Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Cardiac surgery wikipedia , lookup
Pericardial heart valves wikipedia , lookup
Jatene procedure wikipedia , lookup
Artificial heart valve wikipedia , lookup
Hypertrophic cardiomyopathy wikipedia , lookup
Aortic stenosis wikipedia , lookup
Quantium Medical Cardiac Output wikipedia , lookup
PATHOPHYSIOLOGY AND NATURAL HISTORY EXERCISE PHYSIOLOGY Dilfering mechanisms of exercise flow augmentation at the mitral and aortic valves ANIS RASSI, JR., M.D., MICHAEL H. CRAWFORD, M.D., KENT L. RICHARDS, M.D., AND JACELYN F. MILLER, R.D.M.S. Downloaded from http://circ.ahajournals.org/ by guest on June 18, 2017 ABSTRACT To determine the mechanisms by which blood flow increases across the mitral and aortic valves during exercise, 18 normal men were studied during graded supine and upright bicycle exercise at matched workloads. Mitral valve orifice and ascending aortic blood velocities were recorded by Doppler echocardiography during steady states at each stage of exercise. Parasternal two-dimensional echocardiographic imaging of the ascending aorta adjacent to the aortic valve orifice and the mitral valve orifice at the tips of the valve leaflets was used to calculate changes in cross-sectional area during exercise. Heart rate increased from rest to exercise from 67 to 150 beats/min (124%) during supine exercise and from 72 to 147 beats/min (104%) during upright exercise. Stroke volume increased 20% during supine and 46% during upright exercise; the increase in stroke volume was statistically significant when rest and exercise were compared and when the magnitude of change was compared vs position (p < .05). The increase in stroke volume measured at the ascending aorta was accomplished by an increase in the velocity-time integral (+ 15% supine and + 48% upright, p < .05), with little change in aortic cross-sectional area (5% supine and 0% upright, p = NS). By contrast, the increase in flow rate measured at the mitral valve was predominantly due to an increase in mean diastolic cross-sectional area (+ 29% supine and 34% upright, p < .05); the velocity-time integral did not increase significantly ( - 10% supine and 4% upright; p = NS). The data contrast the mechanisms by which aortic and mitral valve flow increase with exercise, and demonstrate an increase in cross-sectional area at the mitral valve orifice and the importance of an increase in velocity-time integral at the aortic valve. These observations support the use of changes in the heart rate times velocity-time integral as an indicator of changes in cardiac output at the aortic valve, but stress the importance of serial cross-sectional area measurements at the mitral valve orifice in the assessments of changes in cardiac output. Circulation 77, No. 3, 543-551, 1988. IF THE LEFT VENTRICLE is conceptualized as a conduit for blood with an inlet at the mitral valve and an outlet at the aorta, then in the absence of valvular regurgitation or interventricular shunting, the stroke volume through the mitral orifice equals the output from the aorta. During isotonic exercise, increases in both stroke volume and heart rate are responsible for the increase in cardiac output.1 The mechanism by which the stroke volume is increased at both valves must involve an increase in cross-sectional area and/or an increase in the product of blood velocity and time (the velocity-time integral). Examination of the changes in time allowed for flow across the mitral vs the aortic valve suggests that the mechanisms available to inFrom the Division of Cardiology, University of Texas Health Science Center and Veterans' Administration Hospital, San Antonio. Supported in part by the Veterans' Administration. Address for correspondence: Michael H. Crawford, M.D., Department of Medicine, Division of Cardiology, University of Texas Health Science Center, 7703 Floyd Curl Dr., San Antonio, TX 78284-7872. Received Aug. 21, 1987; revision accepted Nov. 20, 1987. Vol. 77, No. 3, March 1988 crease flow may differ at the aortic and mitral valves, since as heart rate increases diastolic mitral filling time per cardiac cycle decreases exponentially.2 Studies in humans have documented an increase in diastolic left atrial pressure and a concomitant decrease in left ventricular diastolic pressure during exercise3-5; thus, the driving pressure filling the left ventricle is increased. The exercise-induced increase in filling pressure would be expected to increase mitral valve blood velocity, but could also increase mitral valve cross-sectional area. Consideration of the phasic char- acteristics of mitral valve orifice area during diastole reveals an M-shaped configuration with maximal opening in early diastole and a second period of opening in late diastole. Increases in mitral valve flow also could be accomplished by increasing the mitral valve velocity and/or cross-sectional area during the period of middiastole. Conditions in the aorta are different, with a relatively constant cross-sectional area and a linear decrease in flow time noted during exercise.6 7 Thus, 543 RASSI et al. increase in mean velocity would be expected to be the mechanism by which stroke volume is increased at the aortic valve. Accordingly, the purpose of this study was to use noninvasive Doppler and imaging echocardiographic techniques to contrast the mechanisms by which flow is increased across the mitral valve orifice and the ascending aorta during isotonic exercise. Use of both supine and upright bicycle exercise allowed for the examination of these mechanisms under two different ventricular loading situations. It was hoped that these observations could be used to simplify the complex measurements required to make accurate estimations of exercise-induced changes in cardiac output at these sites. an Downloaded from http://circ.ahajournals.org/ by guest on June 18, 2017 Methods Subject selection. We studied 26 healthy male volunteers who were selected from a larger group because of excellent Doppler echocardiograms in the supine and upright positions at rest. Eight were subsequently excluded because of unsatisfactory imaging and/or velocity tracings during exercise. The remaining 18 represented our final population and their ages ranged from 22 to 37 years (mean 28 + 4 years). Physical fitness varied from subject to subject, but none could be considered a trained athlete. Written informed consent was obtained on a form approved by Institutional Review Board. Exercise protocol. After an initial abbreviated exercise study to familiarize the subjects with the study procedures, all underwent graded, continuous exercise testing in both the supine and upright positions on different days but under similar conditions. Upright exercise was performed on a mechanically braked Monark bicycle ergometer and supine bicycle exercise was performed on a Quinton Uniwork Ergometer model 844, mounted on the foot of a bed. Equivalent workloads for all subjects were used during the supine and upright exercise, starting at 150 kilopond-meters (kpm)/min and then increasing to 300, 450 and 750 kpm/min. The subjects exercised continuously for 3 to 6 min at each level of work, depending on the time required for an adequate echo-Doppler data acquisition, which began after the second minute of each exercise stage. The total exercise time was not significantly different between the two positions (18.4 ± 2.6 min upright vs 18.0 ± 1.4 min supine). The electrocardiogram was monitored continuously. Cuff blood pressure was recorded at rest, during each stage of exercise, 30 sec after exercise, and then at 1 min intervals for a total of 6 min of recovery. Systolic blood pressure increased progressively during exercise and declined rapidly during recovery. Since blood pressure was not significantly different between the two positions it will not be considered further in this report. Doppler echocardiographic examination. Two commercially available Doppler echocardiographic systems with both continuous and pulsed-wave capabilities (Advanced Technology Laboratory, Mark 600 and Ultramark 8) were used in this study. Two-dimensional imaging and mitral Doppler flow velocities were obtained with a 2.25 MHz mechanical transducer. Aortic flow velocities were quantified by continuous-wave Doppler with a 2.25 MHz nonimaging dedicated transducer. Examination and recordings proceeded as follows. First, with the imaging transducer placed at the cardiac apex, an apical four-chamber view of the heart was obtained. The Doppler cursor was initially aligned parallel to the apparent direction of flow and the sample our 544 volume was positioned just distal to the mitral valve leaflets in diastole. From this starting point, the system was switched to the Doppler mode, and the highest mitral velocities with least spectral dispersion were searched with aid of the audio signal and the spectral display. Maximum velocities were noted when the center of the sample volume was between just distal and just proximal to the mitral leaflets. At times, minor adjustments in transducer angulation and/or sample volume position were required to maximize the graphic quality of the Doppler signal. Sampling position was easily checked by switching the instrument back to the real-time imaging mode. Sample volume length was adjusted to optimize the quality of the spectral display and was best between 5 and 10 mm. Hard copies of the spectral velocity displays, with simultaneous electrocardiograms, were obtained at a paper speed of 100 mm/sec. Since the maximum velocity recorded through the normal mitral valve orifice in this study was 182 cm/sec, aliasing was avoided by moving the baseline to the bottom of the tracing and using the maximal pulse repetition frequency (shallowest depth setting) possible. The imaging/Doppler transducer was maintained at the cardiac apex throughout the study. Immediately after the acquisition of the mitral Doppler data, another operator recorded the aortic systolic velocities by placing the continuous-wave transducer at the suprasternal notch. Angling the transducer with the use of auditory and visual monitoring allowed location of maximal velocities across the proximal ascending aorta. Again the velocity tracings were recorded at 100 mm/sec paper speed. Thereafter, the transducer was completely removed from the suprasternal notch. With this technique, the intercept angle was assumed to be minimal and no angle correction was made to calculate mitral and aortic velocities. Wall filters were set at 200 to 400 Hz. The above procedure was performed at rest and was repeated at each stage of exercise and sequentially during recovery. Data obtained from subjects in the supine position, at rest, and at recovery were obtained with their legs raised onto the bicycle pedals. The recordings during upright exercise were obtained with the subjects leaning slightly forward on the bicycle with their arms resting on the top of an adjustable table that the operator also used for support.8 Although the change in mean mitral orifice area during exercise could have been inferred from the velocity data at each valve site by use of the continuity equation and assuming that there was little change in aortic area, we were also interested in observing the changes in orifice size during diastole as exercise progressed. However, we found it difficult to move the imaging transducer to the parasternal position and back to the apex and maintain imaging quality during exercise. Therefore, for this purpose, 10 of the 18 subjects repeated the same exercise protocol (supine and upright) on different days and two-dimensional echocardiograms in the standard parasternal long and short axis were recorded on videotape while they were at rest and during exercise and recovery for subsequent analysis. An M mode echocardiogram of the mitral valve at a paper speed of 100 mm/sec was also obtained by adjusting the M mode cursor across the middle of the maximal mitral orifice area as observed in the short-axis view. No significant difference in exercise duration, heart rate, or blood pressure was observed between the two exercise tests in each position in this subgroup. Doppler echocardiographic measurements and analyses. All measurements were made with a digitizing pad (Summagraphics Model ID-2-CTR1 1), and a microcomputer (IBM-PC) controlled by a dedicated software program (Micro-Sonics, Inc. Version 2.5). For the data recorded on tape (two-dimensional images), a videocassette system equipped with a frame-byframe bidirectional search (JVC model BR 6400U) permitted analysis in a slow-motion, real-time, or stop-frame format. Doppler spectral tracing measurements of both aortic and CIRCULATION PATHOPHYSIOLOGY AND NATURAL HISTORY-EXERCISE Downloaded from http://circ.ahajournals.org/ by guest on June 18, 2017 mitral flows included velocity-time integrals, flow time, and flow time fraction of the cardiac cycle. The cardiac cycle length and corresponding heart rate were also obtained from the simultaneous electrocardiogram. Aortic and mitral velocity-time integrals, systolic ejection time (ST), and diastolic filling time (DT) were calculated as we have previously described.9 The systolic fraction of the cardiac cycle time (CT) was calculated as ST/CT x 100, and the filling fraction of the cardiac cycle as DT/CT x 100. All beats analyzed were those recorded during the expiratory phase of respiration. The maximal mitral orifice area was measured from the parasternal short-axis view by tracing the innermost border of the largest orifice when both leaflets were well visualized and separated from the ventricular walls. Long-axis imaging confirmed that leaflet separation was constant for the distal 10 mm of the leaflets in early diastole. Thus, the orifice area and Doppler recordings were derived from the same anatomic site. Stroke volume and cardiac output at the mitral area was then calculated by the method of Fisher et al.`0 Aortic valve diameter was measured from a parasternal long-axis view by the trailing edge-to-leading edge method just distal to the valve leaflets, as validated by Gardin et al.`1 Stroke volume and cardiac output was calculated by the method of Huntsman et al.`2 All reported measurements were performed by an experienced PHYSIOLOGY single observer in a blinded manner and represent the average of three different cardiac cycles at each stage. Data analysis. All data were analyzed by a two-way analysis of variance for repeated measures. Mean differences were determined for each measure over time in one exercise position and between exercise positions at the same time by the use of the Student-Newman-Kuels mean comparison test based upon the range.13 Mean values are expressed SD and p < .05 was considered indicative of a significant difference. In five subjects mitral and aortic orifice area determinations at rest and at each exercise stage were made by two observers independently to estimate interobserver variability. Also, four subjects underwent repeated exercise imaging studies and the same observer measured the mitral and aortic orifice area on both occasions. The absolute difference between all paired measures was divided by their mean and expressed as percent variability. Results Effect of exercise on mitral stroke volume. Table 1 displays the mean values for each measurement at each stage of exercise and recovery in both positions. Statistical significance over time in each position is indi- TABLE 1 Echocardiographic-Doppler mitral data Stage REC III Rest 150 kpm 300 kpm 450 kpm 750 kpm REC I REC II 67± 12 95+±1A,B ±1A,B 105+ 119±15A,B 150±15A,B 122±20A,B 98+ 16A,B p<.05 NS NS NS NS NS NS NS 13A,B 101j13A,B 119±15A,B 147 ± 20A,B 118 ± 19A,B 97 + 15A.B 90 ± 13A,B 496± 173 p<.05 431± 100 277 52A,B NS 293 ± 56A.B 239 +40A3B NS 256 ± 44A,B 204± 36A, 161±22A.B NS 174± 29A,B 231 294 l 102A.B NS 290 ±67A.B 52±7 NS 43+4A,B NS 41±3 A NS 50 ±4 44±+ 3A,B 42± 3A,B 21.5±3.7 p<.01 17.6± 3.0 20.5 ± 2.9 NS 19.3 3.1AB S 4.2±0.9 4.8 1.0A,B U p<.01 3.5 ±0.5 p<.05 4.20.8A,B 99 ± 28 p<.01 65 ± 15 106±26A.B 6.1± 1.4 p<.01 4.4±0.9 9.8 HR (beats/min) S U DT (msec) S U DT/CT (%) S U 73 ± 12 93 NS 213 ± 31AB 56A,B NS 233 + 38A'B 46+6A 40±3A NS 45±5A,B 42 ±2A 42 ± 3A 45 ±4AB 20.5 ± 3.3 NS 19. 3±31A 20.0 ± 3.7 NS 19.2±2.9A 19.3 ± 3.1A NS 18.3 ±2.9 5.1± 1.0kA 5.2± 1.OA p<.05 O 5.4t0.8A p<.05 5.0±0.8AB p<.01 4.3±0.8A 4.5 ±0.7 4.7±06A0B 112±28A p<.05 111+29A 11020A p<.05 NS NS NS 45 ±5A 93± 12A 290 62A NS 309 ±62A 44±4A NS A VTIm (cm) S U 20.0±4,3A p<.01 17.0± 3.0 19.1± 3.2A p<.01 16.8 ±3.2 4.8±0.8A 4.6±0.7A 4.2+0 6A,B p<.05 4 0+0.7A 3.9±0.7A 108±16 102 ± 26 20.6± 3.3 p<.01 17.8± 2.9 MVOc (cm2) p<.05A p<.05 SVm (ml) S U p<.05 84 ± 23A,B 86 + 23A p<.05 88 ± 23A 89±+ 22A p<.01 75 ±19A,B 16.1 3.0AB p<.05 12.9+3 3A,B 12.2± 1.7A.B p<.01 8 9±2.5A,B 92 ± 18B 70± 17A p<.01 66± 21 9.2± 1.3A,B p<.01 6.5+ 1.6A,B 8.1 ± 1.3A,B p<.01 5.7+ 1.7A p<.01 COrn (1/mmn) 5 U 1.8A,B 11.3 23A.B p<.01 p<.05 7.5+ 1.9A,B 8.5+2.1A 12.7 23A,B p<.05 10.5+2.7A,B All data are mean ± SD. HR = heart rate; MVOc = mean mitral valve orifice area; REC = recovery (I = 0-2 min after exercise; II mitral stroke volume; U = upright; VTIm = mitral velocity-time integral. Ap < .05 vs rest; Bp < .05 vs preceding level. Vol. 77, No. 3, March 1988 = 2-4; III = 4-6); S - supine; SVm = 545 RASSI et aL Supine Exercise .Mitral Doppler 160 C) 0) E C) 1..II:0011...:2..::: ..... ..... 4012010080- 'I0 ..... ....... ..... ..... .,.,.....,f ..... 60 PIE, 4020 o ... a ... Q.0 ....... EG 300 k:prn Rest 150 kpm 4 50 kpm RECI 750:kPm FIGURE 1. Representative single-beat Doppler velocity recordings at rest, during exercise, and during recovery. See text for details. ECG electrocardiogram; REC recovery. = RECK = Downloaded from http://circ.ahajournals.org/ by guest on June 18, 2017 cated next to the mean values by symbols. Significant differences in values at the same time during exercise but in the two different positions is designated in the row between the values. Heart rate increased progressively during exercise in both positions (124% maximum supine, 104% maximum upright). Diastolic flow time decreased progressively during exercise. DT/CT also decreased significantly during the first two stages of exercise, then remained constant until the end of exercise. Although the diastolic flow augmentation coincident with atrial contraction was no longer discernible in the later stages of exercise, peak mitral velocity always occurred early in diastole (figure 1). Despite an increase in peak velocity, the mitral velocity-time integral changed little during exercise because of the truncation of diastolic flow time. In fact, in the supine position mitral velocity-time integral was significantly decreased at peak exercise as compared with rest. Mean mitral valve orifice area increased significantly during early exercise FIGURE 2. Digitized stop-frame echocardiographic images of the maximum early diastolic mitral leaflet orifice from the parasternal short -axis view at rest (tpper left) and at the first (upper right), second (lower left), and third stage of exercise (lower right). 546 CIRCULATION PATHOPHYSIOLOGY AND NATURAL HISTORY-EXERCISE PHYSIOLOGY Echo- Doppler mitral Supine exercise Echo - Doppler mitrol Upright exercise 60+ * MVOc * MVOc A SVn * VTIm SVm A 70 - * VTIm 21 60 - 60 4 so T, 40 E O _ 50 E F c 30 t +1 C c CC U = 0 20 0 Ci 10, ° A0 a- O- , 1 - 20o - 1 20+ 1 - -30 20 + 11 - 30 Downloaded from http://circ.ahajournals.org/ by guest on June 18, 2017 REST 450kpm SOOkp. 0 450 kpn TSOhlpm REC REC n REC m REST iOkDa Stage 300hkp.R 450kpa 750 prp RECI RECU RECM Stage FIGURE 3. Percent change in three mitral echo-Doppler measures during supine (left) and upright (right) exercise as compared with rest. See text for details. MVOc = mean mitral valve orifice area; SVm stroke volume derived from mitral Doppler and echocardiographic data; VTLm = mitral velocity-time integral. = and remained larger than the resting value through the end of exercise (+29% supine and + 34% upright, figure 2). Consequently, mitral stroke volume also increased significantly during early exercise and remained higher than the resting value throughout exercise (figure 3). Cardiac output calculated from the mitral data (COm) increased progressively during exercise (164% supine and 193% upright). decreased less rapidly in supine subjects because of a maintenance of the mitral velocity-time integral, since mitral valve orifice area decreased similarly in both positions. COm was consistently lower throughout exercise and recovery in the upright position because mitral valve orifice area was smaller. aortic stroke volume (table 2). upright position throughout exercise and recovery. Also, the aortic velocity-time integral was less in upright subjects. However, the aortic cross-sectional area was not different between the two positions. Thus, aortic stroke volume and COa were lower in upright subjects because of the reduced flow times and velocities in this position. During recovery aortic stroke volume declined less rapidly in supine subjects because of less change in the aortic velocity-time integral (figure 5). Effect of exercise on Although systolic flow time progressively decreased during exercise, ST/CT increased significantly during exercise. The aortic velocity-time integral increased during early exercise and remained significantly higher than the resting value throughout exercise (+ 15% supine and + 48% upright). Aortic cross-sectional area did not change appreciably during exercise. Consequently, aortic stroke volume increased significantly early in exercise and remained higher than the resting value throughout (figure 4). Cardiac output from the aortic data (COa) also increased progressively during exercise (194% supine and 220% upright). Influence of exercise position on mitral stroke volume (table 1). Except for a slightly faster heart rate at rest in the upright position, there was no significant difference in any of the time intervals at the two positions. The mitral velocity-time integral was not different in the two positions, but mitral valve orifice area was consistently smaller in upright subjects; consequently, so was mitral stroke volume. During recovery, mitral stroke volume Vol. 77, No. 3, March 1988 Influence of exercise position on aortic stroke volume (table 2). ST and ST/CT were significantly less in the Reproducibility of mitral orifice determinations. Two observers analyzed the same supine exercise study recordings from the mitral orifice in the short-axis view and measured the maximum area. The mean difference was 0.45 cm2 or 4.0% (interobservervariability). In the four subjects who repeated upright exercise for mitral imaging, mean difference in mitral orifice area measurements by the same observers was 0.50 cm2 or 6.2% (intrasubject variability). The intraobserver difference in the mean resting and exercise aortic diameters in the parasternal long-axis view was 0.04 + 0.025 cm or 547 RASSI et al. TABLE 2 Echocardiographic-Doppler aortic data Stage Rest 150 kpm 300 kpm 65+ 13 94+±1AB 104± 12A,B 120+ 14A,B 152± 15A.B p<.01 72±12 NS 91 + 14AB NS 101 + 14A.B NS 118 ± 16A.B NS 147 ± 19A,B 299 + 40 267 ± 31 A,B 255 ± 27A.B 235 + 30A,B p<.01 p<.Ol p<.OS 248 ± 37 242 -+ 34 31 ± 4 450 kpm 750 kpm REC I REC II REC III HR (beats/min) S U ST (msec) S U 17AJB 94+ 16A,B 91 ± 12A 106±19A,B NS 93 + 16B NS 88 ± 14A 206 ± 25A,B 222 ± 23A,B 246 ± 29A,B 261 ± 3 1 A,B p<.OS p<.OS p<.Ol p<.Ol 234 ± 39A 214 ± 34A,B 189 ± 32A,B 196 ± 38A 213 + 39A,B 224 ± 43A 44 ± 4A,B p<.Ol 39 ± 6AB 46 ±5A,B p<0l 42 +6AB 52 ± 6A,B p<.Ol 46 7AB 40±+ A,B p<.01 34 +6AB 38 ± 5A p<.Ol 33 ± 6A 39 ± 4A 29 + 4 41 ± 4A-B p<.Ol 36 ± 5A,B 21.4 ±4.9 25.0+ 5.3A,B 25,5 ± 5.6A 25.7 + 5.9A 24.6 ± 5.4A 25.6 ± 5.7A 25.0 ± 5.7A 23.6 +55A,B p<.0l 14.6 +4.6 p<.Ol 19,4+69A,B p<.Ol 210+74A.B 21.6+ 7.3A p<.OS 21.6+ 7.0 p<.Ol 18.3 ±5 7A,B p<.Ol 17.0 ±66A p<.Ol 15.6+ 6. 4.3±0.6 NS 4.3+0.6 4.4+0.6 NS 4.3+0.6 4.4+0.6 NS 4.2+0.6 4.4±0.7 NS 4.3±0.6 4.5±0.7A NS 4.3±0.6 4.4±0.7 NS 4.3±0.6 4.4±0.7 NS 4.3+0.6 4.3±0.6 NS 4.3+0.6 88 ± 22 p<.01 62 ± 19 105 ± 25A,B p<.01 85 ± 30AB 106 + 26A p<.05 89 ± 32A 107 ± 25A p<.05 90 ± 29A 103 ± 19A NS 90 + 31 A 105 ± 20A 101 ± 23A p<.01 73 30A 96 ± 23A 5.2 +0.8 p<.01 4.1 +0.7 9.6± 1.6A,B p<.01 7.4+2.3A B 10.7 +2.0A,B p<.05 8.9±3.1A 12.4 ±2.2A,B p<.05 15.3 +2.7A.B NS 13.1 44AB 10.9±+ 19A,B 90+1 7A,B p<.01 p<.01 6.2+2 3A.B 110+ NS p<.Ol ST/CT (%) S p<.05 U VTIa (cm) Downloaded from http://circ.ahajournals.org/ by guest on June 18, 2017 S U A-CSA (cm2) S U SVa (ml) S U COa (1/min) S U p<.Ol 10.6±3.6A,B All data are mean + SD. A-CSA = aortic cross-sectional area; HR heart rate; REC = recovery (I aortic stroke volume; U = upright; VTIa aortic velocity-time integral. Ap < .05 vs rest; Bp < .05 vs preceding level. = p<.01 78 ± 26A.B 7.9+2 6A,B 0-2 min after exercise; II = 2-4; III = p<.0OI 32+ 6 p<.05 69 ± 30 8.3 ± 1.6A p<.01 5.7+22A 4-6); S = supine; SVa = 1.5% and that for the calculated orifice area was 0.17 ± 0.11 cm2 or 2.9%. The intrasubject difference in aortic diameter was 0.11 + 0.08 cm or 4.4% and the calculated area difference was 0.43 + 0.34 cm2 or 8.6%. There was no difference in the variability of resting as compared with that of exercise values. Discussion Our data demonstrate that stroke volume increases early during exercise, which necessitates higher volume flow at the aortic and mitral orifices. Increased volume flow per cycle at the aortic orifice is accomplished principally by an increase in the velocity-time integral. The increase in aortic velocity-time integral is due in part to an increase in systolic time per cycle, but more importantly to an increase in systolic velocity (figure 4). By contrast, increased mitral volume flow is accomplished mainly by an increase in the maximum diastolic mitral valve orifice. The mitral velocity-time 548 integral actually decreases in the supine position, despite increases in velocity, because of the marked abbreviation of DT (figure 3). Our aortic Doppler echocardiographic results during exercise agree with those of previous studies.14-16 In addition, our mitral Doppler echocardiographic findings are consistent with experimental studies in dog preparations. Fisher et al.10 demonstrated in five openchest dog preparations in which cardiac output was controlled by a roller pump a relationship between maximum diastolic mitral valve area by two-dimensional echocardiographic imaging and cardiac output (r = .85 to .99). However, in the smallest dog mitral valve area plateaued at flows greater than 4 liters/min. Thus, they hypothesized that changes in mitral orifice size must eventually reach a maximum in all animals if the flow is high enough. Stewart et al..17 using a similar study design, also showed that maximum diastolic mitral valve area failed to increase in their dogs CIRCULATION PATHOPHYSIOLOGY AND NATURAL HISTORY-EXERCISE PHYSIOLOGY Echo- Doppler aortic Supine exercise Echo - Doppler aortic Upright exercise * A-CSA A SVa * VTla so 70 Ef 70 t 60 60 t SO-o. %n ff t 40-4- 10 E * A-CSA * SVa * VTIa 50± E 40' 0O _-0 030 C- c @+1 c#+1 2030 - C c .C 4 20 4- 0 a (,- E 20 - 40 40 - F OO- Downloaded from http://circ.ahajournals.org/ by guest on June 18, 2017 - 10t lo0. - 20- 20- - 30- 30J T REST S50Rpm 300Rpm 4501pm 750Rpm REC RECI REC m Stage REST 450Rkpm 300pm 450Rpm 750kpm RECI RECH REC M Stage FIGURE 4. Percent change in three aortic echo-Doppler measures during exercise. Left, supine data; right, upright data. A-CSA = aortic cross-sectional area; SVa = stroke volume calculated from aortic echo-Doppler data; VTIa = aortic velocity-time integral. See text for details. after flows of 4 liters/min. They also pointed out that since the mitral orifice increased, velocity changes with increasing flow were much less at the mitral valve as compared with at the aortic valve, where orifice size changed very little at higher flows. Our results also demonstrate that at identical workloads cardiac output is higher in the supine position. This was a result of higher stroke volume, since heart rate was not significantly different during exercise in the two positions. Systolic flow time per cardiac cycle was consistently higher in supine subjects. Consequently, aortic velocity-time integral was higher in the supine position. Aortic orifice area was no different in the two positions. Interestingly, diastolic time per cycle and mitral velocity-time integral were no different in the two positions. Thus, mitral stroke volume was higher in supine subjects because of a significantly larger mitral orifice size in this position. It is well known from previous exercise physiology studies that cardiac output and stroke volume are higher during supine than during upright exercise at the same workloads.18 Previous investigators have ascribed this difference to less diastolic filling rather than reduced left ventricular performance during upright exercise. 9-2' This conclusion is supported by our data since mitral orifice area was considerably smaller in the upright position. Intracardiac pressure values from other studies have documented lower values during upright exercise, but the effective filling pressure (left Vol. 77, No. 3, March 1988 atrium-ventricle gradient) is unknown.3 Since peak mitral velocities were higher in our supine subjects, the effective filling pressure may have been higher in this position. Data collected by both Doppler techniques during recovery from exercise showed a rapid decrease in stroke volume in the upright position and a more gradual decrease in the supine position. This difference in recovery was largely explained by a more rapid decrease in the velocity-time integral at both valve sites in the upright position. Mitral valve orifice area returned toward resting values at a similar rate in both positions. Recovery values obtained by the two Doppler techniques cannot be compared because recovery is not a steady-state condition and the Doppler data from each valve site were collected sequentially. Our recovery data are in agreement with those from previous hemodynamic studies that have shown that stroke volume decreases rapidly after cessation of upright exercise, but not supine exercise.22 23 More recently Gardin et al.16 showed, using a pulsed Doppler technique, that the highest aortic velocity-time integral occurred at 2 min of recovery. Our continuous-wave aortic data are consistent with this observation. A limitation of our study was that Doppler velocity recordings and orifice imaging by two-dimensional echocardiography could not be done simultaneously at two valve sites or during the same exercise study. Simultaneous recordings with two machines is impos549 RASSI et al C) Wi 'I, N.1 EU, Uprignt Exercise Aortic Doppler 240200160Downloaded from http://circ.ahajournals.org/ by guest on June 18, 2017 (, U,1 120- 0 80400 ECG ... ResT C.) . l3UKpm f75Okpm REC I RE8CIM FIGURE 5. Representative aortic Doppler velocity recordings obtained in patients at rest and during selected stages of exercise and recovery in the two exercise positions. See text for details. sible because of interference from the two sound beams. However, heart rate and blood pressure measurements confirmed steady-state conditions after 2 min of each exercise stage. We also found that moving the transducer position impaired the ability to gather high-quality data during exercise. Thus, with three transducer positions necessary (suprasternal, parasternal, and apical) to gather the data necessary for this study, two exercise studies in each position were required. Since other studies have shown little change in aortic orifice area during alterations in cardiac output, we could have deduced the increase in mean mitral valve orifice area from the Doppler velocity data using the continuity equation.24 25 We also could have measured mitral valve leaflet separation diameter in the apical four-chamber view and calculated orifice area. but this would have required assuming the geometry of the orifice during exercise. Consequently, we decided to directly evaluate orifice area in a subgroup with excellent short-axis mitral valve images during a repeat exercise study. Although there was no significant difference in the heart rate and blood pressure response during each of the two exercise sessions in each position, differences in subject response between studies cannot be 550 excluded and may have influenced the results. Several Doppler echocardiographic techniques have been used successfully to estimate stroke volume and cardiac output, including recording from the mitral anulus.26 However, preliminary pulsed Doppler studies in our normal subjects showed that peak mitral valve velocities at rest and during exercise occurred from just distal to just proximal to the leaflet tips. This observation is consistent with those of other investigators.10' 17, 26 Also, Zhang et al.27 have shown that maximum mitral velocity is the same at the leaflet tips as it is 1 cm above the tips, but is lower at the anulus. Thus, we assumed that the flow limiting site in normal subjects was best approximated by measuring orifice area at or near the mitral leaflet tips. This was readily accomplished since there was usually only one transducer position that would identify both mitral leaflets separate from the ventricular walls (figure 2). Recently, stroke volume estimates from aortic Doppler recordings during exercise have been shown to correlate with those made by invasive techniques.28 In our study, stroke volume measurements were not significantly different by aortic and mitral Doppler methods during exercise. However, since we did not have an invasive standard in our study, we have emphasized the relative CIRCULATION PATHOPHYSIOLOGY AND NATURAL HISTORY-EXERCISE PHYSIOLOGY Downloaded from http://circ.ahajournals.org/ by guest on June 18, 2017 changes observed during exercise, which we believe to be accurate. It is unlikely that the measurements made in this study would be of value for routine clinical studies because of their complexity. However, these observations suggest a potential method for simplification of the analysis of exercise-induced changes in cardiac output. Our data contrast the mechanisms by which aortic and mitral valve flow increase with exercise and demonstrate an increase in cross-sectional area at the mitral valve orifice and the importance of an increase in the velocity-time integral at the aortic valve orifice. These findings support the use of changes in heart rate times velocity-time integral at the aortic valve as indicators of changes in cardiac output for clinical use. However, the importance of orifice area in accommodating changes in cardiac output during exercise at the mitral valve implies that disease states that directly alter mitral valve mobility may impair exercise capacity. This concept is the focus of ongoing research in our laboratory. References 1. Bishop VS, Peterson DF, Horwitz LD: Factors influencing cardiac performance. In Guyton AC, editor: International review of physiology. Cardiovascular physiology II. Baltimore, 1976, University Park Press, p 239 2. Boudoulas H, Rittgers SE, Lewis RP, Leier CV, Weissler AM: Changes in diastolic time with various pharmacologic agents. Implications for myocardial perfusion. Circulation 60: 164, 1979 3. Thadani U, Parker JO: Hemodynamics at rest and during supine and sitting bicycle exercise in normal subjects. Am J Cardiol 41: 52, 1978 4. Carroll JD, Hess OM, Hirzel HO, Krayenbuehl HP: Dynamics of left ventricular filling at rest and during exercise. Circulation 68: 59, 1983 5. Higginbotham MB, Morris KG, Williams RS, McHale PA, Coleman RE, Cobb FR: Regulation of stroke volume during submaximal and maximal upright exercise in normal man. Circ Res 58: 281, 1986 6. Ihlen H, Myhre E, Amlie JP, Forfang K, Larsen S: Changes in left ventricular stroke volume measured by Doppler echocardiography. Br Heart J 54: 378, 1985 7. Pouget JM, Harris WS, Mayron BR, Naughton JP: Abnormal responses of the systolic time intervals to exercise in patients with angina pectoris. Circulation 43: 289, 1971 8. Amon KW, Crawford MH: Upright exercise echocardiography. J Clin Ultrasound 7: 373, 1979 9. Richards KL, Cannon SR, Miller JF, Crawford MH: Calculation of aortic valve area by Doppler echocardiography: a direct application of the continuity equation. Circulation 73: 964, 1986 10. Fisher DC, Sahn DJ, Friedman MJ, Larson D, Valdes-Cruz LM, Horowitz S, Goldberg SJ, Allen HD: The mitral valve orifice method for noninvasive two-dimensional echo Doppler determi- Vol. 77, No. 3, March 1988 nations of cardiac output. Circulation 67: 872, 1983 11. Gardin JM, Tobis JM, Dabestani A, Smith C, Elkayam U, Castleman E, White D, Allfie A, Henry WL: Superiority of twodimensional measurement of aortic vessel diameter in Doppler echocardiographic estimates of left ventricular stroke volume. J Am Coll Cardiol 6: 66, 1985 12. Huntsman LL, Stewart DK, Barnes SR, Franklin SB, Colocousis JS, Hessel EA: Noninvasive Doppler determination of cardiac output in man. Clinical validation. Circulation 67: 593, 1983 13. Ferguson GA: Statistical analysis in psychology and education. New York, 1976, McGraw-Hill, pp 297-299 14. Loeppky JA, Greene ER, Hoekenga DE, Caprihan A, Luft UC: Beat-by-beat stroke volume assessment by pulsed Doppler in upright and supine exercise. J Appl Physiol 50: 1173, 1981 15. Shaw JG, Johnson EC, Voyles WF, Greene ER: Noninvasive Doppler determination of cardiac output during submaximal and peak exercise. 59: 722, 1985 16. Gardin JM, Kozlowski J, Dabestani A, Murphy M, Kusnick C, Allfie A, Russell D, Henry WL: Studies of Doppler aortic flow velocity during supine bicycle exercise. Am J Cardiol 57: 327, 1986 17. Stewart WJ, Jiang L, Mich R, Pandian N, Guerrero JL, Weyman AE: Variable effects of changes in flow rate through the aortic, pulmonary and mitral valves on valve area and flow velocity: impact on quantitative Doppler flow calculations. J Am Coll Cardiol 6: 653, 1985 18. Bevegard S, Holmgren A, Jonsson B: The effect of body position on the circulation at rest and during exercise, with special reference to the influence on the stroke volume. Acta Physiol Scand 49: 279, 1960 19. Crawford MH, White DH, Amon KW: Echocardiographic evaluation of left ventricular size and performance during handgrip and supine and upright bicycle exercise. Circulation 59: 1188, 1979 20. Poliner LR, Dehmer GJ, Lewis SE, Parkey RW, Blomqvist CG, Willerson JT: Left ventricular performance in normal subjects: a comparison of the responses to exercise in the upright and supine positions. Circulation 62: 528, 1980 21. Steingart RM, Wexler J, Slagle S, Scheuer J: Radionuclide ventriculographic responses to graded supine and upright exercise: critical role of the Frank-Starling mechanism at submaximal exercise. Am J Cardiol 53: 1671, 1984 22. Cumming GR: Stroke volume during recovery from supine bicycle exercise. J Appl Physiol 32: 575, 1972 23. Plotnick GD, Becker LC, Fisher ML: Changes in left ventricular function during recovery from upright bicycle exercise in normal persons and patients with coronary artery disease. Am J Cardiol 58: 247, 1986 24. Colocousis JS, Huntsman LL, Curreri PW: Estimation of stroke volume changes by ultrasound Doppler. Circulation 56: 914, 1977 25. Ihlen H, Amlie JP, Dale J, Forfang K, Nitter-Hauge S, Otterstad JE, Simonsen S, Myhre E: Determination of cardiac output by Doppler echocardiography. Br Heart J 51: 54, 1984 26. Lewis JF, Kuo LC, Nelson JG, Limacher MC, Quinones MA: Pulsed Doppler echocardiographic determination of stroke volume and cardiac output: clinical validation of two new methods using the apical window. Circulation 70: 425, 1984 27. Zhang Y, Nitter-Hauge S, Ihlen H, Myhre E: Doppler echocardiographic measurement of cardiac output using the mitral orifice method. Br Heart J 53: 130, 1985 28. Christie J, Sheldahl LM, Tristani FE, Sagar KB, Ptacin MJ, Wann S: Determination of stroke volume and cardiac output during exercise: comparison of two-dimensional and Doppler echocardiography, Fick oximetry, and thermodilution. Circulation 76: 539, 1987 551 Differing mechanisms of exercise flow augmentation at the mitral and aortic valves. A Rassi, Jr, M H Crawford, K L Richards and J F Miller Downloaded from http://circ.ahajournals.org/ by guest on June 18, 2017 Circulation. 1988;77:543-551 doi: 10.1161/01.CIR.77.3.543 Circulation is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231 Copyright © 1988 American Heart Association, Inc. All rights reserved. Print ISSN: 0009-7322. Online ISSN: 1524-4539 The online version of this article, along with updated information and services, is located on the World Wide Web at: http://circ.ahajournals.org/content/77/3/543 Permissions: Requests for permissions to reproduce figures, tables, or portions of articles originally published in Circulation can be obtained via RightsLink, a service of the Copyright Clearance Center, not the Editorial Office. Once the online version of the published article for which permission is being requested is located, click Request Permissions in the middle column of the Web page under Services. Further information about this process is available in the Permissions and Rights Question and Answer document. Reprints: Information about reprints can be found online at: http://www.lww.com/reprints Subscriptions: Information about subscribing to Circulation is online at: http://circ.ahajournals.org//subscriptions/