Atrium Of Human Heart Research Articles

Recurrence quantification analysis for fine-scale characterisation of arrhythmic patterns in cardiac tissue

This paper uses recurrence quantification analysis (RQA) combined with entropy measures and organization indices to characterize arrhythmic patterns and dynamics in computer simulations of cardiac tissue. We performed different simulations of cardiac tissues of sizes comparable to the human heart atrium. In these simulations, we observed four classic arrhythmic patterns: a spiral wave anchored to a highly fibrotic region resulting in sustained re-entry, a meandering spiral wave, fibrillation, and a spiral wave anchored to a scar region that breaks up into wavelets away from the main rotor. A detailed analysis revealed that, within the same simulation, maps of RQA metrics could differentiate regions with regular AP propagation from ones with chaotic activity. In particular, the combination of two RQA metrics, the length of the longest diagonal string of recurrence points and the mean length of diagonal lines, was able to identify the location of rotor tips, which are the active elements that maintain spiral waves and fibrillation. By proposing low-dimensional models based on the mean value and spatial correlation of metrics calculated from membrane potential time series, we identify RQA-based metrics that successfully separate the four different types of cardiac arrhythmia into distinct regions of the feature space, and thus might be used for automatic classification, in particular distinguishing between fibrillation driven by self-sustaining chaos and that created by a persistent rotor and wavebreak. We also discuss the practical applicability of such an approach.

Liénard-class dynamical models of the human heart atrium: How to include the autonomic modulation of heart rate?

Liénard-class dynamical models of the human heart atrium: How to include the autonomic modulation of heart rate?

Neuropeptide Y inhibits acetylcholine release in human heart atrium by activation of Y 2 -receptors

Congestive heart failure and other cardiac diseases are characterized by increased activity of the sympathetic nervous system, whereas at the same time parasympathetic activity is often suppressed. Such imbalance may be a result of or at least enhanced by presynaptic inhibitory effects of sympathetic neurotransmitters on acetylcholine release. We investigated whether the sympathetic cotransmitters neuropeptide Y (NPY), norepinephrine (NE), and ATP are capable of modulating acetylcholine release in human heart atrium. Human atrial appendages were incubated with [(3)H]-choline to label cholinergic transmitter stores and placed in superfusion chambers. Electrical field stimulations (S1, S2) induced a tetrodotoxin-dependent [(3)H]-release, which was taken as an index of endogenous acetylcholine release. NE, NPY, ATP, and a P2-receptor analogue were added before S2. NPY (0.05-1.0 micromol/l) concentration dependently inhibited acetylcholine release. This effect was prevented by the NPY-Y(2)-receptor antagonist BIIE 0246 (0.1 micromol/l) but not by the NPY-Y(1)-receptor antagonist BIBP 3226 (10 micromol/l). ATP (10 micromol/l), a stable analogue ADP-beta S (3 micromol/l), and NE (1 micromol/l) had no effect on acetylcholine release. m-RNA for the NPY-receptor subtypes Y(1), Y(2), Y(4), Y(5), and y(6) was demonstrated by reverse transcription-polymerase chain reaction (RT-PCR). The results suggest that the sympathetic neurotransmitter NPY inhibits parasympathetic neurotransmission in the human heart through activation of presynaptic Y(2)-receptors. NE and ATP seem not to play a role. Since NPY plasma levels are high in chronic heart failure patients, NPY may be one component leading to impaired parasympathetic neurotransmission in those patients.

Pharmacological modification of sodium channels from the human heart atrium in planar lipid bilayers: electrophysiological characterization of responses to batrachotoxin and pentobarbital

Pharmacological modification of sodium channels from the human heart atrium in planar lipid bilayers: electrophysiological characterization of responses to batrachotoxin and pentobarbital

Acetylcholine release in human heart atrium: influence of muscarinic autoreceptors, diabetes, and age.

An imbalance of sympathetic and parasympathetic drive to the heart is an important risk factor for cardiac death in patients with coronary heart disease, diabetes, and renal insufficiency. The amount of neurotransmitter released from peripheral autonomic nerves is modulated by presynaptic receptor systems. In analogy to alpha-autoreceptors on sympathetic nerves, muscarinic autoreceptors activated by endogenous acetylcholine may exist on parasympathetic nerves in the human heart. We developed a technique to study acetylcholine release from human atria and investigated muscarinic autoreceptor function. A pharmacological and molecular approach was used to characterize the subtype involved. Of the 5 muscarinic receptor subtypes cloned, only mRNA encoding for M(2)- and M(3)-receptors were detected. Potencies of several muscarinic antagonists against the release-inhibiting effect of the nonselective muscarinic agonist carbachol at the cardiac autoreceptor were correlated with published data for human cloned M(1)- through M(5)-receptors. This analysis clearly indicates that acetylcholine release in human atria is controlled by muscarinic M(2)-receptors. Blockade of these receptors by atropine doubles the amount of acetylcholine released at a stimulation frequency of 5 Hz. In atria of patients >70 years of age and patients with late diabetic complications, acetylcholine release is reduced. Locally impaired cardiac acetylcholine release may therefore represent a pathophysiological link to sudden cardiac death in elderly and diabetic patients.

Mitochondrial DNA Deletions in Human Cardiac Tissue Show a Gross Mosaic Distribution

The variability of mitochondrial DNA (mtDNA) deletional patterns has been investigated in adjacent slices of human heart atrium. Using quantitative PCR we found differential abundances of one particular mtDNA deletion, that of 4977 bp (mtDNA4977), among sets of adjacent slices of right atrial trabeculae pectinatae from 10 subjects. Some subjects had relatively constant abundance of mtDNA4977among the tissue slices, while others covered a wide range. A qualitative PCR procedure was used to visualize the patterns of multiple deletions within an 8.64-kb segment of the mtDNA genome, in the same set of atrial trabeculae samples. Some subjects showed completely different multiple deletional patterns in each of the trabeculae slices analyzed. There was no correlation between the variation of the abundance of mtDNA4977and that of the multiple deletions. The results are consistent with the notion that the occurrence of mtDNA deletions during aging is a random process, involving their production throughout the lifetime of an individual. In this view, the patterns of new deletions are superimposed on those already accumulated by propagation and segregation of mutations formed earlier in life.

Neuroleptic binding to muscarinic M 2 receptors of normal human heart in vitro and comparison with binding to M 1 and dopamine D 2 receptors of brain

We determined by radioligand binding the equilibrium dissociation constants (K d's) for seventeen neuroleptics at muscarinic M 2 receptors of human heart atrium and compared these data with our previous data for binding to muscarinic M 1 and dopamine D 2 receptors of human brain. At the M 2 receptor, the most potent compound was thioridazine; the least, molindone. If selectivity is defined as K d at one receptor ≤ 0.1 K d at the other receptor, no compound was selective for the M 2 subtype. Two compounds, clozapine and triflupromazine, were selective for the M 1 subtype. Thus, few neuroleptics have the assumed preferred property of M 1 over M 2 subtype selectivity. Such a feature could reduce extrapyramidal side effects, while reducing the likelihood of certain cardiac side effects.