Doppler Tissue Imaging Quantitates Regional Wall Motion During Myocardial Ischemia and Reperfusion
Background—Quantification of regional myocardial function is a major unresolved issue in cardiology. We evaluated the accuracy of pulsed Doppler tissue imaging (DTI), a new echocardiographic technique, to quantify regional myocardial dysfunction induced by acute ischemia and reperfusion.
Methods and Results—In nine open-chest anesthetized pigs, various degrees of regional wall motion abnormalities were induced by graded reduction of left anterior descending coronary artery (LAD) blood flow. Pulsed Doppler tissue imaging was performed from an epicardial apical four-chamber view with the sample placed within the middle part of the septal wall. Peak septal velocities were calculated during systole, isovolumic relaxation, and early and late diastole. Regional myocardial blood flow and systolic and diastolic dysfunctions were assessed by radioactive microspheres and ultrasonic crystals, respectively. Ischemia resulted in a significant rapid reduction of systolic velocities and an early decrease in the ratio of early to late diastolic velocities. Both changes were detected by pulsed DTI within 5 seconds of coronary artery occlusion. The decrease in systolic velocity significantly correlated with both systolic shortening (r=.90, P<.0001) and regional myocardial blood flow (r=.96, P<.0001) during reduction of LAD blood flow.
Conclusions—These results suggest that DTI may be a promising new tool for the quantification of ischemia-induced regional myocardial dysfunction.
Because segmental wall motion abnormalities are the hallmark of coronary artery disease, ultrasound technique is widely used for the evaluation of regional left ventricular function because of its ability to depict endocardial excursion, myocardial thickening, and wall motion in real time.1 2 3 4 5 6 7 However, conventional assessment of wall motion, based on visual interpretation of endocardial excursion and myocardial thickening, suffers from the limitations of a qualitative method and is subjective and experience dependent.8 Quantitative techniques, based on the manual9 10 11 12 13 14 or automatic15 16 myocardial edge detection, have demonstrated acceptable correlations with other available techniques. However, quantitative analysis is complicated by endocardial “dropout” and trabeculae, which can impair the tracing of endocardial border. There is therefore a need for ongoing development for quantification of global and regional left ventricular function.9 10 11 12 13 14 15 16
DTI is a new ultrasound technique that is based on color Doppler imaging principles and allows quantification of intramural myocardial velocities by detection of consecutive phase shifts of the ultrasound signal reflected from the contracting myocardium.17 18 19 To display regional myocardial velocities, thresholding and filtering algorithms are changed to reject the low-amplitude echoes from the blood pool. DTI allows the high-intensity–low-amplitude information from the myocardium to pass to subsequent determination of the mean Doppler shift and hence mean velocity determination by use of standard autocorrelation methodology. Whereas conventional ultrasound techniques derive their information on myocardial function either from parameters measured from the blood-myocardial boundaries or from blood-pool Doppler indexes, DTI directly measures indexes of myocardial function from within the myocardial wall.
Little is known about the ability of pulsed DTI to identify and quantify wall motion alterations during regional ischemia.20 In the present study, we used a classic pig model of ischemia/reperfusion to investigate whether pulsed DTI might be a useful tool to analyze regional myocardial dysfunction. Specifically, we sought (1) to define the pattern of myocardial velocities during regional sequences of ischemia and reperfusion and (2) to compare DTI measurements to modifications in segment length measured by the conventional sonomicrometry technique.21
All experiments performed in this study conformed to the Guiding Principles in the Care and Use of Animals approved by the American Physiological Society.
Nine farm pigs, weighing 28±4 kg, were premedicated with droperidol (1 mg/kg SC) and anesthetized with pentobarbital (15 mg/kg IV). Additional intravenous administration of pentobarbital was performed when needed. Pigs were ventilated with room air through a tracheotomy tube, and tidal volume and rate were adjusted to provide physiological pH and blood gases. Body temperature was monitored with a rectal thermometer and kept constant by means of a heating pad. Cannulas were inserted into the right jugular vein (for administration of drugs and fluids) and the left carotid artery (for measurement of blood pressure). A 5F Gaeltec probe was placed into the LV cavity through the right carotid artery to measure LV pressure and its first derivative, LV dP/dt. A thoracotomy was performed in the fourth left intercostal space, and a segment of the LAD was isolated just before the first diagonal branch. A micrometric constrictor, designed to gradually reduce coronary blood flow, was positioned around the LAD. One pair of ultrasonic crystals, used to assess regional contractile function, was inserted via a small scalpel incision in the middle myocardial layer of the left ventricle and oriented parallel to the short axis as previously described.22 Crystals were placed in the center of the soon-to-be ischemic LAD territory. A catheter was inserted in the left atrium through the left atrial appendage to inject radioactive microspheres for assessment of regional MBF. ECG limb leads, arterial and LV pressures, LV dP/dt, and segment shortening were monitored continuously throughout the experiment on a Gould recorder (Gould Inc). The animals were allowed 30 minutes after these surgical procedures to stabilize.
The echocardiographic recordings were performed by means of an ACUSON 128 XP/10 with a 4-MHz transducer equipped with DTI technology. Before thoracotomy, a first series of velocity measurements was performed on five pigs that were lying on their right sides, with the transducer placed over the left ventricular apex to obtain an apical four-chamber view. These measurements were performed to determine whether opening the chest might induce some change in myocardial velocities. In the open-chest preparation (all pigs), all velocity measurements were performed with the beam positioned on the anterior wall near the apex to obtain an epicardial apical four- chamber view. A fixed sampling gate of 10 mm was placed within the middle part of the interventricular septum. Care was taken to align the echo image so that the interventricular septum be parallel to the DTI cursor. Pulsed-wave DTI was continuously recorded on super-VHS magnetic tape, with a videotape recorder for off-line analysis. The spectral Doppler signal parameters were adjusted to obtain Nyquist limits between 15 and 20 cm/s by use of the lowest filter settings and the optimal gain to minimize noise and eliminate the signals produced by the transmitral flow. We therefore analyzed the myocardial velocities resulting from the long-axis shortening of the heart.23
After baseline measurements, a graded reduction of the LAD blood flow was performed by progressively (and, finally, completely) tightening the micrometric constrictor. In each animal, several degrees of constriction were adjusted to obtain various values of regional wall motion abnormalities ranging from hypokinesis to dyskinesis: this was done in a stepwise manner to reduce function by ≈40%, 60%, and finally dyskinesis during total occlusion.
Echographic and segment length recordings were performed sequentially at the following time points: at baseline, during partial stenosis, during total occlusion, and after reperfusion of the LAD.
At the end of each experiment, the LAD was briefly reoccluded and 0.5 mg/kg IV Unisperse Blue Pigment (Ciba-Geigy) was injected to delineate the in vivo area at risk as previously described.22 Under deep anesthesia, the heart was stopped by intravenous injection of potassium chloride (20 mEq), excised, and cut into 5- to 7-mm-thick transverse slices parallel to the AV groove. We verified that the interventricular septum in the five apical transverse slices was unstained, ie, that the Doppler sampling gate was well in the ischemic area. The correct position of the two ultrasonic crystals within the risk region was checked, and two transmural myocardial samples were excised (one from the ischemic and one from the nonischemic zone) for further measurement of regional MBF.
Heart rate and arterial and LV blood pressures were measured and averaged over 5 continuous cardiac cycles in sinus rhythm at baseline, during coronary artery stenosis or occlusion, and after reperfusion.
From the DTI tracings, we measured the peak velocity of (1) isometric contraction (VIC), (2) systolic excursion (VS), (3) isometric relaxation (VIR), and (4) early (VE) and late (VA) diastolic excursion (Fig 1⇓). Five beats were averaged for each of these measurements. By definition, velocities were encoded positive or negative when the displacement of the myocardium was directed toward or away from the transducer, respectively.
The variation of myocardial velocity during or after coronary occlusion (Voccl) was expressed as a percentage of baseline velocity (Vbasal) as V%=Voccl/Vbasal×100%.
Intraobserver variability was tested in eight pigs by repeating the measurements on two occasions under the same basal conditions. To test the interobserver variability, the measurements were repeated from the videotape recordings by a second observer who was unaware of the results of the first observer. For measurement of systolic velocity, and early and late diastolic velocities, intraobserver and interobserver variability ranged from 3.9% to 4.5%.
Regional Myocardial Function
SS and LDL were used as indexes of systolic and diastolic function, respectively. To define these parameters, ESL and EDL were obtained from three well-separated cardiac cycles in each sample period. LV dP/dt was used to define the timing of the cardiac cycle for segment length measurements with ultrasonic crystals; EDL was measured at the onset of the rapid increase in LV dP/dt, whereas ESL was measured at peak negative LV dP/dt (Fig 2⇓).
SS was defined as SS=[(EDL−ESL)/EDL]×100%. LDL was defined as LDL=[(mSL−EDL)/EDL]×100%, with mSL (minimal segment length) being the lowest point of the wall motion tracing at any time of the cardiac cycle (Fig 2⇑). Both SS and LDL during each sample period were expressed as percentage of the respective baseline values. Measurements of SS and LDL were performed at baseline, during partial and total LAD occlusions, and during reperfusion.
Measurement of Regional MBF
This measurement was performed in each pig to assess the severity of ischemia during partial or total occlusion of the LAD. Regional MBF (in milliliters per minute per gram) was measured by use of radioactive microspheres labeled with either 141Ce or 103Ru (Dupont-New England Nuclear) as previously described.22 Regional MBF was measured at baseline (n=1), during partial stenosis (n=6), or during total coronary occlusion (n=4). Briefly, microspheres were injected into the left atrium via the left atrial catheter, and a reference blood sample was obtained from the carotid artery at a fixed rate of 2.0 mL/min. At the end of the protocol, samples were cut from the center of the ischemic and nonischemic zones, weighed, and counted with the reference blood samples in a gamma counter. Blood flow in the ischemic area (in milliliters per minute per gram) was then computed and expressed as percentage of MBF in the nonischemic region.
Differences between baseline measurements and subsequent values were assessed by repeated-measures ANOVA. Standard linear regression analysis was used to relate changes in myocardial velocities to SS or segment lengthening. Polynomial regression analysis was used to study the relationship between systolic velocities and regional MBF. Myocardial velocities and MBF data (expressed as fractions of control values) obtained from 11 measurements in eight pigs were compared by use of the nonparametric Spearman test because of the small sample size. All values are presented as mean±SE. A value of P<.05 was considered to indicate a statistically significant difference.
Nine pigs were entered into the present study. Each animal underwent 1 to 5 episodes of either partial stenosis or total occlusion of the LAD, each separated by an intervening reperfusion period. The total duration of these ischemic events averaged 6±2 and 6±1 minutes, respectively. This design allowed us to record 59 matched measurements of DTI velocities and segment lengths among the nine animals.
Hemodynamics and Regional MBF
All pigs had similar heart rate and blood pressure at baseline (Table 1⇓). Neither partial stenosis nor total coronary artery occlusion significantly altered heart rate or blood pressure. After partial stenosis, MBF in the risk area averaged 57±2% of that in the nonischemic bed (Table 1⇓). As expected in this collateral-deficient species, total LAD occlusion resulted in a dramatic decrease in MBF that averaged 9±2% of MBF in the remote nonischemic zone (Table 1⇓).
Normal Pattern of Midseptal Wall Velocities
In the open-chest pig under baseline conditions, pulsed DTI of midseptal wall velocities displayed five consecutive waves whose directions varied according to the phase of the cardiac cycle. During systole, two positive waves occurred, one positive and short wave corresponding to the isometric contraction (VIC) (starting at the beginning and ending at the end of the QRS complex) and one single ogival wave corresponding to LV ejection (Vs) (starting at the end of the QRS complex and ending at the end of the T wave). During diastole, one positive and two negative waves were sequentially observed: a positive isometric relaxation wave (VIR) followed by a negative early (VE), rapid-filling wave and a negative late-filling (VA) wave corresponding to atrial contraction.
In the five pigs that underwent pulsed DTI analysis before thoracotomy, similar sequential events were observed, but in all cases, the IR wave was negative instead of positive (Fig 1⇑). In addition, peak systolic velocity values were slightly but significantly higher than in open-chest preparations (Table 2⇓). Myocardial velocities obtained in the open-chest preparations were used as control values for further comparison during LAD occlusion.
Time Sequence and Pattern of Myocardial Velocity Changes During Ischemia/Reperfusion
The time to onset of regional myocardial velocity abnormalities in the ischemic myocardium is presented for the first 60 seconds for 10 episodes of total LAD occlusion in eight pigs (Fig 3⇓). Within 5 seconds of occlusion, systolic velocities (VS) in the ischemic segment decreased to 46% of baseline values (P<.0001). Systolic velocities became negative at ≈30 seconds and peaked at 1 minute of occlusion. These negative velocities corresponded to the paradoxical expansion of the ischemic segment observed on sonomicrometry tracings (Figs 2⇑ and 4⇓). This early decrease in VS was associated with a simultaneous increase in velocities during both isometric systole (VIC) and isometric (VIR) relaxation (Fig 3⇓). Velocity during isometric relaxation progressively increased and peaked at 1 minute after coronary artery occlusion (Fig 3⇓). At 1 minute after reflow, VS and VIR exhibited a transient positive and negative peak, respectively, corresponding to the hyperemic phase (Fig 3⇓). Within 5 minutes of reperfusion, VS progressively decreased, whereas VIR increased and appeared as a positive wave as reperfused myocardium developed postischemic stunning (Figs 3⇓ and 4⇓).
Diastolic abnormalities also occurred very quickly after the onset of ischemia. Immediately after LAD occlusion, VE significantly decreased, and VA increased (Fig 4⇑). As a consequence, VE/VA ratio decreased and further remained stable until reperfusion (Fig 3⇑). VE/VA peaked at 1 minute after reflow (hyperemic response) and thereafter returned nearly ischemic values as diastolic alterations of myocardial stunning appeared on segment length recordings.
In five pigs, we also measured velocities in the remote nonischemic lateral wall during ischemic episodes induced by partial stenosis of LAD. Ischemia in the LAD territory did not significantly alter systolic or diastolic velocities in the lateral wall: VS averaged 8.9±0.7 versus 9.1±0.6 cm/s at baseline (P=NS) and VE/VA averaged 1.3±0.5 versus 1.3±0.4 at baseline (P=NS).
Comparison Between DTI Velocities and Wall Motion Abnormalities
To evaluate whether the severity of ischemia could be accurately predicted by DTI, the individual systolic velocity and diastolic VE/VA ratio (both expressed as a percentage decrease from baseline) were plotted versus corresponding modifications in segment length. There was a significant correlation between the variations of systolic velocity (VS%) and those of SS: VS%=0.78(SS)+10.6 (r=.90, P<.0001; Fig 5⇓). This strongly supports that the DTI measurement of VS accurately quantifies the ischemia-related regional wall motion abnormalities. The diastolic ratio VE/VA also showed a significant correlation with late diastolic lengthening, but the relationship was weak (r=.39, P=.0049) (Fig 6⇓).
Comparison Between DTI Velocities and Regional MBF
Eleven measurements of regional MBF were obtained in eight pigs and plotted versus simultaneous myocardial systolic velocities (Fig 7⇓).
The relationship between the decrease in MBF (MBF%) and in systolic velocity (VS%) was best fitted by a polynomial expression according to the following equation: Vs%=−0.004 MBF%2+1.73 MBF%−49.14 (r=.96; Fig 7A⇑).
A similar correlation existed between SS and MBF%, but this relationship was best fitted by a linear regression equation (Fig 7B⇑).
Myocardial function became severely depressed when MBF decreased <40% of baseline values.
In the present study, we report for the first time that pulsed DTI can identify and quantify myocardial wall velocities during regional ischemia and reperfusion. As demonstrated by concomitant measurement of wall motion by sonomicrometry and assessment of regional MBF by the radioactive microsphere technique, pulsed DTI appears to be accurate and reproducible.
DTI is a new echocardiographic method based on the Doppler principle, which provides a velocity map of the myocardial wall.17 18 19 DTI velocity maps are available by use of two-dimensional imaging and M-mode and pulsed-wave Doppler. Low frame rates available from two-dimensional acquisition associated with the Doppler angle of insonation of the myocardium preclude two-dimensional DTI for measurement of rapid myocardial velocity changes. M-mode DTI interrogation of intramural velocities overcomes the temporal resolution problems inherent with the two-dimensional approach and allows the assessment of endocardial to epicardial velocity gradient.24 25 But it needs the development of special programs for off-line analysis because M-mode quantification of velocities is not yet available on our ultrasound system. Pulsed-wave DTI provides quantitative information available on-line and was therefore used in this study to analyze septal wall velocity resulting from long-axis shortening of the heart and its variations after LAD occlusion.
Normal Patterns of Regional LV Wall Motion and Velocities
Understanding of the normal pattern of myocardial wall movement is necessary for comprehensive assessment of DTI. The complex overall motion of the heart can be divided into three different types of movements: circumferential contraction assessed by short-axis view interrogation, longitudinal contraction assessed by long-axis view, and rotation. The translation of the whole heart also affects the measurement of actual wall velocities, especially in the short-axis view. In the present study, a long-axis recording of mid septal velocities was preferred to a short-axis view to avoid the large incidence angle between the direction of the circumferential septal wall motion and that of the Doppler beam. Indeed, in the short-axis view, a part of the myocardium, particularly the septal or the lateral wall, moves perpendicularly toward the Doppler beam and does not allow accurate myocardial velocity measurement.
In the present experimental preparation, five waves of wall velocity, including two systolic and three diastolic events of the cardiac cycle, can be described for the first time from recordings of midseptal velocities. The same pattern of velocities was described by Rodriguez et al26 27 within the mitral annular and Isaaz et al28 within the LV posterior wall. Both sets of authors reported a good correlation between myocardial velocities derived from M-mode tracings and DTI measurements. However, the determination of myocardial velocities by M-mode appeared difficult, time-consuming, and poorly reproducible, which might explain why M-mode echocardiography has been considered an unreliable tool for assessment of regional wall function.29
It is worth noting that velocity of isometric relaxation shifted from negative to positive values when the chest was opened. Although we did not specifically investigate this issue, we speculate that it may be related to modifications of the transeptal interaction between the two ventricles, secondary to reduction of loading conditions and pericardectomy in the open-chest preparation.30
Detection and Quantification of Ischemia-Related Wall Motion Abnormalities by DTI Velocities
To investigate whether pulsed DTI could accurately identify and quantify the alterations of myocardial wall motion induced by ischemia, we compared the changes in velocities to those in segment lengths as measured by the reference method, ie, sonomicrometry.21 Within 15 seconds of coronary occlusion, systolic contraction decreased and resulted in passive bulging of the myocardium in case of severe ischemia. As expected, these modifications of systolic wall motion were also significantly correlated with the reduction of regional MBF as measured by the radioactive microsphere technique.31 32 33 Simultaneous diastolic dysfunction developed with a rapid increase in EDL and LDL.34
Our DTI data are in close agreement with these observations. Pulsed DTI was able to detect significant systolic and diastolic velocity changes as soon as 5 seconds after LAD occlusion, a time frame comparable to those reported when sonomicrometry was used.31 32 33 Systolic velocity during the ejection phase was well correlated with segment shortening, whatever the severity of ischemia. During isometric relaxation, velocity became positive and markedly increased. This paralleled post–SS observed on segment length recordings and suggests an asynchrony in myocardial contractility as previously reported by Gibson et al35 in patients with coronary artery disease. Early diastolic velocity decreased and late diastolic velocity increased, resulting in an inversion of the VE/VA ratio. Its correlation with LDL, as described with sonomicrometry, was statistically significant but obviously much weaker than analysis of the systolic pattern. The reason for the poor correlation between diastolic indexes is unclear but might be related to the complex translation/rotation of the heart during the cardiac cycle. It might also be related to the fact that DTI analyzed septal wall motion, which is affected by right ventricular pressures whose influence is likely more important in diastole.
Although VS slightly overestimated the degree of regional wall motion abnormalities, it appears to be a useful index for assessment of regional wall motion impairment related to severe, moderate, or even mild ischemia. This was also confirmed by the correlation of ejection systolic velocity and regional MBF. Even slight reductions in regional MBF were associated with a decrease in both myocardial velocities and segment shortening. We observed that ejection systolic velocity became negative for a reduction in MBF reaching 40% of baseline values, which is also associated with the onset of regional bulging as previously described.22
Interestingly, pulsed DTI was able to identify the hyperemic response after reperfusion of the ischemic myocardium. Although this transient increase in regional contractile function is usually short-lived, its identification may be useful as an indicator of reperfusion in the setting of acute myocardial infarction. When postischemic contractile dysfunction (“myocardial stunning”) developed despite restoration of a normal (or nearly normal) MBF, pulsed DTI clearly identified wall motion abnormalities similar to those observed during ischemia.36 37 38 In other words, as expected, pulsed DTI (as any other technique) failed to distinguish ischemia from reperfusion-induced contractile dysfunction. With respect to this, estimation of myocardial perfusion through measurement of myocardial wall velocities must be done cautiously and is valid only in situations of ischemia but not reperfusion.
Potential Clinical Implications
There are major potential clinical implications to the use of pulsed DTI. In particular, we currently lack a reliable technique to accurately quantify regional contractile function in humans. Contrast and radionuclide ventriculography and conventional two-dimensional echocardiography only allow semiquantitative evaluation of LV function. Today, only cine MRI can quantify wall motion, but it is not easily accessible for a large number of patients. Pulsed DTI appears to be a sensitive, reproducible, accurate, noninvasive echographic technique that may become a very useful clinical tool for the diagnostic, follow-up, and evaluation of the prognosis of cardiac diseases. Whereas effective clinical application of DTI was hampered by low acquisition frame rates and a lack of postprocessing software, a new third generation of Doppler myocardial imaging system, with high temporal and spatial resolution, has been developed that allows real-time acquisition with subsequent on-line analysis of regional mean velocities. This new system has recently been shown to provide reproducible and accurate quantification of LV circumferential and longitudinal contraction in all myocardial segments and therefore will allow stress echocardiography to be quantified.39 40 However, further studies are needed to determine whether data in this experimental preparation can be extrapolated to human patients.
Because of the version of the ultrasound machine used in this study, we could not record simultaneously DTI velocities and two-dimensional regional wall motion abnormalities. The DTI velocity measurements were performed in the middle part of the interventricular wall septum, whereas segment length data were recorded from the anterior wall. However, these two regions are supplied by the LAD; moreover, the middle part of the interventricular wall septum was clearly included in the area at risk as shown by the Uniperse Blue Pigment injection in the heart slices. It is therefore likely that wall motion abnormalities in the septum were comparable to those observed in the anterior wall.
DTI measurements, as any other method assessing myocardial excursion, are affected by cardiac translation and/or rotation. Nonetheless, the correlation with segment length measurements (that are poorly influenced by cardiac translation) is good (r=.90), suggesting that movements of the heart did not dramatically alter DTI measurements.
DTI is a new, accurate, sensitive, noninvasive tool to quantify on-line systolic and diastolic ischemia-induced myocardial dysfunction. It appears to be a promising method to quantify regional wall motion abnormalities in the setting of ischemic heart disease.
Selected Abbreviations and Acronyms
|DTI||=||Doppler tissue imaging|
|LAD||=||left anterior descending coronary artery|
|LDL||=||late diastolic lengthening|
|MBF||=||myocardial blood flow|
- Received September 17, 1997.
- Revision received October 28, 1997.
- Accepted December 1, 1997.
- Copyright © 1998 by American Heart Association
Lieberman AN, Weiss JL, Jugdutt BI, Becker LC, Bulkley BH, Garrison JG, Hutchins GM, Kallman CA, Weisfeldt ML. Two-dimensional echocardiography and infarct size: relationship of regional wall motion and thickening to the extent of myocardial infarction in the dog. Circulation. 1981;63:739–746.
Heger JJ, Weyman AE, Wann LS, Rogers EW, Dillon JC, Feigenbaum H. Cross-sectional echocardiographic analysis of the extent of left ventricular asynergy in acute myocardial infarction. Circulation. 1980;61:1113–1118.
Kerber RE, Marcus ML, Ehrhardt J, Wilson R, Abboud FM. Correlation between echocardiographically demonstrated segmental dyskinesis and regional myocardial perfusion. Circulation. 1975;52:1097–1104.
Weiss JL, Bulkley BH, Hutchins GM, Mason SJ. Two-dimensional echocardiographic recognition of myocardial injury in man: comparison with postmortem studies. Circulation. 1981;63:401–408.
Wyatt HL, Meerbaum S, Heng MK, Rit J, Guéret P, Corday E. Experimental evaluation of the extent of myocardial dyssynergy and infarct size by two-dimensional echocardiography. Circulation. 1981;63:607–614.
Gillam LD, Hogan RD, Foale RA, Franklin TD Jr, Newell JB, Guyer DE, Weyman AE. A comparison of quantitative echocardiographic methods for delineating infarct-induced abnormal wall motion. Circulation. 1984;70:113–122.
Haendchen RV, Wyatt HL, Maurer G, Zwehl W, Bear M, Meerbaum S, Corday E. Quantitation of regional cardiac function by two-dimensional echocardiography, I: patterns of contraction in the normal left ventricle. Circulation. 1983;67:1234–1245.
Moynihan PF, Parisi AF, Feldman CL. Quantitative detection of regional left ventricular contraction abnormalities by two-dimensional echocardiography, I: analysis of methods. Circulation. 1981;63:752–760.
Schnittger I, Fitzgerald PJ, Gordon EP, Alderman EL, Popp RL. Computerized quantitative analysis of left ventricular wall motion by two-dimensional echocardiography. Circulation. 1984;70:242–254.
Lang RM, Vignon P, Weinert L, Bednarz J, Korcarz C, Sandelski J, Koch R, Prater D, Mor-Avi V. Echocardiographic quantification of regional left ventricular wall motion with color kinesis. Circulation. 1996;93:1877–1885.
Theroux P, Franklin D, Ross J Jr, Kemper WS. Regional myocardial function during acute coronary artery occlusion and its modification by pharmacologic agents in the dog. Circ Res. 1974;35:896–908.
Ovize M, Przyklenk K, Kloner RA. Partial coronary stenosis is sufficient, and reperfusion mandatory, to precondition ischemic myocardium. Circ Res. 1992;71:1165–1173.
Ingels N, Daughters G, Stinson E, Alderman E. Evaluation of methods for quantitation of left ventricular segmental wall motion in man using myocardial markers as a standard. Circulation. 1980;61:966–972.
Palka P, Lange A, Fleming AD, Fenn LN, Bouki KP, Shaw TRD, Fox KAA, McDicken WN, Sutherland GR. Age-related transmural peak mean velocities and peak velocity gradients by Doppler myocardial imaging in normal subjects. Eur Heart J. 1996;17:940–950.
Rodriguez L, Garcia M, Ares M, Griffin BP, Nakatani S, Thomas JD. Assessment of mitral annular dynamics during diastole by Doppler tissue imaging: comparison with mitral Doppler inflow in subjects without heart disease and in patients with left ventricular hypertrophy. Am Heart J. 1996;131:982–987.
Beyar R, Dong SJ, Smith ER, Belenkie I, Tyberg JV. Ventricular interaction and septal deformation: a model compared with experimental data. Am J Physiol. 1993;265:H2044–H2056.
Gallagher KP, Osakada G, Matsuzaki M, Miller M, Kemper WS, Ross J. Nonuniformity of inner and outer systolic wall thickening in conscious dogs. Am J Physiol. 1985;249:H241–H248.
Heyndrickx GR, Baig H, Nellens P, Leusen I, Fishbein MC, Vatner SF. Depression of regional blood flow and wall thickening after brief coronary occlusions. Am J Physiol. 1978;234:H653–H659.
Gallagher KP, Kumada T, Koziol JA, Mc Kown MD, Kemper WS, Ross J Jr. Significance of regional wall thickening abnormalities relative to transmural myocardial perfusion in anesthetized dogs. Circulation. 1980;62:1266–1274.
Takayama M, Norris RM, Brown MA, Armiger LC, Rivers JT, White HD. Postsystolic shortening for acutely ischemic canine myocardium predicts early and late recovery of function after coronary artery reperfusion. Circulation. 1988;78:994–1007.
Gibson DG, Prewitt TA, Brown DJ. Analysis of left ventricular wall movement during isovolumic relaxation and its relation to coronary artery disease. Br Heart J. 1976;38:1010–1019.
Matsuzaki M, Gallagher KP, Kemper WS, White F, Ross J Jr. Sustained regional dysfunction produced by prolonged coronary stenosis: gradual recovery after reperfusion. Circulation. 1983;68:170–182.
Homans DC, Sublett E, Dai XZ, Bache RJ. Persistence of regional left ventricular dysfunction after exercise-induced myocardial ischemia. J Clin Invest. 1986;77:66–73.
Wilkenshoff UM, Sovany A, Olstad B, Lindström L, Wigström L, Hatle L, Brodin LA, Wranne B, Sutherland GR. Doppler myocardial imaging: a third generation real time acquisition system with post-processing quantification of myocardial motion: normal values and in vitro reproducibility: implications for quantifying stress echocardiography. Eur Heart J. 1997;18:102. Abstract.
Wilkenshoff UM, Sovany A, Engvall J, Janerot-Sjöberg B, Hatle L, Wranne B, Sutherland GR. Do regional myocardial systolic velocities increase in a predictable, reproducible and measureable manner during bicycle stress echocardiography? A colour Doppler myocardial imaging study to determine if quantifiable stress echo could be feasible using this technique. Eur Heart J. 1997;18:103. Abstract.