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)

Application of statistical methods for the analysis or interval related cardiac performance variations during cardiac arrhythmia in man.

To study the influence of the sequence of stimulation intervals on cardiac performance indices the relationship between properties of succeeding arrhythmic aortic pressure pulses of patients with atrial fibrillation has been analysed by methods of correlation and regression analysis. There are high correlations between properties of succeeding pulses and it can be shown that the pressure amplitude of one pulse correlates to the properties (diastole, diastolic pressure, pressure amplitude) of up to five preceding pulses. Furthermore, the diastolic pressure is also highly correlated with properties of more than one preceding pulse whereas the duration of the diastole and the RR-interval is independent of preceding pulse properties. We, therefore, conclude that there is no beat to beat regulation of intervals during atrial fibrillation. The relations between properties of succeeding pressure pulses have been summarised in a transfer function model, which allows the description of pulse properties from preceding pulse properties without lack of it. The parameters of the transfer function models are estimated from a sequence of arrhythmic pressure pulses and a parameter selection procedure was developed which identifies the optimal number of input variables (= properties of preceding pulses) required to describe the time course of one pulse property. In order to obtain informations about the presence of possible interval dependent potentiation effects, the transfer function model was used to stimulate the behaviour of the aortic pressure for different stimulation sequences, which have been used in the literature to study potentiation effect experimentally. From typical sequences of potentiation phenomena in the stimulated pulse sequence we conclude that frequency potentiation effects exist in the human myocardium.

Physiological approaches to respiratory control mechanisms in infants. Assessing the risk for SIDS.

We have examined in a group of normal infants and in an "at-risk" group with clinical sleep apnea syndrome the duration and frequency distribution of apneas during sleep. In order to improve the estimation of an apnea factor, we introduced a weighting function which is based on the expected frequency distribution of apnea durations of normal infants. We were able to observe a good agreement between clinical rating, based on anamnestic symptoms, and numerical scoring. All infants of the at-risk group were treated with aminophylline, and the respiratory state improved significantly in nearly all cases. Breathing hypoxic gas mixtures tended to depress respiration, especially in the at-risk group, with a pronounced drop of pO2-values. Investigations on the coordination of respiration, sucking, and swallowing during nutritive sucking demonstrated a correspondence between disturbed coordination ability and the sleep apnea syndrome (SAS). This relationship is interpreted to be a result of an immaturity of the autonomic nervous system. In order to evaluate possible hereditary components in conjunction with respiratory disorders and, possibly, SIDS, we studied siblings of SIDS victims, of near-miss infants, and of infants with SAS. Only siblings of SAS and near-miss infants showed clinical signs of respiratory disorders with a rather high prevalence, whereas most of the siblings of SIDS victims were completely lacking conspicuous respiratory symptoms. Our results suggest that not all infants with sleep apnea syndrome are necessarily at increased risk for SIDS.

Instrumentation for assessment of tremor, skin vibrations, and cardiovascular variables in MIR space missions.

A versatile and simple to use biomedical instrumentation for noninvasive examinations of cosmonauts at the Russian MIR space station was developed. It consists of a comfortable sensor jacket to assess signals from the body surface, a precision hand dynamometer to produce muscular and cardiovascular loads, and a small interactive microprocessor unit that controls the examination and stores measurement data. The sensor jacket includes highly sensitive piezo-resistive accelerometers, pulse sensors, an ECG system, and a skin-mountable mechanical vibrator. The functionality of this instrumentation was evaluated during long-term space flights and also proved very useful in laboratory and clinical studies.

Temporal disparity between reduction of cot death and reduction of prone sleeping prevalence.

According to several reports sudden infant death rates have decreased significantly after public campaigns aimed at reducing the incidence of sleeping in a prone position. The Styrian population (1.2 million inhabitants), who have been studied from 1984, also showed a significant drop in the incidence of cot death during 1989 (from 2/1000 to 1/1000%). The year before, a campaign for the prevention of cot death had been launched. This included the recommendation to prevent infants from lying in a prone position during sleep. Part of the prevention programme consisted of a detailed questionnaire filled in and returned by the parents. These data, on 29970 infants from 1989 to 1994, provided information on the frequency of prone sleeping in 37% of our total population and as a consequence on parental response to the campaign. Calculating the data per year led to the surprising result that the reduction by half (from 50% to 25%) in the prevalence of sleeping in a prone position did not occur in 1989, when the drop in the incidence of cot death occurred, but 3 years later, in 1992. The following years saw a further decrease of prone position to 7% but no appreciable change in the incidence of cot death. However, during those 11 years of study about 80% of the victims were consistently found dead lying in a prone position. Our results show a temporal disparity between the reduction of sudden infant death and the decrease of prone sleeping in a population. Although we do not deny sleeping in a prone position as a risk factor for cot death, there cannot be a simple relationship between sleeping habits in the population and incidence of cot death.

The predictive value of behavioural risk factors for sudden infant death.

In order to examine the predictive value of risk factors for the Sudden Infant Death Syndrome (SIDS), we have interviewed the parents of 80 SIDS victims and 80 parents of a healthy control group. From these interviews a list of 24 clinical and behavioural symptoms was assembled which appeared to be associated with the risk for SIDS. Out of this list of 24 symptoms the average number of symptoms reported to be observable in SIDS victims was twice as large as the average number of symptoms reported for healthy controls. The following symptoms appeared markedly more often in SIDS victims than in the controls: difficulties in awakening the baby, shrill crying, apathy, few movements during sleep, and cyanosis. We have attempted to consider a possible bias in the report of the parents of deceased infants by the introduction of an "exaggeration factor". By application of Bayes' theorem the highest predictive probability, 2.7%, was found for difficulties in awakening the baby. This is approximately nine times the assumed a priori probability of SIDS of 0.3%. We conclude that behavioural risk factors have a low but still remarkable predictive probability. A behavioural pattern of apathy and sleepiness indicates risk with a high probability.

Neurological status, sleep apnea frequency and blood oxygenation in six weeks old infants.

A study was carried out to investigate the correlation between sleep apnea frequency, blood oxygenation and neurological condition in 21 infants at six weeks of age with inconspicuous medical history. Polygraphic recordings of respiratory behaviour and transcutaneous blood gas monitoring lasted for at least five hours. To quantify the results of the neurological examination we established a neurological optimality score (NOS). We found statistically significant correlations between several indexes of apneas and indexes of blood oxygenation and NOS. Thus, a reduced NOS was strongly correlated with higher apnea frequencies and with pronounced drops of transcutaneous PO2-values. In addition all but one infant who were diagnosed as having a sleep apnea syndrome showed a greater than ten percent reduction of NOS. Some pathophysiological considerations to explain our findings are put forward and the possible role of the neuromodulator adenosine is emphasized.

Variations of pial arteriolar diameter, arterial blood pressure and arterial blood density in the cat.

Feline pial arteriolar diameters (CVD, cerebral vessel diameter), mean arterial blood pressure and blood density were recorded continuously in order to examine the relation between rhythmic diameter variations and oscillations of blood pressure and density. Under constant arterial pressure, blood density and CVD oscillations of 2-6/min were recorded using a photometric technique. Furthermore, pressure and density variations were induced by bleeding and reinfusion of blood, to observe their influence on CVD. The latter over a period of time become synchronized to parallel variations of pressure and density during hemorrhagic hypotension. This observance was noted after an initial lag phase.

Flow and stress characteristics in rigid walled and compliant carotid artery bifurcation models.

Computer simulation of pulsatile non-Newtonian blood flow has been carried out in different human carotid artery bifurcation models. In the first part of the investigation, two rigid walled models are analysed, differing in the bifurcation angle (wide angle and acute angle bifurcation) and in the shape of both the sinus (narrow and larger sinus width) and the bifurcation region (small and larger rounding of the flow divider), in order to contribute to the study of the geometric factor in atherosclerosis. The results show a significant difference in the wall shear stress and in the flow separation. Flow recirculation in the sinus is much more pronounced in the acute angle carotid. An important factor in flow separation is the sinus width. In the second part of the study, flow velocity and wall shear stress distribution have been analysed in a compliant carotid artery bifurcation model. In the mathematical model, the non-Newtonian flow field and the idealized elastic wall displacement are coupled and calculated iteratively at each time step. Maximum displacement of approximately 6% of the diastolic vessel diameter occurs at the side wall of the bifurcation region. The investigation demonstrates that the wall distensibility alters the flow field and the wall shear stress during the systolic phase. Comparison with corresponding rigid wall results shows that flow separation and wall shear stress are reduced in the distensible wall model.

Viscoelastic properties of whole blood. Influence of fast sedimenting red blood cell aggregates.

Red blood cell (RBC) aggregation is known to be of deciding influence on erythrocyte sedimentation-rate (ESR) and on whole blood viscoelastic properties. The rheological behaviour of blood collected from a control-group with normal ESR is compared to the viscoelastic behaviour of blood collected from two groups with high to very high ESR, whose individuals are suffering from chronical polyarthritis and Morbus Bechterew, respectively. The rheological properties are evaluated by means of an oscillating-flow capillary-rheometer where the viscous (eta') and elastic (eta") component of the complex viscosity (eta) is measured at a constant frequency of 2 Hz. Correcting for the varying hematocrit of the different blood samples according to an exponential equation, the viscoelastic data are found to be elevated in the groups with high ESR. For the viscous properties this is only due to the increase of the plasma viscosity. A correction for the plasma viscosity, however, shows that the viscous properties at low shear- rates (2s-1) are significantly reduced, whereas elastic properties in a range of medium shear-rates (10s-1 to 50s-1) are significantly increased (P less than 0.001, t-test of Student). This result is discussed to be due to the high packing density of the RBC in fast sedimenting aggregates. High packing density reduces the effective volume of the RBC but increases the stiffness of the aggregates.

Rheological discrimination between native, rigid and aggregated red blood cells in oscillatory flow.

The viscoelastic behaviour of hardened or aggregated red blood cells is compared with the flow pattern of native red blood cells, all suspended in buffer solution at a hematocrit of 45%. The rheological properties are investigated under oscillatory shear at the constant frequency of 2Hz. Variation of the amplitude covers a range of shear-rates from 0.5/s to 200/s. It can be seen that rigidification of the red cells by treatment with glutardialdehyde leads to changes of the flow properties in the range of shear-rates above 10/s, whereas aggregate formation due to addition of dextran distinctly alters the flow properties in the range of shear-rates below 10/s.

Methods in clinical hemorheology: the continuous measurement of arterial blood density and blood sound speed in man.

Both blood density and sound speed are closely related to total protein concentration in blood and, as a consequence, to rheologically important parameters of blood. Two methods that permit continuous measurement of these properties, the mechanical oscillator technique and the new ultrasonic technique, were used for measuring blood protein concentration over a continuous period of time in a group of hemodialysis patients and in volunteers. It was seen that the concentration of the components of blood varies considerably. This variability is related to transport phenomena within as well as to the flow of masses across the cardiovascular compartment. From the continuous measurement of concentrations during hemodialysis treatment, relative changes in blood volume can be recorded in order to control the fluid balance of the patient. Rapid fluctuations at the macroscopic scale with periods of 5 to 30 seconds are due to heterogeneities at the microscopic scale and to the particular rheological behaviour of the red blood cells at the level of the capillaries and the small blood vessels. The amplitude of rapid oscillations increased up to 1.2% in terms of hematocrit values when there was rhythmic, spontaneous breathing at various frequencies. The measurement of concentrations at an accessible measuring site may be used to investigate the rheology of blood in the human microvasculature.

[Model construction and systems analysis in physiology and pathology]. / Modellbildung und Systemanalyse in Physiologie und Pathologie.

A model is the result of an epidemiological process which can be circumscribed by the words systems analysis and identification. Some characteristics of this process, as well as the problem of teleology and reason of different aspects of systems analysis are discussed in this essay using examples from circulation research. Such a description also makes it understandable that the essence of systems analysis can best be described in conjunction with the example of medical diagnostic procedure.

[Feedback by objective tests for coordination of medical teaching (author's transl)]. / Rückmeldung durch objektive Wissenskontrollen als Hilfe zur Koordination des medizinischen-Unterrichts.

Within the framework of an experimentally introduced curriculum in Medical Physiology during the past three years, voluntary tests of the multiple-choice type were offered at the end of each term in order to provide students with feedback on their achievements. Positive results contribute to the final grade. Analysis of test results reveals improvement after the first year; results of subsequent tests are fairly stable. Selected items are presented in detail in order to show the distribution of choices. As revealed by item analysis the attractivity of distractors seems to be of a specific nature. Statistical results and interpretation of content of questions derived from different fields indicate that valuable feedback might be obtained from objective tests when interdisciplinary coordination of the curriculum is to be achieved.

[Continuous determination of the blood density during haemodialysis (author's transl)]. / Die kontinuierliche Messung der Blutdichte während der Hämodialyse.

Application of the mechanical oscillator technique for measurement of blood density, in combination with a reference method for the determination of the absolute value of the blood volume, enables precise and continuous monitoring of fluid shifts during haemodialysis. The significant correlation between blood volume and density or plasma volume and density allows each variation in blood volume to be calculated from the blood density and the slope of the regression line for each individual patient. The possibility of taking continuous measurements and the high accuracy of the mechanical oscillator technique commends this method for the measurement of short-term and small fluid shifts.

[Air pollution and sudden infant death in Graz 1982 to 1987]. / Luftverschmutzung und plötzlicher Säuglingstod in Graz im Zeitraum von 1982 bis 1987.

We correlated the incidence of the sudden infant death syndrome (SIDS) and the degree of air pollution in each district of Graz over a time period of five years. The degree of air pollution was derived from a mapping of epiphytical lichen vegetation by Grill et al. (1988). We found an increased incidence of SIDS in districts with poor air quality. Although this result is not statistically significant a possible increase in SIDS risk because of air pollution cannot be excluded. Some pathophysiological explanations are discussed.

Monitoring fluid shifts in humans: application of a new method.

Using the "mechanical oscillator technique," the mass density of antecubital venous blood and plasma samples was measured 5-20 times in order to study the influence of postural changes (gravity dependence) on human blood mass density with 0.01 g.L-1 precision, while performing tilt table tests in 17 men. Hemoglobin concentration was measured in 10, and hematocrit in all subjects. Postural fluid shifts were mirrored by accompanying changes in all variables. Blood density (BD) was monitored continuously in five additional experiments from one vein each using two independent densitometers. There were linear relations (p less than 0.01) between all possible combinations of BD, plasma density (PD), blood hemoglobin concentration (Hb), and hematocrit (Ht). Hb can be directly computed from BD (range +/- 10%); the accuracy of Ht determinations from BD increases (range +/- 0.02) if the individual erythrocyte density (ED) and the sample PD are used for calculation. ED was calculated and did not change with body position. ED values of different persons ranged between 1085 g.L-1 and 1095 g.L-1 and did not vary in 15 out of 17 individuals with time (5-75 d). We conclude that ED is closely regulated to an individual set point, that Ht can be computed from BD with higher accuracy if the individual ED and the actual PD values are known, and that BD allows for direct Hb calculation. On-line BD monitoring can be performed with high precision and reveals the individual time-course of spontaneous and postural capillary fluid shifts.

Arm tremor and precision of hand force control in a short and long term flight on the MIR-Space-Station.

To determine whether long and short time exposure of man in 0g alters normal physiological tremor patterns we recorded arm tremor using an accelerometer as well as hand forces and tremor during constant isometric contraction using a load cell. Arm tremor was decreased during both flights in amplitude and frequency. Shortly after the long term flight arm tremor amplitude was increased, indicating adaptive changes in the tonic reflex loop. Isometric hand tremor remained unchanged during the long and short time flight demonstrating that the contractile properties of hand muscles remained constant. Precision of hand force was decreased until the half duration of the long term flight.

Microvibrations: an interrelation between heart beat, muscle tremor and resting muscle tone.

The phenomenon of microvibrations was described by Rohracher in Vienna in the 1950s. Microvibrations consist of oscillationns in the frequency range of 7 to 13 Hz which can be observed on the surface of the body during a complete muscle relaxation. We had the opportunity to study the changes of microvibrations and physiological tremor under the condition of weightlessness in the Russian Space Station MIR during the so called "Austromir" project and the following Russian long term flights including the record flight of cosmonaut Polyakow. The recordings have been made by accelerometers from the body surface. It was found that during wieghtlessness the typical 7 to 13 Hz oscillations disappeared as well from microvibrations as from physiological tremor. By the application of a simple model it can be shown that microvibrations are due to mechanical resonance. The oscillations are apparently elicited by the heart beat. Therefore it appears that microvibrations are cardioballistic phenomena. It can be shown that cardioballistic forces are transmitted by osseous structures to soft tissues like e.g. relaxed muscles. Local resonance finally leads to the oscillations as mentioned above. From the model calculations we conclude that the relaxation is much more pronounced during weightlessness. Thus, resonance is abolished in the frequency region mentioned above. On the ground even during muscle relaxation there is still some muscle tone with an elastic component which under this condition permits the generation of resonance phenomena. Our results permit a new interpretation of microvibrations. Furthermore, the results may have importance for the interpretation of the generation of certain pathological forms of tremor.