Thomas Kenner

Heart rate variability as a prognostic tool in cardiology. A contribution to the problem from a theoretical point of view.

BackgroundRecent clinical studies have proposed standard deviation of heart rate as a diagnostic tool for the outcome of cardiac infarction. Mathematical analysis of heart rate variability shows that heart rate is influenced by different frequency components derived from different parts of the autonomous nervous system. In the experimental part of this study, we investigated the possibility of calculating a variable describing the parasympathetic branch of the autonomous nervous system exclusively. Methods and ResultsIn 60 healthy volunteers, heart rate was measured to 1 millisecond during two different conditions: 5 minutes of rest, and 5 minutes of intermittent handgrip dynamometry; the latter is known to increase sympathetic arousal selectively. Heart rate was found to be lower at rest (65.9±9.7 beats per minute) than during dynamometry (72.8±10.4 beats per minute, P<.001). Respiratory sinus arrhythmia (RSA) calculated from the mean absolute differences between successive heart beats showed no significant change (3.01± 1.62 beats per minute at rest versus 2.97±1.30 beats per minute during dynamometry). In contrast, standard deviation increased from 5.19±1.98 to 9.22±3.56 beats per minute (P<.001). ConclusionsIt can be concluded from these data as well as from other plots presented in this article that RSA is a measure of the parasympathetic vagal tone, whereas standard deviation is increased by both sympathetic and parasympathetic arousal. Clinical evidence and data from physiological experiments are presented to show that a selective measure of vagal tone like RSA may offer advantages over standard deviation as a prognostic tool in cardiology.

The measurement of blood density and its meaning

SummaryDensity is defined as mass per unit volume. The classical technique to measure the density of fluids consists of a determination of mass and volume. Blood density is proportional to hematocrit or, more exactly, to the total protein concentration of blood; only to a minor extent is blood density influenced by other plasma solutes.Since the introduction of the mechanical oscillator technique for the continuous recording of fluid density a sizeable amount of experience has accumulated. This review summarizes recent work performed with this technique. It appears that the scientific interest in a variable like blood density depends on the availability of a suitable and simple method. Until the oscillator technique was available the measurement of density was too complicated or too inaccurate for routine laboratory use. A further new technique permits us to determine fluid densities by measuring sound velocity transmission.The density dilution method can be used for the determination of distribution volumes, of flow through organs, and of the cardiac output. The influence of temperature and of certain artifacts like acceleration forces in the density measuring device have to be considered and may be used for additional diagnostic purposes like determination of erythrocyte sedimentation velocity. The new technique opens a reasonable simple way to study fluid shift between interstitial space and capillaries. The arterio-venous density gradient in an organ depends on the lymph production. The injection of a hypertonic solution leads to an osmotic fluid shift from the extravascular space towards the blood. This fluid shift can be recognized by a reduction of the blood density. A simple model for the description of this reaction is presented.

The continuous high-precision measurement of the density of flowing blood

SummaryThe “mechanical oscillator” technique for the measurement of the density of fluids is based on the influence of mass on the natural frequency of a mechanical oscillator. The practical application of this principle was worked out by Kratky et al. (1969) and Leopold (1970). It is demonstrated in this study that the method permits the continuous high-precision measurement of the density of flowing blood in anesthetized animals. The accuracy is 10−5 g/ml, the maximum sampling rate 20/min.As found in rabbits and cats during the control state, physiological blood density changes related to spontaneous blood pressure variations are up to 2·10−4 g/ml. The method can be combined with i.v. injections of isotonic and iso-oncotic solutions to determine cardiac output and blood volume on the basis of a “density dilution” principle. Since the density of the interstitial fluid is lower than that of blood, fluid shifts through the capillary walls can be detected. The effects of hypertonic glucose and of hyperoncotic dextran have been examined. Changes in the density of the arterial blood appear within 10 s after i.v. injection of these fluids. Similarly, density changes result from hemorrhage and reinfusion. During and after i.v. administration of vasoactive drugs (noradrenaline, angiotensin II, acetylcholine), marked transient changes in blood density are seen which obviously reflect the effects of fluid shifts through the capillary walls. During hemorrhagic hypotension we found periodic variations in the blood density synchronous with spontaneously occurring Mayer waves. The new method seems to be a promising tool for investigations on physiological and pathological capillary fluid dynamics.

A sound‐speed sensor for the measurement of total protein concentration in disposable, blood‐perfused tubes

The aim of this investigation was to develop a sensor containing a disposable measuring cell capable of measuring fluid shifts in blood‐perfused circulation systems. Usually, the determination of fluid shifts in such systems is achieved by tracking the concentration of particles or solutes in the perfusate. Since acoustic properties of blood are closely related to the total protein concentration (TPC) of the sample, a new approach for the calculation of fluid shifts is made by the continuous measurement of sound speed. The measuring principle is based upon the evaluation of the propagation time of short acoustic pulses that are repeatedly transduced to the sample. The retransmission is triggered by means of a new type of delay line. The method stands out for its accuracy (better than 0.1 m/s) and for the short acoustic propagation path (5–10 mm). In order to develop the disposable measuring cell, the acoustic properties of porcine blood were determined at different hematocrits and TPC at temperatures rang...

Numerical blood flow analysis: Arterial bifurcation with a saccular aneurysm

SummaryThe flow pattern and the paths of fluid particles in a saccular aneurysm located at the bifurcation of an intracranial arterial segment are investigated with a numerical method. A normal physiological flow pattern was assumed as imput to the studied segment. The theoretical study is carried out for two different Reynolds numbers and two different geometries of the aneurysm. The governing equations for incompressible Newtonian fluid flow are solved using the finite element method. The results show the disturbed blood flow in the pathologically altered bifurcation and the flow activity in the aneurysms. It is particularly important that blood particles can circulate in a whirl within the aneurysm for a time which seems long enough to permit the generation of cell aggregates or/and blood clots.

In vivo cardiac phase response curve elucidates human respiratory heart rate variability

Recovering interaction of endogenous rhythms from observations is challenging, especially if a mathematical model explaining the behaviour of the system is unknown. The decisive information for successful reconstruction of the dynamics is the sensitivity of an oscillator to external influences, which is quantified by its phase response curve. Here we present a technique that allows the extraction of the phase response curve from a non-invasive observation of a system consisting of two interacting oscillators--in this case heartbeat and respiration--in its natural environment and under free-running conditions. We use this method to obtain the phase-coupling functions describing cardiorespiratory interactions and the phase response curve of 17 healthy humans. We show for the first time the phase at which the cardiac beat is susceptible to respiratory drive and extract the respiratory-related component of heart rate variability. This non-invasive method for the determination of phase response curves of coupled oscillators may find application in many scientific disciplines.

Effects of pressure-controlled intermittent coronary sinus occlusion on regional ischemic myocardial function

Pressure-controlled intermittent coronary sinus occlusion has been reported to reduce infarct size in dogs with coronary artery occlusion, possibly because of increased ischemic zone perfusion and washout of toxic metabolites. The influence of this intervention on regional myocardial function was investigated in open and closed chest dogs. In six open chest dogs with severe stenosis of the left anterior descending coronary artery and subsequent total occlusion, a 10 minute application of intermittent coronary sinus occlusion increased ischemic myocardial segment shortening from 5.5 +/- 1.2 to 8.2 +/- 2.6% (NS) and from -0.1 +/- 2.1 to 2.3 +/- 1.2% (NS), respectively. In eight closed chest anesthetized dogs, intermittent coronary sinus occlusion was applied for 2.5 hours between 30 minutes and 3 hours of intravascular balloon occlusion of the proximal left anterior descending coronary artery. Standardized two-dimensional echocardiographic measurements of left ventricular function were performed to derive systolic sectional and segmental fractional area changes in five short-axis cross sections of the left ventricle. Fractional area change in all the severely ischemic segments (less than 5% systolic wall thickening) was -4.0 +/- 4.7% at 30 minutes after occlusion, and increased with subsequent 60 and 150 minutes of treatment to 13.1 +/- 3.3 and 7.0 +/- 3.3%, respectively (p less than 0.05). At the most extensively involved low papillary muscle level of the ventricle, regional ischemic fractional area change was increased by intermittent coronary sinus occlusion between 30 and 180 minutes of coronary occlusion from -0.4 +/- 0.1 to 14.4 +/- 4% (p less than 0.05), whereas a further deterioration was noted in untreated dogs with coronary occlusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Calculation of pulsatile flow and particle paths in an aneurysm-model.

SummaryThe velocity field and the wall shear stress have been calculated numerically by the finite element method to the time-dependent Navier-Stokes equations for pulsatile flow in a model of an aneurysm. The results show a complex flow field with two eddies growing and disappearing during the cardiac cycle. Downstream at the outlet vessel high wall shear stress occurs, which may lead to a downstream-growing of the aneurysm.With the knowledge of a sufficiently accurate flow field, the calculation of several particle paths has been carried out. Starting points and starting time are varied. The paths demonstrate the time-dependent development, shift and disappearance of vortices during the pulsatile cycle and provide hints on zones of stasis. These are significant factors in thrombogenesis.

Method for the analysis of the entrainment between heart rate and ventilation rate

SummaryA digital computer program was developed which allows to continuously represent the relation between heart rate and ventilation rate. Using this program, experiments in anesthetized rabbits were performed. We found periods of synchronization, periods of transient entrainment and escape, and periods of complete desynchronization. By testing the respective roles for the entrainment mechanism of ventilation rate and heart rate it was found that spontaneous adjustments of the ventilation rate play a more pronounced role. Thus, as soon as spontaneous or induced variations of the heart rate and/or the ventilation rate shift both rhythms close to synchronization, variations of the ventilation pattern, which seem to be of reflex nature, tend to induce entrainment.

Some comments on ventricular afterload.

SummaryIn this issue of Basic Research in Cardiology a paper by Timisjärvi et al. (12) is presented in which the problem of afterload, generated by the resistance against which the left ventricle is ejecting, is discussed. These authors have performed experiments in which they examine the role and validity of the so-called mean outflow resistance (MOR) of the left ventricle.In this editorial, the opportunity is taken to present some thoughts on the different possibilities of expressing the interrelation between the heart and the arterial system. It is intended to show how, from the first ideas about ventricular-arterial interaction bei Ph. Broemser (1935; 1) different concepts about simple descriptions of the functioning of the heart, the arterial system and the matching between both have evolved. In particular, the concept by Sunagawa et al. (11) seems worthy of mention. An examination of this, and several other concepts, prove that the peripheral resistance and, particularly, the MOR, are important parameters that determine the influence of the arterial system on the performance of the heart. However, since MOR by definition is closely related to the total peripheral resistance, there is no essential need to introduce this resistance as a new concept of ventricular afterload. Calculations based on this definition of MOR demonstrate an agreement between theory and experimental results.