- Email: [email protected]
The effect of lower body weight support on arterial wave reflection in healthy adults
Journal of the American Society of Hypertension
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(2014) 1–6
Research Article
The effect of lower body weight support on arterial wave reflection in healthy adults Atif Afzal, MDa, Daniel Fung, MDa, Sean Galligan, MDa, Ellen M. Godwin, PhDb, John G. Kral, MD, PhDc, Louis Salciccioli, MDa, and Jason M. Lazar, MD, MPHa,* a
Division of Cardiovascular Medicine, State University of New York, Downstate Medical Center, Brooklyn, NY, USA; Human Performance Laboratory, State University of New York, Downstate Medical Center, Brooklyn, NY, USA; and c Department of Surgery, State University of New York, Downstate Medical Center, Brooklyn, NY Manuscript received December 20, 2013 and accepted March 13, 2014
b
Abstract Body weight support (WS) during treadmill exercise is used to rehabilitate orthopedic/neurological patients. WS lowers musculoskeletal strain and load. It compresses the lower body and increases intrathoracic volume. We studied short-term effects of WS on wave reflection indices using applanation tonometry during progressive WS of 25%, 50%, and 75% of body weight in 25 healthy men. WS decreased mean heart rate from 79 to 69 beats/min (P < .001). Peripheral and central mean arterial, systolic, and pulse pressures (PP) remained unchanged. There was a trend toward lower peripheral and central diastolic pressure. PP amplification ratio decreased significantly (P ¼ .005). Reflected wave characteristics: Augmented pressure and index increased in a stepwise manner with WS (both P < .001). Both ejection duration and systolic duration of the € r) increased progressively (both P < .001). The round-trip travel time (Dtp) was unchanged. Left reflected pressure wave (At ventricular workload and oxygen demand: Left ventricular wasted pressure energy increased (P < .001), and the subendocardial viability ratio decreased (P ¼ .005), whereas the tension time index remained unchanged. In normal men, WS acutely decreases the PP amplification ratio, increases the amplitude and duration of the reflected aortic pressure wave, and increases measures of wasted left ventricular pressure energy and oxygen demand. J Am Soc Hypertens 2014;-(-):1–6. Ó 2014 American Society of Hypertension. All rights reserved. Keywords: Aortic stiffness; applanation tonometry.
Introduction Weight support (WS) treadmill exercise has been advocated for rehabilitation of patients with orthopedic and neurological conditions.1–5 This method lowers the strain on joints and impact on muscles during treadmill exercise and allows for training in patients with acute and chronic disorders. WS treadmill systems have been used to simulate microgravity conditions and are commercially available.6,7 In general, such systems consist of a computer-controlled Conflict of interest: None. Financial support: None. *Corresponding author: Jason M. Lazar, MD, MPH, Director, Non-Invasive Cardiology, State University of New York, Downstate Medical Center, 450 Clarkson Ave, MSC 1199, Brooklyn, New York 11203-2098. Tel.: (718) 221-5222; fax: (718) 221-5220. E-mail: [email protected]
treadmill equipped with a pressurized air chamber that generates a vertical upward force directly opposing the force of gravity and effectively decreasing body weight. The airtight chamber is formed by neoprene shorts that zip around the waist, and form a kayak type skirt from the waist down. This chamber suspends the subject over the treadmill surface upon inflation. Variable degrees of WS can be achieved by pumping greater air pressure as WS is proportional to the level of lower body positive pressure. WS evokes a number of cardio-respiratory changes as a consequence of increased intrathoracic blood volume and lower extremity compression, including augmenting venous return, increasing stroke volume, and baroreceptor activation.6–15 Applanation tonometry is an increasingly utilized technique to noninvasively measure arterial stiffness, arterial wave reflection, and central aortic (CA) blood pressure (BP). CA-BP and brachial artery (BA) BP may differ substantially because of pressure wave amplification.16–18
1933-1711/$ - see front matter Ó 2014 American Society of Hypertension. All rights reserved. http://dx.doi.org/10.1016/j.jash.2014.03.004
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Greater arterial wave reflection is an independent predictor of adverse cardiovascular events.19,20 Higher CA pressures are due to higher reflected wave amplitude as well as to earlier arrival of the reflected pressure wave from the periphery back to the aortic root in a stiffer vasculature. This augmented pressure increases left ventricular (LV) afterload and adversely impacts ventricular-arterial coupling.21 The augmentation index (AI), which is the most commonly used measure of wave reflection, is the ratio of augmented pressure due to wave reflection to the CA pulse pressure (PP).17 Although widely viewed as a measure of afterload, AI appears to be related to LV contractile performance, as patients with depressed LV systolic function have lower AI values.22,23 Results from use of maneuvers to increase venous return suggest LV preload is an important determinant of wave reflection properties.24,25 However, the effects of increasing venous return on AI appear to depend on the specific technique used to vary preload. Water immersion increases the amplitude and duration of the reflected aortic pressure wave, whereas passive leg raising decreases the amplitude and delays the onset of the reflected wave.24,25 Inflation of the pressurized lower body air chamber of the WS treadmill while stationary provides an opportunity to vary intrathoracic loading conditions and study the effects on arterial wave reflection. Although WS-induced heart rate (HR) and BP changes have been studied, graded lower body compression has not been used to assess arterial functional properties. The objectives of this study were to characterize acute changes in noninvasive measures of arterial stiffness and wave reflection using applanation tonometry during WS in healthy male subjects.
Methods We prospectively studied a convenience sample of 25 healthy men, age 31 9 years (range, 22–59 years). The body mass index (BMI) was 24.5 3.6 kg/m2 (range, 18.6–30.5 kg/m2), and body surface area (BSA) was 1.96 0.21 m2 (range, 1.58–2.36 m2). Participants were without cardiovascular risk factors or disease via history. All subjects had adequate pulses and were in sinus rhythm. The institutional review board approved this study, and participants provided written consent. Baseline measurements (100% body weight) were recorded after 2 minutes of standing on the WS treadmill (AlterG Anti-Gravity Treadmill, Alter G, Fremont, CA, USA). Systolic (BA-SBP) and diastolic (BA-DBP) BA blood pressure was measured using an automated blood pressure cuff (Omron HEM-780) placed around the left arm. The weight of the subject was covertly measured by the treadmill. Baseline radial artery tonometry using SphygmoCor (AtCor Medical, Sydney, Australia) was performed to obtain the aortic waveform and baseline pulse wave analysis measurements.16,17 Then 25%, 50%, or 75% of body weight was supported. After
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2 minutes, BP and arterial tonometry measurements were repeated on the same outstretched arm resting on the treadmill rail. The degree of WS was adjusted to study levels in random order immediately after the measurements were obtained, without a rest period. BA mean arterial pressure (MAP) was calculated as diastolic pressure þ 1/3 pulse pressure (PP).
Pulse Wave Analysis Radial artery pressure waveforms were recorded at the wrist with the applanation tonometer according to previously published methods.17 In brief, the aortic pressure waveform was derived from the radial artery waveform by a previously validated generalized transfer function.26,27 The following parameters were obtained: augmentation pressure or reflected wave amplitude (PsPi), defined as the difference between peak systolic pressure (Ps) and pressure at the inflection point (Pi), which is the merging point of incident and reflected waves, incident (or forward) wave amplitude (PiPd), and AI, defined as reflected wave amplitude divided by PP and expressed as percentage (AI ¼ [PsPi]/[PsPd]). Pd is central diastolic pressure. AI was also normalized to a HR of 75 bpsm (AI75) since AI is heart-rate dependent.28 The round-trip travel time (Dtp) of the pressure wave to and from the major reflecting sites in the lower body was determined from the aortic pressure waveform.29 The systolic duration of the reflected pressure wave (Dtr) was determined from the inflection point to the incisura.17 (DtpþDtr) represents LV ejection duration (ED). ED was corrected for heart rate (EDc) according to the previously reported formula.30 Indices of LV workload and myocardial oxygen demand were also derived from the pressure waveform using the technique of pulse wave analysis.17,31 Wasted LV pressure energy (DEw) is defined as the extra energy that the LV must generate to overcome the augmented pressure. Wasted energy (DEw) is the area under the systolic portion of the reflected wave and is estimated from the equation DEw ¼ 1.05Dtr (PsPi).32 The tension time index (TTI) was obtained as the area under the systolic (AS) portion of the aortic pressure wave and that is related to work of the heart and to myocardial oxygen consumption.33 The ratio of the areas under the diastolic portion (AD) and systolic portion (AS) of the aortic waveform is associated with the perfusion pressure and time to coronary perfusion, and is therefore an approximation of energy supply of the heart. This ratio of supply and demand is termed the subendocardial viability ratio (SEVR) or Buckberg index (SEVR ¼ AD/AS).32–34
Statistical Methods All continuous data were expressed as mean standard deviation. A one-way repeated measures analysis of
A. Afzal et al. / Journal of the American Society of Hypertension
variance was performed using the four stages of weight support (baseline ¼ 0%, 25%, 50%, or 75% of body weight) for each participant. All statistical analyses used the Statistical Package for Social Sciences (SPSS) 20.0 software (SPSS Inc, Chicago, IL, USA). A P value <.05 was considered statistically significant.
Results Peripheral and central hemodynamic values before and during progressive WS are shown in Table 1 with representative aortic pressure waveforms in Figure 1.
Peripheral and Central Hemodynamics With progressive WS, the HR decreased from 79 12 to 69 11 beats per minute (P < .001). BA-SBP, MAP, and PP remained unchanged. BA-DBP decreased nominally upon WS, not reaching statistical significance. Changes in the CA pressures with WS mirrored the changes in the BA pressures. CA-SBP, mean aortic pressure, and central PP remained unchanged, whereas there was a trend toward lowering of CA-DBP. WS resulted in a significant decrease in the amplification ratio (P < .001).
Characteristics of Reflected Wave The amplitude of the reflected wave (augmented pressure or PsPi), AI, and the AI75 all increased in a stepwise
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3
manner from baseline with increasing WS. Both the EDc and Dtr also increased progressively (both P < .001). Dtp did not significantly change upon WS (P ¼ .75).
Measures of LV Workload and Oxygen Demand DEw increased (P < .001) and the SEVR decreased (P ¼ .005) with increasing WS, whereas the TTI remained unchanged (P ¼ .19).
Discussion The present study characterized changes in arterial wave reflection induced by WS at rest. Among a number of hemodynamic changes, the reflective wave component increased in amplitude and duration, but was unchanged in timing during the cardiac cycle. There was a decrease in HR as well as trends toward lowering of BA and central aortic DBP. These changes collectively increased LV workload and oxygen demand. The major finding was that WS increased the amplitude and the duration of the reflected pressure wave with a dose-response relationship to the degree of WS. AI is known to be inversely related to HR, which did decrease with increasing WS; however, in addition to AI, the HR-corrected AI75 also increased in a step-wise manner.28 Greater wave reflection may be related to increased forward stroke volume resulting from higher preload. Lower body
Table 1 Peripheral and central hemodynamic parameters at rest and during weight support Hemodynamic Parameters
Baseline
Heart rate (beats/min) Brachial artery SBP (mm Hg) Brachial artery DBP (mm Hg) Brachial artery PP (mm Hg) Brachial artery MAP (mm Hg) Central aortic SBP (mm Hg) Central aortic DBP (mm Hg) Central aortic PP (mm Hg) Central aortic MAP (mm Hg) PP amplification Augmented pressure (mm Hg) Incident pressure (Pi-Pd) (mm Hg) AI (%) AI75 (%) ED (ms) Corrected ED (EDc) (ms) Round trip travel time (Dtp) (ms) Reflected wave systolic duration (Dtr) (ms) Wasted LV energy (DEw) (dyne-sec-cm-2x 102) TTI (mm Hg/s/min x 102) SEVR (%)
79 121 77 44 92 105 78 26 91 1.7 0.1 25 0.24 2 256 278 146 109 0.54 32 180
12 12 8 10 8 10 8 6 9 0.13 3.2 6 11 10 22 21 8 22 4.4 7 37
25%WS 75 120 74 46 89 102 75 28 88 1.7 1.4 26 4.4 4 268 286 146 120 2.36 31 180
11 11 6 10 7 9 6 7 7 0.19 2.6 6 8.5 8 20 19 9 19 4.2 7 31
50%WS 71 119 74 45 89 104 75 28 88 1.6 2.0 26 7.5 5 283 292 148 134 3.50 31 181
12 10 9 10 9 9 10 6 9 0.16 2.7 6 9.8 10 23 20 8 22 4.6 7 37
75%WS 69 121 74 47 89 105 75 30 89 1.6 2.5 27 7.9 5 293 295 148 143 4.08 31 171
11 11 8 10 8 9 9 5 9 0.16 3.4 5 11.6 12 17 19 10 16 5.7 7 33
P Value <.001 .75 .09 .71 .22 .59 .085 .12 .29 .005 <.001 .41 <.001 .029 <.001 <.001 .75 <.001 <.001 .194 .005
AI, augmentation index; DBP, diastolic blood pressure; ED, ejection duration; LV, left ventricular; MAP, mean arterial pressure; PP, pulse pressure; SBP, systolic blood pressure; SEVR, subendocardial viability ratio; TTI, tension time index; WS, weight support.
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Figure 1. Effect of weight support on aortic pressure waveforms.
positive pressure is well known to centralize blood volume and to enhance venous return.6,7,9–15 WS has been shown to increase right ventricular preload through higher central venous pressure, which in turn increases left ventricular preload.10,12 LV stroke volume is increased, resulting in higher cardiac output despite lowered HR, potentially increasing both the amplitude and duration of the transmitted and reflected pressure wave generated by the same cardiac contraction.8,10 In support of this, prior studies have found AI to be related to LV ejection fraction and stroke volume.35–37 Although the amplitude and duration of the reflected wave increased, its timing remained unchanged, reflected in the unchanged round trip travel time. The higher stroke volume and longer LV ejection duration might be counterbalanced by shorter wave travel distance. The amplitude of the incident wave remained unchanged. The incident wave depends on the proximal aortic impedance, which was not measured. Although speculative, this finding may be a consequence of increased LV stroke volume and lower aortic impedance from lower transmural aortic pressure with WS. Decreased HR is consistent with prior studies and is likely related to baroreceptor activation via increased parasympathetic activity from centripetal blood transfer.6,9,15 Peripheral arterial responses to lower body positive pressure have not been extensively studied. Nishiyasu et al found that forearm blood flow did not change with lower body positive pressure in the upright position but did increase in the supine position.14 Despite baroreceptor activation favoring a balance toward greater parasympathetic tone, greater wave reflection, in some cases, may also be due to increased sympathetic
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tone due to extrinsic compression of the lower body, as inflation of the air chamber to pressures exceeding 20–30 torr has been reported to increase sympathetic tone due to activation of the musculogenic reflex.10,11,13,14,38 A consideration is that lower body arterial diameter may be reduced, which may result in greater impedance mismatch that would enhance waveform reflection. We did not measure changes in femoral artery diameter with WS. There was a nominal, insignificant decrease in the BA and CA-DBP. Although central aortic and BA pulse pressures were unchanged, WS decreased the amplification ratio. Prior studies have found BP changes dependent on the degree of positive pressure because, as previously mentioned, BP decreases or remains the same at pressures <20–30 torr, whereas inflation to higher pressure appears to increase BP via activation of the musculogenic reflex.13,14,38 The present results are similar to those we previously obtained with head-out-of-water immersion, which also increased the magnitude (AI) and duration but not the timing of the reflected wave.24 WS increased the DEw and decreased the SEVR. In addition, ED lengthened, suggesting reduced LV systolic function. Similarities between water immersion and lower body positive pressure on wave reflection are unsurprising given the compressive effects common to both maneuvers and the prior demonstration that water immersion to waist and chest level provide WS for men to roughly 54% and 35% of body weight.39 Both these provocations serve to underscore that AI and other measures of wave reflection are influenced by changes in preload. Although increased arterial stiffness is generally associated with greater pressure wave reflection, the results of the present study should not be interpreted to infer an increase in arterial stiffness. Theoretically, WS could be expected to decrease arterial stiffness due to external compressive forces attenuating transmural pressure gradients. These findings support that wave reflections originating in the lower body have an effect on central hemodynamics. The characteristics of reflected waves are dependent upon a complex interplay of LV function, large artery elasticity, small artery compliance, wave velocity, reflective site distances, and HR. Increased arterial stiffness is generally associated with the reflected wave occurring earlier in the cardiac cycle and shifting from diastole to systole, causing an increase in late systolic pressure.17 Higher amplitude and earlier return of the reflected wave pose deleterious effects on ventricular-arterial coupling due to higher systolic load and reduced diastolic coronary perfusion. This is illustrated in a recent sub-study of the Women’s Ischemia Syndrome Evaluation study, demonstrating higher wave reflection in women with chest pain and non-obstructive coronary artery disease.40 It is unlikely that very shortterm increases in reflected wave amplitude and duration without altered timing during the cardiac cycle would
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have clinically significant effects on healthy subjects. In addition, the HR decreased with WS, which is a main determinant of myocardial oxygen demand, and the DEw and SEVR are crude measures of myocardial oxygen demand. However, the effect of WS on arterial wave reflection in patients with heart disease is unknown. Furthermore, the effect of treadmill exercise in addition to WS is unknown. This study is limited by the brief duration at each level of WS. These results are limited to short-term effects of WS in young healthy men. The short WS duration was selected to avoid confounding effects through renal and neurohormonal activation. Wave reflection indices values cannot be compared with previously reported results as patients were studied while standing to mimic their position during WS treadmill exercise.
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23. Weber T, Auer J, Lamm G, O’Rourke MF, Eber B. Arterial stiffness, central blood pressures, and wave reflections in cardiomyopathy-implications for risk stratification. J Card Fail 2007;13:353–9. 24. Lazar JM, Morris M, Qureshi G, Jean-Noel G, Nichols W, Qureshi MR, et al. The effects of headout-of-water immersion on arterial wave reflection in healthy adults. J Am Soc Hypertens 2008;2:455–61. 25. Kamran H, Salciccioli L, Gusenburg J, Kazmi H, Ko EH, Qureshi G, et al. The effects of passive leg raising on arterial wave reflection in healthy adults. Blood Press Monit 2009;14:202–7. 26. Chen CH, Nevo E, Fetics B, Pak PH, Yin FC, Maughan WL, et al. Estimation of central aortic pressure waveform by mathematical transformation of radial tonometry pressure. Validation of generalized transfer function. Circulation 1997;95:1827–36. 27. Pauca AL, O’Rourke MF, Kon ND. Prospective evaluation of a method for estimating ascending aortic pressure from the radial artery pressure waveform. Hypertension 2001;38:932–7. 28. Wilkinson IB, MacCallum H, Flint L, Cockcroft JR, Newby DE, Webb DJ. The influence of heart rate on augmentation index and central arterial pressure in humans. J Physiol 2000;525:263–70. 29. Murgo JP, Westerhof N, Giolma JP, Altobelli SA. Aortic input impedance in normal man: relationship to pressure wave forms. Circulation 1980;62:105–16. 30. Weissler AM, Harris WS, Schoenfeld CD. Systolic time intervals in heart failure in man. Circulation 1968;37:149–59. 31. O’Rourke MF, Pauca AL. Augmentation of the aortic and central arterial pressure waveform. Blood Press Monit 2004;9:179–85. 32. Casey DP, Beck DT, Nichols WW, Conti CR, Choi CY, Khuddud MA, et al. Effects of enhanced external
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counterpulsation on arterial stiffness and myocardial oxygen demand in patients with chronic angina pectoris. Am J Cardiol 2011;107:1466–72. Sarnoff SJ, Braunwald E, Welch GH Jr, Case RB, Stainsby WN, Macruz R. Hemodynamic determinants of oxygen consumption of the heart with special reference to the tension-time index. Am J Physiol 1958;192: 148–56. Buckberg GD, Towers B, Paglia DE, Mulder DG, Maloney JV. Subendocardial ischemia after cardiopulmonary bypass. J Thorac Cardiovasc Surg 1972;64: 669–84. Merillon JP, Lebras Y, Chastre J, Lerallut JF, Motte G, Fontenier G, et al. Forward and backward waves in the arterial system, their relationship to pressure waves form. Eur Heart J 1983;4:13–20. Karamanoglu M, Feneley MP. Late systolic pressure augmentation: role of left ventricular outflow patterns. Am J Physiol 1999;277:481–7. Tartiere JM, Logeart D, Safar ME, Cohen-Solal A. Interaction between pulse wave velocity, augmentation index, pulse pressure and left ventricular function in chronic heart failure. J Hum Hypertens 2006;20:213–9. Williamson JW, Crandall CG, Potts JT, Raven PB. Blood pressure responses to dynamic exercise with lower-body positive pressure. Med Sci Sports Exerc 1994;26:701–8. Harrison R, Bulstrode S. Percentage weight-bearing during partial immersion in the hydrotherapy pool. Physiotherapy Theory and Practice 1987;3:60–3. Nichols WW, Denardo SJ, Johnson BD, Sharaf BL, Bairey Merz CN, Prpine CJ. Increased wave reflection and ejection duration in women with chest pain and non-obstructive coronary artery disease: ancillary study from the Women’s Ischemia Syndrome Evaluation. J Hyperten 2013;31:1443–55.
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Research Article
The effect of lower body weight support on arterial wave reflection in healthy adults Atif Afzal, MDa, Daniel Fung, MDa, Sean Galligan, MDa, Ellen M. Godwin, PhDb, John G. Kral, MD, PhDc, Louis Salciccioli, MDa, and Jason M. Lazar, MD, MPHa,* a
Division of Cardiovascular Medicine, State University of New York, Downstate Medical Center, Brooklyn, NY, USA; Human Performance Laboratory, State University of New York, Downstate Medical Center, Brooklyn, NY, USA; and c Department of Surgery, State University of New York, Downstate Medical Center, Brooklyn, NY Manuscript received December 20, 2013 and accepted March 13, 2014
b
Abstract Body weight support (WS) during treadmill exercise is used to rehabilitate orthopedic/neurological patients. WS lowers musculoskeletal strain and load. It compresses the lower body and increases intrathoracic volume. We studied short-term effects of WS on wave reflection indices using applanation tonometry during progressive WS of 25%, 50%, and 75% of body weight in 25 healthy men. WS decreased mean heart rate from 79 to 69 beats/min (P < .001). Peripheral and central mean arterial, systolic, and pulse pressures (PP) remained unchanged. There was a trend toward lower peripheral and central diastolic pressure. PP amplification ratio decreased significantly (P ¼ .005). Reflected wave characteristics: Augmented pressure and index increased in a stepwise manner with WS (both P < .001). Both ejection duration and systolic duration of the € r) increased progressively (both P < .001). The round-trip travel time (Dtp) was unchanged. Left reflected pressure wave (At ventricular workload and oxygen demand: Left ventricular wasted pressure energy increased (P < .001), and the subendocardial viability ratio decreased (P ¼ .005), whereas the tension time index remained unchanged. In normal men, WS acutely decreases the PP amplification ratio, increases the amplitude and duration of the reflected aortic pressure wave, and increases measures of wasted left ventricular pressure energy and oxygen demand. J Am Soc Hypertens 2014;-(-):1–6. Ó 2014 American Society of Hypertension. All rights reserved. Keywords: Aortic stiffness; applanation tonometry.
Introduction Weight support (WS) treadmill exercise has been advocated for rehabilitation of patients with orthopedic and neurological conditions.1–5 This method lowers the strain on joints and impact on muscles during treadmill exercise and allows for training in patients with acute and chronic disorders. WS treadmill systems have been used to simulate microgravity conditions and are commercially available.6,7 In general, such systems consist of a computer-controlled Conflict of interest: None. Financial support: None. *Corresponding author: Jason M. Lazar, MD, MPH, Director, Non-Invasive Cardiology, State University of New York, Downstate Medical Center, 450 Clarkson Ave, MSC 1199, Brooklyn, New York 11203-2098. Tel.: (718) 221-5222; fax: (718) 221-5220. E-mail: [email protected]
treadmill equipped with a pressurized air chamber that generates a vertical upward force directly opposing the force of gravity and effectively decreasing body weight. The airtight chamber is formed by neoprene shorts that zip around the waist, and form a kayak type skirt from the waist down. This chamber suspends the subject over the treadmill surface upon inflation. Variable degrees of WS can be achieved by pumping greater air pressure as WS is proportional to the level of lower body positive pressure. WS evokes a number of cardio-respiratory changes as a consequence of increased intrathoracic blood volume and lower extremity compression, including augmenting venous return, increasing stroke volume, and baroreceptor activation.6–15 Applanation tonometry is an increasingly utilized technique to noninvasively measure arterial stiffness, arterial wave reflection, and central aortic (CA) blood pressure (BP). CA-BP and brachial artery (BA) BP may differ substantially because of pressure wave amplification.16–18
1933-1711/$ - see front matter Ó 2014 American Society of Hypertension. All rights reserved. http://dx.doi.org/10.1016/j.jash.2014.03.004
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Greater arterial wave reflection is an independent predictor of adverse cardiovascular events.19,20 Higher CA pressures are due to higher reflected wave amplitude as well as to earlier arrival of the reflected pressure wave from the periphery back to the aortic root in a stiffer vasculature. This augmented pressure increases left ventricular (LV) afterload and adversely impacts ventricular-arterial coupling.21 The augmentation index (AI), which is the most commonly used measure of wave reflection, is the ratio of augmented pressure due to wave reflection to the CA pulse pressure (PP).17 Although widely viewed as a measure of afterload, AI appears to be related to LV contractile performance, as patients with depressed LV systolic function have lower AI values.22,23 Results from use of maneuvers to increase venous return suggest LV preload is an important determinant of wave reflection properties.24,25 However, the effects of increasing venous return on AI appear to depend on the specific technique used to vary preload. Water immersion increases the amplitude and duration of the reflected aortic pressure wave, whereas passive leg raising decreases the amplitude and delays the onset of the reflected wave.24,25 Inflation of the pressurized lower body air chamber of the WS treadmill while stationary provides an opportunity to vary intrathoracic loading conditions and study the effects on arterial wave reflection. Although WS-induced heart rate (HR) and BP changes have been studied, graded lower body compression has not been used to assess arterial functional properties. The objectives of this study were to characterize acute changes in noninvasive measures of arterial stiffness and wave reflection using applanation tonometry during WS in healthy male subjects.
Methods We prospectively studied a convenience sample of 25 healthy men, age 31 9 years (range, 22–59 years). The body mass index (BMI) was 24.5 3.6 kg/m2 (range, 18.6–30.5 kg/m2), and body surface area (BSA) was 1.96 0.21 m2 (range, 1.58–2.36 m2). Participants were without cardiovascular risk factors or disease via history. All subjects had adequate pulses and were in sinus rhythm. The institutional review board approved this study, and participants provided written consent. Baseline measurements (100% body weight) were recorded after 2 minutes of standing on the WS treadmill (AlterG Anti-Gravity Treadmill, Alter G, Fremont, CA, USA). Systolic (BA-SBP) and diastolic (BA-DBP) BA blood pressure was measured using an automated blood pressure cuff (Omron HEM-780) placed around the left arm. The weight of the subject was covertly measured by the treadmill. Baseline radial artery tonometry using SphygmoCor (AtCor Medical, Sydney, Australia) was performed to obtain the aortic waveform and baseline pulse wave analysis measurements.16,17 Then 25%, 50%, or 75% of body weight was supported. After
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2 minutes, BP and arterial tonometry measurements were repeated on the same outstretched arm resting on the treadmill rail. The degree of WS was adjusted to study levels in random order immediately after the measurements were obtained, without a rest period. BA mean arterial pressure (MAP) was calculated as diastolic pressure þ 1/3 pulse pressure (PP).
Pulse Wave Analysis Radial artery pressure waveforms were recorded at the wrist with the applanation tonometer according to previously published methods.17 In brief, the aortic pressure waveform was derived from the radial artery waveform by a previously validated generalized transfer function.26,27 The following parameters were obtained: augmentation pressure or reflected wave amplitude (PsPi), defined as the difference between peak systolic pressure (Ps) and pressure at the inflection point (Pi), which is the merging point of incident and reflected waves, incident (or forward) wave amplitude (PiPd), and AI, defined as reflected wave amplitude divided by PP and expressed as percentage (AI ¼ [PsPi]/[PsPd]). Pd is central diastolic pressure. AI was also normalized to a HR of 75 bpsm (AI75) since AI is heart-rate dependent.28 The round-trip travel time (Dtp) of the pressure wave to and from the major reflecting sites in the lower body was determined from the aortic pressure waveform.29 The systolic duration of the reflected pressure wave (Dtr) was determined from the inflection point to the incisura.17 (DtpþDtr) represents LV ejection duration (ED). ED was corrected for heart rate (EDc) according to the previously reported formula.30 Indices of LV workload and myocardial oxygen demand were also derived from the pressure waveform using the technique of pulse wave analysis.17,31 Wasted LV pressure energy (DEw) is defined as the extra energy that the LV must generate to overcome the augmented pressure. Wasted energy (DEw) is the area under the systolic portion of the reflected wave and is estimated from the equation DEw ¼ 1.05Dtr (PsPi).32 The tension time index (TTI) was obtained as the area under the systolic (AS) portion of the aortic pressure wave and that is related to work of the heart and to myocardial oxygen consumption.33 The ratio of the areas under the diastolic portion (AD) and systolic portion (AS) of the aortic waveform is associated with the perfusion pressure and time to coronary perfusion, and is therefore an approximation of energy supply of the heart. This ratio of supply and demand is termed the subendocardial viability ratio (SEVR) or Buckberg index (SEVR ¼ AD/AS).32–34
Statistical Methods All continuous data were expressed as mean standard deviation. A one-way repeated measures analysis of
A. Afzal et al. / Journal of the American Society of Hypertension
variance was performed using the four stages of weight support (baseline ¼ 0%, 25%, 50%, or 75% of body weight) for each participant. All statistical analyses used the Statistical Package for Social Sciences (SPSS) 20.0 software (SPSS Inc, Chicago, IL, USA). A P value <.05 was considered statistically significant.
Results Peripheral and central hemodynamic values before and during progressive WS are shown in Table 1 with representative aortic pressure waveforms in Figure 1.
Peripheral and Central Hemodynamics With progressive WS, the HR decreased from 79 12 to 69 11 beats per minute (P < .001). BA-SBP, MAP, and PP remained unchanged. BA-DBP decreased nominally upon WS, not reaching statistical significance. Changes in the CA pressures with WS mirrored the changes in the BA pressures. CA-SBP, mean aortic pressure, and central PP remained unchanged, whereas there was a trend toward lowering of CA-DBP. WS resulted in a significant decrease in the amplification ratio (P < .001).
Characteristics of Reflected Wave The amplitude of the reflected wave (augmented pressure or PsPi), AI, and the AI75 all increased in a stepwise
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manner from baseline with increasing WS. Both the EDc and Dtr also increased progressively (both P < .001). Dtp did not significantly change upon WS (P ¼ .75).
Measures of LV Workload and Oxygen Demand DEw increased (P < .001) and the SEVR decreased (P ¼ .005) with increasing WS, whereas the TTI remained unchanged (P ¼ .19).
Discussion The present study characterized changes in arterial wave reflection induced by WS at rest. Among a number of hemodynamic changes, the reflective wave component increased in amplitude and duration, but was unchanged in timing during the cardiac cycle. There was a decrease in HR as well as trends toward lowering of BA and central aortic DBP. These changes collectively increased LV workload and oxygen demand. The major finding was that WS increased the amplitude and the duration of the reflected pressure wave with a dose-response relationship to the degree of WS. AI is known to be inversely related to HR, which did decrease with increasing WS; however, in addition to AI, the HR-corrected AI75 also increased in a step-wise manner.28 Greater wave reflection may be related to increased forward stroke volume resulting from higher preload. Lower body
Table 1 Peripheral and central hemodynamic parameters at rest and during weight support Hemodynamic Parameters
Baseline
Heart rate (beats/min) Brachial artery SBP (mm Hg) Brachial artery DBP (mm Hg) Brachial artery PP (mm Hg) Brachial artery MAP (mm Hg) Central aortic SBP (mm Hg) Central aortic DBP (mm Hg) Central aortic PP (mm Hg) Central aortic MAP (mm Hg) PP amplification Augmented pressure (mm Hg) Incident pressure (Pi-Pd) (mm Hg) AI (%) AI75 (%) ED (ms) Corrected ED (EDc) (ms) Round trip travel time (Dtp) (ms) Reflected wave systolic duration (Dtr) (ms) Wasted LV energy (DEw) (dyne-sec-cm-2x 102) TTI (mm Hg/s/min x 102) SEVR (%)
79 121 77 44 92 105 78 26 91 1.7 0.1 25 0.24 2 256 278 146 109 0.54 32 180
12 12 8 10 8 10 8 6 9 0.13 3.2 6 11 10 22 21 8 22 4.4 7 37
25%WS 75 120 74 46 89 102 75 28 88 1.7 1.4 26 4.4 4 268 286 146 120 2.36 31 180
11 11 6 10 7 9 6 7 7 0.19 2.6 6 8.5 8 20 19 9 19 4.2 7 31
50%WS 71 119 74 45 89 104 75 28 88 1.6 2.0 26 7.5 5 283 292 148 134 3.50 31 181
12 10 9 10 9 9 10 6 9 0.16 2.7 6 9.8 10 23 20 8 22 4.6 7 37
75%WS 69 121 74 47 89 105 75 30 89 1.6 2.5 27 7.9 5 293 295 148 143 4.08 31 171
11 11 8 10 8 9 9 5 9 0.16 3.4 5 11.6 12 17 19 10 16 5.7 7 33
P Value <.001 .75 .09 .71 .22 .59 .085 .12 .29 .005 <.001 .41 <.001 .029 <.001 <.001 .75 <.001 <.001 .194 .005
AI, augmentation index; DBP, diastolic blood pressure; ED, ejection duration; LV, left ventricular; MAP, mean arterial pressure; PP, pulse pressure; SBP, systolic blood pressure; SEVR, subendocardial viability ratio; TTI, tension time index; WS, weight support.
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Figure 1. Effect of weight support on aortic pressure waveforms.
positive pressure is well known to centralize blood volume and to enhance venous return.6,7,9–15 WS has been shown to increase right ventricular preload through higher central venous pressure, which in turn increases left ventricular preload.10,12 LV stroke volume is increased, resulting in higher cardiac output despite lowered HR, potentially increasing both the amplitude and duration of the transmitted and reflected pressure wave generated by the same cardiac contraction.8,10 In support of this, prior studies have found AI to be related to LV ejection fraction and stroke volume.35–37 Although the amplitude and duration of the reflected wave increased, its timing remained unchanged, reflected in the unchanged round trip travel time. The higher stroke volume and longer LV ejection duration might be counterbalanced by shorter wave travel distance. The amplitude of the incident wave remained unchanged. The incident wave depends on the proximal aortic impedance, which was not measured. Although speculative, this finding may be a consequence of increased LV stroke volume and lower aortic impedance from lower transmural aortic pressure with WS. Decreased HR is consistent with prior studies and is likely related to baroreceptor activation via increased parasympathetic activity from centripetal blood transfer.6,9,15 Peripheral arterial responses to lower body positive pressure have not been extensively studied. Nishiyasu et al found that forearm blood flow did not change with lower body positive pressure in the upright position but did increase in the supine position.14 Despite baroreceptor activation favoring a balance toward greater parasympathetic tone, greater wave reflection, in some cases, may also be due to increased sympathetic
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tone due to extrinsic compression of the lower body, as inflation of the air chamber to pressures exceeding 20–30 torr has been reported to increase sympathetic tone due to activation of the musculogenic reflex.10,11,13,14,38 A consideration is that lower body arterial diameter may be reduced, which may result in greater impedance mismatch that would enhance waveform reflection. We did not measure changes in femoral artery diameter with WS. There was a nominal, insignificant decrease in the BA and CA-DBP. Although central aortic and BA pulse pressures were unchanged, WS decreased the amplification ratio. Prior studies have found BP changes dependent on the degree of positive pressure because, as previously mentioned, BP decreases or remains the same at pressures <20–30 torr, whereas inflation to higher pressure appears to increase BP via activation of the musculogenic reflex.13,14,38 The present results are similar to those we previously obtained with head-out-of-water immersion, which also increased the magnitude (AI) and duration but not the timing of the reflected wave.24 WS increased the DEw and decreased the SEVR. In addition, ED lengthened, suggesting reduced LV systolic function. Similarities between water immersion and lower body positive pressure on wave reflection are unsurprising given the compressive effects common to both maneuvers and the prior demonstration that water immersion to waist and chest level provide WS for men to roughly 54% and 35% of body weight.39 Both these provocations serve to underscore that AI and other measures of wave reflection are influenced by changes in preload. Although increased arterial stiffness is generally associated with greater pressure wave reflection, the results of the present study should not be interpreted to infer an increase in arterial stiffness. Theoretically, WS could be expected to decrease arterial stiffness due to external compressive forces attenuating transmural pressure gradients. These findings support that wave reflections originating in the lower body have an effect on central hemodynamics. The characteristics of reflected waves are dependent upon a complex interplay of LV function, large artery elasticity, small artery compliance, wave velocity, reflective site distances, and HR. Increased arterial stiffness is generally associated with the reflected wave occurring earlier in the cardiac cycle and shifting from diastole to systole, causing an increase in late systolic pressure.17 Higher amplitude and earlier return of the reflected wave pose deleterious effects on ventricular-arterial coupling due to higher systolic load and reduced diastolic coronary perfusion. This is illustrated in a recent sub-study of the Women’s Ischemia Syndrome Evaluation study, demonstrating higher wave reflection in women with chest pain and non-obstructive coronary artery disease.40 It is unlikely that very shortterm increases in reflected wave amplitude and duration without altered timing during the cardiac cycle would
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have clinically significant effects on healthy subjects. In addition, the HR decreased with WS, which is a main determinant of myocardial oxygen demand, and the DEw and SEVR are crude measures of myocardial oxygen demand. However, the effect of WS on arterial wave reflection in patients with heart disease is unknown. Furthermore, the effect of treadmill exercise in addition to WS is unknown. This study is limited by the brief duration at each level of WS. These results are limited to short-term effects of WS in young healthy men. The short WS duration was selected to avoid confounding effects through renal and neurohormonal activation. Wave reflection indices values cannot be compared with previously reported results as patients were studied while standing to mimic their position during WS treadmill exercise.
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