运动负荷超声试验对无症状心肌缺血心功能的评价

利用次极量卧位蹬车运动负荷超声试验研究无症状心肌缺血（SMI）患者和心绞痛（AP）患者在心肌缺血发作过程中左心功能的改变。15例SMI患者和12例AP患者在运动负荷超声试验中都出现心肌缺血，14例冠造正常者为对照组。结果：（1）AP组、SMI组和对照组的运动总时间和运动总功量依次增加，三组之间比较差异均有显著性（P＜0．05）。（2）对照组：在运动中，每例患者的收缩功能各项指标都明显升高，LVEF上升大于5％；二尖瓣血流峰值E峰和A峰也明显升高，而E／A比值下降。（3）SMI组：总体收缩功能各项指标在运动早期也呈上升趋势，LVEF上升大于5％，而随运动量进一步增加，收缩功能不再增强；二尖瓣血流峰值E4和A4也升高，但E／A比值变化不明显。（4）AP组：在运动中，心脏收缩功能各项指标基本保持不变，LVEF上升小于5％；二尖瓣血流峰值E峰上升明显，A峰轻微上升，E／A比值明显增加。结论：（1）正常人的左室收缩功能和舒张功能随着运动量的增加而增强。（2）在相同负荷条件下或相同程度的心肌缺血发作过程中，SMI患者左室功能受损程度轻于AP患者。     

Relation between Q-QS changes on the rest electrocardiogram and left ventricular function with healed myocardial infarction

In the Program of Surgical Control of Hyperlipidemia, the relation of the Minnesota Q-QS codes for rest electrocardiograms to left ventricular (LV) function was studied in patients with healed myocardial infarction (MI). Of 838 subjects enrolled in the study, 477 (57%) had codable Q-QS patterns at the time of randomization. There was an extremely high correlation between the level of the Minnesota code and concurrent LV function, the latter being determined on left ventriculography by both ejection fraction and the number of segmental wall motion abnormalities. Subjects without a Q-QS code had less myocardial damage than did those with a code present in a single cardiac area. Extent of LV damage correlated with the level of significance of the Q-QS code, and when the code was present in only 1 cardiac location damage was greatest if the anteroseptal area was involved. Q-QS codes present in 2 rather than 1 cardiac area were associated with an even greater degree of LV damage. A previous study has shown a strong correlation between LV function and the Minnesota codes when the latter were recorded 0.5 to 5 years (mean 2.2) earlier at the time of the acute MI. The present data show that the relation between LV function and the Minnesota codes after an acute MI persists over time and is even stronger when both are determined in the healed state at a time remote from the acute event.     

Relation between left ventricular diastolic function and exercise tolerance in patients with left ventricular dysfunction

Previous studies show no correlation between resting systolic left ventricular performance assessed as the ejection fraction and exercise tolerance. This study examined the relation between left ventricular diastolic performance and exercise tolerance in 63 patients with left ventricular dysfunction (ejection fraction less than 50%) due to known or suspected coronary artery disease. The 51 men and 12 women, aged 54 +/- 8 years (mean +/- standard deviation), underwent symptom-limited upright exercise testing on a bicycle ergometer. The exercise end-points were angina (n:5), dyspnea (n:16), and fatigue (n:42). The patients were divided into three groups: group 1 (n:28) with normal exercise tolerance (9.5 +/- 2.4 minutes), group 2 (n:18) with mild exercise intolerance (5.8 +/- 0.5 minutes), and group 3 (n:17) had severe exercise intolerance (3.7 +/- 0.9 minutes). The three groups did not differ in age, ejection fraction, end-diastolic volume, exercise end-point, exercise heart rate, and left ventricular peak filling rate at rest. The exercise peak filling rate was, however, significantly higher in group 1 (p = 0.03). Stepwise multivariate discriminant analysis of important variables identified the exercise peak filling rate as the only predictor of exercise tolerance (F = 6.0). Thus, variation in exercise peak filling rate may in part explain the variability of exercise tolerance in patients with left ventricular dysfunction; patients with preserved exercise capacity have higher exercise peak filling rate than those with exercise intolerance.     

Global and regional left ventricular ejection fraction abnormalities during exercise in patients with silent myocardial ischemia

Sixteen asymptomatic patients with coronary artery disease and silent myocardial ischemia were studied with exercise radionuclide ventriculography. Radionuclide ventriculograms were analyzed for changes in ejection fraction globally and in three regions. Results were compared with radionuclide ventriculograms in 24 symptomatic patients. Both groups (silent myocardial ischemia and angina) were similar in prevalence of multivessel disease and previous myocardial infarction, as well as in age and sex. Global ejection fraction decreased by 0.06 in both groups during exercise; regional ejection fraction also decreased by similar amounts in the two groups. Furthermore, the percent of regions with normal ejection fraction at rest that demonstrated a decrease during exercise was identical: 19 (60%) of 33 versus 26 (60%) of 46. These exercise radionuclide ventriculographic results suggest that abnormalities in regional and global left ventricular wall motion are similar in patients with coronary artery disease with and without silent myocardial ischemia.     

Correlation between R-wave amplitude and left ventricular volume at rest and with exercise

In 52 patients with exercise angiography (12 normals, 31 with coronary heart disease, 9 with congestive cardiomyopathy) exercise ECGs were examined for R-wave changes. An increasing R-wave amplitude was found an insensitive sign of ischemia in patients with coronary heart disease (sensitivity 29%, specificity 81%). Sensitivity and specificity of the observed ST depression in this study were 83% and 71%, respectively, as reported by others. There was no positive correlation between the changes in the R-wave amplitude and left ventricular end-diastolic volume during exercise, thus there was no proof of the existence of the so-called Brody effect in humans.     

Relation between oscillatory ventilation at rest before cardiopulmonary exercise testing and prognosis in patients with left ventricular dysfunction

BACKGROUND: Although nocturnal Cheyne-Stokes respiration alternating between hyperpnea and hypopnea has been considered a sign of severe heart failure, the clinical status of cardiac patients who exhibit oscillatory ventilation during wakefulness has not been clarified. This study was carried out to determine the relation between oscillatory ventilation during wakefulness and exercise capacity in patients with chronic heart disease. We also evaluated retrospectively whether the presence of oscillatory ventilation influences the long-term prognosis in these patients. METHODS: A total of 164 patients with left ventricular dysfunction performed a symptom-limited incremental exercise test. Respiratory gas exchange was measured on a breath-by-breath basis throughout the test. Oscillatory ventilation was defined when clear ventilatory oscillation of at least two consecutive cycles was identified at rest before exercise testing and the difference between the peak and nadir of oscillating ventilation was > 30% of the mean value of ventilation. RESULTS: Oscillatory ventilation was noted in 45 of 164 cardiac patients (27%), and the magnitude (mean +/- SD) of oscillation in these patients was 45.5 +/- 16.9%. Patients with oscillatory ventilation had significantly lower left ventricular ejection fraction than those without it (40.7 +/- 12.7% vs 44.9 +/- 11.6%, p < 0.05). However, parameters of exercise capacity such as the peak oxygen uptake (O(2)), the slope of the increase in O(2) relative to the increase in work rate (DeltaO(2)/DeltaWR), and the ratio of the increase in ventilation to the increase in carbon dioxide output (DeltaE/DeltaCO(2)) were not significantly different between the two groups. The mortality rate during 1,797 +/- 599 days of follow-up did not differ between the groups (p = 0.65). CONCLUSIONS: Oscillatory ventilation present at rest before cardiopulmonary exercise testing is not significantly related to the peak O(2), DeltaO(2)/DeltaWR, DeltaE/DeltaCO(2), or prognosis in patients with left ventricular dysfunction.     

Thallium-201 myocardial scintigraphy and left ventricular function at rest in patients with rest angina pectoris

The purpose of this study was to examine the rest thallium-201 perfusion pattern during angina-free periods in 40 patients with rest angina pectoris secondary to coronary artery disease (greater than or equal to 70% diameter narrowing). Seventeen patients had previous Q wave myocardial infarction. The perfusion defects were considered fixed or reversible, depending on the absence or presence of redistribution in the 4-hour delayed images. There were 40 perfusion defects (26 fixed and 14 reversible) in 27 patients whereas 13 patients had normal scans. Reversible perfusion defects were present in 10 patients (25%). Of the 26 fixed perfusion defects, 17 did not have corresponding Q waves. Occluded vessels (63%) had more perfusion defects than vessels with subtotal occlusion (30%) (p less than 0.01). The perfusion defect size was larger in patients with lower ejection fraction than in patients with higher ejection fraction. We conclude: (1) perfusion defects are common in patients with rest angina and are reversible in 25% of patients indicating reduced regional coronary blood flow; (2) the degree of stenosis affects the presence of perfusion defect; (3) fixed defects may be present without corresponding Q waves; and (4) global left ventricular function is related to the size of perfusion defects.     

Relation between exercise capacity and left ventricular systolic versus diastolic function during exercise in patients after myocardial infarction

BACKGROUND: It is known that left ventricular systolic function at rest does not correlate well with exercise capacity of patients with heart failure. However, the contribution of left ventricular diastolic dysfunction, especially during exercise, to exercise capacity of cardiac patients remains to be determined. OBJECTIVE: To determine the impact of left ventricular systolic and diastolic function during exercise on exercise capacity of patients with left ventricular dysfunction after myocardial infarction. METHODS: A symptom-limited exercise test was performed with measurements for hemodynamics and uptake of oxygen (Vo2) of 26 men who had previously suffered myocardial infarction. These patients were divided into two groups according to their peak Vo2 (group 1 with peak Vo2 > or = 16 ml/kg per min, n= 13; and group 2 with peak Vo2 < 16 ml/kg per min, n= 13). Pulmonary arterial pressure, left ventricular and systemic arterial pressure, and cardiac output were measured at rest and during exercise. RESULTS: At rest, there was no difference between the two groups in terms of hemodynamic parameters except for minimal dP/dt, minimal left ventricular pressure (LVP) and time constant for decay of left ventricular pressure (tau). During peak exercise, cardiac output, left ventricular end-diastolic pressure (EDP), minimal dP/dt, minimal LVP, and tau for the two groups were significantly different. Furthermore, peak Vo2 was significantly correlated with T, minimal LVP, minimal dP/dt, EDP, and maximal dP/dt during peak exercise for the whole group of patients. CONCLUSION: Left ventricular diastolic function during exercise, i.e. diastolic reserve, may be an important determinant of exercise capacity of patients with left ventricular dysfunction after myocardial infarction.     

Myocardial dysfunction in silent myocardial ischemia as demonstrated by ambulatory radionuclide left ventricular function studies.

Until recently, it has not been possible to combine both ambulatory electrocardiographic monitoring, monitoring and ambulatory left ventricular function monitoring, but new developments have helped solve this problem. A technique based on the nuclear probe was introduced in the early 1980s to allow continuous recording of left ventricular volumes and ejection fraction over a 4 to 6 hour period during ambulatory activities following a single injection of radioisotope; the device was termed the VEST. In addition to validation studies, left ventricular function during ambulatory activities of various types has been measured with the VEST, and there are now several reports that document reduction in left ventricular ejection fraction in patients with coronary artery disease. These episodes meet the criteria for silent ischemia: objective evidence of myocardial ischemia in the absence of angina or anginal equivalents. Thus, patients with coronary artery disease can be followed for hemodynamic evidence of myocardial ischemia (even when they are not aware of the episodes) and results of therapy better monitored than by the ambulatory ECG alone.     

Relation of silent myocardial ischemia to ventricular arrhythmias and sudden death

Silent myocardial ischemia is common in the clinical spectrum of coronary disease. Ambulatory electrocardiographic monitoring has provided the most objective evidence of silent ischemia, but the phenomenon has also been detected in patients with coronary artery disease through analysis of exercise-induced ischemic ST-segment alterations, scintigraphic myocardial perfusion defects and left ventricular wall motion abnormalities. Silent myocardial ischemia frequently occurs in patients with stable angina, unstable angina, myocardial infarction and completely asymptomatic coronary artery disease. In each of these groups, silent ischemia has been associated with an increased risk of subsequent cardiac events. However, it remains unclear whether silent ischemia is directly involved in the occurrence of these events, possibly by provoking ventricular arrhythmias. Only limited data are available on the relation between silent ischemia and arrhythmias in myocardial infarction, vasospastic angina, coronary angioplasty, exercise testing and ambulatory electrocardiography. However, fortuitous ambulatory monitoring coincident with sudden death has detected ischemia associated with lethal arrhythmias in some individual cases. This suggests that an ischemia-arrhythmia association may be important in certain patients at certain times, possibly in combination with other factors.     

Relation between left ventricular global and regional function and extent of myocardial ischemia in the canine heart

To develop a quantitative relation between the overall severity of acute ischemia and left ventricular global and regional function, two minor axis internal diameters and myocardial wall thickness were determined using ultrasonic crystals in 10 open chest dogs with carotid-left anterior descending artery cannulation. The overall extent of ischemia produced by graded stenosis of the cannulation system was estimated by total myocardial blood flow deficit, calculated using radioactive microspheres and a balloon-reservoir perfusion technique permitting precise separation of ischemic from nonischemic tissue. Although cardiac output and left ventricular stroke work were maintained through chamber enlargement until total myocardial blood flow deficit was about 10%, ejection indexes of left ventricular function decreased progressively with increasing ischemia and correlated inversely with total myocardial blood flow deficit (r = -0.55 to -0.73). Ejection indexes of left ventricular global function correlated directly with regional function in the ischemic zone (r = 0.67 to 0.83), although global function decreased at a far slower rate than regional contraction during progressive coronary stenosis with an ischemic region comprising about 25% of total left ventricular weight. During myocardial ischemia, regional dysfunction resulted in progressive global contractile dysfunction; left ventricular hemodynamic status was maintained until ischemia was severe.     

Relation of left ventricular chamber stiffness at rest to exercise capacity in hypertrophic cardiomyopathy

The degree of exercise capacity is poorly predicted by conventional markers of disease severity in patients with hypertrophic cardiomyopathy (HC). The principal mechanism of exercise intolerance in patients with HC is the failure of stroke volume augmentation due to left ventricular (LV) diastolic dysfunction. The role of LV chamber stiffness, assessed noninvasively, as a determinant of exercise tolerance is unknown. Sixty-four patients with HC were studied with Doppler echocardiography, exercise testing, and gadolinium cardiac magnetic resonance. The LV chamber stiffness index was determined as the ratio of pulmonary capillary wedge pressure (derived from the E/Ea ratio) to LV end-diastolic volume (assessed by cardiac magnetic resonance). Maximal exercise tolerance was defined as achieved METs. There were inverse correlations between METs achieved and age (r = -0.38, p = 0.003), heart rate deficit (r = -0.39, p = 0.002), LV outflow tract gradient (r = -0.33, p = 0.009), the E/Ea ratio (r = -0.4, p = 0.001), mean LV wall thickness (r = -0.26, p = 0.04), and LV stiffness (r = -0.56, p <0.001) and a positive correlation between METs achieved and LV end-diastolic volume (r = 0.33, p = 0.01). On multivariate analysis, only LV chamber stiffness was associated with exercise capacity. A LV stiffness level of 0.18 mm Hg/ml had 100% sensitivity and 75% specificity (area under the curve 0.84) for predicting < or =7 METs achieved. In conclusion, LV diastolic dysfunction at rest, as manifested by increased LV chamber stiffness, is a major determinant of maximal exercise capacity in patients with HC.     

ACE inhibition with ramipril improves left ventricular function at rest and post exercise in patients with stable ischaemic heart disease and preserved left ventricular systolic function.

AIMS: To assess the effects of 6 months intervention with +ramipril on resting and post exercise left ventricular function in patients with stable ischaemic heart disease and preserved left ventricular systolic function. METHODS and RESULTS: Patients (n=98, age 65+/-9 years, 37% women) were randomized to double-blind treatment with ramipril 5 mg. day(-1)(n=32), ramipril 1.25 mg. day(-1)(n=34), or placebo (n=32). Resting and post maximum exercise echocardiography/Doppler examinations were performed at baseline and after 6 months. Changes over 6 months in resting transmitral E-wave deceleration time (Edt) and Edt adjusted for heart rate (Edt/RR) differed between the ramipril 5 mg, ramipril 1.25 mg, and placebo groups: Edt 24+/-82, -1+/-69, and -29+/-64 ms, respectively, P=0. 012; Edt/RR 30+/-105, 2+/-61, and -28+/-69 ms, respectively, P=0.015. Changes in the difference between resting and post exercise Edt/RR also varied between groups: -53+/-137, -28+/-118, and 35+/-101 ms, respectively, P=0.029. No differences in E/A indices were noted. Resting atrioventricular plane displacement improved in the combined ramipril groups vs the placebo group: 0.2+/-0.8 vs -0.2+/-1.3 mm, P<0.05.Conclusion Six months ramipril treatment in patients with stable ischaemic heart disease and preserved left ventricular systolic function improved resting left ventricular function and reduced the exercise induced diastolic filling abnormalities usually seen in these patients.     

Relationship between doppler-derived left ventricular diastolic function and exercise capacity in patients with myocardial infarction.

Doppler echocardiographic indices of left ventricular (LV) diastolic function are widely used to evaluate the cardiac function of patients with cardiac disease. However, there have been few reports about the relationship between Doppler indices and exercise capacity and so 44 patients with myocardial infarction were investigated by cardiopulmonary exercise testing and 2-D and Doppler echocardiography. Diastolic performance was assessed using Doppler transmitral flow velocity and pulmonary venous flow velocity. The ratio of peak E wave velocity and peak A wave velocity (E/A) correlated with peak oxygen consumption (peak Vo2) (R=0.72), and there was a negative correlation between the deceleration time of E velocity (Dct) and peak Vo2 or anaerobic threshold (AT) (R=-0.65, -0.62, respectively). The ratio of peak S wave velocity and peak D wave velocity (S/D) negatively correlated with peak Vo2 (R=-0.58). Left ventricular ejection fraction did not correlate to exercise capacity. These results suggest that the Doppler echocardiographic indices of LV diastolic function correlate with exercise capacity in patients with mild cardiac dysfunction.     

QRS记分与陈旧性心肌梗死左室功能的关系

为评价常规心电图ＱＲＳ记分与陈旧性心肌梗死者左室功能的关系，我们对５２例陈旧性心肌梗死者的ＱＲＳ记分与平衡法核素血池测得的ＬＶＥＦ，ＰＥＲ，ＰＥＲ，１／３ＥＦ，１／３ＦＲ，１／３ＥＲ，１／３ＥＦ进行相关分析，发现ＱＲＳ记分不仅与反映收缩功能的ＬＶＥＦ，ＰＥＲ，１／３ＥＦ，１／３ＥＲ明显负相关，而且与反映舒张功能的ＰＥＲ，１／３ＦＲ，１／３ＥＦ明显负相关，结果提示ＱＲＳ记分可用于估测陈旧性心肌梗死的     

Pulmonary thallium uptake: correlation with systolic and diastolic left ventricular function at rest and during exercise

Quantified pulmonary 201-thallium uptake, assessed as pulmonary/myocardial ratios (PM) and body surface area-corrected absolute pulmonary uptake (Pc), was determined from single photon emission computed tomography studies in 22 normal subjects and 46 consecutive patients with coronary artery disease (CAD). By means of equilibrium radionuclide angiography (ERNA), ejection fraction (EF), peak ejection rate (PER) in end-diastolic volume (EDV/sec) and peak filling rate (PFR) in EDV/sec and stroke volume (SV/sec) units, PFR/PER ratio, and time to peak filling rate (TPFR) in milliseconds were computed at rest and during exercise (n = 35). Left ventricular response to exercise was assessed as delta EF, relative delta EF, delta EDV, and delta ESV. In normal subjects the PM ratios showed significant inverse correlation with PER at rest and with EF, PER, and PFRedv during exercise. For the left ventricular response to exercise, delta ESV showed significant correlation with the PM ratios. The body surface area-corrected pulmonary uptake values showed no correlation with any of the variables. In patients with CAD the PM ratios and Pc uptake showed significant inverse correlation with EF, PER, PFRedv and to exercise EF, exercise PER, and exercise PFRedv. For the left ventricular response to exercise, delta EF showed significant inverse correlation with the PM ratios but not with the Pc uptake. Neither in normal subjects nor in patients with CAD did any of the independent diastolic variables show significant correlation with the PM ratios or Pc values. Thus pulmonary thallium uptake is correlated with systolic left ventricular function at rest and during exercise in normal subjects and in patients with CAD but not with diastolic function. In normal subjects delta ESV and in patients with CAD, delta EF showed correlation with pulmonary thallium uptake.     

Study of left ventricular function at rest and post-exercise with thallium-201 myocardial scintigraphy synchronized with ECG

ECG-gated Thallium 201 myocardial scintigraphy provides a simultaneous evaluation of left ventricular perfusion and function. The aims of this study were to determine the changes in left ventricular ejection fraction (LVEF) after exercise and at rest 4 hours after exercise and to compare the results with changes in myocardial perfusion and the severity of the coronary artery disease. Sixty-four men with myocardial ischaemia on scintigraphy who had undergone coronary angiography showing significant lesions within 3 months, were compared with 38 normal men. The ejection fraction was calculated with a validated programme (QGS). The change in LVEF between the post-exercise and resting measurement 4 hours after exercise (delta LVEF) was compared in the normal and ischaemic groups (+7 +/- 6.8% vs -5.6 +/- 5%, p < 0.001). The extent of the ischaemia (percentage myocardium unperfused) was significantly greater in the 34 patients who had an over 5% reduction in LVEF on exercise compared with the 30 others who has a less than 5% reductionin LVEF (11.8 vs 6.3%, p < 0.001). There was a linear correlation between the degree of ischaemia and delta LVEF in the 30 patients without a history of infarction (r = -0.76, p < 0.01). The delta LVEF also correlated with the number and site of the coronary lesions. The authors conclude that in this male population, ECG-gated Thallium 201 myocardial scintigraphy can demonstrate a decrease in LVEF after exercise in ischaemic coronary patients whereas it increases in normal subjects. This decrease in LVEF on exercise is correlated with the extent of ischaemia and the severity of the coronary disease and should therefore be taken into account in patient management.     

Relation between myocardial perfusion and left ventricular function following acute coronary occlusion: disproportionate effects of anterior vs. inferior ischemia

This study examined the relation between left ventricular (LV) function and the severity of acute myocardial ischemia in a conscious dog model. The LV ejection fraction (EF) was measured by multigated equilibrium radionuclide angiography, and regional myocardial blood flow was measured with radioactive microspheres before and 10 minutes after distal and then proximal occlusion of the left anterior descending (LAD, 13 dogs) or left circumflex (LC, 13 dogs) coronary artery. Two methods were used to evaluate the extent of ischemia. The first method determined the mass of myocardium that was ischemic based on different degrees of reduced blood flow. The second method estimated the severity of ischemia expressed as blood flow deficit resulting from each coronary occlusion. Global LV function was very sensitive to ischemia, and the relation between change in function and the degree of ischemia were described best by linear functions. The best linear correlation between mass of ischemic myocardium and percent reduction in EF resulted from the ischemic region defined as all tissue with 25% or greater reduction in blood flow, r = 0.84 for LAD (Y = 0.96X + 1.8) and r = 0.75 for LC (Y = 0.53X + 2.0) occlusions. Defining ischemic mass by more severe reduction in blood flow resulted in exclusion of ischemic myocardium that affected function. The myocardial blood flow deficit also correlated linearly with percent reduction in EF, r = 0.89 for LAD (Y = 1.31X + 2.7) and r = 0.81 for LC (Y = 0.83X - 0.1) occlusions. The slope of the regression lines using both analyses of ischemia were significantly greater (p less than 0.01) for LAD than LC occlusions, indicating that for comparable degrees of ischemia LAD as compared to LC occlusion decreased EF to a greater extent. Calculation of EF from attenuated corrected volumes resulted in small changes in LAD, but not LC, EF and did not account for the disproportionate effects of LAD and LC ischemia. In a separate group of studies (n = 18) EF measured by radionuclide angiography after LAD or LC occlusions correlated well with biplane contrast angiography r = 0.93, SEE 5.1. These data suggest that disproportionately greater effects of LAD compared to LC ischemia on global EF in the dog are due primarily to different pathophysiologic responses to ischemia.     

Monitoring ventricular function at rest and during exercise with a nonimaging nuclear detector.

A portable nonimaging device, the nuclear stethoscope, for measuring beat to beat ventricular time-activity curves in normal people and patients with heart disease, both at rest and during exercise, is being developed and evaluated. The latest device has several operating modes that facilitate left ventricular and background localization, measurement of transit times and automatic calculation and display of left ventricular ejection fraction. The correlation coefficient of left ventricular ejection fraction obtained with the device and with a camera-computer system was 0.92 in 35 subjects. During bicycle exercise the ejection fraction in 15 normal persons increased from 44 to 64 percent (P less than 0.001), whereas among 12 patients with heart disease it was unchanged in 5 and decreased in 7.