Previous models combining the human cardiovascular and pulmonary systems have not addressed their strong dynamic interaction. They are primarily cardiovascular or pulmonary in their orientation and do not permit a full exploration of how the combined cardiopulmonary system responds to large amplitude forcing (e.g., by the Valsalva maneuver). To address this issue, we developed a new model that represents the important components of the cardiopulmonary system and their coupled interaction. Included in the model are descriptions of atrial and ventricular mechanics, hemodynamics of the systemic and pulmonic circulations, baroreflex control of arterial pressure, airway and lung mechanics, and gas transport at the alveolar-capillary membrane. Parameters of this combined model were adjusted to fit nominal data, yielding accurate and realistic pressure, volume, and flow waveforms. With the same set of parameters, the nominal model predicted the hemodynamic responses to the markedly increased intrathoracic (pleural) pressures during the Valsalva maneuver. In summary, this model accurately represents the cardiopulmonary system and can explain how the heart, lung, and autonomic tone interact during the Valsalva maneuver. It is likely that with further refinement it could describe various physiological states and help investigators to better understand the biophysics of cardiopulmonary disease.

PAMM should be considered in patients with 'patch off' visual loss and absence of other fundal signs. We hypothesise that spasm or transient occlusion of central retinal artery leads to arterial hypoperfusion with subsequent ischaemia or infarction of the retina. Underlying arterial disease may have led to pre-existing hypoperfusion that may have been further compromised by raised intraocular pressure during the procedure itself or via raised orbital pressure from the anaesthesia.

We upgraded our human cardiopulmonary (CP) model with additional data that enables it to more accurately simulate normal physiology. We then tested its ability to explain human disease by changing two parameter values that decrease ventricular compliance, and found that it could predict many of the hemodynamic, gas exchange, and autonomic abnormalities found in patients with left ventricular diastolic dysfunction (LVDD). The newly incorporated information includes high-fidelity pressure tracings simultaneously recorded from the RV and LV of a normal human in a cardiac catheterization laboratory, Doppler echocardiographic inlet flow velocity patterns, measures of right and left ventricular impedance, and atrial volumes. The revised cardiovascular section details the hemodynamics of a normal subject to the extent that it can now explain the effects of septal compliance on ventricular interaction, the differences in left and right ventricular pressure development, and venous blood gas mixing in the right atrium. The model can isolate the highly interrelated features of normal and abnormal physiology, and simultaneously demonstrate their interaction in a manner that would be very difficult or impossible using an intact organism. It may therefore help physicians and scientists understand, diagnose, and improve their treatment of complicated cardiovascular and pulmonary diseases. It could also simulate the hemodynamic and respiratory effects of ventricular and pulmonary assist devices, and thus help with their development.

. Cerebral autoregulation and gas exchange studied using a human cardiopulmonary model. Am J Physiol Heart Circ Physiol 286: H584-H601, 2004. First published August 28, 2003 10.1152/ajpheart.00594.2003.-The goal of this work is to study the cerebral autoregulation, brain gas exchange, and their interaction by means of a mathematical model. We have previously developed a model of the human cardiopulmonary (CP) system, which included the whole body circulatory system, lung and peripheral tissue gas exchange, and the central nervous system control of arterial pressure and ventilation. In this study, we added a more detailed description of cerebral circulation, cerebrospinal fluid (CSF) dynamics, brain gas exchange, and cerebral blood flow (CBF) autoregulation. Two CBF regulatory mechanisms are included: autoregulation and CO2 reactivity. Central chemoreceptor control of ventilation is also included. We first established nominal operating conditions for the cerebral model in an open-loop configuration using data generated by the CP model as inputs. The cerebral model was then integrated into the larger CP model to form a new integrated CP model, which was subsequently used to study cerebral hemodynamic and gas exchange responses to test protocols commonly used in the assessment of CBF autoregulation (e.g., carotid artery compression and the thigh-cuff deflation test). The model can closely mimic the experimental findings and provide biophysically based insights into the dynamics of cerebral autoregulation and brain tissue gas exchange as well as the mechanisms of their interaction during test protocols, which are aimed at assessing the degree of autoregulation. With further refinement, our CP model may be used on measured data associated with the clinical evaluation of the cerebral autoregulation and brain oxygenation in patients. physiological modeling; thigh-cuff test; carotid artery compression NORMAL CEREBRAL AUTOREGULATION provides a constant cerebral blood flow (CBF) over a wide range of cerebral perfusion pressures (CPP) (1, 25). Because this regulatory mechanism is complex, several investigators have found that mathematical models can help guide experimental design and provide explanations of experimental results (8, 14-16, 18, 32, 36). These models have largely been directed at developing mechanistic descriptions of cerebral autoregulation or the dynamics of intracranial systems. None have considered the effect of CO 2 on cerebral hemodynamics and autoregulation or described the gas exchange between cerebral vessels and brain tissue. Ursino et al. (37,39) and Czosnyka et al. (5) included CO 2 reactivity in their modeling studies of intracranial dynamics. However, their models did not include gas transport in brain tissue and thus can not simulate the impact of cerebral hemodynamic changes on brain tissue gas content.We recently presented a modeling study of human whole body gas exchange (20), in which our previous human cardiopulmonary (CP) model (19) was significantly extended to include descriptions of ...

ICA cells constitute a delta-opioid-regulated adrenopeptidergic paracrine system conferring robust cardioprotection through beta(2)-AR/CGRP-R co-signalling, resulting in the activation of an anti-apoptotic pathway during ischaemia/reperfusion.