Diastolic ventricular aspiration: a mechanism supporting the rapid filling phase of the human ventricles

During the rapid filling phase of the heart cycle, the internal volumes of the two ventricular cavities approximately double, while the intraventricular pressures rise typically only by an amount of less than 1 kPa. Such a small pressure increase cannot be the sole driving mechanism for the large inflow of blood associated with ventricular expansion during this period. Instead, the rapid filling phase is to be interpreted as being mediated primarily by the heart recoiling elastically from its contracted state, causing blood to be aspirated rapidly into the ventricles. In order to study the role of this mechanism, elastic finite element (FE) simulations of ventricular expansion were performed, taking into account the large deformations occurring during this period and the effective compressibility of the myocardium due to intramural fluid flow. Thereby, a realistic three-dimensional geometry derived from magnetic resonance imaging (MRI) measurements of both human ventricles was used. To validate our FE analyses, the results were compared with published measurements relating to the rapid filling phase of the human left ventricle. Our study shows that, under normal physiological conditions, ventricular aspiration plays a key role in the ventricular filling process.     

Exposure of mice to cigarette smoke and/or light causes DNA alterations in heart and aorta

Cigarette smoke (CS) is a major risk factor for cardiovascular diseases, cancer, and other chronic degenerative diseases. UV-containing light is the most ubiquitous DNA-damaging agent existing in nature, but its possible role in cardiovascular diseases had never been suspected before, although it is known that mortality for cardiovascular diseases is increased during periods with high temperature and solar irradiation. We evaluated whether exposure of Swiss CD-1 mice to environmental CS (ECS) and UV-C-covered halogen quartz lamps, either individually or in combination, can cause DNA damage in heart and aorta cells. Nucleotide alterations were evaluated by (32)P postlabeling methods and by HPLC-electrochemical detection. The whole-body exposure of mice to ECS considerably increased the levels of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) and of bulky DNA adducts in both heart and aorta. Surprisingly, even exposure to a light that simulated solar irradiation induced oxidatively generated damage in both tissues. The genotoxic effects of UV light in internal organs is tentatively amenable to formation of unidentified long-lived mutagenic products in the skin of irradiated mice. Nucleotide alterations were even more pronounced when the mice were exposed to smoke and/or light during the first 5weeks of life rather than during adulthood for an equivalent period of time. Although the pathogenetic meaning is uncertain, DNA damage in heart and aorta may tentatively be related to cardiomyopathies and to the atherogenesis process, respectively.     

Model of hidden heterogeneity in longitudinal data

Variables measured in longitudinal studies of aging and longevity do not exhaust the list of all factors affecting health and mortality transitions. Unobserved factors generate hidden variability in susceptibility to diseases and death in populations and in age trajectories of longitudinally measured indices. Effects of such heterogeneity can be manifested not only in observed hazard rates but also in average trajectories of measured indices. Although effects of hidden heterogeneity on observed mortality rates are widely discussed, their role in forming age patterns of other aging-related characteristics (average trajectories of physiological state, stress resistance, etc.) is less clear. We propose a model of hidden heterogeneity to analyze its effects in longitudinal data. The approach takes the presence of hidden heterogeneity into account and incorporates several major concepts currently developing in aging research (allostatic load, aging-associated decline in adaptive capacity and stress-resistance, age-dependent physiological norms). Simulation experiments confirm identifiability of model's parameters.     

Mathematical Modeling of Mechanically Modulated Rhythm Disturbances in Homogeneous and Heterogeneous Myocardium with Attenuated Activity of Na<Superscript>+</Superscript>–K<Superscript>+</Superscript> Pump

A mathematical model of the cardiomyocyte electromechanical function is used to study contribution of mechanical factors to rhythm disturbances in the case of the cardiomyocyte calcium overload. Particular attention is paid to the overload caused by diminished activity of the sodium-potassium pump. It is shown in the framework of the model, where mechano-calcium feedback is accounted for that myocardium mechanics may significantly enhance arrhythmogenicity of the calcium overload. Specifically, a role of cross-bridge attachment/detachment processes, a role of mechanical conditions of myocardium contractions (length, load), and a role of myocardium viscosity in the case of simulated calcium overload have been revealed. Underlying mechanisms are analyzed. Several approaches are designed in the model and compared to each other for recovery of the valid myocardium electrical and mechanical performance in the case of the partially suppressed sodium-potassium pump.     

Helicobacter pylori lipopolysaccharide provokes iNOS-mediated acute systemic microvascular inflammatory responses in rat cardiac, hepatic, renal and pulmonary tissues

We have examined the effects of intravenous administration of a purified lipopolysaccharide (LPS) from Helicobacter pylori (3 mg kg⁻¹, i.v.) on rat vascular permeability, assessed by the radiolabelled human serum albumin leakage technique in the heart, kidney, liver and lung 4 h after challenge. An increased vascular permeability in cardiac, renal, hepatic and pulmonary tissues after challenge was determined. The albumin leakage observed in all these organs could be prevented by the selective inducible nitric oxide synthase inhibitor, N-(8-(aminomethyl)benzyl)-acetamidine (1400W; 0.2–1 mg kg⁻¹, s.c.) administered concurrently with LPS. Thus, H. pylori LPS can provoke a microvascular inflammatory response in the rat cardiac, renal, hepatic and pulmonary tissues, actions mediated through the activation of the inducible nitric oxide synhase isoenzyme.     

Repeated assessment of the endogenous 24-hour profile of blood pressure under constant routine

The impact of environmental and behavioral factors on the 24-h profile of blood pressure (BP) has been well established. Various attempts have been made to control these exogenous factors, in order to investigate a possible endogenous circadian variation of BP. Recently, we reported the results of the first environmentally and behaviorally controlled laboratory study with 24-h recordings of BP and heart rate (HR) during maintained wakefulness. In this constant-routine study, a pronounced endogenous circadian rhythm of HR was found, but circadian variation of BP was absent. This result suggested that the circadian rhythm of BP observed in earlier controlled studies, with sleep allowed, was evoked by the sleep-wake cycle as opposed to the endogenous circadian pacemaker. In order to verify our previous finding during maintained wakefulness, we repeated the experiment five times with six normotensive, healthy young subjects. Statistical analyses of the hourly measurements of BP and HR confirmed the replicable presence of an endogenous circadian rhythm of HR, as well as the consistent absence of an endogenous circadian variation of BP. Thus, this study provided additional evidence that the 24-h profile of BP—as observed under normal circumstances—is the sole result of environmental and behavioral factors such as the occurrence of sleep, and has no endogenous circadian component. (Chronobiology International, 18(1), 85-98, 2001)     

Modulation of sympathetic actions on the heart by opioid receptor stimulation

The sympathetic nervous system, the most important extrinsic regulatory mechanism of the heart, is inhibited postsynaptically and presynaptically by opioid peptides produced in the heart via their respective receptors. The cardiac actions of beta-adrenergic receptor (beta-AR) stimulation are attenuated by activation of the opioid receptor (OR) with OR agonist at ineffective concentrations, implying cross-talk between the OR and beta-AR. This cross-talk results from inhibition of the Gs protein and adenylyl cyclase of the beta-AR pathway by the pertussis toxin-sensitive G protein of the opioid pathway. Alterations in cross-talk between these two receptors occur in pathological situations to meet bodily needs. In myocardial ischemia, when the sympathetic activity is increased, the inhibition of beta-AR stimulation by kappa-opioid stimulation is also enhanced, thus reducing the workload, oxygen consumption and cardiac injury. Whereas cardiac responsiveness to sympathetic discharges is also reduced after chronic hypoxia, the cross-talk between kappa-OR and beta-AR is reduced to prevent undue suppression of the sympathetic influence on the heart. On the other hand, impairment of the cross-talk may result in abnormality. A lack or a significant reduction in the inhibition of beta-AR stimulation by kappa-OR stimulation may lead to an excessive increase in cardiac activities, which contribute to the maintenance of high arterial blood pressure in spontaneously hypertensive rats. Other than opioid peptides, female sex hormone and adenosine also inhibit the sympathetic actions on the heart. In addition, sympathetic action is also inhibited presynaptically by kappa-opioid peptides via their receptor.     

The pioneer gene, apontic, is required for morphogenesis and function of the Drosophila heart

In an effort to isolate genes required for heart development and to further our understanding of cardiac specification at the molecular level, we screened PlacZ enhancer trap lines for expression in the Drosophila heart. One of the lines generated in this screen, designated B2-2-15, was particularly interesting because of its early pattern of expression in cardiac precursor cells, which is dependent on the homeobox gene tinman, a key determinant of heart development in Drosophila. We isolated and characterized a gene in the vicinity of B2-2-15 that exhibits an identical expression pattern than the reporter gene of the enhancer trap. The product of his gene, apontic (apt; see also Gellon et al., 1997), does not appear to have any homology with known genes. apt mutant embryos show distinct abnormalities in heart morphology as early as mid-embryonic stages when the heat tube assembles, in that segments of heart cells (those of myocardial and pericardial identity) are often missing. Most strikingly, however, apt mutant embryos or larvae only develop a much reduced heart rate, perhaps because of defects in the assembly of an intact heart tube and/or because of defects in the function or physiological control of the myocardial cells, which normally mediate heart contractions. These cardiac defects may be the cause of death of these mutants during late embryonic or early larval stages.     

Understanding autonomic sympathovagal balance from short-term heart rate variations. Are we analyzing noise?

Heart rate variations reflect the output of the complex control of the heart mediated by the autonomic nervous system. Because of that, they also encode different types of information, namely the efferent outflow of reflex mechanisms involved in the beat-to-beat control of cardiac function, the efferent activity of neurohumoral elements involved in the control of other cardiovascular parameters and random noise resulting from the hysteresis of the different controllers. The degree to which power spectrum estimation methods will uncover the periodic component of heart rate variations is in direct relation with the status of the system under study. Although the utility of spectral methods is now established in mammalian research, very little is known on the utility of these techniques in non-mammalian cardiovascular research. This review covers this space by discussing the physiological significance of heart rate variations in non-mammalian vertebrates. A detailed account of the different steps of the technique, its limitations and the ways to overcome these problems are also presented. These are: the recording of the cardiac event signal, the detection and digital processing methods, the satisfaction of stationarity conditions, the problem of spectral leakage and the different methods to estimate the power spectrum.