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Modeling of Mechanisms Providing the Overall Control of Human Circulation

Advances in Human Physiology Research 2022年第1期4卷 5-21页

作者： Grygoryan R.D. Department of“Human Systems Modeling” Cybernetics CenterInstitute of Software Systems of National Academy of SciencesKievUkraine

Multiple humoral and nervous mechanisms,each influencing the cardiovascular system(CVS)with its specific dynamics and power,had been evolutionarily saved both in animals and in human *** of such mechanisms are considered to be controllers of CVS’s function,but there is no concept clearly explaining the interaction of global and local controllers in intact human organisms under physiological or pathological *** and ethical constraints create practically insuperable obstacles while experiments on animals mainly concern artificial situations with certain switched-of ***,mathematical modeling and computer simulations provide the most promising way for expanding and deepening our understanding of regulators’*** most of CVS’s models describe only partial control mechanisms,a special model(SM)capable of simulating every combination of control mechanisms is *** paper has three goals:i)to argue the uncial modeling concept and its physiological basis,ii)to describe SM,and iii)to give basic information about SM’s test *** describes human hemodynamics,which is under influence of arterial baroreceptor reflexes,peripheral chemoreceptor reflexes,central(cRAS)and local(lRAS)renin-angiotensin systems,local ischemia,and autoregulation of total brain ***,performed in form of special software(SS),is tested under specific endogenous and/or exogenous *** physiologist using SS can easily construct the desirable configuration of regulator mechanisms,their actual state,and scenarios of computer *** illustrated the adequateness of SM,are the first step of SM’s *** of the interaction of modeled regulator mechanisms have to be illustrated in special publications.

关键词： Arterial pressure Angiotensin Baroreflex chemoreflex Hypertension Renin-angiotensin systems Ischemia Simulation

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Peripheral reflex feedbacks in chronic heart failure:Is it time for a direct treatment?

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World Journal of Cardiology 2015年第12期7卷 824-828页

作者： Alberto Giannoni Gianluca Mirizzi Alberto Aimo Michele Emdin Claudio Passino Division of Cardiology and Cardiovascular Medicine Fondazione Toscana Gabriele Monasterio Institute of Life Sciences Scuola Superiore Sant’Anna

Despite repeated attempts to develop a unifying hypothesis that explains the clinical syndrome of heart failure(HF),no single conceptual paradigm for HF has withstood the test of time. The last model that has been developed,the neurohormonal model,has the great virtue of highlighting the role of the heart as an endocrine organ,as well as to shed some light on the key role on HF progression of neurohormones and peripheral organs and tissues beyond the heart itself. However,while survival in clinical trials based on neurohormonal antagonist drugs has improved,HF currently remains a lethal condition. At the borders of the neurohormonal model of HF,a partially unexplored path trough the maze of HF pathophysiology is represented by the feedback systems. There are several evidences,from both animal studies and humans reports,that the deregulation of baro-,ergo- and chemo-reflexes in HF patients elicits autonomic imbalance associated with parasympathetic withdrawal and increased adrenergic drive to the heart,thus fundamentally contributing to the evolution of the disease. Hence,on top of guidelinerecommended medical therapy,mainly based on neurohormonal antagonisms,all visceral feedbacks have been recently considered in HF patients as additional potential therapeutic targets.

关键词： Baroreflex chemoreflex Ergoreflex Heart failure Sympathetic system Neurohormones

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Regulation of breathing by Phox2b-expressing neurons in nucleus tractus solitarius

Regulation of breathing by Phox2b-expressing neurons in nucl...

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中国神经科学学会第十二届全国学术会议

作者： Congrui Fu Yixian Liu Yi Zhang Sheng Wang Department of Physiology Hebei Medical University

Central respiratory chemoreflex serves as an important homeostatic mechanism of regulation of breathing and CO excretion. Central respiratory chemoreceptors consist of either neurons or astrocytes in a few of brainstem nuclei such as the nucleus tractus solitarius(NTS). Phox2b, a transcription factor, is selectively expressed in the afferent components of respiratory reflexes. More recently, the majority of Phox2b-expressing retrotrapezoid nucleus neurons have been implicated in the role of control of breathing. Here we ask whether Phox2b-expressing NTS neurons are crucial for regulation of breathing. To address this issue, phrenic nerve activity was recorded to represent central respiratory drives in response to optogenetic stimulation of NTS Phox2b-expressing neurons in anesthetized Phox2b-cre mice. Furthermore, respiratory ventilation was assessed using whole body plethysmography in conscious chemodenervated mice subjected to lesions of Phox2b-expressing NTS neurons. We injected the AAV-DIO-Ch R2-m Cherry into the NTS of Phox2b-cre mice to express specifically Ch R2-m Cherry in Phox2b-contained neurons. Photostimulation of Phox2bexpressing neurons reactivated phrenic nerve discharge during apnea resulting from mechanical hyperventilation in anesthetized mice. Injection of the neurotoxin substance P-saporin into the NTS destroyed Phox2b-expressing neurons. Minute ventilation and tidal volume were both reduced by 13% during exposure to 8% CO in inspired air when 13% of the Phox2b-expressing neurons were eliminated. However, a loss of 18% of these neurons was associated with considerable decreases in minute ventilation by 18% and in tidal volume by 22% when challenged by ≥4% CO. Most CO-activated neurons were immunoreactive to Phox2b. In summary, activation of NTS Phox2b-expressing neurons reinforces excitatory drive to breathing, by contrast, loss of these neurons impairs central respiratory chemorelfex.

关键词： breathing nucleus tractus solitarius Phox2b chemoreflex

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