Relationship between Augmentation Index and Wall Thickening Fraction during Hypotension in an Animal Model of Myocardial Ischemia-Reperfusion and Heart Failure.

AIMS: Non-invasive indices to evaluate left ventricular changes during ischemic heart failure are needed to quantify the myocardial impairment and the effectiveness of therapeutic manoeuvres. The aims of this work were to calculate the Wall Thickening Fraction (WTF) and the Augmentation Index (AIx) and to assess the relationship between WTF and AIx using data obtained from an animal model with heart failure followed by a myocardial ischemia stage and a reperfusion stage. METHODS: Nine Corriedale sheep that had been monitored for 10 minutes during a basal stage underwent 5-minute myocardial ischemia, followed by 60-minute reperfusion. Seven of them were subjected to an induced heart failure through an overdose of halothane, two of which were treated with intra-aortic counterpulsation during the reperfusion stage. The remaining two animals were monitored during their ischemia-reperfusion stage. RESULTS: Data obtained in the 5 animals suffering from heart failure followed by myocardial ischemia showed that: a) heart failure induction determined decrease in cardiac output, cardiac index and systolic and diastolic aortic pressure (AoP) with respect to their basal values (p<0.05), b) myocardial ischemia decreased the WTF compared with basal and induced heart failure values (p<0.05), c) during the reperfusion stage accompanied by induced heart failure, WTF increased with respect to values observed during the ischemia induction stage (p<0.05); nevertheless, basal values were not recovered after reperfusion (p<0.05). During this 60-minute stage, systolic and diastolic AoP values were lower (p<0.05) than those at the basal stage. CONCLUSION: AIx and WTF values calculated from synchronically recorded values of aortic pressure and left ventricular wall thickness during the reperfusion stage in all animals (n = 9) showed a negative correlation (p<0.05). Analysed data provided evidence of a negative relationship between a left ventricular index of myocardial function and an arterial index obtained from AoP waves.

Parameter estimation to study the immediate impact of aortic cross-clamping using reduced order models.

Aortic cross-clamping is a common strategy during vascular surgery, however, its instantaneous impact on hemodynamics is unknown. We, therefore, developed two numerical models to estimate the immediate impact of aortic clamping on the vascular properties. To assess the validity of the models, we recorded continuous invasive pressure signals during abdominal aneurysm repair surgery, immediately before and after clamping. The first model is a zero-dimensional (0D) three-element Windkessel model, which we coupled to a gradient-based parameter estimation algorithm to identify patient-specific parameters such as vascular resistance and compliance. We found a 10% increase in the total resistance and a 20% decrease in the total compliance after clamping. The second model is a nine-artery network corresponding to an average human body in which we solved the one-dimensional (1D) blood flow equations. With a similar parameter estimation method and using the results from the 0D model, we identified the resistance boundary conditions of the 1D network. Determining the patient-specific total resistance and the distribution of peripheral resistances through the parameter estimation process was sufficient for the 1D model to accurately reproduce the impact of clamping on the pressure waveform. Both models gave an accurate description of the pressure wave and had a high correlation (R2 > .95) with experimental blood pressure data.

Characteristics and Determinants of Pulse Pressure-Age Relationship in Healthy and Non-treated Hypertensive Subjects of Argentinean Population.

BACKGROUND: The relationship between the increases in pulse pressure (PP) and arterial stiffness determined by aging or systemic hypertension has been widely reported. These findings are supported by large-cohort analyzes conducted in well-known populations, such as Framingham Study. However, there is evidence that an age-PP curvilinear relationship may exist in hypertensive subjects. This study aimed to evaluate the age-related change in pulse pressure and arterial stiffness in a population-based study. METHODS: Carotid-femoral Pulse Wave Velocity (cfPWV) were obtained in 2075 subjects. RESULTS: Age-related changes of PP showed a curvilinear relationship (R=0.39, p<0.0001) in normotensive subjects, with a nadir at around 50 years of age. On the other hand, the age-cfPWV relationship showed a linear and positive correlation (R=0.72, p<0.0001). PP also showed a curvilinear relationship with age (R=0.36, p<0.0001) in hypertensive subjects, with a nadir around 50 years of age. The age-cfPWV relationship showed a linear and positive correlation (R=0.55, p<0.0001). Similar results were observed in the adult population (age≥16 years). Multivariate analysis showed that age, sex, cfPWV, and mean arterial pressure are determinants of PP values in the entire population; however, this result was not uniform when different subgroups were analyzed. CONCLUSION: In conclusion, age-related changes in PP showed a curvilinear relationship and no parallelism with the age-cfPWV relationship for both normotensive and hypertensive subjects. The determinants of PP impact it differently depending on age and the pathological condition of the subject.

Assessment of Intra-Aortic Counterpulsation in an Animal Model of Heart Failure and Myocardial Ischemia.

The effectiveness of intra-aortic balloon pumping (IABP) is currently evaluated using indirect indexes. The diastolic pressure augmentation is quantified using the subendocardial viability ratio (SEVR) and the DABAC/SABAC index (areas beneath the aortic pressure-time signals during the diastolic and systolic periods, respectively). The SEVR requires invasive recordings of left ventricular pressure; the DABAC/SABAC index may represent an alternative, since it only requires an aortic pressure signal. Nonetheless, it has never been used in an animal model of counterpulsated heart failure and ischemia-reperfusion episode. The aims of this work were: (i) to develop an animal model of heart failure, with a myocardial ischemia-reperfusion episode, treated with IABP during the reperfusion period; (ii) to evaluate the effects of the IABP using the SEVR and DABAC/SABAC indices; and (iii) to assess the relationship between both ratios. Cardiovascular parameters were obtained in anesthetized sheep, in which induced heart failure and ischemia-reperfusion episodes were monitored with and without IABP 1:2. Systolic and diastolic blood pressure signals were assessed in the aorta and in the left ventricle. Values of cardiac output and left ventricular wall thickness signals were obtained. Induction of ischemia and heart failure determined decreases in SEVR and DABAC/SABAC indices with respect to their basal stage (0.807 ± 0.118 vs. 0.601 ± 0.107, P < 0.05 and 1.062 ± 0.136 vs. 0.902 ± 0.161, P < 0.05, respectively). Counterpulsated animals whose myocardial reperfusion was accompanied by heart failure showed a significant improvement of wall thickening fraction along time (R2  = 0.7627, P < 0.001). During counterpulsated heart failure accompanied by myocardial reperfusion, the SEVR was positively correlated with DABAC/SABAC index.

Experimental assessment of a myocyte-based multiscale model of cardiac contractile dysfunction.

Cardiac contractile dysfunction (CD) is a multifactorial syndrome caused by different acute or progressive diseases which hamper assessing the role of the underlying mechanisms characterizing a defined pathological condition. Mathematical modeling can help to understand the processes involved in CD and analyze their relative impact in the overall response. The aim of this study was thus to use a myocyte-based multiscale model of the circulatory system to simulate the effects of halothane, a volatile anesthetic which at high doses elicits significant acute CD both in isolated myocytes and intact animals. Ventricular chambers built using a human myocyte model were incorporated into a whole circulatory system represented by resistances and capacitances. Halothane-induced decreased sarco(endo)plasmic reticulum Ca2+ (SERCA2a) reuptake pump, transient outward K+ (Ito), Na+-Ca2+ exchanger (INCX) and L-type Ca2+ channel (ICaL) currents, together with ryanodine receptor (RyR2) increased open probability (Po) and reduced myofilament Ca2+ sensitivity, reproduced equivalent decreased action potential duration at 90% repolarization and intracellular Ca2+ concentration at the myocyte level reported in the literature. In the whole circulatory system, model reduction in mean arterial pressure, cardiac output and regional wall thickening fraction was similar to experimental results in open-chest sheep subjected to acute halothane overdose. Effective model performance indicates that the model structure could be used to study other changes in myocyte targets eliciting CD.

Arterial Stiffness in Haemodialyzed Patients: Findings and Controversies.

Vascular research in end-stage renal diseases is an interesting field in which the characterization of arterial stiffness proved to be valuable to predict morbidity and mortality. Particularly, patients on renal replacement therapy have been reported to have significant increases in arterial stiffness and cardiovascular mortality. The clinical relevance of the measurement of arterial stiffness is linked to therapeutical and preventive interventions. The purpose of this work is to analyze the results of the scientific research in the field of arterial stiffness, in which hemodialyzed patients were involved, emphasizing on clinical and in-vitro research carried out by our group compared to contributions previously reported in the specialized literature. These investigations are necessary to improve diagnostic strategies and monitor the arterial response to therapeutical interventions in chronic kidney disease.

Central-To-Peripheral Arterial Stiffness Gradient in Hemodialyzed Patients Depends on the Location of the Upper-limb Vascular Access.

BACKGROUND: Pulse wave velocity ratio (PWV-ratio), a measure of central-to-peripheral arterial stiffness gradient, is calculated as a quotient between carotid-femoral and carotid-radial PWV (cf-PWV/cr-PWV). This new index has been reported to be significantly associated with increased mortality in hemodialyzed patients. Since several reports showed differences in arterial stiffness regarding the pathway where the vascular access (VA) is, the purpose of this research was: a) to compare arterial stiffness values obtained in the left and right sides of the body in hemodialyzed and non-hemodialyzed patients, and b) to analyze PWV-ratio values obtained on the side of the body where the VA was placed and compare them to its contralateral intact side. Since it is difficult to adequately measure cr-PWV in patients with a VA in the forearm, we measured the carotid- brachial PWV (cb-PWV) and used it to calculate PWV-ratio (cf-PWV/cb-PWV). METHODS: A Pearson's correlation and Bland & Altman analysis were performed in hemodialyzed (n=135) and non-hemodialyzed (n=77) patients, to quantify the equivalence between arterial stiffness parameters (cf-PWV, cb-PWV, PWV-ratio) obtained on each side of the body with respect to its contralateral side. RESULTS: We conclude that PWV-ratio values measured on the side where the VA is placed were significantly higher than those obtained in its contralateral side, in hemodialyzed patients included in this research. Moreover, cf-PWV, cb-PWV and PWV-ratio values obtained on one side of the body were always highly correlated with its contralateral side. CONCLUSION: According to this research, any research involving PWV-ratio should always consider the observed territory.

Reference intervals and percentiles for carotid-femoral pulse wave velocity in a healthy population aged between 9 and 87 years.

There is little information regarding age-related reference intervals (RIs) of carotid-femoral pulse wave velocity (cfPWV) for large healthy populations in South America. The aims of this study were to determine cfPWV RIs and percentiles in a cohort of healthy children, adolescents, and adults and to generate year-to-year percentile curves and body-height percentile curves for children and adolescents. cfPWV was measured in 1722 healthy participants with no cardiovascular risk factors (9-87 years, 60% men). First, RIs were evaluated for males and females through correlation and covariate analysis. Then, mean and standard deviation age-related equations were obtained for cfPWV using parametric regression methods based on fractional polynomials and age-specific (year-to-year) percentile curves that were defined using the standard normal distribution. Age-specific first, 2.5th, 5th, 10th, 25th, 50th, 75th, 90th, 95th, 97.5th, and 99th percentile curves were calculated. Finally, height-related cfPWV percentile curves for children and adolescents (<21 years) were established. After adjusting for age and blood pressure differences with respect to females, males showed higher cfPWV levels (6.60 vs 6.45 m/s; P < .01). Thus, specific RIs for males and females were reported. The study provides the largest database to date concerning cfPWV in healthy people from Argentina. Specific RIs and percentiles of cfPWV are now available according to age and sex. Specific percentiles of cfPWV according to body height were reported for people younger than 21 years.

The effects of age on pulse wave velocity in untreated hypertension.

Increased arterial stiffness is an important determinant of cardiovascular risk, able to predict morbidity and mortality, and closely associated with ageing and blood pressure. The aims of this study were: (1) To determine the age-dependent reference pulse wave velocity (PWV), and compare it with values from hypertensive patients, and (2) to evaluate the impact of isolated and untreated hypertension on arterial stiffness. A total of 1079 patients were enrolled and divided into a control group (NT) of asymptomatic normotensive patients and a group of asymptomatic hypertensive patients (HT). Blood pressure, carotid-femoral PWV, and body mass index were measured in each subject, whose blood was drawn for laboratory tests. Aortic mean PWV in the NT group was 6.85 ± 1.66 m/s, which increased linearly (R2  = 0.62; P < .05) with age. In patients over 50 years of age, PWV was significantly higher than in younger patients (8.35 vs 5.92 m/s, respectively, P < .001). This significant difference persisted when observing male and female patients separately. In the hypertensive group, mean PWV value was 8.04 ± 1.8 m/s (range 4.5-15.8 m/s) and increased (R2  = 0.243; P < .05) with age. The PWV increase in HT was significantly higher (0.93 m/s per decade, P < .001) than in NT (0.44 m/s per decade). Our study provides normal values of PVW per decade, and shows that these values increase with age, especially after 50 years of age, particularly in HT patients. This stiffness growth rate may be responsible for increased cardiovascular risk in both groups.

Comparative in vivo analysis of the role of the adventitia and the endothelium on arterial mechanical function: relevance for aortic counterpulsation.

PURPOSE: The comparative effect of the intimal and adventitial layers on arterial biomechanics control, in basal and altered conditions, remains to be elucidated. This study aimed (1) to characterize the arterial conduit (CF) and buffering (distensibility) function of the iliac arteries in in vivo animals, in which the intimal and adventitial layers were removed; (2) to determine the effects of intra-aortic ballon pumping (IABP) on simultaneously de-adventitialized (DA) and de-endothelialized (DE) iliac arteries before and after induced heart failure. METHODS: Pressure and diameter signals were measured in the iliac arteries of sheep (n = 7) in which the adventitial and intima layer were removed. Intra-aortic balloon pump (IABP) assistance was used in a control state and after heart failure induction. RESULTS: Both DE and DA determined significant changes in arterial diameter, distensibility and CF. Changes were higher after DA than after DE in terms of distensibility and CF (p<0.05). DA followed by DE (DA + DE) showed significant increases in arterial diameter and CF, accompanied by a decrease in distensibility (p<0.05) with respect to intact arteries. Heart failure induction caused significant hemodynamic changes without modifying the already impaired local biomechanical parameters. Nonsignificant improvements in the biomechanical parameters of DA + DE iliac arteries were observed during IABP before and after heart failure induction. CONCLUSIONS: Biomechanical changes caused by DA of iliac arteries were more important than those observed after DE. The DA + DE arteries showed significant differences with respect to intact arteries and with DA or DE arteries. IABP-related effects on arterial mechanics were absent in DA + DE arteries.

Aortic-Radial Pulse Wave Velocity Ratio in End-stage Renal Disease Patients: Association with Age, Body Tissue Hydration Status, Renal Failure Etiology and Five Years of Hemodialysis.

INTRODUCTION: The etiology of the end-stage renal disease (ESRD) and the hydration status may be involved in the arterial stiffening process observed in hemodialyzed patients. The ratio between carotid-femoral and carotid-radial pulse wave velocity (PWV ratio) was recently proposed to characterize the patient-specific stiffening process. AIMS: to analyze: (1) the PWV-ratio in healthy and hemodialyzed subjects, analyzing potential changes associated to etiologies of the ESRD, (2) the PWV-ratio and hydration status using multiple-frequency bioimpedance and, (3) the effects of hemodialysis on PWV-ratio in a 5-year follow-up. METHODS: PWV-ratio was evaluated in 151 patients differentiated by the pathology determining their ESRD. Total body fluid (TBF), intra and extra cellular fluid (ICF, ECF) were measured in 65 of these patients using bioelectrical-impedance. The association between arterial, hemodynamic or fluid parameters was analyzed. PWV-ratio was evaluated in a group of patients (n = 25) 5 years later (follow-up study). RESULTS: PWV-ratio increased in the ESRD cohort with respect to the control group (1.03 ± 0.23 vs. 1.31 ± 0.37; p < 0.001). PWV-ratio in the diabetic nephropathy group was higher than in all other etiological groups (1.61 ± 0.33; p < 0.05). PWV-ratio was associated with TBF (r = -0.238; p < 0.05), ICF (r = -0.323; p < 0.01), ECF/ICF (r = 0.400; p < 0.001) and ECF/TBF (r = 0.403; p < 0.001). PWV-ratio calculated in ESRD patients in 2007 increased 5 years later (1.14 ± 0.32 vs. 1.43 ± 0.44; p < 0.005). CONCLUSIONS: PWV-ratio increased the most in patients with diabetic nephropathy. PWV ratio was significantly associated with age and body hydration status, but not with the blood pressure. PWV-ratio could be considered a blood pressure-independent parameter, associated with the age and hydration status of the patient.

Hemodialysis Decreases the Etiologically-Related Early Vascular Aging Observed in End-Stage Renal Disease: A 5-Year Follow-Up Study.

AIMS: To analyze the early vascular aging (EVA) in end-stage renal disease (ESRD) patients, attempting to determine a potential association between EVA and the etiology of ESRD, and to investigate the association of hemodialysis and EVA in ESRD patients during a 5-year follow-up period. METHODS: Carotid-femoral pulse wave velocity (cfPWV) was obtained in 151 chronically hemodialyzed patients (CHP) and 283 control subjects, and in 25 CHP, who were followed-up after a 5-year lapse. RESULTS: cfPWV increased in ESRD patients compared to control subjects. The cfPWV-age relationship was found to have a steeper increase in ESRD patients. The highest cfPWV and EVA values were observed in patients with diabetic nephropathy. Regression analysis demonstrated a significant reduction of the EVA in HD patients on a 5-year follow-up. CONCLUSION: Patients in ESRD showed higher levels of EVA. cfPWV and EVA differed in ESRD patients depending on their renal failure etiology. CHP showed an EVA reduction after a 5-year follow-up period.

Hydration Status Is Associated with Aortic Stiffness, but Not with Peripheral Arterial Stiffness, in Chronically Hemodialysed Patients.

Background. Adequate fluid management could be essential to minimize high arterial stiffness observed in chronically hemodialyzed patients (CHP). Aim. To determine the association between body fluid status and central and peripheral arterial stiffness levels. Methods. Arterial stiffness was assessed in 65 CHP by measuring the pulse wave velocity (PWV) in a central arterial pathway (carotid-femoral) and in a peripheral pathway (carotid-brachial). A blood pressure-independent regional arterial stiffness index was calculated using PWV. Volume status was assessed by whole-body multiple-frequency bioimpedance. Patients were first observed as an entire group and then divided into three different fluid status-related groups: normal, overhydration, and dehydration groups. Results. Only carotid-femoral stiffness was positively associated (P < 0.05) with the hydration status evaluated through extracellular/intracellular fluid, extracellular/Total Body Fluid, and absolute and relative overhydration. Conclusion. Volume status and overload are associated with central, but not peripheral, arterial stiffness levels with independence of the blood pressure level, in CHP.

Arterial Stiffness and Renal Replacement Therapy: A Controversial Topic.

The increase of arterial stiffness has been to have a significant impact on predicting mortality in end-stage renal disease patients. Pulse wave velocity (PWV) is a noninvasive, reliable parameter of regional arterial stiffness that integrates the vascular geometry and arterial wall intrinsic elasticity and is capable of predicting cardiovascular mortality in this patient population. Nevertheless, reports on PWV in dialyzed patients are contradictory and sometimes inconsistent: some reports claim the arterial wall stiffness increases (i.e., PWV increase), others claim that it is reduced, and some even state that it augments in the aorta while it simultaneously decreases in the brachial artery pathway. The purpose of this study was to analyze the literature in which longitudinal or transversal studies were performed in hemodialysis and/or peritoneal dialysis patients, in order to characterize arterial stiffness and the responsiveness to renal replacement therapy.

La adventicia arterial: actor olvidado del sistema cardiovascular

Actualmente se acepta que la adventicia tiene: un importante rol fisiológico al determinar el nivel de nutrición, oxigenación, reparación arterial, regulación de la vasomotricidad, control de la poscarga ventricular, control de la función arterial, etcétera, a la vez que tiene una importante participación en procesos patológicos (por ejemplo, aterosclerosis, hipertensión arterial, génesis de aneurismas de aorta abdominal). Sin embargo, dado lo reciente de la mayoría de los estudios que han redefinido el rol de la adventicia, aún persiste mucho desconocimiento en la comunidad biomédica acerca de la fisiología de la capa adventicia arterial. El presente trabajo tiene como objetivo revisar el rol que actualmente se reconoce para la capa adventicia de la pared arterial.

Hemodialysis decreases carotid-brachial and carotid-femoral pulse wave velocities: A 5-year follow-up study.

Aortic stiffness is a prognostic parameter associated with patient mortality. Vascular access creation has been shown to have effects on arterial stiffness both in the aorta and in the upper limb arteries in chronically hemodialyzed patients (CHPs). However, no longitudinal studies have been conducted in order to characterize the evolution of arterial stiffness in CHPs. The aims of this work were (a) to measure baseline pulse wave velocity (PWV) in the carotid-femoral and in right and left carotid-brachial pathways in a cohort of CHP and (b) to conduct a 5-year prospective study on the same cohort to determine possible time-related differences. Pulse wave velocity was measured both in the carotid-femoral and in the carotid-brachial pathways, and clinical and biochemical parameters were collected in 25 CHPs, which were followed up after a 5-year lapse. Right and left carotid-brachial pathway PWV values showed significant decreases after the 5-year follow-up, independently of the presence of the vascular access (P < 0.001). Additionally, baseline carotid-brachial PWV was significantly higher (P < 0.001) than values measured 5 years later for upper limbs with vascular access (11.97 ± 2.97 m/sec vs. 6.76 ± 1.48 m/sec, respectively) and without vascular access (12.25 ± 2.38 m/sec vs. 7.18 ± 1.88 m/sec, respectively). Similarly, PWV values in the carotid-femoral pathway decreased significantly (P < 0.001) over the same period (13.27 ± 2.96 m/sec vs. 9.75 ± 2.99 m/sec, respectively). The 5-year follow-up of PWV showed significant decreases in both carotid-brachial and carotid-femoral pathways. The general changes in arterial stiffness could be related to the vascular access creation, hemodialysis therapy, and to the improvement of arterial pressure management.

A proposal to enhance Engineering education in biology and Medicine by following the legacy of René Favaloro.

The synergy amongst Engineering, Medicine and Biology evolves as fast as these disciplines. We propose to articulate these specialties based on the premise that new professionals must face different situations or crisis due to the so-called islands of excellence. René Favaloro focused his work and struggles against poverty, since malnutrition and environmental degradation may increase the propensity to cardiovascular diseases. Doctor Favaloro has dedicated, throughout his career, a considerable amount of time to prepare and qualify a research group, aware of the importance that an adequate working environment has over the final results. He created a team of young students, engineers, medical doctors, physicists, mathematicians and other specialists. He centered his attention on human resources, in order to disseminate his latest advances in Biology, Medicine and Engineering. We are revising the programs of biomedical engineering education and the application of new pedagogic paradigms, where critical thinking is the key: a holistic challenge that consists of a new way of learning, innovating, communicating and shearing, with a creative attitude that represents quality of perception.

The adventitia layer modulates the arterial wall elastic response to intra-aortic counterpulsation: in vivo studies.

There is a relationship between the intra-aortic balloon pumping (IABP) benefits and the dynamic behavior of muscular arteries, which is associated with induced changes on the vessel walls through an endothelial-dependent mechanism. The arterial wall elastic behavior is influenced by adventitial function; however, no studies were performed in order to elucidate if this layer plays a role in the changes determined by IABP. Our aim was to quantify acute IABP effects on the mechanical properties of muscular arteries in induced acute heart failure (AHF), before and after adventitia removal. Pressure and diameter were recorded in the iliac arteries (IA) of sheep (n = 7), before and during 1:2 IABP: (i) in control state (CS) with intact IA, (ii) in CS after IA adventitia removal, and (iii) in de-adventitialized IA after AHF. Conduit function, compliance and arterial distensibility were calculated in each state. During CS, IABP resulted in intact IA dilatation and in an increase in conduit function, compliance and distensibility; adventitial removal determined an increase of arterial stiffness with respect to the CS, which decreased when IABP was used; the increase in arterial stiffness observed after adventitia removal was also detected in AHF state; IABP improves conduit function and arterial stiffness in de-adventitialized arteries, both before and during AHF. However, the improvement in these properties was lower than in intact arteries. Before and after AHF induction, the improvements of conduit function and arterial distensibility determined by IABP in intact IA were significantly reduced after adventitia removal. Adventitial layer integrity would be necessary to maximize IABP-related beneficial effects on arterial system properties.