Effects of loading conditions and contractile state (methoxamine and dobutamine) on left ventricular early diastolic function in normal subjects

doi:10.1016/0002-9149(85)90158-4

The American Journal of Cardiology

Volume 55, Issue 6, 1 March 1985, Pages 790-796

https://doi.org/10.1016/0002-9149(85)90158-4 Get rights and content

Abstract

The influence of changes in preload, afterload and contractile state on left ventricular (LV) filling characteristics were examined. Normal subjects underwent echocardiographic determination of the peak rates of LV dimension change and wall thinning and their respective timing at rest, after preload augmentation with dextran, during increased afterload with methoxamine and during inotropic stimulation by dobutamine. These 2 peak velocities and their timing in diastole correlated well with each other and responded similarly to interventions. Increased preload resulted in higher peak velocities of dimension change and wall thinning, without changing the time in diastole at which they occur. Both peak velocities moved later into diastole with higher afterload; however, the overall change in magnitude was variable and without statistical significance. Inotropic stimulation resulted in faster rates of peak dimension change and wall thinning, which occurred at an earlier point in diastole. Examination of various measures of LV size and function over a wide range of preload and afterload conditions under a constant contractile state revealed a complex set of relations. The ratio of wall thickness-to-dimension at end-diastole showed the most significant relation to the peak rate of dimension change, whereas peak thinning was best correlated with fractional wall thickening. Both velocities were also significantly but more weakly related to other variables of systolic function. The timing of these peak velocities correlated most closely with the end-systolic wall stress and heart rate. Thus, LV filling and wall thinning depend in a complex fashion on loading conditions, heart rate and contractile state. These interactions must be considered when echocardiographic indexes of diastolic function are used in the clinical setting.

References (30)

H Gewirtz et al.
Ischemia-induced impairment of left ventricular relaxation: relation to reduced diastolic filling rates of the left ventricle
Am Heart J
(1983)
SD Colan et al.
Effects of enhanced afterload (Methoxamine) and contractile state (Dobutamine) on the left ventricular late-systolic wall stress-dimension relation
Am J Cardiol
(1983)
LE Teichholz et al.
Problems in echocardiographic volume determinations: echocardiographic-angiographic correlations in the presence or absence of asynergy
Am J Cardiol
(1976)
RA Slutsky et al.
Analysis of ventricular emptying and filling indexes during acute increases in arterial pressure
Am J Cardiol
(1983)
MT Upton et al.
The study of left ventricular function from digitized echocardiograms
Prog Cardiovasc Dis
(1978)
RC Bahler et al.
The relation of heart rate and shortening fraction to echocardiographic indexes of left ventricular relaxation in normal subjects
JACC
(1983)
KT Weber et al.
Instantaneous force-velocity-length relations: Experimental findings and clinical correlates
Am J Cardiol
(1977)
JD Carroll et al.
Left ventricular isovolumic pressure decay and diastolic mechanics after postextrasystolic potentiation and during exercise
Am J Cardiol
(1983)
KM Borow et al.
Clinical use of pressure-dimension and stressshortening relations in systole and diastole
JW Frederiksen et al.
Time constant of isovolumic pressure fall: determinants in the working left ventricle
Am J Physiol
(1978)

DL Brutsaert et al.

Relaxation of ventricular cardiac muscle

J Physiol (Lond)

(1978)

AS Blaustein et al.

Myocardial relaxation. V. Postextrasystolic contraction-relaxation in the intact dog heart

Circulation

(1981)

JL Weiss et al.

Hemodynamic determinants of the time course of fall in canine left ventricular pressure

J Clin Invest

(1976)

WH Gaasch et al.

Myocardial relaxation II: Hemodynamic determinants of the rate of left ventricular isovolumic pressure decline

Am J Physiol

(1980)

JD Carroll et al.

Dynamics of left ventricular filling at rest and during exercise

Circulation

(1983)

Cited by (64)

Assessment of diastolic function by tissue Doppler echocardiography: Comparison with standard transmitral and pulmonary venous flow
1999, Journal of the American Society of Echocardiography
The objective of this study was to determine the utility of Doppler tissue echocardiography in the evaluation of diastolic filling and in discriminating between normal subjects and those with various stages of diastolic dysfunction. We measured myocardial velocities in 51 patients with various stages of diastolic dysfunction and in 27 normal volunteers. The discriminating power of each of the standard Doppler indexes of left ventricular filling, pulmonary venous flow, and myocardial velocities was determined with the use of Spearman rank correlation and analysis of variance F statistics. Early diastolic myocardial velocity (E_m ) was higher in normal subjects (16.0 ± 3.8 cm/s) than in patients with either delayed relaxation (n = 15, 7.5 ± 2.2 cm/s), pseudonormal filling (n = 26, 7.6 ± 2.3 cm/s), or restrictive filling (n = 10, 7.4 ± 2.4 cm/s, P <.0001). E_m was the best single discriminator between control subjects and patients with diastolic dysfunction (P =.7, F = 64.5). Myocardial velocities assessed by Doppler tissue echocardiography are useful in differentiating patients with normal from those with abnormal diastolic function. Myocardial velocity remains reduced even in those stages of diastolic dysfunction characterized by increased preload compensation. (J Am Soc Echocardiogr 1999;12:609-17.)
New doppler echocardiographic applications for the study of diastolic function
1998, Journal of the American College of Cardiology
Doppler echocardiography is one of the most useful clinical tools for the assessment of left ventricular (LV) diastolic function. Doppler indices of LV filling and pulmonary venous (PV) flow are used not only for diagnostic purposes but also for establishing prognosis and evaluating the effect of therapeutic interventions. The utility of these indices is limited, however, by the confounding effects of different physiologic variables such as LV relaxation, compliance and filling pressure. Since alterations in these variables result in changes in Doppler indices of opposite direction, it is often difficult to determine the status of a given variable when a specific Doppler filling pattern is observed. Recently, color M-mode and tissue Doppler have provided useful insights in the study of diastolic function. These new Doppler applications have been shown to provide an accurate estimate of LV relaxation and appear to be relatively insensitive to the effects of preload compensation. This review will focus on the complementary role of color M-mode and tissue Doppler echocardiography and traditional Doppler indices of LV filling and PV flow in the assessment of diastolic function.
Role of left ventricular mass/volume ratio on transmitral flow velocity patterns from infancy to childhood
1998, International Journal of Cardiology
Age-related changes in left ventricular diastolic filling have been reported to occur in normal children in studies using Doppler echocardiographic methods. However, little information currently exists on the relationships between transmitral flow velocity patterns and the left ventricular mass. We measured left ventricular end-diastolic volume, left ventricular mass, mass/volume ratio, and transmitral flow velocity patterns by M-mode and Doppler echocardiography in 165 normal children aged 5 days to 195 months. Subjects were divided into 6 age groups: <1; 1 to <3; 3 to <5; 5 to <7; 7 to <9; and ≥9 years old. The left ventricular end-diastolic volume and mass increased progressively with increasing age. However, the mass/volume ratio in infants <1 year was significantly higher than that in infants 1 to <3 years (1.32±0.25 vs. 1.14±0.16, p<0.01) without any changes of the ratio thereafter. The peak E wave in infants <1 year was significantly lower than that in 1 to <3 years (71±18 vs. 92±13 cm/s, p<0.01) without changes thereafter. As the flow velocity time integral of E wave increased and that of A wave remained constant, the flow velocity time integral of E/A wave increased with increasing age. The early diastolic tilling fraction in infants <1 year was lower than that in infants 1 to 3 years. (0.61±0.07 vs. 0.70±0.06, p<0.01). The atrial filling fraction in infants <1 year was higher than that in infants 1 to <3 years (0.40±0.08 vs. 0.30±0.06, p<0.01) with a little decrease thereafter. The peak E wave, early diastolic tilling fraction, and the atrial filling fraction correlated with the logarithm of age (p<0.01). Age-related changes in these Doppler echocardiographic findings suggest reduced left ventricular early diastolic filling patterns. The mass/volume ratio correlated linearly with peak E wave, early diastolic filling fraction, and atrial filling fraction (r=−0.38, −0.33, and 0.26, p<0.01). No significant relationships between mass/volume ratio and the other Doppler indices were found. Thus, the age-related reduction in the mass/volume ratio may be one of the mechanisms underlying age-related changes in the early diastolic ventricular filling as assessed by Doppler echocardiography.
Dobutamine stress Doppler echocardiography: Reproducibility and physiologic left ventricular filling patterns
1997, International Journal of Cardiology
Qualitatively, dobutamine stress echocardiography has become an established procedure. Quantitative results are in great demand but this is still difficult due to limited endo- and epicardial border definition. Transmitral Doppler variables are strictly quantitative and less subjective. Furthermore, ischemic alterations precede systolic ones (ischemic cascade). There are preliminary reports of the utility of dobutamine stress Doppler echocardiography, but proof of reproducibility and left ventricular filling patterns are still lacking. Fourteen healthy volunteers (10 men, 4 women, median age 25.9 years, range 21–32 years) were investigated according to the usual dobutamine stress echocardiographic protocol (5, 10, 15, 20, 30, 40 and 40 μg/kg/min+0.5 mg atropine). At each titration step a standardized transmitral PW-Doppler recording with the sample volume positioned at the opened mitral leaflet tips was analyzed three times by two independent, experienced investigators. Of the early, late, and mean velocities (V_maxE, V_maxA, V_mean), time integrals (VTI-E, VTI-A, VTI), their ratios (E/A, E/A VTI), and various time intervals (T_acc, T_dec, E- and A-duration, FillT), V_maxE (0.82 to 1.09 m/s; P<0.0001), VTI-E (16.17 to 17.19 cm; P<0.0001) and V_mean (0.29 to 0.82 m/s; P<0.0001) were found to have the greatest discriminatory power, commencing already at a dose of 10–15 μg/kg/min dobutamine. V_maxE and VTI-E demonstrated the smallest intra- and interobserver variation without any increase in variability during incremental dose titration. Assessment of the early diastolic filling pattern by Doppler echocardiography is a valuable quantitative and reproducible adjunct to conventional dobutamine stress echocardiography. Further controlled studies in coronary artery disease patients have to confirm, whether lower dobutamine doses could be used in the test and sensitivity increased due to better data acquisition in cases of limited echogenicity, less subjectivity, and earlier onset of ischemic alterations.
Abnormal left ventricular early diastolic filling during dobutamine stress Doppler echocardiography is a sensitive indicator of significant coronary artery disease
1994, Journal of the American College of Cardiology
Objectives. This study was designed to assess changes in Doppler indexes of left ventricular ejection and filling in response to high dose (40 μg/kg body weight per min) dobutamine stress and their utility in detection of coronary artery disease compared with that of new wall motion abnormalities.
Methods. Ten patients with a low likelihood of coronary artery disease served as a control group, and 23 patients with documented single-vessel coronary artery disease underwent baseline and peak dobutamine echocardiographic and Doppler studies.
Results. In both groups dobutamine induced similar increases in heart rate and systolic blood pressure. During the test, 14 patients had new wall motion abnormalities, 13 had angina, and 7 had electrocardiographic ST segment changes. No markers of ischemia occurred in the control subjects. Dobutamine induced qualitatively similar changes from baseline to peak dobutamine stress in control subjects and patients in peak aortic velocity (46% vs. 42%, p = NS), average aortic acceleration (61% vs. 43%, p = 0.03) and systolic time-velocity integral (7% vs. 2%, p = NS). Dobutamine caused marked increases in control subjects and decreases in patients in peak early filling velocity (E) (33% vs. −22%, p < 0.0001) and average E acceleration (76% vs. −28%, p < 0.0001). The response of Doppler early filling indexes to dobutamine stress was abnormal in all patients. There was no overlap in the percent change from baseline to peak dobutamine stress between control subjects and patients for E and E acceleration.
Conclusions. During dobutamine stress testing, an abnormal response of Doppler indexes of left ventricular early filling is a more sensitive marker of significant single-vessel coronary disease than are new wall motion abnormalities, and it is far superior to the response of Doppler ejection variables as a predictor of coronary artery disease.
Role of changing loading conditions on atrioventricular flow velocity patterns in normal human fetuses
1994, The American Journal of Cardiology

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^☆: This study was supported in part by Grant HL07193 from the National Heart, Lung, and Blood Institute, Bethesda, Maryland.

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Effects of loading conditions and contractile state (methoxamine and dobutamine) on left ventricular early diastolic function in normal subjects☆

Abstract

Am Heart J

Am J Cardiol

Am J Cardiol

Am J Cardiol

Prog Cardiovasc Dis

JACC

Am J Cardiol

Am J Cardiol

Clinical use of pressure-dimension and stressshortening relations in systole and diastole

Time constant of isovolumic pressure fall: determinants in the working left ventricle

Am J Physiol

Relaxation of ventricular cardiac muscle

J Physiol (Lond)

Myocardial relaxation. V. Postextrasystolic contraction-relaxation in the intact dog heart

Circulation

Hemodynamic determinants of the time course of fall in canine left ventricular pressure

J Clin Invest

Myocardial relaxation II: Hemodynamic determinants of the rate of left ventricular isovolumic pressure decline

Am J Physiol

Dynamics of left ventricular filling at rest and during exercise

Circulation