-induced ST depressions due to either inferior [right coronary artery stenosis (RCA), n = 52] or anterior ischemia [left anterior descending artery stenosis (LAD), n = 51], we evaluated post exercise vagal activity (from 0 to 6 min) by the time constant of heart rate (HR) decay and HR variability by 30-s averages of the absolute values of successive RR interval differences (
RR). Exercise parameters were similar between groups. The time constant was slightly but significantly shorter in RCA than LAD patients (79 ± 24 vs. 93 ± 29 s, P < 0.01). More significantly, RR early after exercise (0.5–2.5 min) was approximately twofold greater in RCA than LAD patients (from +76 to +118%, P < 0.001), indicating pronounced vagal activity stimulated by inferior ischemia. Revascularization prolonged the time constant (P < 0.05) and attenuated recovery RR in RCA patients (P < 0.05, n = 10) but did not change both parameters in LAD patients (n = 12). As well as acute inferior infarction, exercise-induced inferior subendocardial ischemia, which might recurrently occur in daily activities, activates the cardioinhibitory reflex. These new findings must be taken into account in interpreting vagal activity in patients with coronary artery disease.
heart rate variability; vagus nerve; coronary artery disease
EXPERIMENTAL STUDIES in animals have demonstrated that excitation of vagal sensory nerve endings from myocardial ischemia involving the inferoposterior wall of the left ventricle activates potent cardioinhibitory reflex resulting in bradycardia and hypotension (7, 24). In humans, similar observations have been made under particular conditions of severe transmural inferior ischemia and its reperfusion, such as those that occur with myocardial infarction, vasospastic angina, or angioplasty of the right coronary artery (12, 15, 21, 22, 28). For example, in the first hour of the onset of acute myocardial infarction, patients with inferior infarction often (
75%) show sinus bradycardia and/or hypotension, which generally responds to intravenous administration of atropine. This observation contrasts with that in patients with anterior infarction, about 50% of whom show sinus tachycardia and/or hypertension (15).
Despite these well-recognized clinical observations, little attention has been paid to the question as to whether this reflex could be evoked by exercise-induced ischemia that is usually subendocardial with the manifestation of ST depressions and that might be recurrently experienced during daily activities. If it does occur in this condition, this hitherto-unrecognized possibility must be taken into account in the clinical interpretation of vagal activity in patients with coronary artery disease (CAD). It is widely accepted that the higher the estimated measure of vagal activity, the better the patient status and the prognosis according to various reports examining the clinical significance of estimating vagal activity with the use of heart rate (HR) variability (HRV) analysis from 24-h Holter recording (1, 11, 13, 23a) or HR recovery after exercise testing (5, 18, 26). It is possible that vagal activity may be adversely augmented under a certain pathological condition, i.e., in the presence of inducible inferior ischemia, and that vagal estimation may be erroneously interpreted in patients with inducible inferior ischemia. In view of the diagnostic utility of exercise testing, the identification of the pronounced vagal activity induced by exercise may serve as an additive measure for detecting and localizing the presence of inferior ischemia.
On the basis of these considerations, the present study was designed to test the hypothesis that inferior ischemia, even that evoked by physiological stress such as exercise, may invoke the cardioinhibitory reflex, which would in turn influence postexercise HR decay and HRV through a reflex enhancement of vagal activity. The postexercise condition may more readily unmask this phenomenon than during exercise, because vagal activity is physiologically depressed during exercise but markedly reactivated after exercise (2, 20), although this reflex should be activated both during exercise-induced ischemia and after postexercise reperfusion. Thus we compared HR decay and HRV after exercise in patients with exercise-induced inferior ischemia and those with anterior ischemia and then evaluated the effects of revascularization on these parameters.
|
METHODS
|
|---|
Study population.
From consecutive patients who underwent both coronary angiography and conventional treadmill exercise ECG testing within 3 wk for the evaluation of CAD, a total of 103 patients who were documented to have either inducible inferior ischemia due to right coronary artery (RCA) stenosis (n = 52, RCA group) or anterior ischemia due to left anterior descending artery (LAD) stenosis (n = 51, LAD group) were enrolled in the study in a prospective fashion (Table 1). Significant coronary stenosis was defined as >50% luminal narrowing. All had significant exercise-induced ST segment depressions on treadmill ECG. Fifty-one (50%) patients had previous myocardial infarction. The majority (75%) had a single-vessel disease of either RCA stenosis (69%) or LAD stenosis (84%). In 24 patients with multiple vessel disease, exercise single-photon emission computed tomographic thallium-201 scintigraphy was performed to confirm that exercise-inducible ischemia was exclusively localized to either the inferior or anterior wall of the left ventricle. Exclusion criteria included the presence of atrial fibrillation, frequent premature beats (>5 beats/min) during the exercise test, and exercise-induced ST segment elevations (
1.0 mm).
Clinical characteristics, including age, sex, prevalence of prior infarction, left ventricular ejection fraction (by contrast left ventriculography), and drug regimens, were quite similar between the two groups (Table 1). 
-Blockers, calcium antagonists, and nitrates were taken in 44 (43%), 63 (61%), and 64 (62%) patients, respectively. No patient was taking digitalis at the time of the study. Drug regimens were neither altered nor stopped for the exercise test. The study protocol was approved by the ethics committee of our institution. All patients gave informed consent to participate in the study.
Exercise test.
Conventional symptom-limited or submaximal (up to 90% age-predicted maximum HR) graded treadmill exercise testing was performed using a commercially available treadmill system (Formula; Esaote, Italy) equipped with an analog-to-digital converter and hard disk according to our protocol (23), being similar to the modified Bruce protocol. ECGs in lead V2, aVF, and V5 were continuously monitored from rest through the recovery period. Arterial blood pressure was measured at rest, at the end of each stage, peak exercise, and at 1, 2, 4, and 6 min after exercise by a sphygmomanometer. Throughout the test, eight leads of the ECG, including lead I, II, and V1–6, were continuously digitized at 500 Hz (12 bit) and stored on a computer hard disk for subsequent analysis. The standard 12-lead ECGs were hardcopied at rest, at the end of each stage, at peak exercise, immediately after exercise, and at every minute of the recovery period. A significant ST segment depression was defined by the following criteria: 1) a horizontal or downsloping ST segment displacement at J point 0.1 mV and 2) an upsloping ST segment displacement at 80 ms after J point 0.15 mV in at least three consecutive beats at peak exercise.
Assessment of revascularization effects.
In 22 patients who subsequently received successful revascularization, we repeated the exercise test within 1 mo after the procedure. Eighteen patients received successful percutaneous transluminal coronary angioplasty either on the RCA (n = 8) or LAD (n = 10). Coronary artery bypass graft surgery was undertaken in the other four patients (RCA n = 2, LAD n = 2).
On the basis of consideration that a higher attainment of peak HR resulting from increased exercise capacity after the intervention (i.e., different exercise time) and its possible influences on vagal activity would make it difficult to estimate the true effect of revascularization on postexercise HR analysis, the exercise test after revascularization was terminated at the same exercise duration as that before the revascularization. Drug regimens were also kept constant.
Data analysis.
Off-line analysis was performed on a personal computer using our custom-made software. We first determined the beat-by-beat RR intervals throughout the test from rest to recovery period by detecting the peak of R wave deflections. In patients with premature beats, we corrected RR intervals by linear interpolation with the previous and following beats.
Using the time series of RR intervals during recovery periods of 6 min, we computed the time constant of HR decay. We fitted the HR data to a monoexponential curve (HR = A + Be–t/
, where A and B are constants, t is the elapsed time after peak exercise, and is the time constant of recovery) by nonlinear least-squares regression analysis. We then estimated the time course of HRV by time-domain and frequency-domain analysis as follows. Instead of parameters such as the standard deviation of the average interval between normal beats, which is substantially influenced by dynamic changes in overall trend, serial changes in HRV were assessed by 30-s averages of the absolute values of successive beat-to-beat differences in the RR interval (RR). Serial changes in HRV were also evaluated by 30-s averages of the beat-to-beat percent changes [absolute successive differences relative to instantaneous RR interval (%RR)] to eliminate the effect of the individual variation in HR.
Power spectral analysis of RR interval changes was also performed by fast Fourier transformation. We serially computed the spectrum of RR interval data of 1-min duration with 50% overlapping of each segment (0–1 min, 0.5–1.5 min, ...., 4.5–5.5 min, 5–6 min; 11 segments in all). The linear trend in the data was subtracted from the data set in each segment. A Blackman-Harris window was applied to reduce spectral leakage.
Statistical analysis.
Data are presented as means ± SD. Serial changes in variables were evaluated by repeated-measures ANOVA followed by Scheffè's test for intergroup and intragroup comparisons. Student's unpaired and paired t-tests, linear regression analysis, multiple linear regression analysis, and 
2-analysis were used when applicable. A P value of <0.05 was considered statistically significant.
|
RESULTS
|
|---|
All exercise tests were completed without any unfavorable events or serious complications. Exercise test parameters including exercise duration, resting and peak HR, resting and peak systolic blood pressure, the maximum magnitude of ST segment depression, and the occurrence of exercise-induced angina were consistently similar between the RCA and LAD groups (Table 2). Only peak HR tended to be lower in the RCA group (126 ± 22 beats/min) than in the LAD group (135 ± 21 beats/min), but this difference did not reach statistical significance.
Postexercise systolic blood pressure and HR.
There was no significant difference between the groups with respect to postexercise systolic blood pressure and HR at 1, 2, and 4 min of recovery (Fig. 1).
View larger version (19K):
[in this window]
[in a new window]
|
Fig. 1. Time course of systolic blood pressure (top) and heart rate [HR, in beats/min (bpm); bottom] in right coronary artery (RCA) stenosis (closed circles) and left anterior descending artery (LAD) stenosis (open circles) patients. No differences were observed in either parameter. Values are expressed as means ± SD.
|
|
Postexercise HR decay and HRV.
Shown in Fig. 2 are representative examples of the time series of beat-by-beat HR and absolute value of the successive RR interval changes throughout the exercise test. A patient with RCA stenosis (Fig. 2, left) showed a transient increase in RR variability soon after the termination of exercise, whereas such findings were not observed in a patient with LAD stenosis (Fig. 2, right). The time constant was shorter in the former (92 s) than in the latter (112 s).
View larger version (19K):
[in this window]
[in a new window]
|
Fig. 2. Representative trends of beat-by-beat HR (top) and absolute values of successive beat-to-beat differences in the RR interval (RR; bottom) from rest to recovery in a patient with RCA stenosis (left) and in a patient with LAD stenosis (right). A transient increase in HR variability (HRV) can be seen soon after exercise in the patient with RCA stenosis.
|
|
When pooled data were compared between the two groups, the time constant of postexercise HR decay was slightly but significantly shorter in RCA than LAD patients (79 ± 24 vs. 93 ± 29 s, P < 0.01). More significantly, postexercise HRV expressed by RR (average over every 30 s) early after exercise was markedly greater in RCA than LAD patients for a period of 1.0–2.5 min (P < 0.001 for all; Fig. 3A). %RR was similarly greater in RCA patients than in LAD patients in the same period of 1.0–2.5 min after exercise (P < 0.001 for 1.0–2.0 min and P < 0.01 for 2.5 min; Fig. 3B).
Figure 4, top, shows serial changes in the power spectrum of RR intervals in the recovery period analyzed in the same two patients shown in Fig. 2. As can be seen, unlike the patient with LAD stenosis (Fig. 4, right), the patient with RCA stenosis (Fig. 4, left) showed substantial amounts of power spectra in the frequency range between 0.30 and 0.60 Hz. When these data were pooled (Fig. 4, bottom), total power within the frequency range between 0.25 and 0.60 Hz (corresponding to the respiratory rates after exercise) was significantly higher in the RCA group than in the LAD group in the four time window segments early after exercise, i.e., 0.5–1.5 min, 1.0–2.0 min, 1.5–2.5 min, and 2.0–3.0 min (P < 0.005 for the first 3 segments and P < 0.02 for 2.0- to 3.0-min segment).
View larger version (29K):
[in this window]
[in a new window]
|
Fig. 4. Top: representative data of power spectrum analysis of HRV obtained in the same 2 patients shown in Fig. 2 (left, RCA stenosis patient; right, LAD stenosis patient). Horizontal lines depict the frequency (in Hz). The data series of power spectrum for 1 min are shown serially from the top (0–1 min) downward with time of recovery (overlapping 30 s). The spectral component of RR intervals for each segment is shown as the square root of the power (i.e., amplitude). Bottom: pooled data of power spectrum analysis in the RCA stenosis group (left; n = 52) and LAD stenosis group (right; n = 51).
|
|
Figure 5 shows scatterplots of RR at 1.5 min (60–90 s) versus the time constant for all patients. There was a relatively close relationship (r = –0.50, P < 0.001) between these parameters. When RR at 1.5 min (60–90 s) for each patient was plotted separately in RCA and LAD patients (Fig. 6), the prevalence of pronounced HRV (exceeding 12 ms) was much more frequently found in RCA patients (58%) than in LAD patients (16%, P < 0.001). Subgroup analysis of RCA patients showed that those with enhanced HRV were significantly younger (58 ± 11 vs. 64 ± 8 yr, P < 0.01) and had a significantly lower HR at rest (61 ± 10 vs. 70 ± 12 beats/min, P < 0.01) and peak HR (117 ± 19 vs. 139 ± 18 beats/min, P < 0.01) compared with those without this phenomenon. There was no significant difference with respect to sex, left ventricular ejection fraction, the use of cardiovascular drugs (-blockers, calcium antagonists, or nitrates), prevalence of previous myocardial infarction, history of diabetes mellitus, exercise time, magnitude of ST depression, occurrence of exercise-induced angina, or resting RR level. When multiple linear regression analysis that included clinical, angiographic, and exercise variables was used in the overall population, age (P = 0.02), resting HR (P = 0.04), and peak exercise HR (P = 0.02) together with the location of ischemia (P < 0.0001) were independently associated with RR (60–90 s).
View larger version (15K):
[in this window]
[in a new window]
|
Fig. 5. Graph showing the relationship between RR (60–90 s) and the time constant. Closed circles, RCA stenosis patient; open circles, LAD stenosis patient.
|
|
Effects of revascularization on postexercise HR decay and HRV.
In either the RCA or LAD patient group, HR at both rest and the end of exercise were not significantly different before and after revascularization (note that the second test was terminated at the same duration as was achieved at the first test). In RCA patients, HR at 1 and 2 min of recovery were significantly higher (both P < 0.05) after than before revascularization, whereas no such significant differences were observed in LAD patients.
After revascularization, in RCA patients, RR early after exercise was significantly attenuated (from 22 ± 14 to 9 ± 5 ms for 60–90 s, from 25 ± 12 to 11 ± 5 ms for 90–120 s, and from 27 ± 13 to 13 ± 5 ms for 120–150 s, all P < 0.05; Fig. 7). The time constant was concordantly prolonged (from 73 ± 21 to 96 ± 30 s, P < 0.05). Both parameters in RCA patients changed toward the same level as those in LAD patients, in whom both parameters remained unchanged after the revascularization procedure. There was no significant difference in systolic blood pressure at any time point in both RCA and LAD patient groups.
View larger version (12K):
[in this window]
[in a new window]
|
Fig. 7. Changes in the HRV (RR) time course after revascularization in the RCA (left; n = 52) and LAD (right; n = 51) stenosis groups. Open circles depict the values before the procedure, and closed circles depict the values after the procedure. Values are expressed as means ± SD. *P < 0.05, before vs. after revascularization.
|
|
|
DISCUSSION
|
|---|
Although potent cardioinhibitory vagal reflex stimulated by inferior ischemia (the so-called Bezold-Jarisch reflex) has been recognized under particular conditions of transmural ischemia in animal and human studies (7, 12, 15, 21, 22, 24, 28), whether exercise-induced transient subendocardial ischemia could evoke this reflex has received little attention and has not been previously examined. The present study indicated that exercise-induced inferior ischemia with ST depressions reflecting subendocardial ischemia, which might be recurrently experienced in daily activities, activates the cardioinhibitory reflex as evidenced by a faster postexercise HR decay and more pronounced HRV in RCA patients compared with LAD patients. In addition, removal of inferior ischemia by revascularization prolonged the time constant and reduced pronounced HRV in the early recovery in RCA patients, whereas revascularization did not significantly change these parameters in LAD patients. These findings, indicative of the direct role of "localized inferior ischemia" on the appearance of this phenomenon, support the validity of our hypothesis that transmural severe ischemia is not a prerequisite for the manifestation of this reflex.
Estimation of vagal activity.
Numerous previous studies have indicated the clinical importance of estimating the vagal activity regulating the cardiovascular system in patients with heart disease by noninvasive methods such as HRV analysis (1, 11, 13, 23a) and baroreflex sensitivity measurements with phenylephrine injection (3, 13, 14). After a report of Imai et al. (10) demonstrating that the rate of HR decay after exercise is a function of the reactivation of vagal activity, recent studies have shown the postexercise HR fall is a useful marker for predicting mortality in subjects with suspected CAD (5, 18, 26). In the present study, to assess the dynamic changes in vagal activity, serial HRV analysis during recovery was conducted by calculating RR and %RR every 30 s along with the evaluation of the HR decay (time constant). As a result, both HRV parameters in RCA patients markedly increased from 0.5 to 1 min of recovery, remained rather constant up to 2.5 min, and thereafter decreased nearly to the level of those in LAD patients. The group difference was more striking compared with that of the time constant. The characteristic overshooting of the HRV parameters suggests a transiently enhanced vagal activity as a "reperfusion reflex" after the resolution of exercise-induced ischemia. In agreement with its observed time course, frequency analysis also revealed a transient augmentation of power spectrum of RR intervals in high-frequency ranges early after exercise, supporting the validity of reperfusion-stimulated vagal overactivation.
It should be of importance that, in the present study, the exercise duration after revascularization was matched to that before the procedure. This is because a higher level of exercise intensity, as a consequence of the removal of critical stenosis, would alter the postexercise autonomic activity, possibly making it difficult to estimate the direct effects of revascularization.
Cardioinhibitory reflex activated by exercise-induced ischemia.
To the best of our knowledge, no previous study has been systematically conducted to evaluate the possible role of exercise-induced ischemia with ST depressions on this reflex phenomenon. Miller et al. (16) reported on seven patients who developed sinus deceleration during exercise testing, all of whom had angiographically documented RCA lesions. The authors speculated the role of Bezold-Jarisch reflex in this mechanism and stated that the prevalence of deceleration during exercise appears to be very low, which is in agreement with our experiences in the exercise laboratory. Sinus deceleration during exercise may be an extreme example caused by an ischemia-mediated reflex (4, 6).
Thus this reflex phenomenon is presumably operative during exercise-induced ischemia as well as during postexercise reperfusion; however, we focused on postexercise HR dynamics for the following reasons. Because vagal activity is physiologically attenuated in proportion to the increase in exercise intensity, this reflex might be masked during exercise. In contrast, potent reactivation of vagal nerve activity after exercise may accelerate the appearance of this reflex under a higher vagal condition after exercise. In practice, several cases among RCA patients showed a pronounced HRV and marked impairment of HR increase even during exercise indicative of the operation of this reflex during exercise; however, we also found a markedly rapid HR decay and more profound increase in HRV during recovery almost without exception.
The physiological implication of this reflex, namely, what role this reflex may play, is unknown. The possibility that the reflex cardioprotectively works thorough the reduction in myocardial oxygen demand or that the resultant high vagal tone prevents the development of serious ventricular arrhythmias is of interest (9, 19); however, there are few available data to support this so far.
Pronounced HRV after exercise (defined as RR > 12 ms) was observed in 58% of RCA patients but in only 16% of LAD patients. These prevalences are very similar to those during the observation of the "bradycardia-hypotension" pattern observed in patients early after acute inferior and anterior myocardial infarction, respectively (27). The difference probably indicates that the vagal nerves involving this reflex are preferentially distributed in the inferior area but some mounts of fibers are distributed in the anterior area of the left ventricle.
In RCA patients, none of the clinical, angiographic, and exercise parameters differed between patients with and without this phenomenon except in regard to age, resting HR, and peak HR. All of these three parameters were independently associated with HRV early after exercise in our multiple regression analysis. Vagal activity is known to be strongly associated with age and resting HR. Thus it is suggested that the presence or absence of this phenomenon would depend on the basal level of vagal activity rather than other parameters such as severity of ischemia or the presence of previous myocardial infarction.
Clinical implications.
The findings demonstrated in the present study should provide a new insight into the interpretation of estimated vagal activity in patients with CAD. It is widely accepted that autonomic imbalance, i.e., vagal withdrawal and coexisting sympathetic activation, is associated with poor prognosis and pathophysiology in various types of heart disease (25). In other words, we believe that the higher the vagal activity, the better the patient prognosis and status. However, present data suggest that this is not necessarily the case in some patients under certain conditions. For example, studies using Holter recordings showed that a considerable number of patients with documented CAD frequently experience episodes of transient myocardial ischemia in their daily life (17). In such patients, transient enhancement of HRV provoked by inferior ischemia may often occur, leading to an erroneous interpretation of HRV. In addition, there are several studies (5, 18, 26) that related a poor prognosis to attenuated HR recovery after exercise testing on the assumption that a fall in HR recovery immediately after exercise is a function of vagal reactivation. These findings might be true in the overall population; however, it should be noted that a rapid HR decrease after exercise may occur under a pathological condition through an ischemia-mediated cardioinhibitory reflex. HRV measures might be affected not by the patient status but by the presence of inferior ischemia.
We did not analyze postexercise parameters in subjects without CAD. This is because they should be capable of exercising far longer than our patients with exercise-induced ischemia, which may considerably influence the postexercise vagal activity. At present, we can consider that the vagal overactivation after exercise may be useful in predicting the presence of inferior ischemia when significant exercise-induced ST depressions are observed. It may also be useful in patients after angioplasty of RCA disease to predict restenosis or to confirm the therapeutic effects.
Study limitations.
It is generally considered that anterior ischemia is more deleterious than inferior ischemia in terms of hemodynamics, leading to a more severe autonomic impairment, i.e., a more depressed vagal activity in LAD patients. Thus the observed differences in vagal activity between the groups might be caused not only by the cardioinhibitory reflex evoked by inferior ischemia but also by the differences in hemodynamic impairment. For this reason, we evaluated the changes in vagal parameters (time constant and RR) after revascularization and found that these parameters were significantly altered in RCA patients but not in LAD patients. This strongly supports the notion that the differences in estimated vagal activity between the groups are determined primarily by the presence or absence of inferior located ischemia. Nevertheless, we cannot completely exclude the possible contribution of the different sympathetic tone between the groups, because anterior located ischemia, although rare, can stimulate this reflex.
In conclusion, as well as transmural myocardial ischemia with ST elevations such as that occurring with acute inferior myocardial infarction, exercise-induced transient inferior subendocardial ischemia with ST depressions, which might be recurrently experienced in daily activities, activates cardioinhibitory reflex by stimulating vagal nerve endings in humans. This hitherto-unknown findings must be taken into account in the estimation of vagal function conducted in various clinical settings, especially when evaluating patients with CAD.
|
GRANTS
|
|---|
This study was supported by Ministry of Health and Welfare of Japan Research Grant for Cardiovascular Diseases 11C-7, by Japan Society for the Promotion of Science Grant-In-Aid for Scientific Research C-11670730, and by the Program for Promotion of Fundamental Studies in Health Science from the Organization for Pharmaceutical Safety and Research.
|
FOOTNOTES
|
|---|
Address for reprint requests and other correspondence: H. Takaki, Dept. of Cardiovascular Dynamics, National Cardiovascular Center Research Institute, 5-7-1 Fujishiro-dai, Suita, Osaka 565-8565, Japan (E-mail: htakaki{at}res.ncvc.go.jp)
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
|
REFERENCES
|
|---|
- Algra A, Tijssen JGP, Roelandt JRTC, Pool J, and Lubsen J. Heart rate variability from 24-hour electrocardiography and the 2-year risk for sudden death. Circulation 88: 180–185, 1993.[Abstract/Free Full Text]
- Arai Y, Saul JP, Albrecht P, Hartley LH, Lilly LS, Cohen RJ, and Colucci WS. Modulation of cardiac autonomic activity during and immediately after exercise. Am J Physiol Heart Circ Physiol 256: H132–H141, 1989.[Abstract/Free Full Text]
- Bigger JT Jr, La Rovere MT, Steinman RC, Fleiss JL, Rottman JN, Rolnitzky LM, and Schwartz PJ. Comparison of baroreflex sensitivity and heart period variability after myocardial infarction. J Am Coll Cardiol 14: 1511–1518, 1989.[Abstract]
- Chokshi SK, Sarmiento J, Nazari J, Mattioni T, Zheutlin T, and Kehoe R. Exercise-provoked distal atrioventricular block. Am J Cardiol 66: 114–116, 1990.[CrossRef][Web of Science][Medline]
- Cole CR, Blackstone EH, Pashkow FJ, Snader CE, and Lauer MS. Heart rate recovery immediately after exercise as a predictor of mortality. N Engl J Med 341: 1351–1357, 1999.[Abstract/Free Full Text]
- Coplan NL, Morales MC, Romanello P, Wilentz JR, and Moses JW. Exercise-related atrioventricular block: influence of myocardial ischemia. Chest 100: 1728–1730, 1991.[Abstract/Free Full Text]
- Felder RB and Thames MD. Interaction between cardiac receptors and sinoaortic baroreceptors in the control of efferent cardiac sympathetic nerve activity during myocardial ischemia in dogs. Circ Res 45: 728–736, 1979.[Free Full Text]
- Huikuri HV, Valkama JO, Airaksinen KEJ, Seppanen T, Kessler KM, Takkunen JT, and Myerburg RJ. Frequency domain measures of heart rate variability before the onset of nonsustained and sustained ventricular tachycardia in patients with coronary artery disease. Circulation 87: 1220–1228, 1993.[Abstract/Free Full Text]
- Imai K, Sato H, Hori M, Kusuoka H, Ozaki H, Yokoyama H, Takeda H, Inoue M, and Kamada T. Vagally mediated heart rate recovery after exercise is accelerated in athletes but blunted in patients with chronic heart failure. J Am Coll Cardiol 24: 1529–1535, 1994.[Abstract]
- Kleiger RE, Miller JP, Bigger JT Jr, Moss AJ, and the Multicenter Postinfarction Research Group. Decreased heart rate variability and its association with increased mortality after acute myocardial infarction. Am J Cardiol 59: 256–262, 1987.[CrossRef][Web of Science][Medline]
- Koren G, Weiss AT, Ben-David Y, Hasin Y, Luria MH, and Gotsman MS. Bradycardia and hypotension following reperfusion with streptokinase (Bezold-Jarisch reflex): a sign of coronary thrombolysis and myocardial salvage. Am Heart J 112: 468–471, 1986.[CrossRef][Web of Science][Medline]
- La Rovere MT, Bigger JT Jr, Marcus FI, Mortana A, and Schwartz PJ for the Autonomic Tone and Reflexes After Myocardial Infarcion Investigators. Baroreflex sensibility and heart-rate variability in prediction of total cardiac mortality after myocardial infarction. Lancet 351: 478–484, 1998.[CrossRef][Web of Science][Medline]
- La Rovere MT, Specchia G, Mortara A, and Schwartz PJ. Baroreflex sensitivity, clinical correlates, and cardiovascular mortality among patients with a first myocardial infarction: a prospective study. Circulation 78:816–824, 1988.[Abstract/Free Full Text]
- Mark AL. The Bezold-Jarisch reflex revisited: clinical implications of inhibitory reflexes originating in the heart. J Am Coll Cardiol 1: 90–102, 1983.[Abstract]
- Miller TD, Gibbons RJ, Squires RW, Allison TG, and Gau GT. Sinus node deceleration during exercise as a marker of significant narrowing of the right coronary artery. Am J Cardiol 71: 371–373, 1993.[CrossRef][Web of Science][Medline]
- Mulcahy D, Husain S, Zalos G, Rehman A, Andrews NP, Schenke WH, Geller NL, and Quyyumi AA. Can ambulatory monitoring identify high-risk patients with stable coronary artery disease? JAMA 277: 318–324, 1997.[Abstract/Free Full Text]
- Nishime EO, Cole CR, Blackstone EH, Pashkow FJ, and Lauer MS. Heart rate recovery and treadmill exercise score as predictors of mortality in patients referred for exercise ECG. JAMA 284: 1392–1398, 2000.[Abstract/Free Full Text]
- Pedretti R, Etro MD, Laporta A, Braga SS, and Caru B. Prediction of late arrhythmic events after acute myocardial infarction from combined use of noninvasive prognostic variables and inducibility of sustained monomorphic ventricular tachycardia. Am J Cardiol 71: 1131–1141, 1993.[CrossRef][Web of Science][Medline]
- Perini R, Orizio C, Comande A, Castellano M, Beschi M, and Veicsteinas A. Plasma norepinephrine and heart rate dynamics during recovery from submaximal exercise in man. Eur J Appl Physiol 58:879–883, 1989.
- Prez-Gomez F, Martin de Dios R, Rey J, and Aguado AG. Prinzmetal's angina: reflex cardiovascular response during episode of pain. Br Heart J 42: 81–87, 1979.[Abstract/Free Full Text]
- Robertson RM and Robertson D. The Bezold-Jarisch reflex: possible role in limiting myocardial ischemia. Clin Cardiol 4: 75–79, 1981.[Medline]
- Sato I, Tomobuchi Y, Funahashi T, Ohe T, Kamakura S, Matsuhisa M, Haze K, and Shimomura K. Poor responsiveness of heart rate to treadmill exercise in vasospastic angina. Clin Cardiol 8: 206–212, 1985.[Web of Science][Medline]
- Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. Heart rate variability: standards of measurement, physiology interpretation, and clinical use. Circulation 93: 1043–1065, 1996.[Free Full Text]
- Thames MD, Klopfenstein HS, Abboud FM, Mark AL, and Walker JL. Preferential distribution of inhibitory cardiac receptors with vagal afferents to the inferoposterior wall of the left ventricle activated during coronary occlusion in the dog. Circ Res 43: 512–519, 1978.[Abstract/Free Full Text]
- Tsuji H, Larson MG, Venditti FJ, Manders ES, Evans JC, Feldman CL, and Levy D. Impact of reduced heart rate variability on risk for cardiac events: the Framingham Heart Study. Circulation 94: 2850–2855, 1996.[Abstract/Free Full Text]
- Watanabe J, Thamilarasan M, Blackstone EH, Thomas JD, and Lauer MS. Heart rate recovery immediately after treadmill exercise and left ventricular systolic dysfunction as predictors of mortality: the case of stress echocardiography. Circulation 104: 1911–1916, 2001.[Abstract/Free Full Text]
- Webb SW, Adgey AAJ, and Pantridge JF. Autonomic disturbance at onset of acute myocardial infarction. Br Med J 3: 89–92, 1972.[Abstract/Free Full Text]
- Wei JY, Markis JE, Malagold M, and Braunwald E. Cardiovascular reflexes stimulated by reperfusion of ischemic myocardium in acute myocardial infarction. Circulation 67: 796–801, 1983.[Abstract/Free Full Text]
Copyright © 2005 by the American Physiological Society.
TOP
ABSTRACT
METHODS
