Scaling of diastolic intraventricular pressure gradients is related to filling time duration

In early diastole, pressure is lower in the apex than in the base of the left ventricle (LV). This early intraventricular pressure difference (IVPD) facilitates LV filling. We assessed how LV diastolic IVPD and intraventricular pressure gradient (IVPG), defined as IVPD divided by length, scale to the heart size and other physiological variables. We studied 10 mice, 10 rats, 5 rabbits, 12 dogs, and 21 humans by echocardiography. Color Doppler M-mode data were postprocessed to reconstruct IVPD and IVPG. Normalized LV filling time was calculated by dividing filling time by RR interval. The relationship between IVPD, IVPG, normalized LV filling time, and LV end-diastolic volume (or mass) as fit to the general scaling equation Y = kM beta, where M is LV heart size parameter, Y is a dependent variable, k is a constant, and beta is the power of the scaling exponent. LV mass varied from 0.049 to 194 g, whereas end-diastolic volume varied from 0.011 to 149 ml. The beta values relating normalized LV filling time with LV mass and end-diastolic volume were 0.091 (SD 0.011) and 0.083 (SD 0.009), respectively (P < 0.0001 vs. 0 for both). The beta values relating IVPD with LV mass and end-diastolic volume were similarly significant at 0.271 (SD 0.039) and 0.243 (SD 0.0361), respectively (P < 0.0001 vs. 0 for both). Finally, beta values relating IVPG with LV mass and end-diastolic volume were -0.118 (SD 0.013) and -0.104 (SD 0.011), respectively (P < 0.0001 vs. 0 for both). As a result, there was an inverse relationship between IVPG and normalized LV filling time (r = -0.65, P < 0.001). We conclude that IVPD decrease, while IVPG increase with decreasing animal size. High IVPG in small mammals may be an adaptive mechanism to short filling times.     

Improvement in diastolic intraventricular pressure gradients in patients with HOCM after ethanol septal reduction

We sought to validate measurement of intraventricular pressure gradients (IVPG) and analyze their change in patients with hypertrophic obstructive cardiomyopathy (HOCM) after ethanol septal reduction (ESR). Quantitative analysis of color M-mode Doppler (CMM) images may be used to estimate diastolic IVPG noninvasively. Noninvasive IVPG measurement was validated in 10 patients undergoing surgical myectomy. Echocardiograms were then analyzed in 19 patients at baseline and after ESR. Pulsed Doppler data through the mitral valve and pulmonary venous flow were obtained. CMM was used to obtain the flow propagation velocity (Vp) and to calculate IVPG off-line. Left atrial pressure was estimated with the use of previously validated Doppler equations. Data were compared before and after ESR. CMM-derived IVPG correlated well with invasive measurements obtained before and after surgical myectomy [r = 0.8, P < 0.01, Delta(CMM - invasive IVPG) = 0.09 +/- 0.45 mmHg]. ESR resulted in a decrease of resting LVOT systolic gradient from 62 +/- 10 to 29 +/- 5 mmHg (P < 0.001). There was a significant increase in the Vp and IVPG (from 48 +/- 5to 74 +/- 7 cm/s and from 1.5 +/- 0.2 to 2.6 +/- 0.3 mmHg, respectively, P < 0.001 for both). Estimated left atrial pressure decreased from 16.2 +/- 1.1 to 11.5 +/- 0.9 mmHg (P < 0.001). The increase in IVPG correlated with the reduction in the LVOT gradient (r = 0.6, P < 0.01). Reduction of LVOT obstruction after ESR is associated with an improvement in diastolic suction force. Noninvasive measurements of IVPG may be used as an indicator of diastolic function improvement in HOCM.     

Ventricular untwisting: a temporal link between left ventricular relaxation and suction

Left ventricular (LV) untwisting starts early during the isovolumic relaxation phase and proceeds throughout the early filling phase, releasing elastic energy stored by the preceding systolic deformation. Data relating untwisting, relaxation, and intraventricular pressure gradients (IVPG), which represent another manifestation of elastic recoil, are sparse. To understand the interaction between LV mechanics and inflow during early diastole, Doppler tissue images (DTI), catheter-derived pressures (apical and basal LV, left atrial, and aortic), and LV volume data were obtained at baseline, during varying pacing modes, and during dobutamine and esmolol infusion in seven closed-chest anesthetized dogs. LV torsion and torsional rate profiles were analyzed from DTI data sets (apical and basal short-axis images) with high temporal resolution (6.5 +/- 0.7 ms). Repeated-measures regression models showed moderately strong correlation of peak LV twisting with peak LV untwisting rate (r = 0.74), as well as correlations of peak LV untwisting rate with the time constant of LV pressure decay (tau, r = -0.66) and IVPG (r = 0.76, P < 0.0001 for all). In a multivariate analysis, peak LV untwisting rate was an independent predictor of tau and IVPG (P < 0.0001, for both). The start of LV untwisting coincided with the beginning of relaxation and preceded suction-aided filling resulting from elastic recoil. Untwisting rate may be a useful marker of diastolic function or even serve as a therapeutic target for improving diastolic function.     

Estimation of left ventricular operating stiffness from Doppler early filling deceleration time in humans

Shortened early transmitral deceleration times (E(DT)) have been qualitatively associated with increased filling pressure and reduced survival in patients with cardiac disease and increased left ventricular operating stiffness (K(LV)). An equation relating K(LV) quantitatively to E(DT) has previously been described in a canine model but not in humans. During several varying hemodynamic conditions, we studied 18 patients undergoing open-heart surgery. Transesophageal echocardiographic two-dimensional volumes and Doppler flows were combined with high-fidelity left atrial (LA) and left ventricular (LV) pressures to determine K(LV). From digitized Doppler recordings, E(DT) was measured and compared against changes in LV and LA diastolic volumes and pressures. E(DT) (180 +/- 39 ms) was inversely associated with LV end-diastolic pressures (r = -0.56, P = 0.004) and net atrioventricular stiffness (r = -0.55, P = 0.006) but had its strongest association with K(LV) (r = -0.81, P < 0.001). K(LV) was predicted assuming a nonrestrictive orifice (K(nonrest)) from E(DT) as K(nonrest) = (0.07/E(DT))(2) with K(LV) = 1.01 K(nonrest) - 0.02; r = 0.86, P < 0.001, DeltaK (K(nonrest) - K(LV)) = 0.02 +/- 0.06 mm Hg/ml. In adults with cardiac disease, E(DT) provides an accurate estimate of LV operating stiffness and supports its application as a practical noninvasive index in the evaluation of diastolic function.     

MRI assessment of LV relaxation by untwisting rate: a new isovolumic phase measure of tau

Most noninvasive measures of diastolic function are made during left ventricular (LV) filling and are therefore subject to "pseudonormalization," because variation in left atrial (LA) pressure may confound the estimation of relaxation rate. Counterclockwise twist of the LV develops during ejection, but untwisting occurs rapidly during isovolumic relaxation, before mitral opening. We hypothesized that the rate of untwisting might reflect the process of relaxation independent of LA pressure. Recoil rate (RR), the velocity of LV untwisting, was measured by tagged magnetic resonance imaging and regressed against the relaxation time constant (tau), recorded by catheterization, in 10 dogs at baseline and after dobutamine, saline, esmolol, and methoxamine treatment. RR correlated closely (average r = -0.86) with tau and was unaffected by elevated LA pressure. Multiple regression showed that tau, but not LA or aortic pressure, was an independent predictor of RR (P < 0.0001, P = 0.99, and P = 0.18, respectively). The rate of recoil of torsion, determined wholly noninvasively, provides an isovolumic phase, preload-independent assessment of LV relaxation. Use of this novel parameter should allow the detailed study of diastolic function in states known to affect filling rates, such as aging, hypertension, and congestive heart failure.     

Effects of Individual and Coexisting Diabetes and Cardiomyopathy on Diastolic Function in Rats (Rattus norvegicus domestica)

The goal of this study was to evaluate diastolic intraventricular pressure gradients (IVPG) and 2-dimensional tissue tracking (2DTT) patterns during diabetes and cardiomyopathy. Rats (n = 60) were induced to become diabetic (DM group, n = 15) by using streptozotocin, to become cardiomyopathic (CM group, n = 15) by using isoproterenol, and to become both diabetic and cardiomyopathic (DMCM group, n = 15); control rats (CT group, n = 15) were injected with saline. Two months after induction, all rats underwent conventional echocardiography, IVPG, and 2DTT and then were euthanized for microscopic examination of cardiac fibrosis. Compared with the controls, all 3 treated groups showed diastolic dysfunction and delayed cardiac relaxation. DMCM rats showed the most pronounced cardiac abnormalities. In addition, CM and DMCM groups had showed decreased middle IVPG, whereas DMCM rats had decreased midapical IVPG. Although the overall IVPG of the CM group was normal, the middle segment was significantly decreased. 2DTT results showed that the DMCM group had a delay in relaxation compared with other groups. IVPG and 2DTT can be used to overcome the limitation of conventional echocardiographic methods and reveal diastolic dysfunction. DM worsened diastolic function during cardiac disease.

Diabetes mellitus (DM) is a chronic disease identified by hyperglycemia.¹ DM and associated insulin abnormalities result in hypertension, cardiovascular disease, and multiple organ dysfunction.¹⁸ Diabetic cardiomyopathy is defined as abnormal myocardial structure and performance in the absence of other cardiac risk factors, such as coronary artery disease, hypertension, and significant valvular disease, in patients with DM.³ A previous study showed that diastolic dysfunction could result from DM; and cardiac fibrosis in the interstitial and perivascular areas was a hallmark of long-term DM.²³ Cardiac fibrosis in DM rats results from myocardial infarction.Cardiomyopathy can be induced in rats by using isoproterenol.¹⁷ Cardiomyopathy refers to the cardiac disorder in which myocardial abnormalities result from myocyte injury. Cardiomyopathy has several etiologies, including chronic hypertension, valvular abnormality, and toxin.¹⁵ Both DM and cardiomyopathy are fibrotic heart diseases, but their pathogenesis differs. Moreover, DM and CM cause fibrosis in different heart locations.The diastolic function of the left ventricle (LV) can be defined as the pull of blood into the LV under low filling pressure. Two groups have described the pressure differences that pull the blood through the mitral valve into the ventricle during diastole.^6,16 The difference of pressure between the LV and aorta during systole and the importance of regional pressure differences within the ventricle during relaxation has recently gained attention.^9,29 The diastolic intraventricular pressure gradient (IVPG) in the LV is closely related to LV relaxation. Deterioration of the IVPG is associated with abnormal LV blood flow patterns.²2D tissue tracking (2DTT) echocardiography is a promising technique that quantifies myocardial deformation by tracking the ultrasonographic speckle pattern of the cardiac cycle.¹³ Because of the importance of measuring diastolic function, we used conventional echocardiography, IVPG and 2DTT to evaluate the diastolic impairment without altering systolic function. We studied the relationship between mild (DM rats) and moderate (CM rats) cardiac fibrosis due to myocardial injury and infarction together with the severe fibrosis that develops due to the combination of DM and cardiomyopathy.Streptozotocin and isoproterenol were used to induce DM and cardiomyopathy, respectively. Both cause cardiac fibrosis, but the pathogenesis and affected location are different. Our study was designed to evaluate diastolic IVPG and 2DTT as diastolic indices. Our goal was to delineate IVPG and 2DTT patterns in DM, CM, and very severe fibrotic heart disease induced by combining DM and cardiomyopathy.     

Relationship of diastolic intraventricular pressure gradients and aerobic capacity in patients with diastolic heart failure

We sought to elucidate the relationship between diastolic intraventricular pressure gradients (IVPG) and exercise tolerance in patients with heart failure using color M-mode Doppler. Diastolic dysfunction has been implicated as a cause of low aerobic potential in patients with heart failure. We previously validated a novel method to evaluate diastolic function that involves noninvasive measurement of IVPG using color M-mode Doppler data. Thirty-one patients with heart failure and 15 normal subjects were recruited. Echocardiograms were performed before and after metabolic treadmill stress testing. Color M-mode Doppler was used to determine the diastolic propagation velocity (Vp) and IVPG off-line. Resting diastolic function indexes including myocardial relaxation velocity, Vp, and E/Vp correlated well with VO2max (r = 0.8, 0.5, and -0.5, respectively, P < 0.001 for all). There was a statistically significant increase in Vp and IVPG in both groups after exercise, but the change in IVPG was higher in normal subjects compared with patients with heart failure (2.6 +/- 0.8 vs. 1.1 +/- 0.8 mmHg, P < 0.05). Increase in IVPG correlated with peak VO2max (r = 0.8, P < 0.001) and was the strongest predictor of exercise capacity. Myocardial relaxation is an important determinant of exercise aerobic capacity. In heart failure patients, impaired myocardial relaxation is associated with reduced diastolic suction force during exercise.     

Wave intensity analysis of left ventricular filling: application of windkessel theory

We extend our recently published windkessel-wave interpretation of vascular function to the wave intensity analysis (WIA) of left ventricular (LV) filling dynamics by separating the pressure changes due to the windkessel from those due to traveling waves. With the use of LV compliance, the change in pressure due solely to LV volume changes (windkessel pressure) can be isolated. Inasmuch as the pressure measured in the cardiovascular system is the sum of its windkessel and wave components (excess pressure), it can be substituted into WIA, yielding the isolated wave effects on LV filling. Our study of six open-chest dogs demonstrated that once the windkessel effects are removed from WIA, the energy of diastolic suction is 2.6 times greater than we previously calculated. Volume-related changes in pressure (i.e., the windkessel or reservoir effect) must be considered first when wave motion is analyzed.     

Assessment of left ventricular diastolic function by early diastolic mitral annulus peak acceleration rate: experimental studies and clinical application.

We sought to examine the hemodynamic determinants and clinical application of the peak acceleration rate of early (Ea) diastolic velocity of the mitral annulus by tissue Doppler. Simultaneous left atrial and left ventricular (LV) catheterization and Doppler echocardiography were performed in 10 dogs. Preload was altered using volume infusion and caval occlusion, whereas myocardial lusitropic state was altered with dobutamine and esmolol. The clinical application was examined in 190 consecutive patients (55 control, 41 impaired relaxation, 46 pseudonormal, and 48 restrictive LV filling). In addition, in 60 consecutive patients, we examined the relation between it and mean wedge pressure with simultaneous Doppler echocardiography and right heart catheterization. In canine studies, a significant positive relation was present between peak acceleration rate of Ea and transmitral pressure gradient only in the stages with normal or enhanced LV relaxation, but with no relation in the stages where the time constant of LV relaxation (tau) was > or =50 ms. Its hemodynamic determinants were tau, LV minimal pressure, and transmitral pressure gradient. In clinical studies, peak acceleration rate of Ea was significantly lower in patients with impaired LV relaxation irrespective of filling pressures (P < 0.001) and with similar accuracy to peak Ea velocity (area under the curve for septal and lateral peak acceleration rates: both 0.78) in identifying these patients. No significant relation was observed between peak acceleration rate and mean wedge pressure. Peak acceleration rate of Ea appears to be a useful index of LV relaxation but not of filling pressures and can be applied to identify patients with impaired LV relaxation irrespective of their filling pressures.     

Benefits of long-term beta-blockade in experimental chronic aortic regurgitation

The objective of this study was to assess the long-term effects of beta-blockade on survival and left ventricular (LV) remodeling in rats with aortic valve regurgitation (AR). The pharmacological management of chronic AR remains controversial. No drug has been definitively proven to delay the need for valve replacement or to affect morbidity and/or mortality. Our group has reported that the adrenergic system is activated in an animal model of AR and that adrenergic blockade may help maintain normal LV function. The effects of prolonged treatment with a beta-blocker are unknown. Forty Wistar rats with severe AR were divided into 2 groups of 20 animals each and treated with metoprolol (Met, 25 mg.kg(-1).day(-1)) or left untreated for 1 yr. LV remodeling was evaluated by echocardiography. Survival was assessed by Kaplan-Meir curves. Hearts were harvested for tissue analysis. All Met-treated animals were alive after 6 mo vs. 70% of untreated animals. After 1 yr, 60% of Met-treated animals were alive vs. 35% of untreated animals (P = 0.028). All deaths, except one, were sudden. There were no differences in LV ejection fraction (all >50%) or LV dimensions. LV mass tended to be lower in the Met-treated group. There was less subendocardial fibrosis in this group, as well as lower LV filling pressures (LV end-diastolic pressure). beta-Adrenergic receptor ratio (beta(1)/beta(2)) was improved. One year of treatment with Met was well tolerated. Met improved 1-yr survival, minimized LV hypertrophy, improved LV filling pressures, decreased LV subendocardial fibrosis, and helped restore the beta-adrenergic receptor ratio.     

The effect of vortex formation on left ventricular filling and mitral valve efficiency

A new mechanism for quantifying the filling energetics in the left ventricle (LV) and past mechanical heart valves (MHV) is identified and presented. This mechanism is attributed to vortex formation dynamics past MHV leaflets. Recent studies support the conjecture that the natural healthy left ventricle (LV) performs in an optimum, energy-preserving manner by redirecting the flow with high efficiency. Yet to date, no quantitative proof has been presented. The present work provides quantitative results and validation of a theory based on the dynamics of vortex ring formation, which is governed by a critical formation number (FN) that corresponds to the dimensionless time at which the vortex ring has reached its maximum circulation content, in support of this hypothesis. Herein, several parameters (vortex ring circulation, vortex ring energy, critical FN, hydrodynamic efficiencies, vortex ring propagation speed) have been quantified and presented as a means of bridging the physics of vortex formation in the LV. In fact, the diastolic hydrodynamic efficiencies were found to be 60, 41, and 29%, respectively, for the porcine, anti-anatomical, and anatomical valve configurations. This assessment provides quantitative proof of vortex formation, which is dependent of valve design and orientation, being an important flow characteristic and associated to LV energetics. Time resolved digital particle image velocimetry with kilohertz sampling rate was used to study the ejection of fluid into the LV and resolve the spatiotemporal evolution of the flow. The clinical significance of this study is quantifying vortex formation and the critical FN that can potentially serve as a parameter to quantify the LV filling process and the performance of heart valves.     

MRI and echocardiographic assessment of the diastolic dysfunction of normal aging: altered LV pressure decline or load?

Changes in diastolic indexes during normal aging, including reduced early filling velocity (E), lengthened E deceleration time (DT), augmented late filling (A), and prolonged isovolumic relaxation time (IVRT), have been attributed to slower left ventricular (LV) pressure (LVP) decay. Indeed, this constellation of findings is often referred to as the "abnormal relaxation" pattern. However, LV filling is determined by the atrioventricular pressure gradient, which depends on both LVP decline and left atrial (LA) pressure (LAP). To assess the relative influence of LVP decline and LAP, we studied 122 normal subjects aged 21-92 yr by Doppler echocardiography and MRI. LVP decline was assessed by color M-mode (V(p)) and the LV untwisting rate. Early diastolic LAP was evaluated using pulmonary vein flow systolic fraction, pulmonary vein flow diastolic DT, color M-mode (E/V(p)), and tissue Doppler (E/E(m)). Linear regression showed the expected reduction of E, increase in A, and prolongation of IVRT and DT with advancing age. There was no relation of age to parameters reflecting the rate of LVP decline. However, older age was associated with reduced E/V(p) (P = 0.008) and increased pulmonary vein systolic fraction (P < 0.001), pulmonary vein DT (P = 0.0026), and E/E(m) (P < 0.0001), all suggesting reduced early LAP. Therefore, reduced early filling in older adults may be more closely related to a reduced early diastolic LAP than to slower LVP decline. This effect also explains the prolonged IVRT. We postulate that changes in LA active or passive properties may contribute to development of the abnormal relaxation pattern during the aging process.     

Effects of respiration on cardiac performance

The conventional explanation for the fall in left ventricular stroke volume (LVSV) with inspiration is that blood pools in the lungs, thereby decreasing pulmonary venous return. In anesthetized dogs, we have found an increase in left ventricular filling pressure (LVFP) with both constant and increasing lung volume during an inspiratory effort. Transmural aortic diastolic pressure rises as LVSV falls and LVFP rises consistent with the hypothesis that a fall in pleural pressure afterloads the left ventricle. Additionally the increase found in right ventricular filling pressure with inspiration may adversely affect LV performance by decreasing LV compliance and/or contractility. Our findings are incompatible with pooling of blood in the lungs being the primary determinant of the fall in LVSV with inspiration.     

Relationship among diastolic intraventricular pressure gradients, relaxation, and preload: impact of age and fitness

Diastolic intraventricular pressure gradients (IVPGs) are a measure of the ability of the ventricle to facilitate its filling using diastolic suction. We assessed 15 healthy young but sedentary subjects, aged <50 yr (young subjects; age, 35 +/- 9 yr); 13 healthy but sedentary seniors, aged >65 yr with known reductions in ventricular compliance (elderly sedentary subjects; age, 70 +/- 4 yr); and 12 master athletes, aged >65 yr, previously shown to have preserved ventricular compliance (elderly fit subjects; age, 68 +/- 3 yr). Pulmonary capillary wedge pressure (PCWP) and echocardiography measurements were performed at baseline, during load manipulation by lower body negative pressure at -15 and -30 mmHg, and after saline infusion of 10 and 20 ml/kg (elderly) or 15 and 30 ml/kg (young). IVPGs were obtained from color M-mode Doppler echocardiograms. Baseline IVPGs were lower (1.2 +/- 0.4 vs. 2.4 +/- 0.7 mmHg, P < 0.0001), and the time constant of pressure decay (tau(0)) was longer (60 +/- 10 vs. 46 +/- 6 ms, P < 0.0001) in elderly sedentary than in young subjects, with no difference in PCWP. Although PCWP changes during load manipulations were similar (P = 0.70), IVPG changes were less prominent in elderly sedentary than in young subjects (P = 0.02). Changes in stroke volume and IVPGs during loading manipulations correlated (r = 0.96, P = 0.0002). PCWP and tau(0) were strong multivariate correlates of IVPGs (P < 0.001, for both). IVPG response to loading interventions in elderly sedentary and elderly fit subjects was similar (P = 0.33), despite known large differences in ventricular compliance. The ability to regulate IVPGs during changes in preload is impaired with aging. Preserving ventricular compliance during aging by lifelong exercise training does not prevent this impairment.     

Postsystolic shortening of ischemic myocardium: a mechanism of abnormal intraventricular filling

Acute myocardial ischemia has been associated with abnormal filling patterns in the left ventricular (LV) apex. We hypothesized that this may in part be due to postsystolic shortening of ischemic apical segments, which leads to reversal of early diastolic apical flow. Fourteen open-chest anesthetized dogs were instrumented with micromanometers in the LV apex and left atrium and myocardial sonomicrometers in the anterior apical LV wall. Intraventricular filling by color Doppler and wall motion by strain Doppler echocardiography (SDE) were assessed from an apical view. Measurements were taken before and after 5 min of left anterior descending coronary artery (LAD) occlusion. In four dogs, we measured the pressure difference between the LV apex and outflow tract. At baseline, peak early diastolic flow velocities in the distal one-third of the LV were directed toward apex (9.2 +/- 1.6 cm/s). After LAD occlusion, the velocities reversed (-2.3 +/- 0.4 cm/s, P < 0.01), indicating that blood was ejected from the apex toward the base during early filling. This interpretation was confirmed by wall motion analysis, which showed postsystolic shortening of apical myocardial segments. The postsystolic shortening represented 9.7 +/- 1.7% (P < 0.01) and 14.2 +/- 2.4% (P < 0.01) of end-diastolic segment length by SDE and sonomicrometry, respectively. Consistent with the velocity changes, we found reversal of the early diastolic pressure gradient from the LV apex to outflow tract. In the present model, acute LAD occlusion resulted in reversal of early diastolic apical flow, and this was attributed to postsystolic shortening of dyskinetic apical segments. The clinical diagnostic importance of this finding remains to be determined.     

Hemodynamic effects of cardiac cycle-specific increases in intrathoracic pressure

Changes in intrathoracic pressure (ITP) can influence cardiac performance by affecting ventricular loading conditions. Because both systemic venous return and factors determining left ventricular (LV) ejection may vary over the cardiac cycle, phasic increases in ITP may differentially affect preload or afterload if delivered at specific points within the cardiac cycle. We studied the hemodynamic effects of cardiac cycle-specific increases in ITP (pulses) delivered by a high-frequency jet ventilator in an acute closed-chested canine model (n = 11), using electromagnetic flow probes to measure biventricular stroke volume. Measurements were taken during a control condition after the induction of acute ventricular failure (AVF) by propranolol hydrochloride and volume infusion. ITP was independently varied without changing lung volume by the inflation of thoracoabdominal binders. Although synchronous pulses had minimal hemodynamic effects in unbound controls, binding pulses timed to occur in early diastole resulted in decreases in LV filling pressure and left ventricular stroke volume (SVlv) (P less than 0.05). In the AVF condition, pulses increased LV performance, evidenced by increases in SVlv (P less than 0.01), despite decreases in LV filling pressure (P less than 0.05). This effect is maximized by binding and by timing the pulses to occur in systole. We conclude that cardiac cycle-specific increases in ITP can significantly affect cardiac performance. These effects appear to be related to the ability of such timed pulses to selectively affect LV preload and afterload.     

Dynamic effects of positive-pressure ventilation on canine left ventricular pressure-volume relations.

Positive-pressure ventilation (PPV) may affect left ventricular (LV) performance by altering both LV diastolic compliance and pericardial pressure (Ppc). We measured the effect of PPV on LV intraluminal pressure, Ppc, LV volume, and LV cross-sectional area in 17 acute anesthetized dogs. To account for changes in lung volume independent of changes in Ppc and differences in contractility, measures were made during both open- and closed-chest conditions, during closed chest with and without chest wall binding, and after propranolol-induced acute ventricular failure (AVF). Apneic end-systolic pressure-volume relations (ESPVR) were generated by inferior vena caval occlusions. With the open chest, PPV had no effects. With the chest closed, PPV inspiration decreased LV end-diastolic volume (EDV) along its diastolic compliance curve and decreased end-systolic volume (ESV) such that the end-systolic pressure-volume domain was shifted to a point left of the LV ESPVR, even when referenced to Ppc. The decrease in EDV was greater in control than in AVF conditions, whereas the shift of the ESV to the left of the ESPVR was greater with AVF than in control conditions. We conclude that the hemodynamic effects of PPV inspiration are due primarily to changes in intrathoracic pressure and that the inspiration-induced decreases of LV EDV reflect direct effects of intrathoracic pressure on LV filling. The decreases in LV ESV exceed the amount explained solely by a reduction in LV ejection pressure.     

Doppler-echocardiographic characteristics of left ventricular function in patients with pseudoexfoliation glaucoma: a preliminary report

Glaucoma is associated with an increased incidence of cardiovascular disease and risk factors. The aim of the study was to assess the left ventricular (LV) function in patients with pseudoexfoliation (PEX) glaucoma using doppler-echocardiographic examinations. Two-dimensional and pulsed Doppler echocardiography of transmitral flow was performed in 21 patients with (PEX) glaucoma and 24 controls. LV systolic contraction and ejection were assessed using the LV ejection fraction (EF) and fractional shortening (FS). LV diastolic filling assessed parameters were: early, fast diastolic filling (E wave), late diastolic filling (A wave), ratio E/A, velocity time integral E wave (VTIE) and A wave (VTIA), their ratio (VTIE /VTIA), pressure at the end of filling (LVEDP) and a pulmonary capillary wedge pressure (PCWP). A significant difference was found concerning LV filling flow parameters in E, E/A, VTIA and ratio VTIA/ VTIE. No significant difference was found in EF, FS, A, VTIE, LVEDP and PCWP tested parameters. Our study indicates the possibility of slightly impaired diastolic function of LV in patients with PEX glaucoma assessed by Doppler-echocardiographic examinations.     

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.