Control of Whole Heart Geometry by Intramyocardial Mechano-Feedback: A Model Study

Geometry of the heart adapts to mechanical load, imposed by pressures and volumes of the cavities. We regarded preservation of cardiac geometry as a homeostatic control system. The control loop was simulated by a chain of models, starting with geometry of the cardiac walls, sequentially simulating circulation hemodynamics, myofiber stress and strain in the walls, transfer of mechano-sensed signals to structural changes of the myocardium, and finalized by calculation of resulting changes in cardiac wall geometry. Instead of modeling detailed mechano-transductive pathways and their interconnections, we used principles of control theory to find optimal transfer functions, representing the overall biological responses to mechanical signals. As biological responses we regarded tissue mass, extent of contractile myocyte structure and extent of the extra-cellular matrix. Mechano-structural stimulus-response characteristics were considered to be the same for atrial and ventricular tissue. Simulation of adaptation to self-generated hemodynamic load rendered physiologic geometry of all cardiac cavities automatically. Adaptation of geometry to chronic hypertension and volume load appeared also physiologic. Different combinations of mechano-sensors satisfied the condition that control of geometry is stable. Thus, we expect that for various species, evolution may have selected different solutions for mechano-adaptation

Aspects of control measures in occupational hygiene

This thesis focuses on two aspects which are of major importance in the broad field of control measures in occupational hygiene: the selection of control measures in a structured way and the impact of factors modifying the effectiveness of these control measures.The main objectives of the thesis are to determine the feasibility of a model approach in the selection of control measures and to assess the impact of work practices on the exposure to and uptake of chemical agents.Two models, i.e. the "dynamic model of exposure, susceptibility and effect" and the "multiple source model" describe the impact of control measures on workers' exposure. The feasibility of these models and the impact of the factors modifying the effectiveness of control measures was studied in the occupational hygiene practice by performing field studies at different types of workplaces: chromium plateries, lead smelter, battery factory and at construction sites.In the lead and chromium industries environmental and biological monitoring was carried out together with observations and questionnaires to assess hygienic behaviour. In the construction industry quartz exposure was characterized by personal air sampling and workplace observations.From the results of these studies it can be concluded that the application of the two models proved to be an important aid in the determination of sources of exposure. Consequently the selection of control measures in different branches of industry was facilitated.The differences in individual hygienic behaviour and working methods proved to be an important modifier of the relation between external and internal exposure. These results indicate that work practices need to be considered in the implementation of control measures

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

Monitoring of Myocardial Involvement in Early Arrhythmogenic Right Ventricular Cardiomyopathy Across the Age Spectrum

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is characterized by fibrofatty replacement of primarily the right ventricular myocardium, a substrate for life-threatening ventricular arrhythmias (VAs). Repeated cardiac imaging of at-risk relatives is important for early disease detection. However, it is not known whether screening should be age-tailored. OBJECTIVES: The goal of this study was to assess the need for age-tailoring of follow-up protocols in early ARVC by evaluating myocardial disease progression in different age groups. METHODS: We divided patients with early-stage ARVC and genotype-positive relatives without overt structural disease and VA at first evaluation into 3 groups: age 50 years without overt ARVC phenotype at first evaluation. Unlike recommended by current guidelines, our study suggests that follow-up of ARVC patients and relatives should not stop at older age