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 dev...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.展开更多
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 organisms.Most of such mechanisms ...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 organisms.Most 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 conditions.Methodological and ethical constraints create practically insuperable obstacles while experiments on animals mainly concern artificial situations with certain switched-of mechanisms.Currently,mathematical modeling and computer simulations provide the most promising way for expanding and deepening our understanding of regulators’interactions.As most of CVS’s models describe only partial control mechanisms,a special model(SM)capable of simulating every combination of control mechanisms is encouraged.This 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 research.SM 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 flow.SM,performed in form of special software(SS),is tested under specific endogenous and/or exogenous alterations.The physiologist using SS can easily construct the desirable configuration of regulator mechanisms,their actual state,and scenarios of computer experiments.Tests illustrated the adequateness of SM,are the first step of SM’s research.Nuances of the interaction of modeled regulator mechanisms have to be illustrated in special publications.展开更多
文摘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.
文摘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 organisms.Most 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 conditions.Methodological and ethical constraints create practically insuperable obstacles while experiments on animals mainly concern artificial situations with certain switched-of mechanisms.Currently,mathematical modeling and computer simulations provide the most promising way for expanding and deepening our understanding of regulators’interactions.As most of CVS’s models describe only partial control mechanisms,a special model(SM)capable of simulating every combination of control mechanisms is encouraged.This 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 research.SM 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 flow.SM,performed in form of special software(SS),is tested under specific endogenous and/or exogenous alterations.The physiologist using SS can easily construct the desirable configuration of regulator mechanisms,their actual state,and scenarios of computer experiments.Tests illustrated the adequateness of SM,are the first step of SM’s research.Nuances of the interaction of modeled regulator mechanisms have to be illustrated in special publications.
