scholarly journals Mathematical Modeling of the Antihypertensive Drugs Action

2019 ◽  
Vol 14 (1) ◽  
pp. 233-256
Author(s):  
I.N. Kiselev ◽  
E.O. Kutumova ◽  
A.F. Kolpakova ◽  
G.I. Lifshits ◽  
F.A. Kolpakov
Keyword(s):  
Mathematical Modeling ◽  
Blood Pressure ◽  
Clinical Trials ◽  
Cardiovascular System ◽  
Antihypertensive Drugs ◽  
Mechanisms Of Action ◽  
Virtual Patients ◽  
Blood Pressure Decrease ◽  
Human Cardiovascular System ◽  
Good Agreement

Arterial hypertension is one of the most common diseases of the human cardiovascular system and is characterized by persistent increase in blood pressure. Normalization of blood pressure can be achieved by using antihypertensive drugs with various mechanisms of action. In this work, we investigated a modular mathematical model of the human cardiovascular system created earlier, and complemented it with pharmacodynamic models of five different classes of antihypertensive drugs with such exemplars as aliskiren, losartan, bisoprolol, enalapril and amlodipine. We used clinical trials found in the literature in order to validate the resulting model. Specifically, we generated a population of virtual patients with high blood pressure and modeled their treatment with these antihypertensive drugs. Eventually, the model predicted blood pressure decrease in good agreement with clinical trials. In this way, our model can be further used to optimize the choice of drugs for a particular patient.In silico

Bifurcation in a Simple Model of the Cardiovascular System

2000 ◽  
Vol 39 (02) ◽  
pp. 118-121 ◽  
Author(s):  
S. Akselrod ◽  
S. Eyal
Keyword(s):  
Nonlinear Dynamics ◽  
Blood Pressure ◽  
Heart Rate ◽  
Fixed Point ◽  
Cardiovascular System ◽  
Modified Model ◽  
Mayer Waves ◽  
Sustained Oscillations ◽  
Human Cardiovascular System ◽  
Physiological Values

Abstract:A simple nonlinear beat-to-beat model of the human cardiovascular system has been studied. The model, introduced by DeBoer et al. was a simplified linearized version. We present a modified model which allows to investigate the nonlinear dynamics of the cardiovascular system. We found that an increase in the -sympathetic gain, via a Hopf bifurcation, leads to sustained oscillations both in heart rate and blood pressure variables at about 0.1 Hz (Mayer waves). Similar oscillations were observed when increasing the -sympathetic gain or decreasing the vagal gain. Further changes of the gains, even beyond reasonable physiological values, did not reveal another bifurcation. The dynamics observed were thus either fixed point or limit cycle. Introducing respiration into the model showed entrainment between the respiration frequency and the Mayer waves.

scholarly journals Antihypertensive Treatment in the Elderly and Very Elderly: Always “the Lower, the Better?”

2012 ◽  
Vol 2012 ◽  
pp. 1-4 ◽  
Author(s):  
Alberto Mazza ◽  
Emilio Ramazzina ◽  
Stefano Cuppini ◽  
Michela Armigliato ◽  
Laura Schiavon ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Clinical Trials ◽  
Antihypertensive Treatment ◽  
Antihypertensive Drugs ◽  
The Elderly ◽  
Organ Damage ◽  
Very Elderly ◽  
Age Dependent ◽  
Prolongation Of Life ◽  
Per Se

Arterial hypertension (HT) is age dependent and, with the prolongation of life expectancy, affects more and more elderly people. In the elderly, HT is a risk factor for organ damage and cardiovascular (CV) events. Both pharmacologic and nonpharmacologic reduction of blood pressure (BP) is associated with a corresponding decrease in systolic-diastolic or isolated systolic HT. Clinical trials have shown that BP lowering is associated with a decrease in stroke and other CV events. Therefore, BP reductionper seappears more important than a particular class of antihypertensive drugs. The benefit of antihypertensive treatment has been confirmed up to the age of 80 years, remaining unclear in the octogenarians. The benefit in lowering diastolic BP between 80 and 90 mmHg is well established, while that of lowering systolic BP below 140 mmHg requires further confirmations.

scholarly journals Fixed combination of lercanidipine with enalapril - pharmacological features, clinical feasibility, advantages in the treatment of hypertension

2021 ◽  
pp. 21-24
Author(s):  
P. О. Lazarev
Keyword(s):  
Oxidative Stress ◽  
Blood Pressure ◽  
Arterial Hypertension ◽  
Fixed Combination ◽  
Antihypertensive Drugs ◽  
Mechanisms Of Action ◽  
High Efficacy ◽  
National Guidelines ◽  
Treatment Of Hypertension ◽  
And Oxidative Stress

According to current international and national guidelines for the management of arterial hypertension preference is given to the use of fixed combinations of antihypertensive drugs of different classes, thus increasing the effectiveness of therapy acting in a complementary manner to affect different pathogenic mechanisms of arterial hypertension and reducing the frequency of side effects. A fixed combination of lercanidipine and enalapril contains antihypertensive drugs that have complementary mechanisms of action. This combination effectively reduces blood pressure, has high efficacy and tolerability, it may provide an additive effect on macro- and microvascular structures, arterial stiffness and oxidative stress. It has a beneficial influence on renal function, especially in patients with comorbidities.

scholarly journals Fixed-Dose Triple Combination of Antihypertensive Drugs Improves Blood Pressure Control: From Clinical Trials to Clinical Practice

2017 ◽  
Vol 34 (4) ◽  
pp. 975-985 ◽  
Author(s):  
Alberto Mazza ◽  
Salvatore Lenti ◽  
Laura Schiavon ◽  
Antonella Paola Sacco ◽  
Fabio Dell’Avvocata ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Clinical Trials ◽  
Clinical Practice ◽  
Blood Pressure Control ◽  
Antihypertensive Drugs ◽  
Pressure Control ◽  
Fixed Dose ◽  
Triple Combination

scholarly journals A computational physiology approach to personalized treatment models: the beneficial effects of slow breathing on the human cardiovascular system

2014 ◽  
Vol 307 (7) ◽  
pp. H1073-H1091 ◽  
Author(s):  
Maria Fonoberova ◽  
Igor Mezić ◽  
Jennifer F. Buckman ◽  
Vladimir A. Fonoberov ◽  
Adriana Mezić ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Heart Rate Variability ◽  
Cardiovascular System ◽  
Empirical Support ◽  
System Level ◽  
Heart Period ◽  
Heart Rate Variability Biofeedback ◽  
Human Cardiovascular System ◽  
Slow Breathing

Heart rate variability biofeedback intervention involves slow breathing at a rate of ∼6 breaths/min (resonance breathing) to maximize respiratory and baroreflex effects on heart period oscillations. This intervention has wide-ranging clinical benefits and is gaining empirical support as an adjunct therapy for biobehavioral disorders, including asthma and depression. Yet, little is known about the system-level cardiovascular changes that occur during resonance breathing or the extent to which individuals differ in cardiovascular benefit. This study used a computational physiology approach to dynamically model the human cardiovascular system at rest and during resonance breathing. Noninvasive measurements of heart period, beat-to-beat systolic and diastolic blood pressure, and respiration period were obtained from 24 healthy young men and women. A model with respiration as input was parameterized to better understand how the cardiovascular processes that control variability in heart period and blood pressure change from rest to resonance breathing. The cost function used in model calibration corresponded to the difference between the experimental data and model outputs. A good match was observed between the data and model outputs (heart period, blood pressure, and corresponding power spectral densities). Significant improvements in several modeled cardiovascular functions (e.g., blood flow to internal organs, sensitivity of the sympathetic component of the baroreflex, ventricular elastance) were observed during resonance breathing. Individual differences in the magnitude and nature of these dynamic responses suggest that computational physiology may be clinically useful for tailoring heart rate variability biofeedback interventions for the needs of individual patients.

scholarly journals A Bioinformatics Perspective on the Links Between Tetraspanin-Enriched Microdomains and Cardiovascular Pathophysiology

2021 ◽  
Vol 8 ◽  
Author(s):  
Ge Sun ◽  
Junxiong Chen ◽  
Yingjun Ding ◽  
Jonathan D. Wren ◽  
Fuyi Xu ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Cardiovascular System ◽  
Target Genes ◽  
Mapk Signaling ◽  
Immunoglobulin Superfamily ◽  
Membrane Domains ◽  
Expression Levels ◽  
Blood Pressure Data ◽  
Human Cardiovascular System ◽  
Cell Adhesion Proteins

Background: Tetraspanins and integrins are integral membrane proteins. Tetraspanins interact with integrins to modulate the dynamics of adhesion, migration, proliferation, and signaling in the form of membrane domains called tetraspanin-enriched microdomains (TEMs). TEMs also contain other cell adhesion proteins like immunoglobulin superfamily (IgSF) proteins and claudins. Cardiovascular functions of these TEM proteins have emerged and remain to be further revealed.Objectives: The aims of this study are to explore the roles of these TEM proteins in the cardiovascular system using bioinformatics tools and databases and to highlight the TEM proteins that may functionally associate with cardiovascular physiology and pathology.Methods: For human samples, three databases—GTEx, NCBI-dbGaP, and NCBI-GEO—were used for the analyses. The dbGaP database was used for GWAS analysis to determine the association between target genes and human phenotypes. GEO is an NCBI public repository that archives genomics data. GTEx was used for the analyses of tissue-specific mRNA expression levels and eQTL. For murine samples, GeneNetwork was used to find gene–phenotype correlations and gene–gene correlations of expression levels in mice. The analysis of cardiovascular data was the focus of this study.Results: Some integrins and tetraspanins, such as ITGA8 and Cd151, are highly expressed in the human cardiovascular system. TEM components are associated with multiple cardiovascular pathophysiological events in humans. GWAS and GEO analyses showed that human Cd82 and ITGA9 are associated with blood pressure. Data from mice also suggest that various cardiovascular phenotypes are correlated with integrins and tetraspanins. For instance, Cd82 and ITGA9, again, have correlations with blood pressure in mice.Conclusion:ITGA9 is related to blood pressure in both species. KEGG analysis also linked ITGA9 to metabolism and MAPK signaling pathway. This work provides an example of using integrated bioinformatics approaches across different species to identify the connections of structurally and/or functionally related molecules to certain categories of diseases.

scholarly journals Simulating Dynamics of Circulation in the Awake State and Different Stages of Sleep Using Non-autonomous Mathematical Model With Time Delay

2021 ◽  
Vol 11 ◽  
Author(s):  
Anatoly S. Karavaev ◽  
Yurii M. Ishbulatov ◽  
Mikhail D. Prokhorov ◽  
Vladimir I. Ponomarenko ◽  
Anton R. Kiselev ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Mathematical Model ◽  
Cardiovascular System ◽  
Healthy Subjects ◽  
Blood Circulation ◽  
Control Loops ◽  
Awake State ◽  
Proposed Model ◽  
Human Cardiovascular System ◽  
First Time

We propose a mathematical model of the human cardiovascular system. The model allows one to simulate the main heart rate, its variability under the influence of the autonomic nervous system, breathing process, and oscillations of blood pressure. For the first time, the model takes into account the activity of the cerebral cortex structures that modulate the autonomic control loops of blood circulation in the awake state and in various stages of sleep. The adequacy of the model is demonstrated by comparing its time series with experimental records of healthy subjects in the SIESTA database. The proposed model can become a useful tool for studying the characteristics of the cardiovascular system dynamics during sleep.

scholarly journals Beneficial and Adverse Effects of Testosterone on the Cardiovascular System in Men

2013 ◽  
Vol 98 (11) ◽  
pp. 4300-4310 ◽  
Author(s):  
Johannes B. Ruige ◽  
D. Margriet Ouwens ◽  
Jean-Marc Kaufman
Keyword(s):  
Blood Pressure ◽  
Cardiovascular Disease ◽  
Clinical Trials ◽  
Cardiovascular System ◽  
Ventricular Function ◽  
Randomized Clinical Trials ◽  
Evidence Synthesis ◽  
Cardiovascular Effects ◽  
Left Ventricular ◽  
Aging Men

Context: The widespread use of T therapy, particularly in aging males, necessitates knowledge of the relationship between T and the cardiovascular system. Evidence Acquisition: The review is based on a 1970 to 2013 PubMed search with terms related to androgens in combination with cardiovascular disease, including T, dihydrotestosterone, trial, mortality, cardiovascular disease, myocardial infarction, blood pressure, endothelial function, dyslipidemia, thrombosis, ventricular function, and arrhythmia. Original articles, systematic reviews and meta-analyses, and relevant citations were screened. Evidence Synthesis: Low T has been linked to increased blood pressure, dyslipidemia, atherosclerosis, arrhythmia, thrombosis, endothelial dysfunction, as well as to impaired left ventricular function. On the one hand, a modest association is suggested between low endogenous T and incident cardiovascular disease or cardiovascular mortality, implying unrecognized beneficial T effects, residual confounding, or a relationship with health status. On the other hand, treatments with T to restore “normal concentrations” have so far not been proven to be beneficial with respect to cardiovascular disease; neither have they definitely shown specific adverse cardiovascular effects. The cardiovascular risk-benefit profile of T therapy remains largely evasive in view of a lack of well-designed and adequately powered randomized clinical trials. Conclusions: The important knowledge gap as to the exact relationship between T and cardiovascular disease would support a cautious, restrained approach to T therapy in aging men, pending clarification of benefits and risks by adequately powered clinical trials of sufficient duration.

scholarly journals A New Blood Pulsation Simulator Platform Incorporating Cardiovascular Physiology for Evaluating Radial Pulse Waveform

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Tae-Heon Yang ◽  
Jaeuk U. Kim ◽  
Young-Min Kim ◽  
Jeong-Hoi Koo ◽  
Sam-Yong Woo
Keyword(s):  
Blood Pressure ◽  
Cardiovascular System ◽  
Radial Artery ◽  
Pressure Sensors ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Artery Pressure ◽  
Age Dependent ◽  
Radial Artery Pressure ◽  
Human Cardiovascular System

To meet the need for “standard” testing system for wearable blood pressure sensors, this study intends to develop a new radial pulsation simulator that can generate age-dependent reference radial artery pressure waveforms reflecting the physiological characteristics of human cardiovascular system. To closely duplicate a human cardiovascular system, the proposed simulator consists of a left ventricle simulation module, an aorta simulation module, a peripheral resistance simulation module, and a positive/negative pressure control reservoir module. Simulating physiologies of blood pressure, the compliance chamber in the simulator can control arterial stiffness to produce age-dependent pressure waveforms. The augmentation index was used to assess the pressure waveforms generated by the simulator. The test results show that the simulator can generate and control radial pressure waveforms similar to human pulse signals consisting of early systolic pressure, late systolic pressure, and dicrotic notch. Furthermore, the simulator’s left ventricular pressure-volume loop results demonstrate that the simulator exhibits mechanical characteristics of the human cardiovascular system. The proposed device can be effectively used as a “standard” radial artery pressure simulator to calibrate the wearable sensor’s measurement characteristics and to develop more advanced sensors. The simulator is intended to serve as a platform for the development, performance verification, and calibration of wearable blood pressure sensors. It will contribute to the advancement of the wearable blood pressure sensor technology, which enables real-time monitoring of users’ radial artery pressure waveforms and eventually predicting cardiovascular diseases.

Mathematical modeling of human cardiovascular system for simulation of orthostatic response

1992 ◽  
Vol 262 (6) ◽  
pp. H1920-H1933 ◽  
Author(s):  
F. M. Melchior ◽  
R. S. Srinivasan ◽  
J. B. Charles
Keyword(s):  
Mathematical Modeling ◽  
Cardiovascular System ◽  
Cardiovascular Regulation ◽  
Comprehensive Model ◽  
Short Term ◽  
Different Types ◽  
Consistent Manner ◽  
Human Cardiovascular System ◽  
Cardiovascular Models ◽  
Term Response

This paper deals with the short-term response of the human cardiovascular system to orthostatic stresses in the context of developing a mathematical model of the overall system. It discusses the physiological issues involved and how these issues have been handled in published cardiovascular models for simulation of orthostatic response. Most of the models are stimulus specific with no demonstrated capability for simulating the responses to orthostatic stimuli of different types. A comprehensive model incorporating all known phenomena related to cardiovascular regulation would greatly help to interpret the various orthostatic responses of the system in a consistent manner and to understand the interactions among its elements. This paper provides a framework for future efforts in mathematical modeling of the entire cardiovascular system.

Sign in / Sign up

Export Citation Format

Share Document