Background: Neither homografts nor bioprostheses have previously been seen to acquire a host endo... more Background: Neither homografts nor bioprostheses have previously been seen to acquire a host endothelium. We previously reported a direct relation between aldehyde tanning and bioprosthesis calcification and the absence of calcification in the absence of aldehyde. Methods and results: Bovine pericardium was 1) treated with 0.625% glutaraldehyde and stored in 4% formaldehyde, 2) treated with 99.5% glycerol, and 3) treated with 99.5% glycerol and stored in formaldehyde (0.25-4%). The treated pericardium was used to construct stentless mitral valve prostheses (of a single pattern) that were implanted in weanling sheep. After the animals were killed, a strip of anterior cusp from annulus to papillary muscle was processed and examined by scanning electron microscopy for the presence of host endothelial growth. Avoidance of aldehyde allowed host endothelial growth in all cases (six of six), and pure aldehyde treatment inhibited growth in five of six animals. Exposure to aldehyde after glycerol treatment interfered with endothelialization significantly; after longer periods of implantation, however, endothelial growth occurred almost invariably in this group (12 of 13 implanted longer than 200 days). For this group, there was a statistically significant difference for duration of implantation between the valves that grew endothelium and those that did not (218.4 +/- 61.9 versus 128.5 +/- 65.4 days). Conclusions: Aldehyde treatment inhibits endothelial growth. With glycerol treatment, growth is uniformly present. Limited exposure to aldehydes after glycerol treatment inhibits endothelial growth, but this effect was ameliorated by prolonged implantation. The possibility of host endothelium-covered, noncalcifying bioprostheses is now real.
Journal of The American Society of Echocardiography, Sep 1, 1995
Creation of pressure-area relationships (loops) with automated border detection (ABD) involves co... more Creation of pressure-area relationships (loops) with automated border detection (ABD) involves correction for the variable inherent delay in the ABD signal relative to the pressure recording. This article summarizes (1) the results of in vitro experiments performed to define the range of, and factors that might influence, the ABD delay; (2) the difficulties encountered in evaluating a thin-walled structure like the left atrium in the dog model; and (3) the solutions to some of the difficulties found. The in vitro experiments showed that the ABD delay relative to high-fidelity pressure recordings ranges from 20 to 34 msec and 35 to 57 msec at echocardiographic frame rates of 60/sec and 33/sec, respectively. The delay was not influenced significantly by the type of transducer used, distance from the target area, or size of the target area. The delay in the ABD signal, relative to the echocardiographic image, ranges from nil to less than one frame duration, whereas it is delayed one to two frame durations relative to the electrocardiogram processed by the imaging system. In the dog model, inclusion of even small areas outside the left atrium rendered curves with apparent physiologic contour but inappropriately long delays of 90 to 130 msec. To exclude areas outside the left atrial cavity, time-gain compensation and lateral gain compensation were used much more extensively than during left ventricular ABD recording. By changing the type of sonomicrometers used in our experiments, we were able to record simultaneously ABD and ultrasonic crystal data. However, both spontaneous contrast originating from a right-sided heart bypass pump and electronic noise from the eletrocautery severely interferred with ABD recording.
A mathematical model of left ventricular pressure (LVP) during isovolumic contraction in the time... more A mathematical model of left ventricular pressure (LVP) during isovolumic contraction in the time domain shows the following predictions: 1) td, the time from onset of contraction to dP/dtmax and (dP/dt)/P, reflect only the time-dependent aspects of contraction, and are independent of preload; 2) dP/dtmax depends on both preload and the time-dependent aspects of contraction. To test preload independence we reduced filling volume (FV) by the method of ventricular volume clamps with a remote-controlled mitral valve in 7 anesthetized open-chest dogs. A decrease in FV of 80 +/- 15% produced a 29 +/- 12% (p < 0.001) decrease in LVP, 34 +/- 13% (p < 0.001) decrease in dP/dtmax, 13 +/- 4% (p < 0.001) decrease in t-dP/dtneg, and no change in td (-3 +/- 5%, NS). The heart rate (HR) dependence on td was assessed in other 5 anesthetized open-chest dogs. HR was changed with atrial pacing (50-240 bpm). td was linearly and inversely related to HR in each dog, and at each HR: dobutamine lowered and propranolol elevated this relation when compared to control (p < .001, both). Since dP/dtmax occurs usually before the opening of the aortic valve, td is, thus, also afterload-independent. Conclusion. This study supports the theoretical predictions that td is independent of preload and that it can serve, at any given HR, as a reliable index of contractility, provided that dP/dtmax occurs before the opening of the aortic valve.
Background Preservation of the mitral subvalvular apparatus during mitral valve replacement (MVR)... more Background Preservation of the mitral subvalvular apparatus during mitral valve replacement (MVR) has become more popular, in part because of the clinically and experimentally demonstrated more optimal left ventricular (LV) performance after surgery; the mechanisms responsible for this beneficial influence, however, have not been clearly elucidated. Methods and Results Fourteen dogs underwent placement of 26 myocardial markers into the LV and septum. One week later, the animals were studied while awake, sedated, and atrially paced (120 beats per minute) both under baseline conditions and after inotropic stimulation (calcium). The animals then underwent MVR and were randomized into either chord-sparing (MVR-Intact) or chord-severing (MVR-Cut) techniques. Two weeks later, the animals were studied under the same conditions. LV systolic function was assessed by the slope of the end-systolic pressure-volume relation (E es ); early LV diastolic filling was analyzed by the pressure-time constant of relaxation (Ï„). The instantaneous longitudinal gradient of torsional deformation for the LV (twist) was also calculated, as were the changes in twist with respect to time during systole and early diastole (LV recoil). Intergroup comparison showed a trend toward increased contractility (E es , P =.061, before versus after MVR), as well as faster relaxation for the MVR-Intact group. Concurrent analysis of LV systolic function and the rate of systolic twist revealed a significant inverse relation, which disappeared after MVR when the chordae were severed. Conclusions These observations suggest that the mitral subvalvular apparatus acts as a modulator of LV systolic torsional deformation into LV pump (or ejection) performance.
The increased use of autologous, homologous or heterologous aortic root demands a detailed knowle... more The increased use of autologous, homologous or heterologous aortic root demands a detailed knowledge of its anatomy and function. The advent of 3-D digital sonomicrometry offered the opportunity to acquire precise information on the root and leaflet movements during the cardiac cycle. Under cardiopulmonary bypass, sonomicrometry crystals were implanted in the aortic root and valve of eight sheep. Crystals were sutured at each commissure (n = 3), the top of the sinotubular junction (n = 3), lowest point of the annulus (n = 3), and leaflet tip (n = 3). 3-D coordinates of each crystal were recorded, together with left ventricular and aortic root pressures and ECG. When the animal had returned to a stable hemodynamic condition, the maximum and minimum distances between two crystals, and areas between three crystals, were calculated. Changes in root volume and leaflet position were time-related to the pressure changes. The most significant change between maximum and minimum distance betw...
Cardiac Mechanics and Function in the Normal and Diseased Heart, 1989
Cardiovascular dynamics is one of the oldest lines of medical research, having its origins in the... more Cardiovascular dynamics is one of the oldest lines of medical research, having its origins in the work of William Harvey in the seventeenth century. Yet despite its long history, conceptual understanding of cardiac performance is advancing more rapidly than ever, and many different scientifc approaches are currently yielding exciting new insights. This chapter reviews 15 years of work from our laboratories at Duke University on the quantitative assessment of diastolic and systolic ventricular function. Our approach to the analysis of chamber geometry, ventricular interaction, and diastolic mechanical properties is described, leading to the observation of a fundamentally linear relationship between myocardial energy production (net external work) and end diastolic fiber length. This relationship is further validated and expanded to provide a useful estimate of myocardial inotropism that is applicable to pathophysiologic analysis of myocardial ischemia and hypertrophy. Finally, recent extensions of this technique to human studies have proven useful to the understanding of cardiopulmonary interactions and valvular heart disease. As knowledge of myocardial adaptive mechanisms improves, enhanced diagnostic and therapeutic capabilities could translate into significant advances in patient care.
American Journal of Physiology-heart and Circulatory Physiology, Apr 1, 1996
We investigated left ventricular (LV) diastolic volume changes (suction inflows) with left atrial... more We investigated left ventricular (LV) diastolic volume changes (suction inflows) with left atrial pressure (LAP) clamped to ambient pressure in six open-chest, anesthetized dogs. The left atrium was cannulated and connected to a servo pump, and LAP was clamped to a set point near 0 mmHg for four beats by withdrawing blood. LAP averaged 5.88 +/- 1.44 mmHg before the clamp and fell to 0.74 +/- 0.61 mmHg (P < 0.0001) after the clamp. During the first clamped beat a transmitral pressure gradient of 1.0 +/- 0.6 mmHg was observed, resulting in LV filling of 2.6 +/- 1.8 ml. Subsequent beats developed suction-driven (mean negative LV pressure: -1.5 +/- 1.3 mmHg; P < 0.005 vs. zero) LV filling of 4.5 +/- 2.8 ml/beat with a peak transmitral pressure gradient of 1.7 +/- 0.6 mmHg. These data are consistent with the hypothesis that LV suction can be an important filling mechanism under condition in which LV end-systolic volume is reduced, e.g., reduced filling pressures, high heart rates, exercise, or increased inotropic drive.
In this chapter we have described a unique method of left ventricular volume clamping designed to... more In this chapter we have described a unique method of left ventricular volume clamping designed to quantify the passive properties of the intact ventricle. We prevented complete (end-systolic clamping) or partial filling at different times in diastole. The ventricle thus relaxed completely at different volumes, and we generated pressure-volume coordinates for the passive ventricle that included negative, as welll as positive, values of pressure. We then determined the equilibrium volume, that is, volume at zero transmural pressure, in the working ventricle. We characterized the passive pressure-volume relation with a logarithmic approach that is physically more realistic than the traditional exponential. Finally, we discussed the importance of the concepts of equilibrium volume an restoring forces for diastolic mechanics.
ANF is a polypeptide with important influence on blood pressure, cardiac output and sodium excret... more ANF is a polypeptide with important influence on blood pressure, cardiac output and sodium excretion. As the physiological stimulus for ANF release right atrial volume, i.e. right atrial distension has been demonstrated in animals [3, 4] and patients [5, 7]. Significant changes in ANF serum level have been reported during CPB [2]: after onset of CPB ANF level rises and stays elevated. During CPB RAP is very low or negative so that right atrial distension cannot account for this increase in secretion. Aim of this study was to determine if the inversion of the right atrium during CPB causes the increased release of ANF.
American Journal of Physiology-Heart and Circulatory Physiology, 1996
To determine left ventricular (LV) viscoelastic properties during acute volume changes, the relax... more To determine left ventricular (LV) viscoelastic properties during acute volume changes, the relaxation of LV pressure (2-Fr, Millar) at steady LV volume after a known volume change was measured in 14 isolated guinea pig left ventricles arrested in diastole. The left ventricle was loaded and unloaded by manual injection and withdrawal of saline in 10 x 0.1-ml steps, controlling the steadiness of LV volume by measuring LV major and minor diameters (ultrasonic crystals). Cyclic stepwise volume loading and unloading resulted in a hysteresis loop, the complexity of which was caused by stress relaxation at each steady volume. With the use of linear regression analysis, the gross elastic effect of the pressure signal was separated from the viscoelastic part, decomposed into the fast and the slow component with time constants of relaxation equal to 1 and 20 s, respectively. The amplitudes of the fast and the slow component showed that 1) stress relaxation is more expressed at higher LV volu...
American Journal of Physiology-Heart and Circulatory Physiology, 1990
This study was designed to investigate the relationship between left ventricular (LV) eccentricit... more This study was designed to investigate the relationship between left ventricular (LV) eccentricity, volume, and passive elastic properties. Eight open-chest fentanyl-anesthetized dogs were instrumented with an LV micromanometer, a remote-controlled mitral valve occluder, and two pairs of ultrasonic crystals to measure anterior-posterior and base-apex dimensions. We identified the presence of elastic recoil forces with negative LV diastolic pressure in nonfilling diastoles (end-systolic volume clamp). Using linear regression analysis we related midwall eccentricity to volume in nonfilling diastoles at the time of LVPmin and at end diastole, and in normal beats at end systole at LVPmin and at end-diastole. Intersection of the end-systolic and end-diastolic lines (transitional volume, Vt = 38.0 + 6.4 ml) divides cycles with and without the presence of elastic recoil forces. Vt is analogous to the equilibrium volume (V0), determined as the volume intercept of the logarithmic passive pre...
Background: Neither homografts nor bioprostheses have previously been seen to acquire a host endo... more Background: Neither homografts nor bioprostheses have previously been seen to acquire a host endothelium. We previously reported a direct relation between aldehyde tanning and bioprosthesis calcification and the absence of calcification in the absence of aldehyde. Methods and results: Bovine pericardium was 1) treated with 0.625% glutaraldehyde and stored in 4% formaldehyde, 2) treated with 99.5% glycerol, and 3) treated with 99.5% glycerol and stored in formaldehyde (0.25-4%). The treated pericardium was used to construct stentless mitral valve prostheses (of a single pattern) that were implanted in weanling sheep. After the animals were killed, a strip of anterior cusp from annulus to papillary muscle was processed and examined by scanning electron microscopy for the presence of host endothelial growth. Avoidance of aldehyde allowed host endothelial growth in all cases (six of six), and pure aldehyde treatment inhibited growth in five of six animals. Exposure to aldehyde after glycerol treatment interfered with endothelialization significantly; after longer periods of implantation, however, endothelial growth occurred almost invariably in this group (12 of 13 implanted longer than 200 days). For this group, there was a statistically significant difference for duration of implantation between the valves that grew endothelium and those that did not (218.4 +/- 61.9 versus 128.5 +/- 65.4 days). Conclusions: Aldehyde treatment inhibits endothelial growth. With glycerol treatment, growth is uniformly present. Limited exposure to aldehydes after glycerol treatment inhibits endothelial growth, but this effect was ameliorated by prolonged implantation. The possibility of host endothelium-covered, noncalcifying bioprostheses is now real.
Journal of The American Society of Echocardiography, Sep 1, 1995
Creation of pressure-area relationships (loops) with automated border detection (ABD) involves co... more Creation of pressure-area relationships (loops) with automated border detection (ABD) involves correction for the variable inherent delay in the ABD signal relative to the pressure recording. This article summarizes (1) the results of in vitro experiments performed to define the range of, and factors that might influence, the ABD delay; (2) the difficulties encountered in evaluating a thin-walled structure like the left atrium in the dog model; and (3) the solutions to some of the difficulties found. The in vitro experiments showed that the ABD delay relative to high-fidelity pressure recordings ranges from 20 to 34 msec and 35 to 57 msec at echocardiographic frame rates of 60/sec and 33/sec, respectively. The delay was not influenced significantly by the type of transducer used, distance from the target area, or size of the target area. The delay in the ABD signal, relative to the echocardiographic image, ranges from nil to less than one frame duration, whereas it is delayed one to two frame durations relative to the electrocardiogram processed by the imaging system. In the dog model, inclusion of even small areas outside the left atrium rendered curves with apparent physiologic contour but inappropriately long delays of 90 to 130 msec. To exclude areas outside the left atrial cavity, time-gain compensation and lateral gain compensation were used much more extensively than during left ventricular ABD recording. By changing the type of sonomicrometers used in our experiments, we were able to record simultaneously ABD and ultrasonic crystal data. However, both spontaneous contrast originating from a right-sided heart bypass pump and electronic noise from the eletrocautery severely interferred with ABD recording.
A mathematical model of left ventricular pressure (LVP) during isovolumic contraction in the time... more A mathematical model of left ventricular pressure (LVP) during isovolumic contraction in the time domain shows the following predictions: 1) td, the time from onset of contraction to dP/dtmax and (dP/dt)/P, reflect only the time-dependent aspects of contraction, and are independent of preload; 2) dP/dtmax depends on both preload and the time-dependent aspects of contraction. To test preload independence we reduced filling volume (FV) by the method of ventricular volume clamps with a remote-controlled mitral valve in 7 anesthetized open-chest dogs. A decrease in FV of 80 +/- 15% produced a 29 +/- 12% (p < 0.001) decrease in LVP, 34 +/- 13% (p < 0.001) decrease in dP/dtmax, 13 +/- 4% (p < 0.001) decrease in t-dP/dtneg, and no change in td (-3 +/- 5%, NS). The heart rate (HR) dependence on td was assessed in other 5 anesthetized open-chest dogs. HR was changed with atrial pacing (50-240 bpm). td was linearly and inversely related to HR in each dog, and at each HR: dobutamine lowered and propranolol elevated this relation when compared to control (p < .001, both). Since dP/dtmax occurs usually before the opening of the aortic valve, td is, thus, also afterload-independent. Conclusion. This study supports the theoretical predictions that td is independent of preload and that it can serve, at any given HR, as a reliable index of contractility, provided that dP/dtmax occurs before the opening of the aortic valve.
Background Preservation of the mitral subvalvular apparatus during mitral valve replacement (MVR)... more Background Preservation of the mitral subvalvular apparatus during mitral valve replacement (MVR) has become more popular, in part because of the clinically and experimentally demonstrated more optimal left ventricular (LV) performance after surgery; the mechanisms responsible for this beneficial influence, however, have not been clearly elucidated. Methods and Results Fourteen dogs underwent placement of 26 myocardial markers into the LV and septum. One week later, the animals were studied while awake, sedated, and atrially paced (120 beats per minute) both under baseline conditions and after inotropic stimulation (calcium). The animals then underwent MVR and were randomized into either chord-sparing (MVR-Intact) or chord-severing (MVR-Cut) techniques. Two weeks later, the animals were studied under the same conditions. LV systolic function was assessed by the slope of the end-systolic pressure-volume relation (E es ); early LV diastolic filling was analyzed by the pressure-time constant of relaxation (Ï„). The instantaneous longitudinal gradient of torsional deformation for the LV (twist) was also calculated, as were the changes in twist with respect to time during systole and early diastole (LV recoil). Intergroup comparison showed a trend toward increased contractility (E es , P =.061, before versus after MVR), as well as faster relaxation for the MVR-Intact group. Concurrent analysis of LV systolic function and the rate of systolic twist revealed a significant inverse relation, which disappeared after MVR when the chordae were severed. Conclusions These observations suggest that the mitral subvalvular apparatus acts as a modulator of LV systolic torsional deformation into LV pump (or ejection) performance.
The increased use of autologous, homologous or heterologous aortic root demands a detailed knowle... more The increased use of autologous, homologous or heterologous aortic root demands a detailed knowledge of its anatomy and function. The advent of 3-D digital sonomicrometry offered the opportunity to acquire precise information on the root and leaflet movements during the cardiac cycle. Under cardiopulmonary bypass, sonomicrometry crystals were implanted in the aortic root and valve of eight sheep. Crystals were sutured at each commissure (n = 3), the top of the sinotubular junction (n = 3), lowest point of the annulus (n = 3), and leaflet tip (n = 3). 3-D coordinates of each crystal were recorded, together with left ventricular and aortic root pressures and ECG. When the animal had returned to a stable hemodynamic condition, the maximum and minimum distances between two crystals, and areas between three crystals, were calculated. Changes in root volume and leaflet position were time-related to the pressure changes. The most significant change between maximum and minimum distance betw...
Cardiac Mechanics and Function in the Normal and Diseased Heart, 1989
Cardiovascular dynamics is one of the oldest lines of medical research, having its origins in the... more Cardiovascular dynamics is one of the oldest lines of medical research, having its origins in the work of William Harvey in the seventeenth century. Yet despite its long history, conceptual understanding of cardiac performance is advancing more rapidly than ever, and many different scientifc approaches are currently yielding exciting new insights. This chapter reviews 15 years of work from our laboratories at Duke University on the quantitative assessment of diastolic and systolic ventricular function. Our approach to the analysis of chamber geometry, ventricular interaction, and diastolic mechanical properties is described, leading to the observation of a fundamentally linear relationship between myocardial energy production (net external work) and end diastolic fiber length. This relationship is further validated and expanded to provide a useful estimate of myocardial inotropism that is applicable to pathophysiologic analysis of myocardial ischemia and hypertrophy. Finally, recent extensions of this technique to human studies have proven useful to the understanding of cardiopulmonary interactions and valvular heart disease. As knowledge of myocardial adaptive mechanisms improves, enhanced diagnostic and therapeutic capabilities could translate into significant advances in patient care.
American Journal of Physiology-heart and Circulatory Physiology, Apr 1, 1996
We investigated left ventricular (LV) diastolic volume changes (suction inflows) with left atrial... more We investigated left ventricular (LV) diastolic volume changes (suction inflows) with left atrial pressure (LAP) clamped to ambient pressure in six open-chest, anesthetized dogs. The left atrium was cannulated and connected to a servo pump, and LAP was clamped to a set point near 0 mmHg for four beats by withdrawing blood. LAP averaged 5.88 +/- 1.44 mmHg before the clamp and fell to 0.74 +/- 0.61 mmHg (P < 0.0001) after the clamp. During the first clamped beat a transmitral pressure gradient of 1.0 +/- 0.6 mmHg was observed, resulting in LV filling of 2.6 +/- 1.8 ml. Subsequent beats developed suction-driven (mean negative LV pressure: -1.5 +/- 1.3 mmHg; P < 0.005 vs. zero) LV filling of 4.5 +/- 2.8 ml/beat with a peak transmitral pressure gradient of 1.7 +/- 0.6 mmHg. These data are consistent with the hypothesis that LV suction can be an important filling mechanism under condition in which LV end-systolic volume is reduced, e.g., reduced filling pressures, high heart rates, exercise, or increased inotropic drive.
In this chapter we have described a unique method of left ventricular volume clamping designed to... more In this chapter we have described a unique method of left ventricular volume clamping designed to quantify the passive properties of the intact ventricle. We prevented complete (end-systolic clamping) or partial filling at different times in diastole. The ventricle thus relaxed completely at different volumes, and we generated pressure-volume coordinates for the passive ventricle that included negative, as welll as positive, values of pressure. We then determined the equilibrium volume, that is, volume at zero transmural pressure, in the working ventricle. We characterized the passive pressure-volume relation with a logarithmic approach that is physically more realistic than the traditional exponential. Finally, we discussed the importance of the concepts of equilibrium volume an restoring forces for diastolic mechanics.
ANF is a polypeptide with important influence on blood pressure, cardiac output and sodium excret... more ANF is a polypeptide with important influence on blood pressure, cardiac output and sodium excretion. As the physiological stimulus for ANF release right atrial volume, i.e. right atrial distension has been demonstrated in animals [3, 4] and patients [5, 7]. Significant changes in ANF serum level have been reported during CPB [2]: after onset of CPB ANF level rises and stays elevated. During CPB RAP is very low or negative so that right atrial distension cannot account for this increase in secretion. Aim of this study was to determine if the inversion of the right atrium during CPB causes the increased release of ANF.
American Journal of Physiology-Heart and Circulatory Physiology, 1996
To determine left ventricular (LV) viscoelastic properties during acute volume changes, the relax... more To determine left ventricular (LV) viscoelastic properties during acute volume changes, the relaxation of LV pressure (2-Fr, Millar) at steady LV volume after a known volume change was measured in 14 isolated guinea pig left ventricles arrested in diastole. The left ventricle was loaded and unloaded by manual injection and withdrawal of saline in 10 x 0.1-ml steps, controlling the steadiness of LV volume by measuring LV major and minor diameters (ultrasonic crystals). Cyclic stepwise volume loading and unloading resulted in a hysteresis loop, the complexity of which was caused by stress relaxation at each steady volume. With the use of linear regression analysis, the gross elastic effect of the pressure signal was separated from the viscoelastic part, decomposed into the fast and the slow component with time constants of relaxation equal to 1 and 20 s, respectively. The amplitudes of the fast and the slow component showed that 1) stress relaxation is more expressed at higher LV volu...
American Journal of Physiology-Heart and Circulatory Physiology, 1990
This study was designed to investigate the relationship between left ventricular (LV) eccentricit... more This study was designed to investigate the relationship between left ventricular (LV) eccentricity, volume, and passive elastic properties. Eight open-chest fentanyl-anesthetized dogs were instrumented with an LV micromanometer, a remote-controlled mitral valve occluder, and two pairs of ultrasonic crystals to measure anterior-posterior and base-apex dimensions. We identified the presence of elastic recoil forces with negative LV diastolic pressure in nonfilling diastoles (end-systolic volume clamp). Using linear regression analysis we related midwall eccentricity to volume in nonfilling diastoles at the time of LVPmin and at end diastole, and in normal beats at end systole at LVPmin and at end-diastole. Intersection of the end-systolic and end-diastolic lines (transitional volume, Vt = 38.0 + 6.4 ml) divides cycles with and without the presence of elastic recoil forces. Vt is analogous to the equilibrium volume (V0), determined as the volume intercept of the logarithmic passive pre...
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