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PubMed1978

Comparative dromotropic activity of timolol and propranolol in anesthetized dogs.

The comparative dromotropic activity of timolol (TML) and propranolol (PPL) was studied by means of His bundle electrograms in two groups of pentobarbital-anesthetized dogs: group I, 7 non-atropinized dogs; group II, 8 atropinized dogs. beta-Blocking agents were injected in 4 cumulative doses in each dog at 3 days' interval. The effects upon heart rate (HR), and A-V nodal (AH), His--Purkinje (HV) and intraventricular (QS) conduction times were measured. The dromotropic effects of PPL and TML during atrial electrical stimulation and their effects upon chronotropic and dromotropic isoprenaline-induced changes were compared. TML exerted a 9--10 times more potent negative chronotropic effect than PPL and a 4--5 times more potent negative dromotropic effect than PPL on AH conduction time. PPL and TML increased the duration of HV only in higher doses. This effect which was not modified by isoprenaline may be related to their membrane depressant effect. Neither TML, nor PPL nor isoprenaline modified QS duration. TML was 25 times more potent than PPL to antagonize the chronotropic action of isoprenaline and 11--8 times more potent than PPL to antagonize the dromotropic action of isoprenaline upon AH. Parasympathic blockade with atropine did not modify the negative dromotropic activity of PPL and TML but modified their chronotropic effects.

Animals↗
PubMed2005

Head-tail interactions in numerical simulations of reentry in a ring of cardiac tissue.

BACKGROUND: The relationships between action potential duration (APD) and conduction velocity (CV) to the previous diastolic interval (DI) are known as the APD and CV restitution relationships. There is considerable debate regarding the importance of these relationships in the development and stability of reentry. OBJECTIVES: The purpose of this study was to increase the understanding of the ionic basis for restitution during reentry. METHODS: APD and CV were studied numerically during one-dimensional reentry as ring length (L) was shortened. A three-state variable model (u, v, w) was used to analyze the effect of gating variables of the fast (v) and slow (w) currents on the spatial and temporal dynamics of transmembrane potential (u). Three parameter sets were used corresponding to three APD and CV restitution curves. RESULTS: Sustained spatial oscillations of APD and CV larger than the ring length were observed in two of the parameter sets (cytochalasin-D model [CYTO] and model 3 [M3]) before block occurred at L = 6 cm. The last model (diacetyl monoxime [DAM]) resulted in uniform APD and CV for all L until block occurred at L = 3 cm. Multivalued APD and CV restitution relationships due to "dephasing" of w and v with DI were observed in M3 and CYTO simulations. Overall, these dynamics could be explained by the wavelength-to-ring length ratio and the sensitivity of APD on the value of the gating variables w and v. CONCLUSION: Propagation stability is mostly controlled by APD sensitivity to w, but the APD restitution slope does not always reflect this sensitivity. The interaction of the dynamic history (i.e., memory) of the fast and slow currents and electrotonic effects resulted in multivalued restitution curves.

Action Potentials↗
PubMed1997

Gender-specific differences in the QT interval and the effect of autonomic tone and menstrual cycle in healthy adults.

Gender differences in the corrected QT interval have been noted since Bazett's initial description during the 1920s. The mechanism of this gender difference is unknown, and this study was undertaken to evaluate potential autonomic and menstrual cycle effects on the QT interval. The study population consisted of a healthy volunteer sample of 23 women and 20 men. Twelve-lead electrocardiographic determinations were made at rest and following double autonomic blockade (with atropine and propranolol) during the menstrual, follicular, and luteal phases of the menstrual cycle. Men were studied during 3 separate visits as controls. The corrected QT interval at baseline tended to be longer in women than men (421 +/- 16 ms vs 414 +/- 15 ms: p <0.07). Following double autonomic blockade, the corrected QT interval increased to 439 +/- 11 ms: p <0.001). However, the gender difference in corrected QT interval was unchanged (443 +/- 15 ms vs 437 +/- 12 ms). At baseline, there was no significant difference in the corrected QT interval among the 3 phases of the menstrual cycle (421 +/- 10, 423 +/- 18, and 420 +/- 18 in the menstrual, follicular, and luteal phases, respectively) and the corrected QT interval was longer in women than men at each visit. Following double autonomic blockade, the corrected QT interval in women was shorter in the luteal phase (438 +/- 16 ms) versus the menstrual (446 +/- 15 ms) or the follicular phase (444 +/- 13 ms; p <0.05). However, this difference, which was not present at baseline, does not appear to be responsible for the gender difference in the QT interval at rest. In conclusion, our results confirm that the corrected QT interval tends to be longer in women than men. Differences in autonomic tone and menstrual cycle variability in the corrected QT in women at rest do not appear to be responsible for the gender differences in the QT interval. The mechanism responsible for the longer QT interval in women remains to be defined.

Adult↗
PubMed1995

Karhunen-Loève transform as a tool to analyze the ST-segment. Comparison with QT interval.

The spatial and temporal courses of ventricular repolarization are quite sensitive to the biochemical and biophysiologic environment of the myocardial cells, and are therefore often an early marker of heart disease, particularly of ischemia. The detailed morphology of the surface electrocardiogram contains considerable information about the repolarization process. The ST-segment changes with ischemia, injury, and drugs. The QT interval is affected by drugs, heart rate, and autonomic tone, and in some situations may identify individuals at high risk for arrhythmias and sudden death. Variability in the shape, including duration, of the ST-T waves reflects autonomic nervous system activity and may identify high-risk patients. Automated methods for quantitatively characterizing ST-T complexes are important in studying long-term electrocardiographic records. Two computer-based measurement procedures for characterizing the repolarization period were comparatively analyzed: Karhunen-Loève (KL) transform representation of the ST-T shape and measurement of beat-to beat durations of repolarization (QT intervals). The results of KL transform representation and time-domain QT measurement algorithms for studying the repolarization period of the electrocardiogram on the European ST-T database are presented. It was found that about 20% of the records present a quasiperiodic KL pattern of ischemic ST-T activity and another 20% exhibit repetitive but not clearly periodic patterns of ischemic ST-T changes. From these ischemic records, 50% showed QT variations in at least one lead associated with the ischemic episodes.

Algorithms↗
PubMed2001

Electrocardiographic changes during postnatal development in conscious swine with cardiac autonomic imbalance.

Using a conscious swine model, we studied the effects of different patterns of cardiac autonomic denervation on alterations of R-R and Q T intervals for 8 postnatal weeks. Newborn pigs were assigned randomly to four different groups: sham-operated controls (C), stellate ganglion ablation (SGX), either left (LSGX) or right (RSGX), and the right cardiac vagus nerve (RCVX) transection. The ECGs were recorded by telemetry while animals rested quietly or were judged behaviorally to be asleep. Analyses of the ECG included measurements of R-R and Q-T intervals, as well as corrected Q-T intervals (QTc). Poincaré plots were used to display age-related differences in R-R and Q-T intervals. For stellectomized animals, significantly prolonged R-R intervals were first observed at post-surgical week 3 in the RSGX group and at week 5 in the LSGX group. Significantly prolonged QTc was found only in the RSGX group. In the RCVX group, shortened QTc and R-R intervals were noted at 6 and 7 weeks after denervation. Furthermore, three of six RSGX animals (50%) and one of four RCVX animals (25%) exhibited marked pauses in sinus rhythm that were unrelated to changes in heart rate or to sinus arrhythmia. These results in conscious animals support our hypothesis that abnormal autonomic innervation of the heart during maturation, e.g., withdrawal of vagal cardiac modulation or asymmetry of sympathetic innervation, impairs cardiac electrical stability.

Aging↗
PubMed1999

Aging alteration of cardiac vagosympathetic balance assessed through the tone-entropy analysis.

BACKGROUND: Age-associated alterations of cardiac autonomic functions have been investigated intensively through heart rate variability analyses. However, changes with age in cardiac vagosympathetic balance remain to be elucidated. METHODS: We studied 142 male subjects (30-69 yr) at a health care center in Kyoto, Japan. Electrocardiographic data were collected from subjects in a recumbent position for 10 min in the morning. Analysis was done by classifying the subjects into four age groups. In a pharmacological experiment carried out in December 1996, tone was verified to reflect the cardiac vagosympathetic balance, and entropy the total autonomic neural efferent activity. We assessed the heart rate variability through the tone-entropy (T-E) analysis that was described previously. In essence, two indexes, tone and entropy, were defined on a distribution of successive variations of heart period. RESULTS: No significant differences were detected in clinical conditions among the four age groups. Tone increased and entropy decreased significantly with age. The aging process was expressed as a curvilinear path in T-E space. Compared to the pharmacological experiment, it was observed that aging degenerated the heart function from an ordinary to a denervated one. The same aging path was superimposed in the opposite direction on the heart recovery path after dynamic exercise in which cardiac vagosympathetic balance tended toward vagus division, corresponding with restoration of total autonomic activity. CONCLUSIONS: An age-related reduction in cardiac autonomic function was consistent with previous reports. The vagosympathetic balance was altered with this reduction: vagal predominance was impaired significantly in proportion to the withdrawal of total cardiac autonomic activity.

Adrenergic beta-Antagonists↗
PubMed1998

Heart rate variability.

Heart rate variability is a recognized tool for the estimation of cardiac autonomic modulations. Recently, several studies have advanced the field of heart rate variability in three areas: 1) in technical modes of electrocardiogram processing and heart rate variability assessment, 2) in physiologic understanding and interpretation, and 3) in clinical and practical use. The most recent technical studies concentrate on the analysis of nonlinear aspects of heart period variations and on coherence between electrocardiogram variability and other physiologic factors such as respiration. Principal physiologic investigations studied the components of heart rate variability attributable to the individual limbs of the autonomic nervous system. It is becoming recognized that behavior and responses to the environment, including the psychosocial environment, play an important role in long-term heart rate variability. Established clinical applications of heart rate variability are presently restricted to the assessment of risk after myocardial infarction and to the early diagnosis of diabetic neuropathy. Nevertheless, recent studies indicate that heart rate variability might soon become a similarly powerful tool for risk prediction and monitoring of disease progression in congestive heart failure and for monitoring or reinnervation after heart transplantation.

Autonomic Nervous System↗
PubMed2004

Stochastic heart-rate model can reveal pathologic cardiac dynamics.

A simple one-dimensional Langevin-type stochastic difference equation can simulate the heart-rate fluctuations in a time scale from minutes to hours. The model consists of a deterministic nonlinear part and a stochastic part typical of Gaussian noise, and both parts can be directly determined from measured heart-rate data. Data from healthy subjects typically exhibit the deterministic part with two or more stable fixed points. Studies of 15 congestive heart-failure subjects reveal that the deterministic part of pathologic heart dynamics has no clear stable fixed points. Direct simulations of the stochastic model for normal and pathologic cases can produce statistical parameters similar to those of real subjects. Results directly indicate that pathologic situations simplify the heart-rate control system.

Computer Simulation↗
PubMed1983

Modulation of the Q-T interval by the autonomic nervous system.

Recent investigations have clarified some of the effects of the autonomic nervous system on duration and spatial distribution of the Q-T interval in humans. The use of atrial pacing to fix heart rate or 24-hour continuous electrocardiographic recording to develop a regression formula for individual patients has provided a means to interpret the effects of an intervention that alters both the heart rate and the Q-T interval. Drugs that affect the autonomic nervous system can influence Q-T interval directly or by changing rate. Bazett's formula to correct for rate may be misleading after certain drug interventions. For example, the Q-T interval during sinus rhythm or atrial pacing and the ventricular effective refractory period shorten after atropine plus propranolol, but corrected Q-T interval using Bazett's formula does not change. No change occurs in the Q-T interval during sinus rhythm or atrial pacing, or in ventricular effective refractory period after administration of propranolol although corrected Q-T interval using Bazett's formula markedly shortens. Q-T interval during sinus rhythm and atrial pacing and ventricular effective refractory period decrease after atropine but correct Q-T interval lengthens.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

Influence of the autonomic nervous system on the genesis of cardiac arrhythmias.

The purpose of this report is to present a brief overview of the concepts concerned with the potential effects of the autonomic nervous system on the genesis of cardiac arrhythmias. First, we present data indicating the functional importance of presynaptic and postsynaptic vagal modulation of adrenergic neurotransmission on electrical activity in sinus and A-V nodes, and contractile activity of canine cardiac Purkinje fibers. Second, we indicate the possible intraventricular adrenergic and vagal pathways to the ventricles, suggesting that sympathetic fibers travel in the epicardium while vagal fibers appear to cross the A-V groove in the epicardium but then take an intramural route for part of their course. Finally, we demonstrate that a lesion such as a myocardial infarction can interrupt neural fibers traveling through the infarction to affect noninfarcted myocardium distal to the infarction. These factors may play a role in the genesis of some cardiac arrhythmias.

Adrenergic Fibers↗
PubMed1993

Effects of acute ischemia on anisotropic conduction in canine ventricular muscle.

The effects of acute ischemia on conduction velocities in the longitudinal (theta L) and transverse (theta T) fiber axis were determined from epicardial activation patterns, recorded with 48 bipolar electrodes (plaque electrode, 25 x 35 mm) on the left anterior ventricular wall of eight dogs and the posterior wall of seven dogs. During left ventricular stimulation (cycle length = 300 msec) in the center of the plaque electrode, theta L, theta T, and the ratio of longitudinal to transverse conduction velocities (theta L/T) were measured before and 2 to 5 minutes after occlusion of the left anterior descending coronary artery or the left circumflex coronary artery. During the control state theta L was greater than theta T demonstrating anisotropic properties of cardiac muscle, not only in the anterior but also in the posterior wall. During acute ischemia theta L and theta T were decreased from the control value and theta T was decreased by a greater extent than theta L resulting in an increase in theta L/T from 1.83 +/- 0.31 (mean +/- SD) to 2.19 +/- 0.36 in the anterior wall and from 1.58 +/- 0.17 to 1.92 +/- 0.28 in the posterior wall. During ventricular fibrillation some lines of conduction block were parallel to the long axis of epicardial muscle fiber bundle and the others were perpendicular. In conclusion, acute ischemia increased anisotropic conduction (theta L/T) in the epicardial ventricular muscle mainly due to greater reduction in theta T, in the anterior and the posterior wall. This augmented anisotropic ventricular conduction may have some relation to the initiation of ventricular fibrillation during acute ischemia.

Animals↗
PubMed1991

Regulation of atrial autonomic receptors in experimental cyanotic heart disease.

During chronic hypoxemia, left ventricular beta-adrenergic receptor density is decreased and a dissociation occurs between increased chronotropic and decreased inotropic responses to chronically elevated sympathetic tone. To determine whether this dissociation was related to alterations in autonomic receptor populations in the right atrium, we studied right atrial cholinergic and beta-adrenergic receptors in chronically hypoxemic newborn lambs and in normoxemic controls. Heart rate response was determined by infusing isoproterenol at 0.1 or 0.5 microgram.kg-1.min-1. Muscarinic receptors were quantified with [3H]quinuclidinyl benzilate and beta-adrenergic receptors with [125I]iodocyanopindolol. Competition with ICI 118,551 was used to determine beta 1- vs. beta 2-receptor subtypes. In the hypoxemic lambs, isoproterenol resulted in a lesser percentage increase in heart rate (hypoxemic, 46 +/- 6% vs. control, 89 +/- 17%, P less than 0.05); however, because baseline heart rate was higher in the hypoxemic lambs (213 +/- 7 vs. 177 +/- 12 beats/min, P less than 0.05), maximal heart rate responses were similar (310 +/- 7 vs. 326 +/- 6 beats/min, NS). There was no change in receptor density or affinity of either muscarinic or beta-adrenergic receptors and no change in the proportion of beta 1- vs. beta 2-receptor subtypes. Thus the dissociation between the chronotropic and inotropic responses to chronic hypoxemia may be in part secondary to a differential regulation of beta-adrenergic receptors between the left ventricle and the right atrium.

Animals↗