Ventricular End-systolic Elastance Research Articles

Noninvasive quantification of left ventricular elastance and ventricular-arterial coupling using three-dimensional echocardiography and arterial tonometry

Most techniques previously used to assess left ventricular (LV) end-systolic elastance (E(es)) and ventricular-arterial coupling (C(LV-A)) relied on invasive measurements and data acquisition over a wide range of loading conditions. Our goals were to 1) assess the feasibility of noninvasive assessment of E(es) and C(LV-A) using real-time three-dimensional echocardiography (RT3DE) and arterial tonometry; 2) test the ability of this approach to detect changes in LV contractility; and 3) study its reproducibility. We studied pharmacologically induced changes in inotropic state (5 and 10 μg·kg(-1)·min(-1) dobutamine) in normal volunteers (N = 8) and compared 10 normal volunteers with 10 patients with dilated cardiomyopathy (DCM; ejection fraction < 35%). RT3DE LV images, calibrated carotid artery tonometry, and Doppler tracings were obtained to noninvasively estimate E(es) and C(LV-A), using two alternative calculations. Dobutamine caused a significant stepwise increase in blood pressure, heart rate, ejection fraction, and E(es) and a decreased C(LV-A). In patients with DCM, E(es) was significantly reduced and C(LV-A) elevated, compared with controls. Both inter- and intraobserver variability were good for all measured parameters, as reflected by intraclass correlation coefficients (>0.8) and coefficients of variation (<20%). While both E(es) estimates showed significant differences between DCM patients and controls, one estimate resulted in no overlap and better reproducibility (interobserver intraclass correlation coefficient: 0.83 vs. 0.47, coefficients of variation: 20 vs. 29%). This is the first study to test the feasibility of using RT3DE-derived LV volumes in conjunction with arterial tonometry to noninvasively quantify LV elastance and C(LV-A). This approach was found to be sensitive enough to detect expected differences in LV contractility and reproducible. Due to its noninvasive nature, this methodology may have clinical implications in various disease states.

PUCA Pump and IABP Comparison: Analysis of Hemodynamic and Energetic Effects Using a Digital Computer Model of the Circulation

The pulsatile catheter pump (PUCA pump) is a left ventricular assist device that provides additional flow to the left ventricle. It is usually run in order to ensure a counterpulsation effect, as in the case of the intra-aortic balloon pump (IABP). Because of this similarity, a comparison between the PUCA pump and the IABP was conducted from both the hemodynamic and energetic points of view. Numerical models of the two devices were created and connected to the CARDIOSIM cardiovascular simulator. The PUCA and IABP models were then verified using in vivo experimental data and literature data, respectively. Numerical experiments were conducted for different values of left ventricular end systolic elastance (Els) and systemic arterial compliance (Csa). The energetic comparison was conducted taking into account the diastolic pressure time index and the endocardial viability ratio. Hemodynamic results expressed as cardiac output (CO) and mean coronary blood flow (CBF) show that both the IABP and the PUCA pump efficacy decrease with higher values of Els and Csa. The IABP especially shows higher sensitivity to these parameters, to the extent that in some cases CO actually drops and CBF does not increase. On the other hand, for lower values of Csa, IABP performance improves so much that the PUCA pump flow needs to be increased in order to ensure a hemodynamic effect comparable to that of the IABP. Energetic results show a trend similar to the hemodynamic ones. The study will be continued by investigating other energetic variables and the autonomic response of the cardiovascular system.

Acute elevation of triglycerides increases left ventricular contractility and alters ventricular-vascular interaction

Acute elevation of circulating lipids, such as the postprandial state, contributes to increased cardiovascular risk. However, the effect of acutely elevated triglycerides on arterial and left ventricular function is not completely understood. We aimed to assess whether an acute increase in triglycerides affects ventricular-vascular interaction. Fifteen healthy men (age, 49 ± 8 yr) underwent blinded, randomized infusion of saline and intravenous fat emulsion to acutely raise plasma triglycerides. All subjects underwent both randomization trials, in random order on two separate days. Ventricular-vascular interaction measures were recorded by tonometry (central blood pressure) and echocardiography (left ventricular volumes, strain, and strain rate) at baseline and after 1 h infusion. Net ventricular-vascular interaction was defined by the effective arterial elastance (E(A))-to-left ventricular end-systolic elastance (E(LV)) ratio (E(A)/E(LV)). When compared with saline, the infusion of intravenous fat emulsion increased triglycerides and free fatty acids (ΔP < 0.001 for both) and improved left ventricular contractility (ΔE(LV), end-systolic volume and strain rate; P < 0.05 for all). However, arterial function was unchanged (ΔE(A), brachial and central blood pressure; P > 0.05 for all). Overall, E(A)/E(LV) was decreased by an infusion of intravenous fat emulsion (P = 0.004) but not saline (P > 0.05, P = 0.001 for Δ between trials). We conclude that intravenous fat emulsion and acute elevation of blood lipids (including triglycerides and free fatty acids) alter ventricular-vascular interaction by increasing left ventricular contractility without affecting arterial load. These findings may have implications for cardiovascular responses to parenteral nutrition.

EVALUATION OF RIGHT VENTRICULOARTERIAL COUPLING IN PULMONARY HYPERTENSION: A MAGNETIC RESONANCE STUDY

Inadequate right ventriculo-arterial coupling is an important determinant of heart failure in pulmonary hypertension, in turn the main determinant of outcome in this disease. Coupling can be quantified as the ratio of pulmonary artery effective elastance (Ea, an index of arterial load) to right ventricular maximal end-systolic elastance (Emax, an index of contractility).

The Effects of Aerobic Exercise Training on Arterial‐Ventricular Coupling in Patients with Metabolic Syndrome: A Pilot Study

Arterial‐ventricular coupling (EA/Ees) is an important determinant of cardiovascular (CV) function, and can be indexed by the ratio of arterial elastance (EA; net arterial load), to left ventricular (LV) end‐systolic elastance (Ees; LV performance). Metabolic syndrome (MetS) patients have an abnormal CV function, which may be due to a suboptimal EA/Ees.PURPOSETo examine EA/Ees, at rest and peak exercise, in MetS patients before and after 8 weeks of exercise training.METHODSMetS patients (n=13, 46±8) were defined according to ATPIII. Using echocardiography we noninvasively characterized Ees (single beat elastance), and EA (end‐systolic pressure/stroke volume) from which EA/Ees was calculated, and compared to healthy controls (n=4, 48±7). MetS patients were separated into exercise or non‐exercising groups for 8 weeks.RESULTSAt rest, EA/Ees was 21% lower in MetS vs. controls due to a 24% higher Ees in MetS vs. controls. The reduction in EA/Ees during exercise was blunted in MetS (31% vs. 52%, p&lt;.01) because of a blunted increase in Ees in MetS vs. controls (102% vs. 234%, p&lt;.05). 8 weeks of exercise training in MetS increased EA/Ees at rest, and enhanced the reduction in EA/Ees (25%, p=.05) during exercise due to a 61% (p&lt;.05) greater increase in Ees.CONCLUSIONThe abnormal EA/Ees at rest and peak exercise in MetS patients was restored to similar levels noted in healthy controls after 8 weeks of aerobic training

Evaluation of right ventriculoarterial coupling in pulmonary hypertension: a magnetic resonance study

Inadequate right ventriculo-arterial coupling is an important determinant of heart failure in pulmonary hypertension, in turn the main determinant of outcome in this disease. Coupling can be quantified as the ratio of pulmonary artery effective elastance (Ea, an index of arterial load) to right ventricular maximal end-systolic elastance (Emax, an index of contractility).

Measuring right ventricular function in the normal and hypertensive mouse hearts using admittance-derived pressure-volume loops

Mice are a widely used animal model for investigating cardiovascular disease. Novel technologies have been used to quantify left ventricular function in this species, but techniques appropriate for determining right ventricular (RV) function are less well demonstrated. Detecting RV dysfunction is critical to assessing the progression of pulmonary vascular diseases such as pulmonary hypertension. We used an admittance catheter to measure pressure-volume loops in anesthetized, open-chested mice before and during vena cava occlusion. Mice exposed to chronic hypoxia for 10 days, which causes hypoxia-induced pulmonary hypertension (HPH), were compared with control (CTL) mice. HPH resulted in a 27.9% increase in RV mass (P < 0.005), a 67.5% increase in RV systolic pressure (P < 0.005), and a 61.2% decrease in cardiac output (P < 0.05). Preload recruitable stroke work (PRSW) and slope of the maximum derivative of pressure (dP/dt(max))-end-diastolic volume (EDV) relationship increased with HPH (P < 0.05). Although HPH increased effective arterial elastance (E(a)) over fivefold (from 2.7 ± 1.2 to 16.4 ± 2.5 mmHg/μl), only a mild increase in the ventricular end-systolic elastance (E(es)) was observed. As a result, a dramatic decrease in the efficiency of ventricular-vascular coupling occurred (E(es)/E(a) decreased from 0.71 ± 0.27 to 0.35 ± 0.17; P < 0.005). Changes in cardiac reserve were evaluated by dobutamine infusion. In CTL mice, dobutamine significantly enhanced E(es) and dP/dt(max)-EDV but also increased E(a), causing a decrease in E(es)/E(a). In HPH mice, slight but nonsignificant decreases in E(es), PRSW, dP/dt(max)-EDV, and E(a) were observed. Thus 10 days of HPH resulted in RV hypertrophy, ventricular-vascular decoupling, and a mild decrease in RV contractile reserve. This study demonstrates the feasibility of obtaining RV pressure-volume measurements in mice. These measurements provide insight into ventricular-vascular interactions healthy and diseased states.

Differential effects of sevoflurane and propofol anesthesia on left ventricular–arterial coupling in dogs

General anesthetics interfere with arterial and ventricular mechanical properties, often altering left ventricular-arterial (LVA) coupling. We hypothesized that sevoflurane and propofol alter LVA coupling by different effects on arterial and ventricular properties. Experiments were conducted in six anesthetized open-chest dogs for the measurement of left ventricular pressure and aortic pressure and flow. Measurements were performed during anesthesia with 0.5, 1.0 and 1.5 minimum alveolar concentration sevoflurane and 12, 24 and 36 mg/kg/h propofol. LVA coupling was assessed as the ratio of ventricular end-systolic elastance (E(es), measuring ventricular contractility) to effective arterial elastance (E(a), measuring ventricular afterload). The steady component of afterload, arterial tone, was assessed by systemic vascular resistance and arterial pressure-flow curves. The pulsatile component of afterload was assessed by aortic impedance and compliance. Sevoflurane decreased aortic pressure and cardiac output more than propofol. Sevoflurane reduced arterial tone, increased arterial stiffness and did not affect wave reflections. It increased E(a), decreased E(es) and reduced LVA coupling. Propofol reduced arterial tone, did not affect arterial stiffness and decreased wave reflections. It did not affect E(a), E(es) or LVA coupling. Sevoflurane increased ventricular afterload and decreased ventricular performance, thereby altering LVA coupling. Propofol did not affect ventricular afterload or ventricular performance, thereby preserving LVA coupling. Thus, propofol preserves LVA coupling in dogs better, and might be a better choice for patients with compromised left ventricular function.

Elevated augmentation index derived from peripheral arterial tonometry is associated with abnormal ventricular–vascular coupling

Although typically derived from the contour of arterial pressure waveform, augmentation index (AIx) may also be derived from the digital pulse volume waveform using finger plethysmography (peripheral arterial tonometry, PAT). Little is known regarding the physiologic correlates of AIx derived from PAT. In this study, we investigated the relation of PAT-AIx with measures of ventricular-vascular coupling. Pulse volume waves were measured via PAT and used to derive AIx. Using 2-dimensional echocardiography, effective arterial elastance index (EaI) was estimated as end-systolic pressure/stroke volume index. Left ventricular (LV) end-systolic elastance index (E(LV)I) was calculated as end-systolic pressure/end-systolic volume index. Ventricular-vascular coupling ratio was defined as EaI/E(LV)I. Given the bi-directional nature of ventricular-vascular uncoupling as measured by echocardiography, patients were separated into three groups: low EaI/E(LV)I (<0.6, n = 21), optimal EaI/E(LV)I (mean 0.6-1.2, n = 16) and high EaI/E(LV)I (>1.2, n = 10). Adjusting for potential confounders (age, mean arterial pressure, height and heart rate), patients with optimal EaI/E(LV)I had lower AIx (1 +/- 4%, P<0.05) compared to those with low EaI/E(LV)I (13 +/- 4%) and high EaI/E(LV)I (19 +/- 5%). Abnormal ventricular-vascular coupling, arising from either increased effective arterial elastance or increased ventricular elastance, is associated with increased AIx as measured by PAT. Additional research is needed to examine other vascular correlates of PAT-AIx.

Quantitative synthesis of dynamic baroreflex pressure regulation using baroreflex induced changes in ventricular and vascular properties

BackgroundBaroreflex (BR) stabilizes arterial pressure (AP) by changing ventricular and vascular properties. However, how those changes quantitatively determine AP remains unknown. We previously developed a framework of circulatory equilibrium (AJP 2004, 2005) where we can algebraically derive the equilibrium using ventricular end‐systolic elastance (Ees), heart rate (HR), vascular resistance (R) and stressed blood volume (V). Using the framework we investigated if we can quantitatively synthesize AP responses on the basis of BR induced those properties.Methods and ResultsIn 5 anesthetized with isolated carotid sinuses, we randomly perturbed carotid sinus pressure (CSP) using a servo‐pump while recording hemodynamic variables including ventricular pressure‐volume relations. We estimated transfer functions from CSP to HR, Ees, R and V and predicted time domain values of each variable in response to changes in CSP. We then synthesized changes in AP using the equilibrium framework. Synthesized AP matched well with those measured (r2=0.80~0.91). A sensitivity analysis indicated that V and R accounted for 80±6% and 17±6%, respectively, while Ees and HR less than 2% of the BR induced AP changes.ConclusionThe BR induced AP changes can be quantitatively predicted on the basis of BR regulated ventricular and vascular properties. V mainly contributes to the BR induced AP changes.

Activation of apoptotic pathways in experimental acute afterload-induced right ventricular failure*

The pathobiology of persistent right ventricular failure observed after an acute increase in right ventricular afterload remains incompletely understood. We hypothesized that persistent right ventricular dysfunction might be related to activation of apoptotic pathways. Prospective, randomized, controlled animal study. University research laboratory. Mongrel dogs. Fourteen anesthetized dogs were randomized to a transient 90-min pulmonary artery constriction operation to induce persistent right ventricular failure or to a sham operation followed 30 mins later by hemodynamic measurements and sampling of cardiac tissue. We evaluated effective arterial elastance to estimate right ventricular afterload and end-systolic elastance to estimate right ventricular contractility. Transient increase in pulmonary artery pressure persistently increased effective arterial elastance from 0.75 +/- 0.08 to 1.37 +/- 0.18 mm Hg/mL and decreased end-systolic elastance from 1.06 +/- 0.09 to 0.49 +/- 0.09 mm Hg/mL, end-systolic elastance/effective arterial elastance from 1.44 +/- 0.06 to 0.34 +/- 0.03, and cardiac output from 3.78 +/- 0.16 to 1.46 +/- 0.10 L/min, indicating right ventricular failure. At the pathobiologic level, we assessed apoptosis by real-time quantitative polymerase chain reaction, Western blotting, enzyme-linked immunosorbent assay, and immunohistochemistry. As compared with the sham-operated group, and with the left ventricle in animals with persistent right ventricular failure, there were decreased right ventricular and septal expressions of Bcl-2 with no changes in expressions of Bax, resulting in an increased Bax/Bcl-2 ratio. Right ventricular and septal Bcl-XL, and right ventricular Bcl-w gene expressions were decreased as compared with the sham-operated group, whereas Bak gene expression did not change. There were activations of right ventricular caspases-8 and -9 and of right ventricular and septal caspase-3. Diffuse right ventricular and septal apoptosis was confirmed by terminal deoxynucleotidyl transferase dUTP nick-end labeling staining. There were also increased right ventricular and septal protein expressions of tumor necrosis factor-alpha. Acute afterload-induced persistent right ventricular failure appears to be related to an early activation of apoptotic pathways and to a local overexpression of tumor necrosis factor-alpha, a proinflammatory cytokine.

Activation of apoptotic pathways in experimental acute afterload-induced right ventricular failure

The pathobiology of persistent right ventricular failure observed after an acute increase in right ventricular afterload remains incompletely understood. We hypothesized that persistent right ventricular dysfunction might be related to activation of apoptotic pathways.Prospective, randomized, controlled animal study.University research laboratory.Mongrel dogs.Fourteen anesthetized dogs were randomized to a transient 90-min pulmonary artery constriction operation to induce persistent right ventricular failure or to a sham operation followed 30 mins later by hemodynamic measurements and sampling of cardiac tissue.We evaluated effective arterial elastance to estimate right ventricular afterload and end-systolic elastance to estimate right ventricular contractility. Transient increase in pulmonary artery pressure persistently increased effective arterial elastance from 0.75 +/- 0.08 to 1.37 +/- 0.18 mm Hg/mL and decreased end-systolic elastance from 1.06 +/- 0.09 to 0.49 +/- 0.09 mm Hg/mL, end-systolic elastance/effective arterial elastance from 1.44 +/- 0.06 to 0.34 +/- 0.03, and cardiac output from 3.78 +/- 0.16 to 1.46 +/- 0.10 L/min, indicating right ventricular failure. At the pathobiologic level, we assessed apoptosis by real-time quantitative polymerase chain reaction, Western blotting, enzyme-linked immunosorbent assay, and immunohistochemistry. As compared with the sham-operated group, and with the left ventricle in animals with persistent right ventricular failure, there were decreased right ventricular and septal expressions of Bcl-2 with no changes in expressions of Bax, resulting in an increased Bax/Bcl-2 ratio. Right ventricular and septal Bcl-XL, and right ventricular Bcl-w gene expressions were decreased as compared with the sham-operated group, whereas Bak gene expression did not change. There were activations of right ventricular caspases-8 and -9 and of right ventricular and septal caspase-3. Diffuse right ventricular and septal apoptosis was confirmed by terminal deoxynucleotidyl transferase dUTP nick-end labeling staining. There were also increased right ventricular and septal protein expressions of tumor necrosis factor-alpha.Acute afterload-induced persistent right ventricular failure appears to be related to an early activation of apoptotic pathways and to a local overexpression of tumor necrosis factor-alpha, a proinflammatory cytokine.

Prognostic Value of Ventricular-Arterial Coupling and B-Type Natriuretic Peptide in Patients After Myocardial Infarction: A Five-Year Follow-Up Study

The aim of this study was to determine the prognostic role of ventricular-arterial coupling compared with B-type natriuretic peptide (BNP) in patients after myocardial infarctions. Forty-one consecutive patients with history of myocardial infarctions were enrolled. Ventricular-arterial coupling was assessed as the ratio between arterial elastance (E(a)) and end-systolic ventricular elastance (E(es)). E(a) and E(es) were calculated using systolic and diastolic blood pressure, echocardiographically derived stroke volume, left ventricular ejection fraction, and the ratio between aortic preejection time and total systolic time. Cardiovascular mortality was the prespecified endpoint, with 5-year follow-up. BNP was significantly correlated with New York Heart Association class and known echocardiographic parameters of systolic and diastolic left ventricular function and also with the E(a)/E(es) ratio (P = .001), which emerged as an independent correlate of BNP in multivariate analysis. The E(a)/E(es) ratio demonstrated good accuracy in predicting long-term cardiovascular mortality (area under the receiver operating characteristic curve, 0.73; P = .019), comparable with that of BNP in patients after myocardial infarctions. Ventricular-arterial coupling assessed using the E(a)/E(es) ratio is an independent echocardiographic correlate of BNP levels in patients with previous myocardial infarctions and has a significant role in predicting long-term cardiovascular mortality in this setting.

Arterial Load and Ventricular-Arterial Coupling

Accurate quantification of arterial function is crucial to distinguishing disease states from normal variants. However, there are little data regarding methods to scale arterial load to body size in humans. We studied 2365 adults aged 35 to 55 years free of overt cardiovascular disease. We assessed arterial hemodynamics and ventricular-vascular coupling with carotid tonometry and Doppler echocardiography. To define normal (physiological) relationships between hemodynamic indices and body size, we used nonlinear regression to analyze a selected reference subsample (n=612) with normal weight (body mass index 18 to 25 kg/m(2)), waist circumference, and metabolic parameters. Most arterial hemodynamic indices demonstrated important relationships with body size, which were frequently allometric (nonlinear). Allometric indexation using appropriate powers (but not ratiometric indexation) effectively eliminated the relationships between indices of arterial load and body size in normal subjects. In the entire sample (n=2365), the adverse effects of obesity on arterial load and end-systolic ventricular stiffening were clearly demonstrated only after appropriate indexation to account for the expected normal relationship to body size. After adjustment for age and sex, a progressive increase in indexed systemic vascular resistance, effective arterial and ventricular end-systolic elastance, and a decrease in total arterial compliance were seen from normal weight to obesity (P<0.0001). Arterial load relates to body size in an allometric fashion, calling for scaling with the use of appropriate powers. Obesity exerts adverse effects on arterial load and ventricular stiffening that go beyond the normal relationship with body size. Allometric normalization should allow more accurate quantification of arterial load in future studies.

Usefulness of systolic time intervals in the identification of abnormal ventriculo‐arterial coupling in stable heart failure patients*

The ratio of effective arterial elastance (Ea) to ventricular end-systolic elastance (Ees) indicates the status of ventriculo-arterial coupling. We investigated if systolic time intervals (pre-ejection period, PEP; ejection time, ET; and their ratio, PEP/ET) can be used to identify heart failure patients with abnormal ventriculo-arterial coupling. Age and sex-matched study subjects included 54 apparently healthy subjects with normal left ventricular (LV) function, and stable patients with LV diastolic (n=54) and systolic dysfunction (n=54). Ees and Ea were estimated non-invasively by echocardiography, and abnormal ventriculo-arterial coupling was defined as Ea/Ees>1.2. PEP, ET, and PEP/ET were measured automatically using electrocardiography, phonocardiography, and brachial pulse volume recording. Ea/Ees>1.2 was present in 48.1% of subjects with systolic dysfunction. The PEP/ET was significantly associated with most parameters of LV structure and function, and Ea/Ees (r=0.67, p<0.001). Using PEP/ET> or =0.423 as cut point, the sensitivity and specificity to identify patients with Ea/Ees>1.2 were 85.7% and 84.3%, respectively for the whole population, and 84.6% and 78.6%, for patients with systolic dysfunction. Abnormal ventriculo-arterial coupling was present in almost half of stable patients with systolic dysfunction. PEP/ET was useful in identifying such patients.

Transition of ventricular function and energy efficiency after a primary or staged Fontan procedure

The transitional changes of the ventricular function at different time points after total cavopulmonary connection (TCPC) were examined. A total of 29 patients were divided into a primary TCPC group and a staged TCPC group. In both groups, phase I was defined as within 2 months after TCPC and phase II as beyond at least a year after TCPC. Changes in ventricular end-diastolic volume (EDV), ventricular end-systolic elastance (Ees), effective arterial elastance (Ea), and ventriculoarterial coupling (Ea/Ees) were evaluated. The results for the primary TCPC group are as follows. Phase I: The EDV decreased (P < 0.05). The Ees and Ea both increased (P < 0.05). Ea/Ees showed a tendency to increase (P = 0.08). Phase II: The EDV decreased (P < 0.05). The Ees increased significantly, and Ea showed no significant change. Ees/Ea showed a tendency to decrease (P = 0.07). The results for the staged TCPC group were as follows. Phase I: The EDV decreased significantly after bidirectional cavopulmonary shunt (BCPS). The Ees showed no significant change after BCPS and TCPC. Although Ea increased after BCPS (P < 0.05), it showed no significant change after TCPC. Ea/Ees showed no significant change. Phase II: The Ees increased (P < 0.05) without significant changes of EDV and Ea. As a result, Ea/Ees showed a tendency to decrease. This study suggested improved ventricular function in both groups. These results suggest hemodynamic adaptation to the Fontan circulation. The deleterious effects on ventricular function caused by the Fontan procedure disappeared within a couple of years. This acute effect can be ameliorated by the staged approach to the Fontan circulation.

Arterial-ventricular coupling: mechanistic insights into cardiovascular performance at rest and during exercise.

Understanding the performance of the left ventricle (LV) requires not only examining the properties of the LV itself, but also investigating the modulating effects of the arterial system on left ventricular performance. The interaction of the LV with the arterial system, termed arterial-ventricular coupling (E(A)/E(LV)), is a central determinant of cardiovascular performance and cardiac energetics. E(A)/E(LV) can be indexed by the ratio of effective arterial elastance (E(A); a measure of the net arterial load exerted on the left ventricle) to left ventricular end-systolic elastance (E(LV); a load-independent measure of left ventricular chamber performance). At rest, in healthy individuals, E(A)/E(LV) is maintained within a narrow range, which allows the cardiovascular system to optimize energetic efficiency at the expense of mechanical efficacy. During exercise, an acute mismatch between the arterial and ventricular systems occurs, due to a disproportionate increase in E(LV) (from an average of 4.3 to 13.2, and 4.7 to 15.5 mmHg.ml(-1).m(-2) in men and women, respectively) vs. E(A) (from an average of 2.3 to 3.2, and 2.3 to 2.9 mmHg.ml(-1).m(-2) in men and women, respectively), to ensure that sufficient cardiac performance is achieved to meet the increased energetic requirements of the body. As a result E(A)/E(LV) decreases from an average of 0.58 to 0.34, and 0.52 to 0.27 in men and women, respectively. In this review, we provide an overview of the concept of E(A)/E(LV), and examine the effects of age, hypertension, and heart failure on E(A)/E(LV) and its components (E(A) and E(LV)) in men and women. We discuss these effects both at rest and during exercise and highlight the mechanistic insights that can be derived from studying E(A)/E(LV).

Ventricular-arterial coupling in patients with heart failure treated with cardiac resynchronization therapy: may we predict the long-term clinical response?

To evaluate the effects of cardiac resynchronization therapy (CRT) on ventricular-arterial coupling (VAC) in patients with refractory congestive heart failure (HF), left bundle brunch block, and sinus rhythm. The ratio between arterial elastance (Ea) and left ventricular end-systolic elastance (Ees), the so-called VAC, defines the efficiency of the myocardium in pumping blood. Seventy-eight patients were studied with echocardiography before CRT, and 1 year later. End-systolic elastance was calculated according to the method of Chen. Arterial elastance (ratio of the systolic pressure to the stroke volume), end-systolic volume (ESV), and quality of life (QoL) (Minnesota Living with Heart Failure Questionnaire) were assessed at the baseline and after 1 year. Patients with a reduction>15% of ESV or a decrease>33% in QoL score were considered responders to CRT. QRS duration and interventricular delay were significantly reduced with CRT compared with baseline (156+/-2 vs. 195+/-3 ms, P<0.001; and 25+/-2 vs. 55+/-3 ms, P<0.001, respectively). Arterial elastance/Ees decreased significantly on CRT (2.47+/-1.48 vs. 1.41+/-0.87, P<0.0001). The lowering of Ea/Ees was congruent to a decrease in intraventricular delay (83.1+/-55.7 vs. 28.4+/-49.5 ms, P<0.0001) and an increase in ejection fraction (26+/-6.3 vs. 36.9+/-8.0%, P<0.0001). Responders to CRT were 74 and 71% of the overall patient population, considering as endpoint QoL or ESV, respectively. The analysis of VAC showed a baseline cut-off value of 2, above which 88% and 69% of patients responded to CRT, considering as endpoint QoL or ESV, respectively. The non-invasive assessment of VAC may be proposed as an immediate, easy, and optimal tool for quantifying the effect of CRT in patients with HF.

Hypoxic Preconditioning Preserves Cardiac Contractility and Reduces Infarct Size In Vivo

Background: Preconditioning is a powerful endogenous mechanism to protect the heart against ischemic dam- age. The second window of preconditioning (SWOP) is therapeutically the most attractive, but is hard to achieve by local cardiac ischemia 24 hrs before the index ischemia in the many mice models for cardiovascular pathology, because of ex- cessive mortality during the two procedures or the period in between. Hypoxic preconditioning is an attractive alternative preconditioning stimulus. To date, the SWOP after hypoxic preconditioning has not been studied in mice concerning in- farct size reduction and preservation of left ventricular contractility in vivo. Aim: To determine whether transient hypoxia can induce a SWOP in vivo in mice. Methods: Hypoxic preconditioning was induced by 5 cycles of 6 minutes of 6% oxygen in 24-week-old wild type mice. Twenty-four hours later, a 30 minutes coronary occlusion was performed. After 1 hour of reperfusion, in vivo cardiac pressure-conductance catheterization was performed with determination of the load-dependent and load-independent pa- rameters. Infarct size was determined by TTC-staining. Sham procedures were used to obtain non-preconditioned con- trols. Results: There was no mortality with the hypoxic preconditioning protocol. The left ventricular contractile parameters ejection fraction, end-systolic elastance and preload recruitable stroke work were significantly better preserved after ischemia in the preconditioned group. Diastolic relaxation (tau) was also significantly better preserved. Infarct size was reduced to half that of the non-preconditioned group. Conclusion: Hypoxic preconditioning is a feasible stimulus to induce in vivo a second window of preconditioning in mice. Infarct size is reduced and cardiac contractility better preserved after 30 min regional ischemia in vivo by hypoxic precon- ditioning 24 hrs earlier.

The role of the autonomic nervous system in hypertension: a bond graph model study

A bond graph model of the cardiovascular system with embedded autonomic nervous regulation was developed for a better understanding of the role of the autonomic nervous system (ANS) in hypertension. The model is described by a pump model of the heart and a detailed representation of the head and neck, pulmonary, coronary, abdomen and extremity circulation. It responds to sympathetic and parasympathetic activities by modifying systemic peripheral vascular resistance, heart rate, ventricular end-systolic elastance and venous unstressed volumes. The impairment of ANS is represented by an elevation of the baroreflex set point. The simulation results show that, compared with normotensive, in hypertension the systolic and diastolic blood pressure (SBP/DBP) rose from 112/77 mmHg to 144/94 mmHg and the left ventricular wall thickness (LVWT) increased from 10 mm to 12.74 mm. In the case that ANS regulation was absent, both the SBP and DBP further increased by 8 mmHg and the LVWT increased to 13.22 mm. The results also demonstrate that when ANS regulation is not severely damaged, e.g. the baroreflex set point is 97 mmHg, it still has an effect in preventing the rapid rise of blood pressure in hypertension; however, with the worsening of ANS regulation, its protective role weakens. The results agree with human physiological and pathological features in hemodynamic parameters and carotid baroreflex function curves, and indicate the role of ANS in blood pressure regulation and heart protection. In conclusion, the present model may provide a valid approach to study the pathophysiological conditions of the cardiovascular system and the mechanism of ANS regulation.