Effects of an aging vascular model on healthy and diseased hearts

The vitamin D(3) and nicotine (VDN) model is a model of isolated systolic hypertension (ISH) due to arterial calcification raising arterial stiffness and vascular impedance similar to an aged and stiffened arterial tree. We therefore analyzed the impact of this aging model on normal and diseased hearts with myocardial infarction (MI). Wistar rats were treated with VDN (n = 9), subjected to MI by coronary ligation (n = 10), or subjected to a combination of both MI and VDN treatment (VDN/MI, n = 14). A sham-treated group served as control (Ctrl, n = 10). Transthoracic echocardiography was performed every 2 wk, whereas invasive indexes were obtained at week 8 before death. Calcium, collagen, and protein contents were measured in the heart and the aorta. Systolic blood pressure, pulse pressure, thoracic aortic calcium, and end-systolic elastance as an index of myocardial contractility were highest in the aging model group compared with MI and Ctrl groups (P(VDN) < 0.05, 2-way ANOVA). Left ventricular wall stress and brain natriuretic peptide (P(VDNxMI) = not significant) were highest, while ejection fraction, stroke volume, and cardiac output were lowest in the combined group versus all other groups (P(VDNxMI) < 0.05). The combination of ISH due to this aging model and MI demonstrates significant alterations in cardiac function. This model mimics several clinical phenomena of cardiovascular aging and may thus serve to further study novel therapies.

In vivo application and validation of a novel noninvasive method to estimate the end-systolic elastance

Vasiliki Bikia, Stamatia Zoi Pagoulatou, Georgios Rovas, Nikolaos Stergiopulos

Accurate assessment of the left ventricular (LV) systolic function is indispensable in the clinic. However, estimation of a precise index of cardiac contractility, i.e., the end-systolic elastance (E-es), is invasive and cannot be established as clinical routine. The aim of this work was to present and validate a methodology that allows for the estimation of E-es from simple and readily available noninvasive measurements. The method is based on a validated model of the cardiovascular system and noninvasive data from arm-cuff pressure and routine echocardiography to render the model patient-specific. Briefly, the algorithm first uses the measured aortic flow as model input and optimizes the properties of the arterial system model to achieve correct prediction of the patient's peripheral pressure. In a second step, the personalized arterial system is coupled with the cardiac model (time-varying elastance model) and the LV systolic properties, including E-es, are tuned to predict accurately the aortic flow waveform. The algorithm was validated against invasive measurements of E-es (multiple pressure-volume loop analysis) taken from n = 10 patients with heart failure with preserved ejection fraction and n = 9 patients without heart failure. Invasive measurements of E-es (median = 2.4 mmHg/mL, range = [1.0, 5.0] mmHg/mL) agreed well with method predictions (normalized root mean square error = 9%, rho = 0.89, bias = -0.1 mmHg/mL, and limits of agreement = [-0.9, 0.6] mmHg/mL). This is a promising first step toward the development of a valuable tool that can be used by clinicians to assess systolic performance of the LV in the critically ill. NEW & NOTEWORTHY In this study, we present a novel model-based method to estimate the left ventricular (LV) end-systolic elastance (E-es) according to measurement of the patient's arm-cuff pressure and a routine echocardiography examination. The proposed method was validated in vivo against invasive multiple-loop measurements of E-es, achieving high correlation and low bias. This tool could be most valuable for clinicians to assess the cardiovascular health of critically ill patients.

2021

The effect of a myocardial infarction on the normalized time-varying elastance curve

Rafaela Fernandes Da Silva, David Jegger, Nikolaos Stergiopulos

It has been suggested that the shape of the normalized time-varying elastance curve [E(n)(t(n))] is conserved in different cardiac pathologies. We hypothesize, however, that the E(n)(t(n)) differs quantitatively after myocardial infarction (MI). Sprague-Dawley rats (n = 9) were anesthetized, and the left anterior descending coronary artery was ligated to provoke the MI. A sham-operated control group (CTRL) (n = 10) was treated without the MI. Two months later, a conductance catheter was inserted into the left ventricle (LV). The LV pressure and volume were measured and the E(n)(t(n)) derived. Slopes of E(n)(t(n)) during the preejection period (alpha(PEP)), ejection period (alpha(EP)), and their ratio (beta = alpha(EP)/alpha(PEP)) were calculated, together with the characteristic decay time during isovolumic relaxation (tau) and the normalized elastance at end diastole (E(min)(n)). MI provoked significant LV chamber dilatation, thus a loss in cardiac output (-33%), ejection fraction (-40%), and stroke volume (-30%) (P < 0.05). Also, it caused significant calcium increase (17-fold), fibrosis (2-fold), and LV hypertrophy. End-systolic elastance dropped from 0.66 +/- 0.31 mmHg/microl (CTRL) to 0.34 +/- 0.11 mmHg/microl (MI) (P < 0.05). Normalized elastance was significantly reduced in the MI group during the preejection, ejection, and diastolic periods (P < 0.05). The slope of E(n)(t(n)) during the alpha(PEP) and beta were significantly altered after MI (P < 0.05). Furthermore, tau and end-diastolic E(min)(n) were both significantly augmented in the MI group. We conclude that the E(n)(t(n)) differs quantitatively in all phases of the heart cycle, between normal and hearts post-MI. This should be considered when utilizing the single-beat concept.

2006

Quantification of the contribution of cardiac and arterial remodeling to hypertension

Patrick Segers, Nikolaos Stergiopulos, Nico Westerhof

The study aim was to quantify the individual and combined contributions of both the arterial system and the heart to systolic blood pressure in hypertension. We assessed the parameters of a heart-arterial model for normotensive control subjects and hypertensive patients with left ventricular adaptation patterns classified as normal, concentric remodeling, concentric hypertrophy, or eccentric hypertrophy. The present simulations show that vascular stiffening alone increases the pulse pressure without increasing systolic blood pressure. It is only in combination with an increased peripheral resistance that arterial stiffening leads to systolic hypertension in concentric remodeling and concentric hypertrophy. The contribution of cardiac pump function to the increase in blood pressure depends on cardiac remodeling, hypertrophy, or both. In hypertensive patients with a normal left ventricle, the heart is responsible for 55% of the increase in systolic blood pressure. In concentric remodeling, concentric hypertrophy, and eccentric hypertrophy, the cardiac contribution to the increase in systolic blood pressure is 21%, 65%, and 108%, respectively. We conclude that along with arterial changes, cardiac remodeling and hypertrophy contribute to hypertension.

2000

In vivo application and validation of a novel noninvasive method to estimate the end-systolic elastance

Vasiliki Bikia, Stamatia Zoi Pagoulatou, Georgios Rovas, Nikolaos Stergiopulos

2021