Myocardial function defined by strain rate and strain during alterations ...

Am J Physiol Heart Circ Physiol 283: H792–H799, 2002. First published April 4, 2002; 10.1152/ajpheart.00025.2002.

Myocardial function defined by strain rate and strain during alterations in inotropic states and heart rate FRANK WEIDEMANN, FADI JAMAL, GEORGE R. SUTHERLAND, PIET CLAUS, MIROSLAW KOWALSKI, LIV HATLE, IVAN DE SCHEERDER, BART BIJNENS, AND FRANK E. RADEMAKERS Department of Cardiology, University Hospital Gasthuisberg, B-3000 Leuven, Belgium Received 14 January 2002; accepted in final form 26 March 2002

Weidemann, Frank, Fadi Jamal, George R. Sutherland, Piet Claus, Miroslaw Kowalski, Liv Hatle, Ivan De Scheerder, Bart Bijnens, and Frank E. Rademakers. Myocardial function defined by strain rate and strain during alterations in inotropic states and heart rate. Am J Physiol Heart Circ Physiol 283: H792–H799, 2002. First published April 4, 2002; 10.1152/ajpheart.00025.2002.—For porcine myocardium, ultrasonic regional deformation parameters, systolic strain (⑀sys) and peak systolic strain rate (SRsys), were compared with stroke volume (SV) and contractility [contractility index (CI)] measured as the ratio of endsystolic strain to end-systolic wall stress. Heart rate (HR) and contractility were varied by atrial pacing (AP ⫽ 120–180 beats/min, n ⫽ 7), incremental dobutamine infusion (DI ⫽ 2.5–20 ␮g 䡠 kg⫺1 䡠 min⫺1, n ⫽ 7), or continuous esmolol infusion (0.5 mg 䡠 kg⫺1 䡠 min⫺1) ⫹ subsequent pacing (120–180 beats/min) (EI group, n ⫽ 6). Baseline SRsys and ⑀sys averaged 5.0 ⫾ 0.4 s⫺1 and 60 ⫾ 4%. SRsys and CI increased linearly with DI (20 ␮g 䡠 kg⫺1 䡠 min⫺1; SRsys ⫽ 9.9 ⫾ 0.7 s⫺1, P ⬍ 0.0001) and decreased with EI (SRsys ⫽ 3.4 ⫾ 0.1 s⫺1, P ⬍ 0.01). During pacing, SRsys and CI remained unchanged in the AP and EI groups. During DI, ⑀sys and SV initially increased (5 ␮g 䡠 kg⫺1 䡠 min⫺1; ⑀sys ⫽ 77 ⫾ 6%, P ⬍ 0.01) and then progressively returned to baseline. During EI, SV and ⑀sys decreased (⑀sys ⫽ 38 ⫾ 2%, P ⬍ 0.001). Pacing also decreased SV and ⑀sys in the AP (180 beats/min; ⑀sys ⫽ 36 ⫾ 2%, P ⬍ 0.001) and EI groups (180 beats/min; ⑀sys ⫽ 25 ⫾ 3%, P ⬍ 0.001). Thus, for normal myocardium, SRsys reflects regional contractile function (being relatively independent of HR), whereas ⑀sys reflects changes in SV. myocardial contraction; contractility; echocardiography

eters can now be derived noninvasively using validated ultrasound techniques (12, 24). Recent studies have investigated the accuracy of these two deformation parameters for the assessment of ischemia-induced myocardial dysfunction (12–14, 24–25). It has been shown that the regional magnitude of deformation is related to global ejection performance as assessed by stroke volume (SV) (15) and ejection fraction (26). In addition, because the magnitude of deformation is influenced by both heart rate (HR) and loading conditions (24, 26), it does not only reflect the inotropic status of the myocardium. We hypothesized that SRsys might better reflect the change in myocardial contractility. Thus the aim of the study was to investigate, in a closed-chest pig model, how the two regional deformation parameters, ⑀sys and SRsys, are related to left ventricular (LV) contractility and SV over a wide range of HR and during varying positive or negative sympathetic pharmacological stimulation in normal myocardium. METHODS

Twenty cross-bred pigs (weight 31 ⫾ 4 kg) were anesthetized using intravenous propofol (0.3 mg 䡠 kg⫺1 䡠 min⫺1) and fentanyl (0.5 ␮g 䡠 kg⫺1 䡠 min⫺1) and ventilated with a mixture of air and oxygen. All animals were treated in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals. Experimental Preparation

of regional myocardial function is usually based on the evaluation of local deformation both in the experimental (4, 24) and clinical settings (4, 10, 12, 22). Systolic function could be characterized by two regional deformation parameters (8, 12, 24, 25): 1) regional systolic strain (⑀sys), which represents the magnitude of myocardial deformation from a reference point (usually end diastole) to end systole and 2) peak systolic strain rate (SRsys), which represents the maximal velocity of deformation during mechanical systole (8). These two deformation param-

LV pressure (LVP) and its first derivative (dP/dt) were measured with the use of a micromanometer-tipped catheter (Millar) calibrated against a mercury column. The catheter was positioned in the LV cavity via the left carotid artery. Analog signals were digitized using commercially available software (Windaq). A unipolar pacemaker lead was passed via the right jugular vein and positioned in the right atrium to allow controlled right atrial pacing.

Address for reprint requests and other correspondence: F. Rademakers, Dept. of Cardiology, Univ. Hospital Gasthuisberg, Herestraat 49, B-3000 Leuven, Belgium (E-mail: [email protected]. ac.be).

The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked ‘‘advertisement’’ in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

THE

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ASSESSMENT

Ultrasonic Data Acquisition Echocardiographic studies were performed using a Vingmed System 5 (GE Ultrasound) and a 2.5-MHz transducer.

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B-mode color Doppler myocardial imaging (CDMI) data were acquired using parasternal short-axis views at a frame rate of 180 frames/s. Pulse repetition frequency was adjusted to avoid aliasing, and three consecutive heart cycles during brief apnea were recorded. Experimental Protocol After 20 min of stabilization, hemodynamic and echocardiographic data were acquired. The animals were divided into the following three groups. Group 1: control atrial pacing group. The control atrial pacing (AP) group (n ⫽ 7) underwent incremental right AP (120, 140, 160, and 180 beats/min). For each stage, continuous AP was done for 5 min before CDMI and hemodynamic data acquisition. Group 2: dobutamine infusion group. The dobutamine infusion (DI) group (n ⫽ 7) had incremental positive inotropic stimulation (sequentially 2.5, 5, 10, and 20 ␮g 䡠 kg⫺1 䡠 min⫺1). Each dose was given over 5 min by continuous intravenous administration before data acquisition. Group 3: esmolol infusion group. The esmolol infusion (EI) group (n ⫽ 6) underwent negative inotropic stimulation induced by an intravenous infusion of esmolol (0.5 ⫾ 0.15 mg 䡠 kg⫺1 䡠 min⫺1) to achieve a HR reduction of 20%. After HR and blood pressure stabilization, incremental right AP was performed (to achieve 120, 140, 160, and 180 beats/min). For each stage, during continuous EI, AP was done for 5 min before data acquisition. During the study, the underlying native HR was checked during intermittent brief episodes when pacing was stopped. Hemodynamic and CDMI data were recorded at each step in all three groups. Data Analysis Echocardiographic CDMI data. CDMI data were analyzed using dedicated software (TVI, GE Ultrasound) as previously described (14). Briefly, radial strain rate was estimated by measuring the spatial velocity gradient over a computation area of 5 mm. The region of interest was continuously positioned within the LV posterior wall. A septal myocardial velocity profile was used for the timing of end diastole (onset of isovolumic contraction) and end systole (aortic valve closure) (14). Strain rate profiles were averaged over three consecutive cardiac cycles and integrated over time to derive the natural strain profile using end diastole as the reference point (Speqle, K. U. Leuven) (8). From the averaged strain rate and strain data, SRsys and ⑀sys were calculated (Fig. 1). Echocardiographic gray-scale data. From the same CDMI data sets, high-resolution digital gray-scale B-mode data could be displayed after the subtraction of the color myocardial velocity data from the clips. The myocardial end-diastolic and end-systolic wall thickness and LV diameters were measured from an anatomic M-mode tracing. End-diastolic and end-systolic LV volumes were calculated using the Teichholz equation (23) V⫽

7 䡠 D3 2.4 䡠 D

Hemodynamic data. The maximal rate of pressure development (⫹dP/dtmax) and pressure fall (⫺dP/dtmax) was used for the evaluation of global contractile function and ventricular relaxation. The meridional wall-stress of the posterior wall was estimated assuming an ellipsoid LV geometry (9) ␴⫽

冋

册

P 䡠 D2 䡠 0.133 4 䡠 h共D ⫹ h兲

where ␴ is wall stress (in kPa), P is the LVP (in mmHg), h is the posterior wall thickness (in mm), D is the LV cavity minor axis (in mm), and 0.133 is a conversion factor from mmHg to kPa. ␴ was calculated at end systole (␴es) and end diastole (␴ed) to estimate the relative changes in afterload and preload, respectively. The regional contractile function of the posterior wall was evaluated using a contractility index (CI; in kPa⫺1) calculated as the end-systolic strain-to-stress ratio (3, 16) ⑀ sys CI ⫽ ␴ es where ⑀sys is the systolic strain (in %) and ␴es is the endsystolic wall stress (in kPa). Statistical Methods Data are presented as means ⫾ SE. Multiple comparisons were performed using ANOVA with a post hoc Duncan’s test. A linear Pearson correlation was used to compare the deformation parameters with the volume and hemodynamic parameters. A forward stepwise (F to enter ⫽ 10) multiple regression analysis with SV, ⫹dP/dtmax, HR, ␴ed, and ␴es as independent variables and SRsys and ⑀sys as dependent variables was used. CI was not included in the independent variables because it is calculated by the dependent parameter ⑀sys. Statistical significance was inferred for P ⬍ 0.05. RESULTS

where V is the LV volume and D is the short-axis LV diameter. LV SV was calculated as SV ⫽ LVEDV ⫺ LVESV where LVEDV is the LV end-diastolic volume and LVESV is the LV end-systolic volume. AJP-Heart Circ Physiol • VOL

Fig. 1. A: normal strain rate (SR) profile during 1 cardiac cycle of left ventricular (LV) radial deformation, derived at baseline (BS) from the posterior wall. Arrow, measurement point used for peak systolic SR (SRsys) estimation. B: normal radial strain profile during 1 cardiac cycle derived from the posterior wall by integrating the SR curve. Arrow, systolic strain. AVC, aortic valve closure.

Five CDMI data sets (4%) were subsequently excluded from the analysis because of reverberation artifacts. The hemodynamic data for each of the three groups are presented in Table 1. At baseline, there were no significant differences in HR, LV end-diastolic pressure (LVEDP), LV end-systolic pressure (LVESP),

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Table 1. Hemodynamic data in the AP, DI, and EI groups Peak ⫹dP/dt

LVESP

Peak ⫺dP/dt

HR

LVEDP

Baseline AP 120 beats/min 140 beats/min 160 beats/min 180 beats/min

110 ⫾ 3

12 ⫾ 1

78 ⫾ 3

1,720 ⫾ 96

⫺2,500 ⫾ 96

120 140 160 180

11 ⫾ 1 9 ⫾ 1† 6 ⫾ 1* 5 ⫾ 1*

84 ⫾ 3 83 ⫾ 4 82 ⫾ 5 78 ⫾ 5

1,740 ⫾ 121 1,730 ⫾ 80 1,800 ⫾ 93 1,815 ⫾ 102

⫺2,786 ⫾ 243 ⫺2,750 ⫾ 160 ⫺2,841 ⫾ 150 ⫺2,706 ⫾ 170

Baseline DI 2.5 ␮g 䡠 kg⫺1 䡠 min⫺1 5 ␮g 䡠 kg⫺1 䡠 min⫺1 10 ␮g 䡠 kg⫺1 䡠 min⫺1 20 ␮g 䡠 kg⫺1 䡠 min⫺1

107 ⫾ 3

12 ⫾ 1

77 ⫾ 3

1,690 ⫾ 95

⫺2,756 ⫾ 355

122 ⫾ 3† 141 ⫾ 3* 160 ⫾ 4* 178 ⫾ 5*

12 ⫾ 1 9 ⫾ 1† 6 ⫾ 1* 5 ⫾ 1*

85 ⫾ 6 84 ⫾ 6 82 ⫾ 3 81 ⫾ 3

2,473 ⫾ 151* 3,369 ⫾ 178* 3,967 ⫾ 149* 4,592 ⫾ 159*

⫺3,099 ⫾ 292 ⫺3,430 ⫾ 317 ⫺3,738 ⫾ 213† ⫺3,915 ⫾ 252†

111 ⫾ 3 90 ⫾ 4†

11 ⫾ 1 13 ⫾ 1

76 ⫾ 6 61 ⫾ 5

1,700 ⫾ 96 768 ⫾ 65*

⫺2,512 ⫾ 156 ⫺1,277 ⫾ 173†

120 140 160 180

12 ⫾ 2 11 ⫾ 2 8⫾2 7 ⫾ 1†

62 ⫾ 4 64 ⫾ 6 66 ⫾ 4 65 ⫾ 6

888 ⫾ 76* 972 ⫾ 107* 1,101 ⫾ 74* 975 ⫾ 173*

⫺1,481 ⫾ 159† ⫺1,490 ⫾ 206† ⫺1,677 ⫾ 135† ⫺1,561 ⫾ 484†

AP group

DI group

EI group Baseline EI without pacing EI with pacing 120 beats/min 140 beats/min 160 beats/min 180 beats/min

Values are means ⫾ SE. AP, atrial pacing; DI, dobutamine infusion; EI, esmolol infusion; HR, heart rate (in beats/min); LVEDP, left ventricular (LV) end-diastolic pressure (in mmHg); LVESP, LV end-systolic pressure (in mmHg); peak dP/dt, maximal rate of pressure development (in mmHg/s); peak-dP/dt, maximal rate of pressure fall (in mmHg/s). * P ⬍ 0.001 vs. baseline; † P ⬍ 0.05 vs. baseline.

⫹dP/dtmax, and ⫺dP/dtmax among the three groups. For each stage of DI, HR was comparable to the pacing stages in the AP and EI groups (Table 1). ⫹dP/dtmax, ⫺dP/dtmax, and CI increased gradually in the DI group, decreased significantly during EI, and remained constant during AP in both the AP and EI groups. LV Volume

dial relaxation was impaired during EI, resulting in a delayed myocardial thinning occurring mainly in late diastole during atrial contraction. At baseline, SRsys and ⑀sys were comparable in the three groups, averaging 5 ⫾ 0.4 s⫺1 and 60 ⫾ 3%, respectively. SRsys increased with DI and decreased Table 2. Volumes in the AP, DI, and EI groups

Both LVEDV and LVESV decreased gradually in the DI group with an increasing DI rate (Table 2). However, the SV showed a biphasic response during the DI. SV initially increased at a low dose of dobutamine (2.5–5 ␮g 䡠 kg⫺1 䡠 min⫺1) and then decreased at higher doses (10–20 ␮g 䡠 kg⫺1 䡠 min⫺1) (Fig. 2). In the AP group, the decrease was more pronounced for LVEDV than for LVESV, resulting in a diminished SV (Fig. 2). In the EI group, LVESV remained unchanged, whereas LVEDV decreased with increasing HR, resulting in a decreased SV (Fig. 2). Myocardial Deformation Typical examples of extracted strain and strain rate curves at a HR of 140 beats/min from each of the three groups are shown in Fig. 3. In all groups, strain rate values were positive during systole and typically featured two negative peaks in diastole during early filling and atrial contraction. Strain profiles for radial deformation showed myocardial thickening in systole and thinning in diastole. DI resulted in an increase in the peak systolic velocity of deformation and magnitude of deformation of the posterior wall. In contrast, during EI, both systolic deformation parameters were clearly reduced. In addition, during diastole, myocarAJP-Heart Circ Physiol • VOL

LVEDV

LVESV

AP group Baseline AP 120 beats/min 140 beats/min 160 beats/min 180 beats/min

81 ⫾ 3

43 ⫾ 2

78 ⫾ 3 72 ⫾ 3 63 ⫾ 3* 57 ⫾ 3*

40 ⫾ 2 39 ⫾ 2 38 ⫾ 2 34 ⫾ 2#

DI group Baseline DI 2.5 ␮g 䡠 kg⫺1 䡠 min⫺1 5 ␮g 䡠 kg⫺1 䡠 min⫺1 10 ␮g 䡠 kg⫺1 䡠 min⫺1 20 ␮g 䡠 kg⫺1 䡠 min⫺1

80 ⫾ 2

44 ⫾ 2

79 ⫾ 4 73 ⫾ 4 61 ⫾ 4* 58 ⫾ 4*

37 ⫾ 3 30 ⫾ 2* 28 ⫾ 2* 27 ⫾ 2*

EI group Baseline EI without pacing EI with pacing 120 beats/min 140 beats/min 160 beats/min 180 beats/min

80 ⫾ 2 74 ⫾ 3

42 ⫾ 3 49 ⫾ 4

72 ⫾ 6 68 ⫾ 10 63 ⫾ 10† 54 ⫾ 8†

53 ⫾ 5 51 ⫾ 5 51 ⫾ 6 46 ⫾ 5

Values are means ⫾ SE. LVEDV, LV end-diastolic volume (in ml); LVESV, LV end-systolic volume (in ml). * P ⬍ 0.001 vs. baseline; † P ⬍ 0.05 vs. baseline.

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changes paralleled the previously described variations of SRsys in each group (Fig. 4). Statistical Correlation For all the measured hemodynamic (LVEDP and LVESP), volume (LVEDV, LVESV, and SV), contractility (CI), and wall stress parameters (␴ed and ␴es), SRsys correlated best with CI (r ⫽ 0.84, P ⬍ 0.0001) and ⑀sys correlated best with SV (r ⫽ 0.61, P ⬍ 0.0001). In the forward stepwise multiple regression analysis with SRsys and ⑀sys as the dependent variable and with SV, ⫹dP/dtmax, HR, ␴ed, and ␴es as the independent variables, SRsys correlated best with ⫹dP/dtmax (␤ ⫽ 0.81) and ⑀sys correlated best with SV (␤ ⫽ 0.48). The results of the multiple regression analysis investigating the predictors of SRsys and ⑀sys are shown in Fig. 5. DISCUSSION

The finding that ⑀sys is closely related to SV and not only to contractility is not new (15). A decrease in ⑀sys does not necessarily reflect an alteration in regional contractile function but can be related to increased HR and altered loading conditions, as occurring with DI. In contrast, this study suggests that SRsys could better reflect the changes in myocardial contractility than regional systolic deformation alone. Regional Myocardial Strain

Fig. 2. Changes in regional systolic strain (⑀sys; in %) and stroke volume (SV; in ml) in the atrial pacing (AP) group (A), the dobutamine infusion (DI) group (B), and the continuous esmolol infusion (EI) ⫹ AP group (C). Measurements were made first at BS and then during each step of the protocol. HR, heart rate. * P ⬍ 0.01 vs. BS measurement.

with EI (P ⬍ 0.05). During AP, SRsys remained unchanged with increasing HR in both the AP and EI groups (Fig. 4). Conversely, ⑀sys decreased with esmolol and AP and had a biphasic response to dobutamine, increasing for low dobutamine doses and decreasing for high dobutamine doses. The changes in ⑀sys paralleled changes in LV SV (Fig. 2). Regional Wall Stress and Contractility The ␴ed of the posterior wall decreased in all three groups with increasing HR (P ⬍ 0.001). ␴es decreased with increasing HR in both the AP and DI groups, being more pronounced in the latter. In contrast, no significant change of ␴es was observed in the EI group (Table 3). The CI was comparable at baseline for all three groups and averaged 7.14 ⫾ 0.75 kPa⫺1. The CI AJP-Heart Circ Physiol • VOL

Regional ⑀sys (measured at end systole) represents the magnitude of deformation, which takes place from end diastole (reference point) to end systole. For the radial direction, this parameter quantifies the percentage of systolic thickening. In agreement with Morris et al. (15), this study shows that regional ⑀sys is mainly related to LV SV (Fig. 2). Thus, during incremental DI, regional ⑀sys and global SV showed a biphasic response with a significant initial increase and a decrease to baseline values at maximal dobutamine dose. This is in agreement with the clinical study of Pellikka et al. (18), who observed a similar biphasic SV response in normal patients. The initial increase in ⑀sys and SV is due to the effects of increasing inotropic stimulation (18, 19). Thereafter, the shortened time for ventricular filling and the decrease in venous return (decreased LVEDV), secondary to the dobutamine-induced increase in HR, will result in a decrease of both SV and ⑀sys. During incremental AP of normal myocardium, SV decreases gradually in agreement with prior work (17, 21). The local contribution to the ejection process (i.e., ⑀sys) also decreases, probably due to lower preload and shortened ejection time, despite unchanged contractile state (Fig. 2). The reduction in ⑀sys during esmolol administration with pacing relates to the previously mentioned factors combined with a diminished contractility. In addition, EI resulted in an abnormal ventricular relaxation, as suggested by the global decrease in ⫺dP/dtmax. This abnormal relaxation (Fig. 3) in combination with a shortened diastolic period during higher HR resulted in a decreased end-diastolic volume. Therefore, global SV and thus ⑀sys decreased.

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Fig. 3. An example of a typical SR and strain curve during 1 cardiac cycle from the posterior wall in the 3 different groups. A: during AP with a HR of 140 beats/ min. B: during DI of 5 ␮g 䡠 kg⫺1 䡠 min⫺1 (equivalent of a HR of 142 beats/min in this case). C: during continuous EI and simultaneous AP at 140 beats/min. Note the abnormal delayed thinning during EI due to delayed relaxation. Dotted vertical line, AVC.

These changes of global hemodynamic are in agreement with prior pharmacological studies on the ␤-adrenoreceptor antagonist esmolol (2, 11). In summary, for normal myocardium, systolic strain quantifies regional systolic deformation of the LV and is mainly determined by the ejection performance, i.e., the SV. The effects of a decrease in SV can offset even a significant increase in inotropic stimulation. Regional Myocardial Strain Rate Strain estimation, however, does not take into account the temporal dimension, i.e., the time that is necessary for the myocardium to achieve this deformation. In contrast, strain rate measurement quantifies the velocity of myocardial deformation. Peak radial SRsys, the parameter that was investigated in this study, represents the maximal velocity of myocardial thickening in systole (8). Our findings in normal myocardium suggest that changes in SRsys parallel induced changes in contractility (Fig. 4). As an in vivo parameter for contractility, we used the ratio of end-systolic strain to end-systolic wall stress. This parameter is known to be relatively independent of loading and is sensitive to changes in contractility (3, 16). During DI, myocardial contractility is mainly influenced by three different factors: 1) the increase in inotropic state (i.e., the pharmacological effect of dobutamine) leads to an extrinsic increase in contractility; 2) the increase in HR leads to an additional intrinsic increase in contractility (Bowditch effect); and 3) the decrease of preload results in an intrinsic decrease of contractility, because the sarcomere filaments are not any longer optimally overAJP-Heart Circ Physiol • VOL

Fig. 4. Changes in regional SRsys (in s⫺1) and the ratio of end-systolic strain-to-end-systolic wall stress (in kPa⫺1) as a contractility index (CI) in the AP group (A), the DI group (B), and the continuous EI ⫹ AP group (C). Measurements were made first at BS and then during each step of the protocol. *P ⬍ 0.01 vs. BS measurement; #P ⬍ 0.001 vs. BS measurement.

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Table 3. Wall stress in the AP, DI, and EI groups LV End-Diastolic Stress

LV End-Systolic Stress

AP group Baseline AP 120 beats/min 140 beats/min 160 beats/min 180 beats/min

4 ⫾ 0.4

9.4 ⫾ 0.7

3.5 ⫾ 0.4 2.3 ⫾ 0.2* 1.2 ⫾ 0.1* 0.8 ⫾ 0.1*

8.8 ⫾ 0.7 8.1 ⫾ 0.7 6.9 ⫾ 0.6† 5.4 ⫾ 0.5†

DI group Baseline DI 2.5 ␮g 䡠 kg⫺1 䡠 min⫺1 5 ␮g 䡠 kg⫺1 䡠 min⫺1 10 ␮g 䡠 kg⫺1 䡠 min⫺1 20 ␮g 䡠 kg⫺1 䡠 min⫺1

4.2 ⫾ 0.4

9.3 ⫾ 0.7

3.3 ⫾ 0.4 2.0 ⫾ 0.3* 1.2 ⫾ 0.2* 0.8 ⫾ 0.2*

6.8 ⫾ 0.5† 5.6 ⫾ 0.4* 4.4 ⫾ 0.6* 3.7 ⫾ 0.5*

3.9 ⫾ 0.3 3.6 ⫾ 0.4

9.2 ⫾ 0.7 8.1 ⫾ 1.3

2.9 ⫾ 0.5 2.4 ⫾ 0.6 1.6 ⫾ 0.5† 1 ⫾ 0.3*

8.6 ⫾ 1.7 8.4 ⫾ 1.8 8.6 ⫾ 1.7 7.2 ⫾ 1.6

effect of increased contractility due to the Bowditch effect and decreased contractility due to the decreased preload). Additionally, the results obtained with AP provide evidence that the dobutamine-induced variations in strain rate are not secondary to the chronotropic effects of the drug. In short, this study shows that SRsys is a regional myocardial deformation parameter that, in normal myocardium, is closely related to the changes in contractility. However, it should be noted that SRsys is not directly measuring contractility, because it does not take into account myocardial stress and therefore remains load sensitive. Deformation Imaging With Other Techniques

EI group Baseline EI without pacing EI with pacing 120 beats/min 140 beats/min 160 beats/min 180 beats/min

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Values are means ⫾ SE. LV end-diastolic and end-systolic stress were measured in kPa. * P ⬍ 0.001 vs. baseline; † P ⬍ 0.05 vs. baseline.

lapped (negative Frank-Starling mechanism). Thus SRsys reflects on a regional myocardial level the sum of these extrinsic and intrinsic adaptations. Moreover, because SRsys remained constant during the increase in HR in the AP group (Fig. 4), it would appear to be relatively independent of HR (balanced

The regional contractile response to inotropic stimulation is complex, and therefore evaluation of the changes in regional function requires quantitative measurements with high temporal resolution. Magnetic resonance imaging (MRI) tagging offers the major advantage of three-dimensional regional strain analysis (20). However, to resolve regional strain rate requires sampling rates of ⬎120 frames/s (7). Currently, the MRI tagging technique is based on sampling rates of 30–40 frames/s and thus can only obtain mean strain rate (19) but not peak SRsys, which was used in our study. In contrast, measuring of myocardial segment lengths in the experimental setting by sonomicrometry (24) does provide accurate information on regional deformation properties. However, this technique requires a sternotomy and opening of the pericardium, which

Fig. 5. Relation between regional deformation parameters (SRsys and ⑀sys) and global parameters [maximal rate of pressure development (⫹dP/dtmax), HR, SV, LV end-diastolic wall stress (␴ed), and LV endsystolic wall stress (␴es)] using a stepwise forward multiple regression analysis. Predicted values are plotted versus measured values for both peak SRsys and ⑀sys.

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itself can have an impact on regional myocardial function (1, 5, 6). Thus ultrasonic strain rate imaging is currently the only technique that can quantify SRsys noninvasively in vivo. Clinical Implications One of the common clinical situations where HR and contractility feature important variations is stress echocardiography. The quantitative evaluation of the velocity of deformation (strain rate) and not only deformation as assessed by the human eye might be of clinical value for the accurate quantitation of changes in the contractile function during an inotropic stress. A decrease in systolic deformation at peak stimulation might not necessary indicate an induced abnormality in contractility and should be interpreted with caution for the identification of stress-induced regional ischemia.

In conclusion, the understanding of normal myocardial mechanics is an important prerequisite for the accurate investigation of myocardial dysfunction. The combined use of the magnitude and maximal velocity of myocardial deformation provide complementary information on the variation of myocardial performance and contractility. This should be a promising approach for the noninvasive assessment of cardiac function. APPENDIX

This appendix describes the concepts of regional SR and ⑀ measurements and how these parameters are derived from myocardial velocities measured with the CDMI technique. Strain Rate This corresponds to the rate of the deformation of an object. Local myocardial SR (in s⫺1) can be calculated from the spatial gradient in velocities recorded between two neighboring points in the tissue (points 1 and 2 with velocities v1 and v2)

Limitations We measured strain rate and strain only in the radial direction, because in closed-chest pigs only parasternal views (and not apical views for longitudinal function) can be obtained. Another limitation of the study is that we chose to record data only from one sampling site in the posterior wall. This was related to limitations in the current data acquisition and postprocessing methodology: because of the angle dependency of strain rate, imaging radial deformation in a closed-chest animal model can only be calculated for the posterior wall and the interventricular septum. Because septal deformation can be influenced by both LV and right ventricular function, only the posterior wall was investigated. Accordingly, our results show trends in the variations of radial myocardial deformation in a normal myocardial segment during inotropic and chronotropic modulation and cannot be directly extrapolated to all segments. In a normal heart with only a small degree of regional and temporal inhomogeneity, it can be expected that the present results can be extrapolated to all regions and strains, although this remains to be confirmed. In a diseased heart, however, interactions between normal and abnormal regions could have important effects which can change the observed relations. Further studies on this subject in ischemic models and individuals are thus warranted. All Doppler techniques are angle dependent. This is also applicable to myocardial Doppler velocities and deformation indexes. This limitation was minimized in this study by a careful alignment of the ultrasound beam with the radial contraction of the posterior wall. Another inherent limitation to regional CDMI indexes is the influence of global cardiac translation and motion. Prior investigations have clearly shown the translation dependency of myocardial velocities. Because strain rate computation is based on velocity gradients (see APPENDIX), this translation dependency is minimized as suggested by prior publications (24). AJP-Heart Circ Physiol • VOL

SR ⫽

v1 ⫺ v2 L

with L reflecting the distance between points 1 and 2 (8). When a segment thickens in the radial direction, SR is defined to have a positive SR value. When a segment thins in the radial direction, it is characterized by a negative value (Fig. 1). Strain Regional ⑀ values can be obtained by integrating the regional SR curve over time. ⑀ defines the relative amount of local deformation caused by an applied force (8). Myocardial radial ⑀ increases during myocardial thickening and decreases during thinning. Both thickening and thinning can be measured over time throughout the cardiac cycle. The ultrasound technique, as currently formatted, estimates the instantaneous change in segment length. This is the natural ⑀ value (⑀N) (8), which is expressed as a percentage, and is described by the equation t

兰

⑀ N ⫽ SRdt t0

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