Several Theoretical and Applied Problems of Human Extreme Physiology: Mathematical Modeling

Human cardiovascular system (CVS) and hemodynamics are critically sensitive to essential alterations of mechanical inertial forces in directions of head-legs (+Gz) or legs-head (-Gz). Typically, such alterations appear during pilotage maneuvers of modern high maneuverable airspace vehicles (HMAV).The vulnerability of pilots or passengers of HMAV to these altering forces depends on their three main characteristics: amplitude, dynamics, and duration. Special protections, proposed to minimize this vulnerability, should be improved in parallel with the increasing of these hazardous characteristics of HMAVs. Empiric testing of novel protection methods and tools is both expensive and hazardous. Therefore computer simulations are encouraged. Autonomic software (AS) for simulating and theoretical investigating of the main dynamic responses of human CVS to altering Gz is developed. AS is based on a system of quantitative mathematical models (QMM) consisting of about 1300 differential and algebraic equations. QMM describes the dynamics of both CVS (the cardiac pump function, baroreceptor control of parameters of cardiovascular net presented by means of lumped parameter vascular compartments) and non-biological variables (inertial forces, and used protections). The main function of AS is to provide physiologist-researcher by visualizations of calculated additional data concerning characteristics of both external and internal environments under high sustained accelerations and short-time microgravity. Additionally, AS can be useful as an educational tool able to show both researchers and young pilots the main hemodynamic effects caused by accelerations and acute weightlessness with and without use of different protection tools and technics. In this case, AS does help users to optimize training process aimed to ensure optimal-like human tolerance to the altered physical environment. Main physiological events appearing under different scenarios of accelerations and microgravity have been tested.

Electro-energetics of Biventricular, Septal and Conduction System Pacing

Abnormal electrical activation of the ventricles creates abnormalities in cardiac mechanics. Local contraction patterns, as reflected by strain, are not only out of phase, but also show opposing length changes in early and late activated regions. Consequently, the efficiency of cardiac pump function (the amount of stroke work generated by a unit of oxygen consumed), is approximately 30% lower in dyssynchronous than in synchronous hearts. Maintaining good cardiac efficiency appears important for long-term outcomes. Biventricular, left ventricular septal, His bundle and left bundle branch pacing may minimise the amount of pacing-induced dyssynchrony and efficiency loss when compared to conventional right ventricular pacing. An extensive animal study indicates maintenance of mechanical synchrony and efficiency during left ventricular septal pacing and data from a few clinical studies support the idea that this is also the case for left bundle branch pacing and His bundle pacing. This review discusses electro-mechanics and mechano-energetics under the various paced conditions and provides suggestions for future research.

Pacemaker associated reduction of left ventricle systolic function

In recent years, data have been accumulated on the negative effect of right ventricular (RV) stimulation, leading to left ventricular (LV) asynchrony, proarrhythmias and progressive heart failure (HF). On the other hand, biventricular pacing has been shown to affect ventricular asynchrony, reduce HF manifestations, and improve prognosis in patients with LV dysfunction and wide QRS complex. The induced asynchrony from apical right ventricular pacing is unequivocally associated with changes in myocardial perfusion, LV dysfunction, and poorer prognosis for patients over time. This has led researchers for decades to look for an alternative position for electrode placement. The incidence of pacemaker-induced cardiomyopathy (PICM) ranges from 5.9 to 39% in patients with RV pacing, depending on the given definition and the limit for the degree of pacing. Upgrading to biventricular pacing has been shown to reverse the cardiomyopathy. Recently, there has been evidence of a positive effect of His bundle pacing (HBP) in the treatment of PICM even in patients with no improvement after biventricular pacing. The question about the pathogenetic mechanisms of PICM is currently unanswered. The connection between electrical asynchrony and the negative effect on cardiac pump function is clear. There is also evidence of an established relationship between asynchrony and coronary blood flow. The predisposing individual characteristics of the patient in which these negative effects are manifested are not clear. This is an issue that requires further studies.

Surrogate models based on machine learning methods for parameter estimation of left ventricular myocardium

A long-standing problem at the frontier of biomechanical studies is to develop fast methods capable of estimating material properties from clinical data. In this paper, we have studied three surrogate models based on machine learning (ML) methods for fast parameter estimation of left ventricular (LV) myocardium. We use three ML methods named K-nearest neighbour (KNN), XGBoost and multi-layer perceptron (MLP) to emulate the relationships between pressure and volume strains during the diastolic filling. Firstly, to train the surrogate models, a forward finite-element simulator of LV diastolic filling is used. Then the training data are projected in a low-dimensional parametrized space. Next, three ML models are trained to learn the relationships of pressure–volume and pressure–strain. Finally, an inverse parameter estimation problem is formulated by using those trained surrogate models. Our results show that the three ML models can learn the relationships of pressure–volume and pressure–strain very well, and the parameter inference using the surrogate models can be carried out in minutes. Estimated parameters from both the XGBoost and MLP models have much less uncertainties compared with the KNN model. Our results further suggest that the XGBoost model is better for predicting the LV diastolic dynamics and estimating passive parameters than other two surrogate models. Further studies are warranted to investigate how XGBoost can be used for emulating cardiac pump function in a multi-physics and multi-scale framework.

Cardiomyocyte Transplantation after Myocardial Infarction Alters the Immune Response in the Heart

We investigated the influence of syngeneic cardiomyocyte transplantation after myocardial infarction (MI) on the immune response and cardiac function. Methods and Results: We show for the first time that the immune response is altered as a result of syngeneic neonatal cardiomyocyte transplantation after MI leading to improved cardiac pump function as observed by magnetic resonance imaging in C57BL/6J mice. Interestingly, there was no improvement in the capillary density as well as infarct area as observed by CD31 and Sirius Red staining, respectively. Flow cytometric analysis revealed a significantly different response of monocyte-derived macrophages and regulatory T cells after cell transplantation. Interestingly, the inhibition of monocyte infiltration accompanied by cardiomyocyte transplantation diminished the positive effect of cell transplantation alone. The number of CD68+ macrophages in the remote area of the heart observed after four weeks was also different between the groups. Transcriptome analysis showed several changes in the gene expression involving circadian regulation, mitochondrial metabolism and immune responses after cardiomyocyte transplantation. Conclusion: Our work shows that cardiomyocyte transplantation alters the immune response after myocardial infarction with the recruited monocytes playing a role in the beneficial effect of cell transplantation. It also paves the way for further optimization of the efficacy of cardiomyocyte transplantation and their successful translation in the clinic.

Effect of myofibre architecture on ventricular pump function by using a neonatal porcine heart model: from DT-MRI to rule-based methods

Myofibre architecture is one of the essential components when constructing personalized cardiac models. In this study, we develop a neonatal porcine bi-ventricle model with three different myofibre architectures for the left ventricle (LV). The most realistic one is derived from ex vivo diffusion tensor magnetic resonance imaging, and other two simplifications are based on rule-based methods (RBM): one is regionally dependent by dividing the LV into 17 segments, each with different myofibre angles, and the other is more simplified by assigning a set of myofibre angles across the whole ventricle. Results from different myofibre architectures are compared in terms of cardiac pump function. We show that the model with the most realistic myofibre architecture can produce larger cardiac output, higher ejection fraction and larger apical twist compared with those of the rule-based models under the same pre/after-loads. Our results also reveal that when the cross-fibre contraction is included, the active stress seems to play a dual role: its sheet-normal component enhances the ventricular contraction while its sheet component does the opposite. We further show that by including non-symmetric fibre dispersion using a general structural tensor, even the most simplified rule-based myofibre model can achieve similar pump function as the most realistic one, and cross-fibre contraction components can be determined from this non-symmetric dispersion approach. Thus, our study highlights the importance of including myofibre dispersion in cardiac modelling if RBM are used, especially in personalized models.

Central venous pressure monitoring

The circulatory dynamics of patients are maintained by a triad of vascular capacitance, effective circulating volume and cardiac pump function. These components interact to provide blood pressure, cardiac output and tissue perfusion. Central venous pressure (CVP) is one of the parameters which is known to be useful in evaluating the interaction of these modalities. It will also help to determine volume status of the patient and need to fill in, as well as the efficacy of the volume therapy. Sometimes central line will be inserted to infuse vasoactive infusions or blood nd blood products. Its an invasive procedure and has its complications. The intensivists need to be fully conversant with the standard guidelines for this procedure for patient safety. Received: 15 Sep 2018Reviewed: 18 Sep 2018Corrected: 28 Sep, 18 Oct 2018Accepted: 5 Nov 2018 Citation: Gupta J. Central venous pressure monitoring. Anaesth Pain & Intensive Care 2018;22 Suppl 1:S137-S141

Cardiac mechanics

Cardiac mechanics involves the study of the mechanical properties of the heart (ventricles) as a pump, and the physical factors that alter these properties. Neurohumoral factors aside, the function of the heart is determined by its intrinsic physical properties as well as extrinsic physical factors. The intrinsic properties include ventricular wall stress, elastance (stiffness) of the ventricle, contractility, and heart rate. The main extrinsic physical factors are blood volume, vessels properties, and extracardiac pressures. This chapter will review these intrinsic properties and how they interact with extrinsic factors to alter the cardiac (pump) function. Neurohumoral factors are excluded in this consideration. LaPlace’s law will be introduced to explain the idea of ventricular wall stress, hence the concepts of preload and afterload. The left ventricular pressure–volume relationship will be reviewed to explain how preload, afterload, and ventricular contractility interact and affect stroke volume. Finally, for completeness, the Frank–Starling relationship and Guyton’s venous return graph will be covered to explain steady state cardiac output.

Interrelationship between Alzheimer’s disease and cardiac dysfunction: the brain–heart continuum?

Dementia, a devastating neurological disorder commonly found in the elderly, is characterized by severe cognitive and memory impairment. Ample clinical and epidemiological evidence has depicted a close association between dementia and heart failure. While cerebral blood under perfusion and neurohormonal activation due to the dampened cardiac pump function contribute to the loss of nutrient supply and neuronal injury, Alzheimer’s disease (AD), the most common type of dementia, also provokes cardiovascular function impairment, in particular impairment of diastolic function. Aggregation of amyloid-β proteins and mutations of Presenilin (PSEN) genes are believed to participate in the pathological changes in the heart although it is still debatable with regards to the pathological cue of cardiac anomalies in AD process. In consequence, reduced cerebral blood flow triggered by cardiac dysfunction further deteriorates vascular dementia and AD pathology. Patients with atrial fibrillation, heart failure, and other cardiac anomalies are at a higher risk for cognitive decline and dementia. Conclusion: Due to the increased incidence of dementia and cardiovascular diseases, the coexistence of the two will cause more threat to public health, warranting much more attention. Here, we will update recent reports on dementia, AD, and cardiovascular diseases and discuss the causal relationship between dementia and heart dysfunction.