Absence of diastolic mitral annular oscillations is a marker for relaxation-related diastolic dysfunction

Although Doppler tissue imaging frequently indicates the presence of mitral annular oscillations (MAO) following the E' wave (E' wave, etc.), only recently was it shown that annular "ringing" follows the rules of damped harmonic oscillatory motion. Oscillatory model-based analysis of E' and E' waves provides longitudinal left ventricular (LV) stiffness (k'), relaxation/viscoelasticity (c'), and stored elastic strain (x(o)') parameters. We tested the hypothesis that presence (MAO(+)) vs. absence (MAO(-)) of diastolic MAO is an index of superior LV relaxation by analyzing simultaneous echocardiographic-hemodynamic data from 35 MAO(+) and 20 MAO(-) normal ejection fraction (EF) subjects undergoing cardiac catheterization. Echocardiographic annular motion and transmitral flow data were analyzed with a previously validated kinematic model of filling. Invasive and noninvasive diastolic function (DF) indexes differentiated between MAO(+) and MAO(-) groups. Specifically, the MAO(+) group had a shorter time constant of isovolumic relaxation [tau; 51 (SD 13) vs. 67 (SD 27) ms; P<0.01] and isovolumic relaxation time [63 (SD 16) vs. 82 (SD 17) ms; P<0.001] and greater ratio of peak E-wave to peak A-wave velocity [1.19 (SD 0.31) vs. 0.97 (SD 0.31); P<0.05]. The MAO(+) group had greater peak lateral mitral annulus velocity [E'; 17.5 (SD 3.1) vs. 13.5 (SD 3.8) cm/s; P<0.001] and LVEF [71.2 (SD 7.5)% vs. 65.4 (SD 9.1)%; P<0.05] and lower heart rate [65 (SD 9) vs. 74 (SD 9) beats/min, P<0.001]. Additional conventional and kinematic modeling-derived indexes were highly concordant with these findings. We conclude that absence of early diastolic MAO is an easily discernible marker for relaxation-related diastolic dysfunction. Quantitation of MAO via stiffness and relaxation/viscoelasticity parameters facilitates quantitative assessment of regional (i.e., longitudinal) DF and may improve diagnosis of diastolic dysfunction.     

Stiffness- and relaxation-based quantitation of radial left ventricular oscillations: elucidation of regional diastolic function mechanisms.

Traditionally, global and longitudinal (i.e., regional) left ventricular (LV) diastolic function (DF) assessment has utilized features of transmitral Doppler E and A waves or Doppler tissue imaging (DTI)-derived mitral annular E' and A' waves, respectively. Quantitation of regional DF has included M-mode echocardiography-based approaches and strain and strain rate imaging (in selected imaging planes), while analysis of mitral annular "oscillations" has recently provided a new window into longitudinal (long-axis) function. The remaining major spatial degree of kinematic freedom during diastole, radial (short-axis) motion, has not been fully characterized, nor has it been exploited for its potential to provide radial LV stiffness (k'(rad)) and relaxation/damping (c'(rad)) indexes. Prior characterization of regional (longitudinal) DF used only annular E'- and A'-wave peak velocities or, alternatively, myocardial strain and strain rate. By kinematically modeling short-axis tissue motion as damped radial oscillation, we present a novel method of estimating k'(rad) and c'(rad) during early filling. As required by the (near) constant-volume property of the heart and tissue/blood incompressibility, in subjects (n = 10) with normal DF, we show that oscillation duration-determined longitudinal (k'(long) and c'(long)) and radial (k'(long) and c'(rad)) parameters are highly correlated (R = 0.69 and 0.92, respectively). Selected examples of diabetic and LV hypertrophic subjects yield radial (k'(long) and c'(rad)) parameters that differ substantially from controls. Results underscore the utility of the incompressibility-based causal relation between DTI-determined mitral annular long-axis (longitudinal mode) and short-axis (radial mode) oscillations in healthy subjects. Selected pathological examples provide mechanistic insight and illustrate the value and potential role of regional (longitudinal and radial) DF indexes in fully characterizing normal vs. impaired DF states.     

The effects of caloric restriction- and exercise-induced weight loss on left ventricular diastolic function

Little is known about the effects of weight loss on diastolic function. Furthermore, it is not known whether both caloric restriction (CR)- and exercise (Ex)-induced weight loss have salutary effects on diastolic function. Therefore, we assessed the effects of yearlong CR (n = 12) and Ex (n = 13) interventions, which induced approximately 12% weight loss, on diastolic function in healthy, nonobese (body mass index = 23.5-29.9 kg/m2) men and women aged 50 to 60 yr. Recordings of Doppler transmitral flow and Doppler tissue imaging were acquired and analyzed by conventional approaches and a validated parameterized diastolic filling (PDF) formalism. Isovolumic relaxation time decreased after weight loss in both groups (P < 0.05). Septal peak early mitral annular velocity (E') increased (P < 0.01) and peak E-wave velocity/E' decreased (P < 0.05) after weight loss in the CR group. Based on the PDF-derived indexes, CR resulted in a decrease in global ventricular stiffness (k) and increases in longitudinal (septal annulus motion) stored elastic strain (chi'o), peak force (k'chi'o), and peak stored strain energy (1/2k'chi'o2). In the Ex group, k was unchanged, although septal chi'o and 1/2k'chi'o2 increased significantly and k'chi'o (P = 0.13) tended to increase. We conclude that weight loss, whether induced by CR or Ex, has salutary effects on diastolic function.     

Elucidation of spatially distinct compensatory mechanisms in diastole: radial compensation for impaired longitudinal filling in left ventricular hypertrophy.

Cardiac output maintenance is so fundamental that, when regional systolic function is impaired, as during ischemia, nonischemic segments compensate by becoming hypercontractile. By analogy, diastolic compensatory mechanisms that maintain filling volume must exist but remain to be fully elucidated. Viewing filling in spatially distinct (longitudinal, radial) mechanistic terms facilitates elucidation of diastolic compensatory mechanisms. Because impairment of longitudinal (long axis) diastolic function (DF) in left ventricular hypertrophy (LVH) is established, we hypothesized that to maintain filling volume, radial (short-axis) filling function would compensate. In 20 normal left ventricular ejection fraction (LVEF) subjects (10 with LVH, 10 without LVH), we analyzed longitudinal function via Doppler tissue imaging of mitral annular motion and radial function as change in short-axis endocardial dimension via M-mode. The spatial (long axis, short axis) endocardial LV dimensions and their changes allowed assignment of E-wave filling volume into (cylindrical geometry-based) longitudinal and radial components. Despite indistinguishable (P = 0.70) E-wave velocity-time integrals (E-wave filling volume surrogate), systolic stroke volumes, and end-diastolic volumes in the LVH and control groups, longitudinal volume in absolute terms and the percent of E-wave volume accommodated longitudinally were reduced in the LVH group (P < 0.05 and P < 0.01, respectively), whereas the percent of E-wave volume accommodated radially was enhanced (P < 0.01). We conclude that, in normal LVEF (decreased longitudinal volume accommodation) LVH subjects vs. controls, spatially distinct compensatory mechanisms in diastole manifest as increased radial volume accommodation per unit of E-wave filling volume. Assessment of spatially distinct diastolic compensatory mechanisms in other pathophysiological subsets is warranted.     

Left ventricular diastolic filling and systolic function of young and older trained and untrained men.

Aging is associated with impaired early diastolic filling; however, the effect of endurance training on resting diastolic function in older subjects is unclear. Heart rate and ventricular loading conditions affect mitral inflow velocities measured by Doppler echocardiography; therefore, tissue Doppler imaging of mitral annular velocity, which is relatively preload independent, was combined with mitral inflow velocity and maximal oxygen consumption (V(o2 max)) in young (20-35 yr) and older (60-80 yr) trained and untrained men to determine whether endurance training is associated with an attenuation of age-associated changes in diastolic filling. As expected, V(o2 max) was higher in trained men (P < 0.01) and lower in older men (P < 0.01). Peak early mitral inflow velocity (E) and early-to-late mitral inflow velocity ratios were lower in older vs. young men (P < 0.01); however, there was no training effect (P > 0.05). Peak early mitral annular velocity (E') was higher and peak late mitral annular velocity (A') was lower in young vs. older men (P < 0.01). A significant interaction effect was found for A', E'/A', and peak systolic mitral annular velocity (S'). Training was associated with lower A' in young and higher A' in older men. S' was greater in trained vs. untrained older men (P < 0.05), but it was similar in trained and untrained young men. These findings suggest that early diastolic filling is not affected by training in older men, and the effect of training on A' and S' is different in young and older men.     

Isovolumic pressure-to-early rapid filling decay rate relation: model-based derivation and validation via simultaneous catheterization echocardiography.

Transmitral Doppler echocardiography is the preferred method of noninvasive diastolic function assessment. Correlations between catheterization-based measures of isovolumic relaxation (IVR) and transmitral, early rapid filling (Doppler E-wave)-derived parameters have been observed, but no model-based, causal explanation has been offered. IVR has also been characterized in terms of its duration as IVR time (IVRT) and by tau, the time-constant of IVR, by approximating the terminal left ventricular IVR pressure contour as Pt= Pinfinity + P(o)e(-t/tau), where Pt is the continuity of pressure, Pinfinity and Po are constants, t is time, and tau is the time constant of IVR. To characterize the relation between IVR and early rapid filling more fully, simultaneous (micromanometric) left ventricular pressure and transmitral Doppler E-wave data from 25 subjects undergoing elective cardiac catheterization and having normal physiology were analyzed. The time constant tau was determined from the dP/dt vs. P (phase) plane and, simultaneous Doppler E-waves provided global indexes of chamber viscosity/relaxation (c), chamber stiffness (k), and load (xo). We hypothesize that temporal continuity of pressure decay at mitral valve opening and physiological constraints permit the algebraic derivation of linear relations relating 1/tau to both peak atrioventricular pressure gradient (kxo) and E-wave-derived viscosity/relaxation (c) but does not support a similar, causal (linear) relation between deceleration time and tau or IVRT. Both predicted linear relations were observed: kxo to 1/tau (r = 0.71) and viscosity/relaxation to 1/tau (r = 0.71). Similarly, as anticipated, only a weak linear correlation between deceleration time and IVRT or tau was observed (r = 0.41). The observed in vivo relationship provides insight into the isovolumic mechanism of relaxation and the changing-volume mechanism of early rapid filling via a link of the respective relaxation properties.     

Smooth muscle stiffness variation due to external longitudinal oscillations

This research focuses on an in vitro investigation of the stiffness changes of contracted airway smooth muscles (ASM) subjected to external longitudinal oscillations. ASM tissues were dissected from excised pig tracheas and stimulated by a chemical stimulus (acetylcholine, 10(-3) M) to produce maximum contractions. The tissues were then systematically excited with external oscillations. Various frequencies, amplitudes and durations were used in the experiments to determine stiffness changes in response to these variations. Force changes were recorded to reflect the muscle stiffness changes. Two stiffness definitions were used to quantify the results, dynamic stiffness to reflect variations during oscillation and static stiffness to reflect the net effect of oscillation. Under isometric contractions, these two stiffnesses were determined before, during and after oscillations. Incorporating an empirical stiffness equation, a two-dimensional finite element model (FEM) was developed to generalize the tissue responses to oscillation. The main outcomes from this work are: the dynamic stiffness has the tendency to decrease as the frequency and/or amplitude of external oscillation increases; the static stiffness has the tendency of decreasing with an increase in the frequency and/or amplitude of excitation until it reaches almost a constant value for frequencies at and above 25 Hz. The difference in the behavior of the dynamic and static stiffness changes may be attributed to the effect of elasticity and mass inertia that are involved in the dynamic motion. The findings of this research are in agreement with the hypothesis that oscillations exert a direct action on the contractile processes by causing an increased rate of actin-myosin detachments.     

Frequency-based analysis of the early rapid filling pressure-flow relation elucidates diastolic efficiency mechanisms

Stiffness- and relaxation-based diastolic function (DF) assessment can characterize the presence, severity, and mechanism of dysfunction. Although frequency-based characterization of arterial function is routine (input impedance, characteristic impedance, arterial wave reflection), DF assessment via frequency-based methods incorporating optimization/efficiency criteria is lacking. By definition, optimal filling maximizes (E wave) volume and minimizes "loss" at constant stored elastic strain energy (which initiates mechanical, recoil-driven filling). In thermodynamic terms, optimal filling delivers all oscillatory power (rate of work) at the lowest harmonic. To assess early rapid filling optimization, simultaneous micromanometric left ventricular pressure and echocardiographic transmitral flow (Doppler E wave) were Fourier analyzed in 31 subjects. A validated kinematic filling model provided closed-form expressions for E wave contours and model parameters. Relaxation-based DF impairment is indicated by prolonged E wave deceleration time (DT). Optimization was assessed via regression between the dimensionless ratio of 2nd (Q2) and 3rd flow harmonics (Q3) to the lowest harmonic (Q1), i.e., (Q2/Q1) or (Q3/Q1) vs. DT or c, the filling model's viscosity/damping (energy loss) parameter. Results show that DT prolongation or increased c generated increased oscillatory power at higher harmonics (Q2/Q1 = 0.00091DT + 0.09837, r = 0.70; Q3/Q1 = 0.00053DT + 0.02747, r = 0.60; Q2/Q1 = 0.00614c + 0.15527, r = 0.91; Q3/Q1 = 0.00396c + 0.05373, r = 0.87). Because ideal filling is achieved when all oscillatory power is delivered at the lowest harmonic, the observed increase in power at higher harmonics is a measure of filling inefficiency. We conclude that frequency-based analysis facilitates assessment of filling efficiency and elucidates the mechanism by which diastolic dysfunction associated with prolonged DT impairs optimal filling.     

Effect of healthy aging on left ventricular relaxation and diastolic suction

Doppler ultrasound measures of left ventricular (LV) active relaxation and diastolic suction are slowed with healthy aging. It is unclear to what extent these changes are related to alterations in intrinsic LV properties and/or cardiovascular loading conditions. Seventy carefully screened individuals (38 female, 32 male) aged 21-77 were recruited into four age groups (young: <35; early middle age: 35-49; late middle age: 50-64 and seniors: ≥65 yr). Pulmonary capillary wedge pressure (PCWP), stroke volume, LV end-diastolic volume, and Doppler measures of LV diastolic filling were collected at multiple loading conditions, including supine baseline, lower body negative pressure to reduce LV filling, and saline infusion to increase LV filling. LV mass, supine PCWP, and heart rate were not affected significantly by aging. Measures of LV relaxation, including isovolumic relaxation time and the time constant of isovolumic pressure decay increased progressively, whereas peak early mitral annular longitudinal velocity decreased with advancing age (P < 0.001). The propagation velocity of early mitral inflow, a noninvasive measure of LV suction, decreased with aging with the greatest reduction in seniors (P < 0.001). Age-related differences in LV relaxation and diastolic suction were not attenuated significantly when PCWP was increased in older subjects or reduced in the younger subjects. There is an early slowing of LV relaxation and diastolic suction beginning in early middle age, with the greatest reduction observed in seniors. Because age-related differences in LV dynamic diastolic filling parameters were not diminished significantly with significant changes in LV loading conditions, a decline in ventricular relaxation is likely responsible for the alterations in LV diastolic filling with senescence.     

Diastolic dysfunction is associated with cardiac fibrosis in the senescence-accelerated mouse

Diastolic heart failure is a major cause of mortality in the elderly population. It is often preceded by diastolic dysfunction, which is characterized by impaired active relaxation and increased stiffness. We tested the hypothesis that senescence-prone (SAMP8) mice would develop diastolic dysfunction compared with senescence-resistant controls (SAMR1). Pulsed-wave Doppler imaging of the ratio of blood flow velocity through the mitral valve during early (E) vs. late (A) diastole was reduced from 1.3 ± 0.03 in SAMR1 mice to 1.2 ± 0.03 in SAMP8 mice (P < 0.05). Tissue Doppler imaging of the early (E') and late (A') diastolic mitral annulus velocities found E' reduced from 25.7 ± 0.9 mm/s in SAMR1 to 21.1 ± 0.8 mm/s in SAMP8 mice and E'/A' similarly reduced from 1.1 ± 0.02 to 0.8 ± 0.03 in SAMR1 vs. SAMP8 mice, respectively (P < 0.05). Invasive hemodynamics revealed an increased slope of the end-diastolic pressure-volume relationship (0.5 ± 0.05 vs. 0.8 ± 0.14; P < 0.05), indicating increased left ventricular chamber stiffness. There were no differences in systolic function or mean arterial pressure; however, diastolic dysfunction was accompanied by increased fibrosis in the hearts of SAMP8 mice. In SAMR1 vs. SAMP8 mice, interstitial collagen area increased from 0.3 ± 0.04 to 0.8 ± 0.09% and perivascular collagen area increased from 1.0 ± 0.11 to 1.6 ± 0.14%. Transforming growth factor-β and connective tissue growth factor gene expression were increased in the hearts of SAMP8 mice (P < 0.05 for all data). In summary, SAMP8 mice show increased fibrosis and diastolic dysfunction similar to those seen in humans with aging and may represent a suitable model for future mechanistic studies.     

Right and left ventricular adaptation to hypoxia: a tissue Doppler imaging study

Hypoxia has been reported to alter left ventricular (LV) diastolic function, but associated changes in right ventricular (RV) systolic and diastolic function remain incompletely documented. We used echocardiography and tissue Doppler imaging to investigate the effects on RV and LV function of 90 min of hypoxic breathing (fraction of inspired O(2) of 0.12) compared with those of dobutamine to reproduce the same heart rate effects without change in pulmonary vascular tone in 25 healthy volunteers. Hypoxia and dobutamine increased cardiac output and tricuspid regurgitation velocity. Hypoxia and dobutamine increased LV ejection fraction, isovolumic contraction wave velocity (ICV), acceleration (ICA), and systolic ejection wave velocity (S) at the mitral annulus, indicating increased LV systolic function. Dobutamine had similar effects on RV indexes of systolic function. Hypoxia did not change RV area shortening fraction, tricuspid annular plane systolic excursion, ICV, ICA, and S at the tricuspid annulus. Regional longitudinal wall motion analysis revealed that S, systolic strain, and strain rate were not affected by hypoxia and increased by dobutamine on the RV free wall and interventricular septum but increased by both dobutamine and hypoxia on the LV lateral wall. Hypoxia increased the isovolumic relaxation time related to RR interval (IRT/RR) at both annuli, delayed the onset of the E wave at the tricuspid annulus, and decreased the mitral and tricuspid inflow and annuli E/A ratio. We conclude that hypoxia in normal subjects is associated with altered diastolic function of both ventricles, improved LV systolic function, and preserved RV systolic function.     

Electromechanical coupling between the atria and mitral valve

Anterior leaflet (AL) stiffening during isovolumic contraction (IVC) may aid mitral valve closure. We tested the hypothesis that AL stiffening requires atrial depolarization. Ten sheep had radioopaque-marker arrays implanted in the left ventricle, mitral annulus, AL, and papillary muscle tips. Four-dimensional marker coordinates (x, y, z, and t) were obtained from biplane videofluoroscopy at baseline (control, CTRL) and during basal interventricular-septal pacing (no atrial contraction, NAC; 110-117 beats/min) to generate ventricular depolarization not preceded by atrial depolarization. Circumferential and radial stiffness values, reflecting force generation in three leaflet regions (annular, belly, and free-edge), were obtained from finite-element analysis of AL displacements in response to transleaflet pressure changes during both IVC and isovolumic relaxation (IVR). In CTRL, IVC circumferential and radial stiffness was 46 ± 6% greater than IVR stiffness in all regions (P < 0.001). In NAC, AL annular IVC stiffness decreased by 25% (P = 0.004) in the circumferential and 31% (P = 0.005) in the radial directions relative to CTRL, without affecting edge stiffness. Thus AL annular stiffening during IVC was abolished when atrial depolarization did not precede ventricular systole, in support of the hypothesis. The likely mechanism underlying AL annular stiffening during IVC is contraction of cardiac muscle that extends into the leaflet and requires atrial excitation. The AL edge has no cardiac muscle, and thus IVC AL edge stiffness was not affected by loss of atrial depolarization. These findings suggest one reason why heart block, atrial dysrhythmias, or ventricular pacing may be accompanied by mitral regurgitation or may worsen regurgitation when already present.     

Left ventricular endocardial longitudinal and transverse changes during isovolumic contraction and relaxation: a challenge

Left ventricular (LV) longitudinal and transverse geometric changes during isovolumic contraction and relaxation are still controversial. This confusion is compounded by traditional definitions of these phases of the cardiac cycle. High-resolution sonomicrometry studies might clarify these issues. Crystals were implanted in six sheep at the LV apex, fibrous trigones, lateral and posterior mitral annulus, base of the aortic right coronary sinus, anterior and septal endocardial wall, papillary muscle tips, and edge of the anterior and posterior mitral leaflets. Changes in distances were time related to LV and aortic pressures and to mitral valve opening. At the beginning of isovolumic contraction, while the mitral valve was still open, the LV endocardial transverse diameter started to shorten while the endocardial longitudinal diameter increased. During isovolumic relaxation, while the mitral valve was closed, LV transverse diameter started to increase while the longitudinal diameter continued to decrease. These findings are inconsistent with the classic definitions of the phases of the cardiac cycle.     

The role of displacement of the mitral annulus in left atrial filling and emptying in the intact dog

The variations in ventricular-atrial mitral annular position during the cardiac cycle and the simultaneous changes in left atrial silhouette area (obtained by angiography after injections of contrast material into the main pulmonary artery) were investigated in six experiments on intact dogs with chronically implanted intracardiac markers. Frame-by-frame measurements of the angiograms (120 frames/s) were used to determine, under various hemodynamic conditions, the duration, magnitude, and average rate of the mitral annular motion and of the simultaneous changes in left atrial area during atrial filling (ventricular systole) and atrial emptying (early in ventricular diastole). The mitral annulus was seen to move towards the ventricular apex during systole and towards the atrium early in diastole with the duration, average rate, and magnitude of displacement (although varying widely) showing good statistical correlations (P less than 0.0005-0.005) with the changes in projected left atrial area. These findings suggest that the duration, rate, and magnitude of atrial filling and emptying may be, in the intact heart, determined by the movements of the atrioventricular junction.     

Mapping the spatial variation of mitral valve elastic properties using air-pulse optical coherence elastography

The mitral valve is a highly heterogeneous tissue composed of two leaflets, anterior and posterior, whose unique composition and regional differences in material properties are essential to overall valve function. While mitral valve mechanics have been studied for many decades, traditional testing methods limit the spatial resolution of measurements and can be destructive. Optical coherence elastography (OCE) is an emerging method for measuring viscoelastic properties of tissues in a noninvasive, nondestructive manner. In this study, we employed air-pulse OCE to measure the spatial variation in mitral valve elastic properties with micro-scale resolution at 1 mm increments along the radial length of the leaflets. We analyzed differences between the leaflets, as well as between regions of the valve. We found that the anterior leaflet has a higher elastic wave velocity, which is reported as a surrogate for stiffness, than the posterior leaflet, most notably at the annular edge of the sample. In addition, we found a spatial elastic gradient in the anterior leaflet, where the annular edge was found to have a greater elastic wave velocity than the free edge. This gradient was less pronounced in the posterior leaflet. These patterns were confirmed using established uniaxial tensile testing methods. Overall, the anterior leaflet was stiffer and had greater heterogeneity in its mechanical properties than the posterior leaflet. This study measures differences between the two mitral leaflets with greater resolution than previously feasible and demonstrates a method that may be suitable for assessing valve mechanics following repair or during the engineering of synthetic valve replacements.     

Regional stiffening of the mitral valve anterior leaflet in the beating ovine heart

Left atrial muscle extends into the proximal third of the mitral valve (MV) anterior leaflet and transient tensing of this muscle has been proposed as a mechanism aiding valve closure. If such tensing occurs, regional stiffness in the proximal anterior mitral leaflet will be greater during isovolumic contraction (IVC) than isovolumic relaxation (IVR) and this regional stiffness difference will be selectively abolished by β-receptor blockade. We tested this hypothesis in the beating ovine heart. Radiopaque markers were sewn around the MV annulus and on the anterior MV leaflet in 10 sheep hearts. Four-dimensional marker coordinates were obtained from biplane videofluoroscopy before (CRTL) and after administration of esmolol (ESML). Heterogeneous finite element models of each anterior leaflet were developed using marker coordinates over matched pressures during IVC and IVR for CRTL and ESML. Leaflet displacements were simulated using measured left ventricular and atrial pressures and a response function was computed as the difference between simulated and measured displacements. Circumferential and radial elastic moduli for ANNULAR, BELLY and EDGE leaflet regions were iteratively varied until the response function reached a minimum. The stiffness values at this minimum were interpreted as the in vivo regional material properties of the anterior leaflet. For all regions and all CTRL beats IVC stiffness was 40–58% greater than IVR stiffness. ESML reduced ANNULAR IVC stiffness to ANNULAR IVR stiffness values. These results strongly implicate transient tensing of leaflet atrial muscle during IVC as the basis of the ANNULAR IVC–IVR stiffness difference.     

Left atrial conduit volume is generated by deviation from the constant-volume state of the left heart: a combined MRI-echocardiographic study

Although modeling the four-chambered heart as a constant-volume pump successfully predicts causal physiological relationships between cardiac indexes previously deemed unrelated, the real four-chambered heart slightly deviates from the constant-volume state by ventricular end systole. This deviation has consequences that affect chamber function, specifically, left atrial (LA) function. LA attributes have been characterized as booster pump, reservoir, and conduit functions, yet characterization of their temporal occurrence or their causal relationship to global heart function has been lacking. We investigated LA function in the context of the constant-volume attribute of the left heart in 10 normal subjects using cardiac magnetic resonance imaging (MRI) and contemporaneous Doppler echocardiography synchronized via ECG. Left ventricular (LV) and LA volumes as a function of time were determined via MRI. Transmitral flow, pulmonary vein (PV) flow, and lateral mitral annular velocity were recorded via echocardiography. The relationship between the MRI-determined diastolic LA conduit-volume (LACV) filling rate and systolic LA filling rate correlate well with the relationship between the echocardiographically determined average flow rate during the early portion of the PV D wave and the average flow rate during the PV S wave (r = 0.76). We conclude that the end-systolic deviation from constant volume for the left heart requires the generation of the LACV during diastole. Because early rapid filling of the left ventricle is the driving force for LACV generation while the left atrium remains passive, it may be more appropriate to consider LACV to be a property of ventricular diastolic rather than atrial function.     

Differential effects of neuropeptides on circular and longitudinal muscles of the crayfish hindgut

Proctolin (Arg-Tyr-Leu-Pro-Thr-OH) and crayfish peptide "DF(2)" (Asp-Arg-Asn-Phe-Leu-Arg-Phe-NH(2)) enhance spontaneous contractions of isolated crayfish hindguts. Both peptides increase the frequency and amplitude of spontaneous, rapid contractions. Proctolin induces a slow contraction, which gives the appearance of an increase in overall tonus. DF(2) has no such effect. To determine whether the peptides affect both longitudinal and circular muscles, hindguts were cut into longitudinal strips and into rings, and contractions were recorded from each. The longitudinal strips generated only rapid contractions, and both peptides increased the frequency and amplitude of such contractions without significantly altering tonus. Rapid contractions were observed in only 1 of 14 preparations of rings. Proctolin induced slow contractions in the rings, and DF(2) had no such effect. The results indicate that neuropeptides have different effects on circular and longitudinal muscles of hindgut.     

Thermodynamic phase plane analysis of ventricular contraction and relaxation

Background  

Ventricular function has conventionally been characterized using indexes of systolic (contractile) or diastolic (relaxation/stiffness) function. Systolic indexes include maximum elastance or equivalently the end-systolic pressure volume relation and left ventricular ejection fraction. Diastolic indexes include the time constant of isovolumic relaxation - and the end-diastolic pressure-volume relation. Conceptualization of ventricular contraction/relaxation coupling presents a challenge when mechanical events of the cardiac cycle are depicted in conventional pressure, P, or volume, V, terms. Additional conceptual difficulty arises when ventricular/vascular coupling is considered using P, V variables.     

Quantification of Global Diastolic Function by Kinematic Modeling-based Analysis of Transmitral Flow via the Parametrized Diastolic Filling Formalism

Quantitative cardiac function assessment remains a challenge for physiologists and clinicians. Although historically invasive methods have comprised the only means available, the development of noninvasive imaging modalities (echocardiography, MRI, CT) having high temporal and spatial resolution provide a new window for quantitative diastolic function assessment. Echocardiography is the agreed upon standard for diastolic function assessment, but indexes in current clinical use merely utilize selected features of chamber dimension (M-mode) or blood/tissue motion (Doppler) waveforms without incorporating the physiologic causal determinants of the motion itself. The recognition that all left ventricles (LV) initiate filling by serving as mechanical suction pumps allows global diastolic function to be assessed based on laws of motion that apply to all chambers. What differentiates one heart from another are the parameters of the equation of motion that governs filling. Accordingly, development of the Parametrized Diastolic Filling (PDF) formalism has shown that the entire range of clinically observed early transmitral flow (Doppler E-wave) patterns are extremely well fit by the laws of damped oscillatory motion. This permits analysis of individual E-waves in accordance with a causal mechanism (recoil-initiated suction) that yields three (numerically) unique lumped parameters whose physiologic analogues are chamber stiffness (k), viscoelasticity/relaxation (c), and load (x_o). The recording of transmitral flow (Doppler E-waves) is standard practice in clinical cardiology and, therefore, the echocardiographic recording method is only briefly reviewed. Our focus is on determination of the PDF parameters from routinely recorded E-wave data. As the highlighted results indicate, once the PDF parameters have been obtained from a suitable number of load varying E-waves, the investigator is free to use the parameters or construct indexes from the parameters (such as stored energy 1/2kx_o², maximum A-V pressure gradient kx_o, load independent index of diastolic function, etc.) and select the aspect of physiology or pathophysiology to be quantified.