Left Ventricular Pressure Difference Research Articles

Synchrony of sarcomeric movement regulates left ventricular pump function in the in vivo beating mouse heart.

Sarcomeric contraction in cardiomyocytes serves as the basis for the heart's pump functions. It has generally been considered that in cardiac muscle as well as in skeletal muscle, sarcomeres equally contribute to myofibrillar dynamics in myocytes at varying loads by producing similar levels of active and passive force. In the present study, we expressed α-actinin-AcGFP in Z-disks to analyze dynamic behaviors of sequentially connected individual sarcomeres along a myofibril in a left ventricular (LV) myocyte of the in vivo beating mouse heart. To quantify the magnitude of the contribution of individual sarcomeres to myofibrillar dynamics, we introduced the novel parameter "contribution index" (CI) to measure the synchrony in movements between a sarcomere and a myofibril (from -1 [complete asynchrony] to 1 [complete synchrony]). First, CI varied markedly between sarcomeres, with an average value of ∼0.3 during normal systole. Second, when the movements between adjacent sarcomeres were asynchronous (CI < 0), a sarcomere and the ones next to the adjacent sarcomeres and farther away moved in synchrony (CI > 0) along a myofibril. Third, when difference in LV pressure in diastole and systole (ΔLVP) was lowered to <10 mm Hg, diastolic sarcomere length increased. Under depressed conditions, the movements between adjacent sarcomeres were in marked asynchrony (CI, -0.3 to -0.4), and, as a result, average CI was linearly decreased in association with a decrease in ΔLVP. These findings suggest that in the left ventricle of the in vivo beating mouse heart, (1) sarcomeres heterogeneously contribute to myofibrillar dynamics due to an imbalance of active and passive force between neighboring sarcomeres, (2) the force imbalance is pronounced under depressed conditions coupled with a marked increase in passive force and the ensuing tug-of-war between sarcomeres, and (3) sarcomere synchrony via the distal intersarcomere interaction regulates the heart's pump function in coordination with myofibrillar contractility.

Diastolic Intra–Left Ventricular Pressure Difference During Exercise: Strong Determinant and Predictor of Exercise Capacity in Patients With Heart Failure

Although the enhancement of early-diastolic intra-left ventricular pressure difference (IVPD) during exercise is considered to maintain exercise capacity, little is known about their relationship in heart failure (HF). Cardiopulmonary exercise testing and exercise-stress echocardiography were performed in 50 HF patients (left ventricular [LV] ejection fraction 39 ± 15%). Echocardiographic images were obtained at rest and submaximal and peak exercise. Color M-mode Doppler images of LV inflow were used to determine IVPD. Thirty-five patients had preserved exercise capacity (peak oxygen consumption [VO2] ≥14 mL·kg-1·min-1; group 1) and 15 patients had reduced exercise capacity (group 2). During exercise, IVPD increased only in group 1 (group 1: 1.9 ± 0.9 mm Hg at rest, 4.1 ± 2.0 mm Hg at submaximum, 4.7 ± 2.1 mm Hg at peak; group 2: 1.9 ± 0.8 mm Hg at rest, 2.1 ± 0.9 mm Hg at submaximum, 2.1 ± 0.9 mm Hg at peak). Submaximal IVPD (r = 0.54) and peak IVPD (r = 0.69) were significantly correlated with peak VO2. Peak IVPD determined peak VO2 independently of LV ejection fraction. Moreover, submaximal IVPD could well predict the reduced exercise capacity. Early-diastolic IVPD during exercise was closely associated with exercise capacity in HF. In addition, submaximal IVPD could be a useful predictor of exercise capacity without peak exercise in HF patients.

Altered Spatial Distribution of the Diastolic Left Ventricular Pressure Difference in Heart Failure

The left ventricle fills in early diastole because of a progressive intraventricular pressure difference (IVPD) that extends from the left atrium to the left ventricular (LV). The aim of this study was to test the hypothesis that in patients with symptomatic heart failure (HF) regardless of LV ejection fraction (EF), an increase in left atrial (LA) pressure maintains early diastolic filling because of a preserved IVPD from the left atrium to the mid left ventricle, while the IVPD from the mid left ventricle to the apex is diminished because of reduced LV suction. One hundred fifty-one patients with HF (50 with HF with preserved EF [HFpEF; EF ≥ 50%] and 101 with HF with reduced EF [HFrEF; EF < 50%]) and 28 normal controls were prospectively enrolled. The IVPDs from the left atrium to the LV apex (total IVPD), the left atrium to the mid left ventricle (basilar IVPD), and the mid left ventricle to the apex (apical IVPD) were determined using color M-mode Doppler echocardiographic data to integrate the Euler equation. The propagation of early diastolic filling was also assessed by color M-mode Doppler. The mean LV EF was 0.63±0.07 in patients with HFpEF, 0.32±0.09 in those with HFrEF, and 0.64±0.06 in controls. Peak early diastolic transmitral flow velocities (E) were similar among the groups, and basilar IVPDs were maintained in the HFpEF and HFrEF groups (HFpEF, 1.59±0.62mm Hg; HFrEF, 1.49±0.75mm Hg; controls, 1.80±0.61mm Hg; P= NS, analysis of variance). However, apical IVPDs were decreased in both HF groups (HFpEF, 1.18±0.56mm Hg [P<.01 vs controls]; HFrEF, 0.87±0.48mm Hg [P<.01 vs controls]; controls, 1.65±0.62mm Hg), resulting in decreased total IVPDs in patients with HF (HFpEF, 2.55±0.80mm Hg [P<.01 vs controls]; HFrEF, 2.16±0.80mm Hg [P<.01 vs controls]; controls, 3.17±0.91mm Hg). E/e' ratios were increased in patients with HF, consistent with elevated LA pressure. In patients with HF, E was correlated with basilar IVPD but not with apical IVPD, whereas propagation of the filling was correlated with the apical IVPD but not with the basilar IVPD. In patients with HFpEF and those with HFrEF, apical IVPDs were reduced while basilar IVPDs were maintained by elevated LA pressure, resulting in preserved E.

Left ventricular vortex formation is unaffected by diastolic impairment

Normal left ventricular (LV) filling occurs rapidly early in diastole caused by a progressive pressure gradient within the ventricle and with a low left atrial pressure. This normal diastolic function is altered in patients with heart failure. Such impairment of diastolic filling is manifested as an abrupt deceleration of the early filling wave velocity. Although variations within the early filling wave have been observed previously, the underlying hydrodynamic mechanisms are not well understood. Previously, it was proposed that the mitral annulus vortex ring formation time was the total duration of early diastolic filling and provided a measure of the efficiency of diastolic filling. However, we found that the favorable LV pressure difference driving early diastolic filling becomes zero simultaneously with the deceleration of the early filling wave propagation velocity and pinch-off of the LV vortex ring. Thus we calculated the vortex ring formation time using the duration of the early diastolic filling wave from its initiation to the time of the early filling wave propagation velocity deceleration when pinch-off occurs. This formation time does not vary with decreasing intraventricular pressure difference or with degree of diastolic dysfunction. Thus we conclude the vortex ring pinch-off occurs before the completion of early diastole, and its formation time remains invariant to changes of diastolic function.

The E-Wave Delayed Relaxation Pattern to LV Pressure Contour Relation: Model-Based Prediction With in vivo Validation

The transmitral Doppler E-wave “delayed relaxation” (DR) pattern is an established sign of diastolic dysfunction (DD). Furthermore, chambers exhibiting a DR filling pattern are also expected to have a prolonged time-constant of isovolumic relaxation (τ). The simultaneous observation of a DR pattern and normal τ in the same heart is not uncommon, however. The simultaneous hemodynamic equivalent of the DR pattern has not been proposed. To determine the feature of the left ventricular (LV) pressure contour during the E-wave that is causally related to its DR pattern we applied kinematic and fluid mechanics based arguments to derive the pressure recovery ratio ( PRR). The PRR is dimensionless and is defined by the left ventricular pressure difference between diastasis and minimum pressure, normalized to the pressure difference between a fiducial diastolic filling pressure and minimum pressure [ PRR=(P Diastasis-P Min)/(P Fiducial-P Min)]. We analyzed 354 cardiac cycles from 40 normal sinus rhythm (NSR) subjects and 113 beats from nine atrial fibrillation (AF) subjects from our database of simultaneous transmitral flow-micromanometric LV pressure recordings. The fiducial pressure is defined by the end diastolic pressure in NSR and by the pressure at dP/dt MIN in the setting of AF. Consistent with derivation, PRR was linearly related to a DR pattern related, model-based relaxation parameter ( R 2 = 0.77, 0.83 in NSR and AF, respectively). Furthermore, the PRR successfully differentiated subjects with a DR pattern from subjects with partial DR or normal E-wave pattern ( p < 0.05). We conclude that the PRR may differentiate between subjects having a DR pattern and subjects with normal E-waves, even when τ cannot. (E-mail: sjk@wuphys.wustl.edu)

Effects of propofol on the systolic and diastolic performance of the postischaemic, reperfused myocardium in rabbits.

The effect of propofol on myocardial dysfunction during ischaemia and reperfusion is controversial yet important because of its frequent use in cardiac anaesthesia. Although animal studies suggest a free radical-scavenging potential, the cardioprotective properties of propofol have not been demonstrated consistently in vivo. Previous studies focused on systolic function while diastolic function may be a more sensitive marker of ischaemic injury. The main aim was to document the effect of propofol on diastolic function in isolated, blood perfused rabbit hearts subjected to moderate global ischaemia and reperfusion. Propofol 168 micromol L(-1), or the equivalent of its vehicle, Intralipid, was administered to 34 paced parabiotic Langendorff blood-perfused isolated rabbit hearts before and after 30 min of global normothermic ischaemia. Recovery of systolic function was quantified with the maximum rate of rise of left ventricular pressure. Diastolic performance was assessed using the time constant of the decline in left ventricular pressure (tau) and chamber stiffness (VdP/dV at 12 mmHg). Recovery of systolic function during reperfusion was comparable in the two groups. There was no difference in left ventricular pressure between the two groups at any time during the experiments. Chamber stiffness increased significantly during ischaemia and reperfusion in the control group (from 34 +/- 9 to 54 +/- 8 mmHg during ischaemia, and 43 +/- 5 mmHg after 30 min reperfusion; mean +/-95% confidence interval) but not in the propofol-treated group (29 +/- 5, 36 +/- 8 and 30 +/- 8 at baseline, ischaemia and 30 min reperfusion, respectively). Propofol has no protective effect on active relaxation or on systolic function in the present model, but it reduces ischaemic and postischaemic chamber stiffness.

Cardioprotection afforded by ischemic preconditioning interferes with chronic beta‐blocker treatment

Objectives—The efficacy of ischemic preconditioning of the heart has remained controversial. We investigated whether chronic treatment with beta‐blockers affects the ischemic preconditioning in the isolated rat heart model.Design—Wistar rats were treated with propranolol (50 mg/kg/day, p.o.) (PRL), with nipradilol (10 mg/kg/day, p.o.) (NPL), or with vehicle, for 4 weeks. Isolated rat hearts were divided into global ischemia hearts (GI, PRL and NPL, each n=6) and ischemic preconditioned hearts (IP, PRL+IP and NPL+IP, each n=6).Results—Significant differences in left ventricular pressure were observed between the PRL and PRL+IP, and between the NPL and NPL+IP groups. In the NPL group, significant amelioration and preservation of left ventricular peak pressure, coronary flow, reduction of infarct size, and NOx preservation were observed. Lipid peroxidation in the NPL group was significantly reduced before and after global ischemia compared to the GI group.Conclusions—The effect of ischemic preconditioning was abolished in the hearts of rats following oral treatment of propranolol or nipradilol. However, the administration of nipradilol protected the ischemic and reperfused myocardium, partly due to the prevention of lipid peroxide formation.

Effect of catheter device closure of atrial septal defect on diastolic mitral annular motion

Atrial septal defect closure with the Amplatzer septal occluder has a negative effect on diastolic mitral annulus motion in terms of decreasing longitudinal septal annular motion and changing the relation between the annulus motion and mitral inflow.

Wave-intensity analysis: a new approach to left ventricular filling dynamics.

In order to explore a new approach to the analysis of diastolic dysfunction, we adapted wave-intensity analysis (WIA), a time-domain analysis that provides information regarding both upstream and downstream events, to left ventricular (LV) filling. WIA considers the pressure and flow waves as summations of successive wavelets, characterised by the direction they travel and by the sign of the pressure gradient associated with them. Wave intensity is the product, dPdU, calculated from the incremental differences in LV pressure (dP) and mitral velocity (dU) and, during the diastolic filling interval, yields up to five dPdU peaks. Peak 1 is caused by backward-travelling expansion waves that accelerate the blood while LV pressure falls, and may be related to "diastolic suction". Peak 2 is caused by forward-travelling compression waves which occur if acceleration continues after LV pressure begins to increase. Peak 3 is caused by backward compression waves and is associated with rising LV pressure and deceleration. Peak 4 is caused by forward compression waves and is associated with the increasing LV pressure and acceleration caused by atrial contraction. Peak 5 is caused by backward compression waves and is associated with increasing pressure and deceleration. These preliminary observations suggest that WIA can be useful in describing the mechanics of LV filling and, after much further work has been accomplished, it might prove useful in the detection and characterization of diastolic dysfunction.

Contributors of characteristic mitral flow velocity pattern in congestive heart failure--from clinical observations back to experimental validations.

Mitral flow velocity pattern in patients with left ventricular (LV) diastolic dysfunction usually includes decreased peak early diastolic filling velocity (E), slowed deceleration of the early diastolic filling wave and increased peak filling velocity at atrial contraction (A). However, the abnormal mitral flow velocity pattern can be normalized in the presence of concomitant congestive heart failure. In such cases E can be equal to or even higher than normal, its deceleration is normal or faster than normal value, and A can be normal or lower than normal value. Clinical observations in patients with severe heart failure showed that the mitral flow velocity pattern changes with vasodilating therapy, reflecting the changes in the left atrial (LA) to LV pressure difference rather than those in the absolute LA pressure or LV pressure alone. This was validated in the canine study in which levels of LV dysfunction were made by the injection of microspheres into the left coronary artery to study the interrelation among the mitral flow velocity pattern and LA and LV pressures. In this experiment, the changes in the mitral flow velocity pattern could not be explained by the changes in LA or LV pressure alone but was better explained by the changes in the LA to LV pressure difference. Not only LA-LV crossover pressure but also LA compliance seem to be important as determinants of LA pressure level in diastole. In addition to LV relaxation rate, incompleteness of relaxation, elastic recoil and LV passive elastic properties, extracardiac constraint is also considered to be an important determinant of the level of the LV diastolic pressure and hence of the mitral flow velocity pattern at least in the presence of congestive heart failure. Thus, mitral flow velocity pattern is determined by the interaction of LA and LV pressures, both of which are affected by chamber properties as well as loading conditions.

Effects of nitroprusside on transmitral flow velocity patterns in extreme heart failure: A combined hemodynamic and Doppler echocardiographic study of varying loading conditions

To explore the mechanisms of change of left ventricular diastolic filling associated with preload and afterload reduction, the influence of nitroprusside on the transmitral flow velocity pattern, pulmonary capillary wedge pressure and left ventricular pressure interaction was studied in 11 patients with end-stage heart failure. Pulsed Doppler echocardiographic recordings of mitral inflow were obtained with simultaneous high fidelity left ventricular and phase-corrected pulmonary capillary wedge pressure recordings before and during levels of nitroprusside infusion. With nitroprusside, left ventricular systolic and end-diastolic pressures decreased by 14% and 41% (p < 0.05, p < 0.05), respectively, and cardiac output increased by 67% (p < 0.05). The pulmonary cspillary wedge-left ventricular crossover pressure decreased by 41% (p < 0.05), but the time constant of isovolumetric left ventricular pressure decrease T was insignificantly changed. Isovolumetric relaxation time and acceleration and deceleration times of the early diastolic filling wave were significantly prolonged with nitroprusside infusion (p < 0.05, p < 0.05 and p < 0.85, respectively). Peak early diastolic filling velocity was maintained (65 ± 11 to 62 ± 13 cm/s, p = NS) in spite of the decreased absolute crossover pressure. Changes in peak early diastolic filling velocity correlated weakly with changes in the crossover pressure (r = 0.48, p < 0.05) and correlated better with the crossover to left ventricular minimal pressure difference (r = 0.78, p < 0.05). Peak early diastolic filling velocity appears to be most affected by the early diastolic pulmonary capillary wedge to left ventricular pressure difference rather than the absolute pulmonary capillary wedge pressure.The lack of peak flow velocity change during nitroprusside infusion could be explained by either the associated decrease in left ventricular minimal pressure or downward shift of left ventricular diastolic pressure by the same amount as the decrease in pulmonary capillary wedge pressure. This may reflect a reduction of external constraint to ventricular distensibility produced by a reduction in filling volume in patients with a markedly dilated ventricle. Thus, a prolonged early diastolic filling period and preserved peak early diastolic filling velocity in spite of decreased left ventricular filling pressure and constant relaxation rate are associated with the beneficial effects of nitroprusside on left ventricular function in patients with severe congestive heart failure.

ALTERATIONS OF ENERGY METABOLISM IN HYPERTROPHIED HEARTS DURING ANOXIA: A P-31 NUCLEAR MAGNETIC RESONANCE STUDY

The metabolic effect of anoxia on hypertrophied myocardium was investigated using P-31 NMR spectroscopy. Hearts from 18 mo. SHR (hypertrophied, n=7) and age-matched WKY (control, n=6) rats were mounted on a modified Langendorff apparatus, paced at 240/min and perfused with 36°C phosphate-free, glucose-containing buffer bubbled with oxygen or nitrogen (anoxia). Left ventricular pressure (LVP), LV dP/dt and perfusion pressure were continuously recorded while consecutive 3-min spectra were collected. This allowed temporal assessment of myocardial phosphate levels [incl. inorganic phosphate (Pi), creatine phosphate (CP) and ATP] during baseline conditions, anoxia and recovery. Anoxia was maintained until a 70% fall in LVP occured. Compared to the WKY, SHR rats had higher in vivo BP (163 vs 104; p<.001) and cardiac hypertrophy (heart/ body weight = 5.3 vs 3.5 mg/g; p<.001). During baseline perfusion, SHR hearts had higher resistance (9.8 vs 5.9 mmHg/cc/min/g; p=.003) but no significant difference in LVP or dP/dt. SHR hearts demonstrated a faster fall in high-energy phosphates and LVP during anoxia (SHR fell to 30% baseline LVP in 8.5 vs 13.0 mins; p=.018). Throughout the protocol SHR hearts had lower CP (3.8 vs 5.6 umoles/g; p=.008), ATP (3.2 vs 3.9 umoles/g; p=.047) and CP/Pi ratio (1.5 vs 2.5; p=.043). We conclude that chronically hypertrophied hearts have: (1) less ATP/g and CP/g than age-matched controls, and (2) a faster decline in mechanical and metabolic function during anoxia.