Hemodynamic patterns and duration of post-dynamic exercise hypotension in hypertensive humans

We investigated: 1 the mechanism of the hypotensive effect of a single bout of dynamic exercise in hypertensive subjects by measuring hemodynamic parameters before and for 2 h after trea

Medicine & Science in Sports & Exercise: Volume 28(1) January 1996 pp 24-32

Hemodynamic patterns and duration of

post-dynamic exercise hypotension in hypertensive humans

RUECKERT, PATRICIA A.; SLANE, PETER R.; LILLIS, DIANE L.; HANSON, PETER

Department of Medicine, Cardiology Section, University of Wisconsin Medical School, Madison,

WI 53792-3248

Submitted for publication February 1995

Accepted for publication August 1995

We thank the patients who participated in this study and Shari Clark for her technical assistance with the hemodynamic measurements

Address for correspondence: Patricia A Rueckert, Ph.D., Cardiology Section H6/349, University

of Wisconsin Medical School, 600 Highland Avenue, Madison, WI 53792-3248

We investigated: 1) the mechanism of the hypotensive effect of a single bout of dynamic exercise

in hypertensive subjects by measuring hemodynamic parameters before and for 2 h after treadmill exercise, and 2) the duration of the effect using ambulatory blood pressure (BP) monitoring once the subjects left the test site Ten minutes after exercise there was a significant decrease from baseline systolic pressure (SP; -14 ± 3 mm Hg), mean arterial pressure (MAP; -7

± 2 mm Hg), total peripheral resistance(TPR; 3.7 ± 1.2 units), calf vascular resistance (CVR; -25.4 ± 4.1 units), and an increase in HR (19 ± 2 bpm) The changes in SP, DP, MAP, and HR were maintained during the 2 h of post-exercise monitoring; CVR remained decreased for 1 h; TPR returned to baseline within 20 min and then tended to be slightly elevated CO was

significantly decreased at 50, 60, and 120 min after exercise We conclude that the early decline

in BP after dynamic exercise in hypertensive subjects follows a biphasic pattern: 1) an initial decrease in total and regional vascular resistance with maintained CO, 2) followed by increasing resistance and decrease CO Pre-exercise hypertensive BP values returned during subsequent ambulatory monitoring

Resting blood pressure (BP) in hypertensive individuals is often lower or normalized after

exercise training (2,22) as well as after a single bout of dynamic

exercise(9,13,18,21,23,33,40) There is less consensus concerning the hypotensive effect

of an acute bout of exercise in normotensive individuals, although there are also reports of lowered BP after such exercise in this group(10,21,40) The mechanism of thispost-exercise hypotension, however, is poorly understood

Reported decreases in regional vascular resistance after a single bout of dynamic exercise (9,10) may be due to lowered efferent muscle sympathetic nerve activity (13), reduced alpha-adrenergic responsiveness (17), vasodilatory metabolites (10,21), or

thermoregulatory-induced increases in skin blood flow (15) Although most investigators observe a decrease in total peripheral resistance (TPR)(9,21), this is not a universal finding

Changes in post-exercise heart rate (HR) and cardiac output (CO) have also been

inconsistent and may be influenced by exercise intensity or initial hemodynamic state of the subjects Hagberg et al (18) found that older subjects had decreased CO because of a reduced stroke volume(SV) and unchanged HR after exercise, whereas other studies found increased CO(9) and HR (13) Reductions in CO were suggested as the primary

hemodynamic mechanism for the post-exercise hypotension in hypertensive rats (32)

Few investigators have addressed the question of the duration of the acute post-exercise decline in BP Using ambulatory BP monitoring, Pescatello et al.(33) concluded that post-exercise BP were lower than pre-post-exercise levels for 8-12 h after post-exercise Somers et al.(40), however, could demonstrate no sustained drop in either systolic (SP) or diastolic pressure (DP) once their subjects left the lab and took their own BP at home

Thus, many unanswered questions remain regarding not only the mechanism of the acute hypotensive effect of dynamic exercise but the time course and duration of the effect Our study is unique in that it measured central and peripheral hemodynamics during the first 2 h after exercise and then continued to assess the duration of BP changes using ambulatory blood pressure monitoring

We hypothesized that regional vasodilation in the legs contributing to a decrease in TPR after treadmill exercise would play an important role in the post-exercise decline in BP Frequent measurements were designed to allow the determination of the time course of both central and regional hemodynamic changes early after exercise Since only two studies with conflicting results have examined the duration of the hypotensive response to dynamic exercise, it was hoped that our study would provide additional needed information

on this aspect of post-exercise hypotension

METHODS TOP

Subjects TOP

Eighteen nonsmokers (50 ± 2 yr of age; height 177 ± 2 cm; weight 87 ± 3 kg; 5 females, 13 males) with Stage 1 to Stage 2 essential hypertension participated in the study They were former participants in research and clinical protocols in our laboratory and were familiar with exercise testing and the measurement procedures we used Eight of the subjects had never

taken medication for hypertension and the others were taking ACE inhibitors (N = 4), calcium channel antagonists(N = 2), betablockers (N =3), or diuretics (N = 1) None were

receiving antihypertensive therapy during the study; those treated pharmacologically for hypertension stopped taking their medications at least 2 wk before the study Subjects gave written consent for participation in the study, which was approved by the University of Wisconsin-Madison Center for Health Sciences Human Subjects Committee and was in accordance with the policy statements of the American College of Sports Medicine

Protocol TOP

On the exercise day, subjects reported to the lab at 0800 They were asked to avoid caffeine that morning but were told to eat breakfast if it was their normal routine ECG and transthoracic CO impedance electrodes were applied, and a flexible intravenous catheter was inserted into an antecubital vein for multiple blood sampling Subjects then moved to a semi-recumbent position on a padded table and rested for 15 min while the measuring instruments were calibrated Pre-exercise hemodynamic measurements were made and a blood sample was obtained The subjects then moved from the table, went to the bathroom

if necessary, and were weighed to the nearest 0.1 kg

After a brief warm-up period on the treadmill, the subjects walked for 45 min at a speed and grade that was adjusted to maintain their HR at 70% of HR reserve (Resting HR +

0.70[Predicted max HR - Resting HR]) BP were measured every 5 min by

sphygmomanometry and HR were continuously monitored by ECG and recorded every 5 min Room temperature was maintained at 23-24°C throughout the morning

Subjects were weighed after exercise, rehydrated by mouth with water equivalent to the weight lost during exercise, and resumed the semi-recumbent resting position for the next

60 min Post-exercise hemodynamic measurements were made every 10 min during this hour Blood samples were drawn at 10, 30, 60, and 120 min

During the second hour, subjects moved from the padded table, the ambulatory BP monitor was positioned, and comparisons were made between auscultatory BP in the seated and standing positions and monitor readings A final set of post-exercise hemodynamic

measurements was made 2 h after exercise when the subjects had again been in the semi-recumbent position for 10 min

Resting Control Study TOP

A subset of subjects was asked to return to the test site at a later date to study the effect of

45 min of rest followed by 1 h of semi-recumbency on the hemodynamic parameters The subjects were told that they were returning for a reproducibility study of the treadmill exercise protocol Afterpre-exercise measurements were made, the subjects were then told

to relax in a chair for 45 min instead of exercise Hemodynamic measurements were performed every 10 min for 1 h after this rest period

Hemodynamic Measurements TOP

BP were measured with a mercury manometer by the same person and in the same arm; disappearance of the fourth Korotkoff sound was used as the DP HR was obtained from the ECG Calf blood flow (CBF) was measured by venous occlusion plethysmography (17) and calf vascular resistance (CVR) calculated from mean arterial pressure (MAP)/CBF

Transthoracic impedance cardiography utilizing R-wave triggered computerized ensemble signal averaging analysis (SORBA Medical Systems, Inc., Brookfield, WI) was used to determine SV and CO CO obtained with this technology are equivalent to those determined

by thermodilution(30,34) over a broad range of values and are particularly reliable when used for repeated resting measurements as was done in this study In our hands, the coefficient of variation for resting measurements is 5.5% TPR was calculated from

MAP/CO and the Heather Index(HI) for cardiac contractility was calculated from the quotient

of dZ/dtmax/QZ1 (30) DZ/dtmax, the magnitude of the peak value of the impedance derivative, correlates closely with aortic velocity (26) The quotient of dZ/dtmax and the pre-ejection time (Q) and rapid ejection time (Z1) provides a timed index of myocardial contractility (26)

Plasma Volume Change Determination TOP

The hematocrit (Hct), measured in duplicate using a microhematocrit method, was

corrected for plasma trapped with red blood cells and for venous-to-total body Hct ratio (7) Hemoglobin (Hb) was measured in duplicate on a Copenhagen OSM3 Hemoximeter Hct and Hb values were used to calculate percentage change in plasma volume using the equations of Dill and Costill (12)

Ambulatory BP Monitoring TOP

Thirteen of the hypertensive subjects underwent ambulatory BP monitoring with a Suntech Accutracker II monitor on two days: 1) a nonexercise control day and 2) after the

hemodynamic measurements on the exercise day Subjects were asked to plan similar levels of activity for the two days of monitoring but otherwise went about their normal activities The recording was considered acceptable if at least 85% of the readings met the editing criteria BP were deleted if DP were ≥ 130 mm Hg, if systolic blood pressures (SP) were<80 mm Hg or >240 mm Hg, or if the pulse pressure was <20 mm Hg Eleven of the 13 patients met the 85% acceptable values criteria

Data Analysis TOP

Results are reported as mean ± SE Repeated measures analysis of variance (ANOVA) was used to compare post-exercise values to pre-exercise values during the 2-h

hemodynamic portion of the study Where overall significance was found, the least

significant difference posthoc test (protected LSD) was used to detect significant differences

between individual means (38) Student's t-tests for paired data were used to compare control day and exercise day BP and HR.P-values of less than 0.05 were required for

statistical significance

RESULTS TOP

Pre-exercise TOP

To examine the possibility that there may be an anticipatory increase in BP before exercise,

we compared pre-exercise pressures with those obtained in the morning on the nonexercise control day during the application of the ambulatory monitor There were no significant differences in SP exercise: 150 ± 4 mm Hg; control day: 148 ± 5 mm Hg), DP (pre-exercise: 102 ± 2 mm Hg; control day: 101 ± 2 mm Hg), or MAP(pre-(pre-exercise: 118 ± 2 mm Hg; control day: 117 ± 3 mm Hg) on the two days HR on the two days was also not

significantly different(pre-exercise: 71 ± 4 bpm; control day: 72±3 bpm)

Exercise TOP

During the 45 min of treadmill exercise the mean HR was 141 ± 2 bpm, SP was 171 ± 4 mm

Hg, and DP was 91 ± 2 mm Hg The average weight loss from the exercise was 0.5 ± 0.1 kg

Acute Hemodynamic Changes after Exercise TOP

Figure 1 presents the BP and HR measured in the lab before and after exercise

SP was significantly decreased at every measurement point during the entire 2 h after exercise The average drop in SP during the first hour was 11 ± 1 mm Hg

DP was significantly lower at 10 and 20 min after exercise and then gradually returned to pre-exercise levels The reading taken with the Suntech monitor at

120 min post-exercise was significantly lower than the auscultatory pre-exercise

DP MAP was significantly decreased during the first 60 min after exercise, with an average decline of 5 ± 1 mm Hg during this time The 120-min Suntech reading was also significantly decreased Ten minutes after exercise, there was

an increase in HR of 19 ± 2 bpm compared with rest, and a significant

tachycardia was maintained during the entire first hour and at 2 h post-exercise.

Figure 1-Blood pressures and heart rates before exercise (Pre), at 10-min intervals during the first hour after exercise, and at 120 min after exercise SP, systolic blood pressure; MAP, mean arterial

pressure; DP, diastolic blood pressure; HR, heart rate Values are mean ± SE N = 18 * Significantly

different from Pre

Total and regional vascular resistance changes are shown inFigure 2 TPR decreased

significantly after exercise (by 11% at 10 min) but then increased and tended to

be higher than the pre-exercise levels CVR fell by 48% 10 min after exercise

compared to pre-exercise It then remained significantly decreased during the

rest of the first hour and returned to pre-exercise levels at 2 h.

Figure 2-Total peripheral resistance and calf vascular resistance before exercise (Pre), at 10-min intervals during the first hour after exercise, and at 120 min after exercise TPR, total peripheral resistance (mm Hg/[l·min-1]); CVR, calf vascular resistance (mm Hg/[ml·100 ml-1·min-1]) Values

are mean ± SE N = 18 * Significantly different from Pre

CO, SV, plasma volume (PV), and cardiac contractility Heather index (HI) values are

presented in Table 1 CO initially tended to increase due to significant tachycardia and then

gradually decreased until it was significantly lower than the pre-exercise levels at 50, 60,

and 120 min after cessation of exercise SV was depressed significantly for the entire

post-exercise measurement period Changes in the HI of contractility were similar to those seen

for CO Relative changes in PV and HI were small compared with the - 14% to - 21%

decreases in SV and neither variable was significantly correlated with SV

TABLE 1 Cardiac output, stroke volume, plasma volume, and contractility changes after exercise

Resting Control Study TOP

Table 2 summarizes the data obtained prior to and for 1 h after 45 min of rest There was no significant drop in BP from pre- to post- measurements and no decline during the 1 h of semi-recumbency Rather, the tendency was for BP to rise slightly during this time The only significant changes observed were a decline in HR and an increase in CVR compared with pre-rest values

TABLE 2 Control hemodynamic parameters before and after 45 min of rest

Ambulatory BP and HR Results TOP

The ambulatory data were analyzed in two ways: 1) the mean BP and HR for the 12-h period from noon to midnight on the exercise day were compared with those on the control day, and 2) individual hourly BP and HR from noon to midnight on the exercise day were also compared with those on the control day There were no significant differences between exercise and control day SP, DP, and MAP when the 12-h blocks of time were compared (Table 3) There were no significant differences between hourly average SP or DP on the two days, with the exception of higher SP from 1300 to 1400 on the exercise day (Fig 3, A and B) HR on the exercise day tended to be higher than those on the control day until about 1800 HR were significantly higher from 1300-1400 and from 1600-1700 (Fig 4)

TABLE 3 Exercise day and control day blood pressures and heart rates for the 12 h from 1200

to 2400

Figure 3-A Hourly Accutracker ambulatory systolic blood pressures(SP) on the exercise day (▪) and on the control day (○) AM value = morning auscultatory SP measured either prior to exercise on the exercise day or during the application of the Accutracker on the

control day Values are mean ± SE N = 11 * P < 0.05 exercise day vs control day B

Hourly Accutracker ambulatory diastolic blood pressures (DP) on the exercise day(▪) and

on the control day (○) AM value = morning auscultatory DP measured either prior to exercise on the exercise day or during the application of the Accutracker on the control

day Values are mean ± SE N = 11.

Figure 4-Hourly Accutracker ambulatory heart rates (HR) on the exercise day (▪) and on the control day (○) AM value = morning HR prior to exercise on the exercise day or during

the application of the Accutracker on the control day Values are mean ± SE N = 11 * P <

0.05 exercise day vs control day.

DISCUSSION TOP

The major new finding of this study was that in middle-aged hypertensive subjects

performing a single 45-min session of treadmill exercise, there was an acute decline in BP, which was associated with a biphasic hemodynamic pattern Early after cessation of exercise vascular resistance was significantly lower than pre-exercise A dramatic decrease

in regional resistance in the previously active calf muscles contributed to the lower TPR As TPR normalized, a significant decrease in CO during the second hour after exercise contributed to the decline in BP

Conflicting results have been reported by the only two groups of investigators (33,40) who have examined the duration of post-exercise hypotension Our analysis using ambulatory

BP monitoring demonstrated that the post-exercise hypotension was transient, a finding in agreement with Somers et al (40) BP recorded once the subjects left the test site were not significantly different from those recorded at the same time period on a control nonexercise day

Initial Hemodynamic Changes (First 30 min after Exercise) TOP

We observed a dramatic 48% decrease in CVR 10 min after exercise This change is similar

in magnitude to that seen by Casiglia et al.(6) 10 min after semi-supine bicycle exercise The early decrease in regional resistance may be due to a number of factors including the effect of exercise induced metabolites(10,21), flow-mediated vasodilation(29), reduced alpha-adrenergic responsiveness(20) and thermodilation (15) The subsequent gradual increase in vascular resistance is consistent with a time-dependent clearance of

vasodilators and decreased thermodilation as normal body temperature is restored The stimulus for flow-mediated dilation would also decrease as leg blood flow returned to resting levels after exercise

Vasodilation in areas other than the exercised muscles may also contribute to the early decline in TPR Decreased forearm(6,9,10) and hand (9) vascular resistance have been documented following upright and semi-supine bicycle exercise

Although gripping the handlebars may result in some local forearm vasodilation early after bicycle exercise, there is also evidence that neural mechanisms may contribute to this decreased vascular resistance Cleroux et al (8) found that the decreased baseline forearm vascular resistance (FVR) seen 30 min after exercise resulted in a downward shift of the FVR-central venous pressure relationship and lead them to speculate that modulation of the cardiopulmonary baroreflex control of FVR contributes to the antihypertensive effect of exercise

Plasma levels of the vasodilatory peptide hormone atrial natriuretic peptide (ANP) are dramatically increased during exercise in patients with hypertension (25) and may play a role in post-exercise hypotension early after cessation of exercise Although the peptide has

a very short plasma half-life, the natriuretic response has been reported to persist for at least 1.5 h after completion of infusion (1) If the vasodilatory properties also persist, ANP may contribute to the sustained drop in BP

The early post-exercise decline in BP in humans (4) and spontaneously hypertensive rats (37) has been blocked with naloxone, an opioid receptor antagonist Activation of thin myelinated afferent fibers from exercising skeletal muscle may cause a reflex elevation of central endorphins and decrease central sympathetic outflow The observation that levels of norepinephrine are decreased 30 min after exercise compared with 30 min after a rest period on a control day(9) lends indirect support to this idea Furthermore, there is a similarity of the effects of cardiac afferent blockade using procainamide and opiate receptor antagonism that suggests that the signals from the heart regulate sympathetic

vasoconstrictors via an endogenous opioid mechanism (11) Thus, the inhibitory influence

of cardiac afferents on the circulation may be enhanced after exercise

Later Hemodynamic Changes (30 min-2 h after Exercise) TOP

During the interval from 30 min-2 h after exercise, TPR returned to pre-exercise levels but regional CVR continued to be reduced 30-60 min after exercise Our observation of a sustained drop in CVR 60 min after exercise is consistent with the findings of Floras et al (13) of decreased muscle sympathetic peroneal nerve activity 60 min after the same exercise protocol used in our study

There is also the possibility that local production of vasodilators such as lactate and nitric oxide (NO) continues beyond 30 min post exercise Plasma lactate levels after bicycle ergometer exercise remain elevated for approximately 25 min (5) A recent study provided evidence that skeletal muscle may be a source of NO production(3) Addition of muscle to incubation medium caused a 30-fold increase in the amount of NO during the initial hour of incubation demonstrating an efflux of NO from skeletal muscle Although reduced, efflux of

NO continued during the second hour of incubation The most prominent release of NO occurred from muscle that had been contracted by electrical stimulation

A significantly lower post-exercise CO contributed to the fall in SP 50 min-2 h after exercise Since the reduction in SV seen immediately after exercise was maintained during the entire post-exercise measurement period, changes in HR were the primary determinants of changes in post-exercise CO Early after exercise, CO was maintained by increased HR but from 50 min to 2 h, the increase in HR was not sufficient to prevent a significant decline in CO

A reduction in CO 1-3 h after exercise has been reported with older hypertensives (18) as well as with young hypertensives having rapid resting HR (14) Both groups of investigators speculated that there may have been a transient decrease in myocardial performance after