Perioperative Quality Initiative (POQI) consensus statement on the physiology of blood pressure control as applied to perioperative medicine.

Background: A multi-disciplinary, international working subgroup of the Third Perioperative Quality Initiative (POQI) consensus meeting reviewed the (patho)physiology and measurement of arterial blood pressure (ABP), as applied to perioperative medicine. Methods: We addressed predefined questions by undertaking a modified Delphi analysis, in which primary clinical research and review articles were identified using MEDLINE. Strength of recommendations, where applicable, were graded by NICE guidelines. Results: Perioperative ABP management is a physiologically-complex challenge influenced by multiple factors: (i) ABP is the input pressure to organ blood flow, but is not the sole determinant of perfusion pressure; (ii) blood flow is often independent of changes in perfusion pressure, due to autoregulatory changes in vascular resistance; (iii) microvascular dysfunction uncouples microvascular blood flow from ABP (haemodynamic incoherence) From a practical clinical perspective, we identified that: (i) ambulatory measurement is the optimal method to establish baseline ABP; (ii) automated and invasive ABP measurements have inherent physiological and technical limitations; (iii) individualised ABP targets may change over time, especially during the perioperative period. There remains a need for research in non-invasive, continuous arterial pressure measurements, macro- and microcirculatory control, regional perfusion pressure measurement and the development of sensitive, specific and continuous measures of cellular function to evaluate blood pressure management in a physiologically coherent manner. Conclusion: The multivariable, complex physiology contributing to dynamic changes in perioperative ABP may be underappreciated clinically. The frequently unrecognised dissociation between ABP, organ blood flow, microvascular and cellular function requires further research that develops a more refined, contextualized clinical approach to this routine measurement

Modelling the characteristics of the baroreceptor

A dissertation submitted to the Faculty of Engineering and the Built Environment, University of Witwatersrand in fulfilment of the requirements for the degree of Master of Science in Engineering. 2017The baroreceptor is a stretch receptor which detects changes in pressure in arterial blood vessels. Baroreceptor nerves inform the brainstem of changes in blood pressure, which then influences sympathetic and parasympathetic nervous activity to counteract that change. Due to the relationship between essential hypertension, sympathetic nervous activity and the baroreflex, there is some debate in the literature about whether the baroreflex can act as a long-term controller of blood pressure. This debate has increased in recent years, due to the high prevalence of essential hypertension in all societies and the introduction of new technologies to counteract drug-resistance hypertension. The baroreflex has become a source of debate due to the complex physiological feedback control that regulates blood pressure and due to new stimulating electrical devices, which have shown promising results in reducing drug-resistant essential hypertension. system. This is done through a literature survey extending through experimental and modelling research, where selected mathematical models of the baroreceptor are then analysed and simulated to find the best performing model, so that they may be simulated for an extended frequency response than what would be experimentally possible. The purpose of this investigation is to determine, through simulation, what the sensor static and dynamic characteristics are. Through this characterisation of the sensor behaviour of the baroreceptor in the baroreflex control loop, it is then possible to infer whether the baroreflex can act as a long-term controller of blood pressure. An overview of experimental and analytical investigations on the baroreceptor over the last 70 years is summarised. This overview includes mathematical models, which predict experimental results. A subset of four models from Srinivasen et al., Bugenhagen et al., Beard et al. and Mahdi et al. are selected. These models are implemented in MATLAB and Simulink. The parameters and experimental conditions are integrated into the Simulink models, and the simulated results are compared to the reported experimental data. In this way, each mathematical model is evaluated using secondary data for its ability to simulate the expected behaviour. Thereafter, all simulated models are compared under the same input conditions (a 0-230 mmHg step input over 12 s). These results are used to select the best performing models, based on how well they were parameterised and validated for experimental tests. The best performing models are those of Beard et al. and Bugenhagen et al. They are tested for a wide range of artificial inputs at different frequencies, with sinusoidal inputs which have periods that range from 0.1 s to 10 days and have a 100 mmHg operating point with a 1 mmHg peak amplitude. All modelling techniques studied show that the baroreceptor firing response resets due to the rate of change in strain in the visco-elastic arterial wall. Both tested model frequency responses, although parameterised for different species and for different major vessels, show high sensitivity to inputs in range from 1 s to 1 min 36 s (0.01 Hz 1Hz), and very low sensitivity for changes that are longer than 16 min 36s (0.001 Hz). This extrapolated simulation suggests a zero gain near DC. The simulated frequency response of the best performing baroreceptor models, which were validated against short-term experimental data, indicate that the baroreceptor is only able to sense changes that happen in less than 1 min 16s. The critical analysis of all the simulated baroreceptor models show that this characteristic of the baroreceptor is caused by the visco-elastic layers of the arterial wall, and is likely in all baroreceptors regardless of type or species. It also indicates that under electrical stimulation of the baroreceptor, the input signal from the electrical device bypasses the baroreceptor nerve ending (which is embedded in the arterial wall) and that the electrical signal of the baroreceptor is bypassed by the new stimulated electrical signal of the device. Furthermore, if the sensor can only detect short-term changes, then it is unlikely that the baroreceptor can inform the brainstem on longterm changes to mean arterial blood pressure. Therefore, based on the models examined in this study, this suggests that the baroreceptor is unlikely to be involved in long-term blood pressure control. This analysis of the best performing model is presented to show the limitations of the baroreflex in long term control of blood pressure. It serves as a simulated experiment to rationalise the contentious debate around the role of the baroreflex in long term blood pressure control, and to allow for future improvements that can be made on the baroreceptor model to allow for more extended modelling on sor characteristics. An improvement that could be applied to the best performing baroreceptor models, implemented in this study, is to examine the effects of ageing and inter-species variability on carotid sinus dimensions and visco-elastic wall properties.CK201

A computational analysis of the long-term regulation of arterial pressure

The asserted dominant role of the kidneys in the chronic regulation of blood pressure and in the etiology of hypertension has been debated since the 1970s. At the center of the theory is the observation that the acute relationships between arterial pressure and urine production—the acute pressure-diuresis and pressure-natriuresis curves—physiologically adapt to perturbations in pressure and/or changes in the rate of salt and volume intake. These adaptations, modulated by various interacting neurohumoral mechanisms, result in chronic relationships between water and salt excretion and pressure that are much steeper than the acute relationships. While the view that renal function is the dominant controller of arterial pressure has been supported by computer models of the cardiovascular system known as the “Guyton-Coleman model”, no unambiguous description of a computer model capturing chronic adaptation of acute renal function in blood pressure control has been presented. Here, such a model is developed with the goals of: 1. representing the relevant mechanisms in an identifiable mathematical model; 2. identifying model parameters using appropriate data; 3. validating model predictions in comparison to data; and 4. probing hypotheses regarding the long-term control of arterial pressure and the etiology of primary hypertension. The developed model reveals: long-term control of arterial blood pressure is primarily through the baroreflex arc and the renin-angiotensin system; and arterial stiffening provides a sufficient explanation for the etiology of primary hypertension associated with ageing. Furthermore, the model provides the first consistent explanation of the physiological response to chronic stimulation of the baroreflex

Arterial Stiffening Provides Sufficient Explanation for Primary Hypertension

<div><p>Hypertension is one of the most common age-related chronic disorders, and by predisposing individuals for heart failure, stroke, and kidney disease, it is a major source of morbidity and mortality. Its etiology remains enigmatic despite intense research efforts over many decades. By use of empirically well-constrained computer models describing the coupled function of the baroreceptor reflex and mechanics of the circulatory system, we demonstrate quantitatively that arterial stiffening seems sufficient to explain age-related emergence of hypertension. Specifically, the empirically observed chronic changes in pulse pressure with age and the impaired capacity of hypertensive individuals to regulate short-term changes in blood pressure arise as emergent properties of the integrated system. The results are consistent with available experimental data from chemical and surgical manipulation of the cardio-vascular system. In contrast to widely held opinions, the results suggest that primary hypertension can be attributed to a mechanogenic etiology without challenging current conceptions of renal and sympathetic nervous system function.</p></div

Vascular smooth muscle cells and arterial stiffening : relevance in development, aging, and disease

The cushioning function of large arteries encompasses distension during systole and recoil during diastole which transforms pulsatile flow into a steady flow in the microcirculation. Arterial stiffness, the inverse of distensibility, has been implicated in various etiologies of chronic common and monogenic cardiovascular diseases and is a major cause of morbidity and mortality globally. The first components that contribute to arterial stiffening are extracellular matrix (ECM) proteins that support the mechanical load, while the second important components are vascular smooth muscle cells (VSMCs), which not only regulate actomyosin interactions for contraction but mediate also mechanotransduction in cell-ECM homeostasis. Eventually, VSMC plasticity and signaling in both conductance and resistance arteries are highly relevant to the physiology of normal and early vascular aging. This review summarizes current concepts of central pressure and tensile pulsatile circumferential stress as key mechanical determinants of arterial wall remodeling, cell-ECM interactions depending mainly on the architecture of cytoskeletal proteins and focal adhesion, the large/small arteries cross-talk that gives rise to target organ damage, and inflammatory pathways leading to calcification or atherosclerosis. We further speculate on the contribution of cellular stiffness along the arterial tree to vascular wall stiffness. In addition, this review provides the latest advances in the identification of gene variants affecting arterial stiffening. Now that important hemodynamic and molecular mechanisms of arterial stiffness have been elucidated, and the complex interplay between ECM, cells, and sensors identified, further research should study their potential to halt or to reverse the development of arterial stiffness