Physiological considerations about a statement by Gaius Petronius.

In my inauguration speech on November 8, 1989 as Rector of the Karl-Franzens-University in Graz (1) I have warned not to split off the Medical Faculty as a separate Medical University "... since such a separation of a part of a University corresponds to an amputation." In spite of this and of other warnings the decision was made by a federal law to permit this separation. The irrevocable and definite step to execute the separation was done by a vote of the Medical Faculty in Graz. The logical consequence is now the development of isolationism, which will lead to a narrowness of Medicine in a kind of "Splendid Isolation." The observation of systems like a University shows, that in such a community time, time course and periods play an important role. It seems interesting to discuss the time course of the development of Universities from the first foundations in Europe and to analyze the effect of sudden changes produced by external influences. In particular the new laws, which came into effect in the last decades and years and changed the function of the Universities markedly, are of interest. From a discussion of the development of Universities until recent events one can conclude, that the splitting of each of the three Austrian Universities, which included Medical Faculties, into a new Medical University and a Rest University will lead to the growth of two "daughter cells" with each growing to a larger size than the former whole University. Another conclusion indicates that even in simpler systems instability can be produced, if new disturbing inputs are effective in a too fast sequence.

[Karl E. Hammerschmidt. Humanist, natural scientist and pioneer in anesthesia]. / Karl E. Hammerschmidt. Humanist, Naturwissenschaftler und Narkosepionier.

Karl Eduard Hammerschmidt was born in Vienna in 1801. There are indications that after studying law he passed on to studies in medicine and surgery in Vienna, though it has to be said there is no trace of his attaining any qualification. After this he worked in various scientific sectors and in recognition of his achievements he was accepted as a member of the Kaiser Leopold Academy of Researchers in Natural Sciences in Bonn. From February 1847 to March 1848 he induced numerous general anaesthetics with ether, working with Dr. J. Weiger, a dentist in Vienna. On 11 July 1847 he published preliminary statistics based on 1560 dental operations performed under ether anaesthesia and also on numerous experiments performed on himself and investigations conducted with ether in animals and in healthy subjects. From the viewpoint of scientific research into and widening of the applications of ether anaesthesia, his most meritorious achievements include the early publication of a staging classification for ether anaesthesia, the introduction of an anaesthetic protocol for patients that also lent itself to data recording for statistical purposes and the early realization that the ability to hear is retained for a very long time during anaesthesia. In 1848 Hammerschmidt was obliged to flee to Istanbul by way of Hungary because of his involvement in the October Revolution. Once there, he continued to work as a doctor and later became Professor of Medicine at the University of Istanbul. He converted to Islam, taking the name of Abdullah Bey, and also became a colonel in the Turkish army. He was one of the founders of the Red Crescent, the humanitarian sister organization of the Red Cross, and the Turkish Post commemorated this with the issue of a stamp honouring him when the organization celebrated the centenary of its formation in 1968. In 1869 the Hapsburg dynasty also honoured him with orders and distinctions. He died in Istanbul in 1874 as a highly esteemed personage.

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.

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.

Effects of an eight-day space flight on microvibration and physiological tremor.

Microgravity was used to study accelerometrically recorded microvibration (MV) and postural tremor (PT) at reduced muscle tone on one cosmonaut before, during, and after an 8-day space flight on the Russian Mir station. MV of the relaxed forearm in the 1 g environment showed the typical 7- to 13-Hz resonance oscillations triggered by the heart beat. In 0 g, these pulsations shifted to below 5 Hz and the waveform became similar to an ultralow frequency acceleration ballistocardiogram. PT of the arm stretched forward showed an irregular waveform in 1 g. In 0 g, the higher-frequency components were reduced and again an ultralow frequency ballistocardiogram emerged. As a control, hand force tremor was recorded as well; it was not affected by the gravity condition. A second-order analog with muscle stiffness (C) as parameter was used to evaluate the measurements. For MV it could be shown that cardiac impacts produce damped resonance oscillations when C is high enough (1 g). At low C (0 g), this resonance phenomenon is essentially filtered out. For PT both neuromuscular and cardiovascular forces produce an irregular output; when C is lowered (0 g) the higher-frequency content is strongly reduced. It is concluded that both MV and PT waveforms are sensitive to musculoskeletal stiffness, such that at the lowest stiffness achieved the cardiac impact dominates. In 1 g, the cosmonaut's data were not significantly different from the results in a control group (n = 6).

Effect of controlled extracorporeal blood cooling on ultrafiltration-induced blood volume changes during hemodialysis.

Considerable amounts of heat may be lost or gained through the extracorporeal circuit during hemodialysis and influence the hemodynamic stability of the dialysis patient. The effects of two levels of extracorporeal heat flux (Jtherm in W) on blood pressures and ultrafiltration-induced blood volume changes were studied in eight patients on conventional hemodialysis. Treatments were controlled automatically for mild to medium Jtherm of either -13.4 +/- 3.3 W (group A) or -30.2 +/- 3.7 W (group B) (1 W = 1 J/s = 3.6 kJ/h = 0.239 cal/s = 0.86 kcal/h) and repeated once. Values are given as mean +/- SD. With low blood flows (Qb = 251 +/- 21 ml/min), dialysate temperatures were automatically set at 37.3 +/- 0.3 degrees C (group A) and 35.3 +/- 0.2 degrees C (group B) for the two levels of Jtherm, respectively. Arterial blood temperatures increased by 0.4 +/- 0.4 degree C with mild extracorporeal cooling (group A), whereas arterial blood temperatures slightly decreased by -0.1 +/- 0.4 degree C in the group with medium negative heat flux (group B) (P < 0.01). Blood pressures tended to drop in the warm dialysate group and to remain unchanged in the cool dialysate group (P = NS). Relative blood volume changes calculated from on-line ultrasonic blood measurements were significantly larger with cool (-12.8 +/- 8.3 vol%) than with warm (-7.2 +/- 5.5 vol%, P < 0.05) dialysate, indicating reduced fluid removal from peripheral body compartments during cool hemodialysis ultrafiltration. Despite the larger reduction in intravascular volume, intradialytic hemodynamic stability was maintained with extracorporeal cooling and cool dialysate prescription.

Characterisation of arm microvibration recorded on an accelerometer.

Microvibration (MV) of the freely hanging and firmly supported lower arm was studied (n = 8) using two accelerometers, one located over muscle tissue (brachioradialis muscle) and one over bony tissue (processus styloideus). Measurements were made in the completely relaxed arm (REST), during arterial occlusion (CUFF) and during mild handgrip (GRIP), first with the arm relaxed and hanging beside the chair and then repeated with the arm supported in a special rest. At REST. ballistocardiac forces were identified as the driving mechanism for the regular MV pattern, whereas actions of local pulse waves (CUFF) could be excluded. During GRIP irregular MV, related to the contraction process, became superimposed on both signals. The MV at REST was sensitive to arm position. In the freely hanging state, when the arm was family coupled to the trunk, ballistocardiac body motion was present over bony tissue, producing a low damped 7-13 Hz resonant response over muscle tissue. In the supported state, the arm became isolated from body motions. Nevertheless, ballistocardiac forces reached the arm, producing smaller oscillatory responses over bone and muscle tissue. Regionally produced MV (GRIP) was not sensitive to arm position, but the spectrum content in the 7-13 Hz region was very similar to REST. From these results it would appear, that a low damped 7-13 Hz resonance process exists in relaxed muscle tissue, which physiologically becomes stimulated by cardiac and muscle forces. From the close relationship of the simultaneous MV waveforms in the supported arm, evidence for mechanical coupling between bone and muscle tissue is given.

Lipoprotein(a) inhibits collagen-induced aggregation of thrombocytes.

Lipoprotein(a) [Lp(a)] is known to interact with human platelets in vitro. In the present study the effect of physiological concentrations of Lp(a) on platelet aggregation was studied. Freshly prepared gel-filtered platelets from healthy donors were incubated for 30 minutes at 37 degrees C with various concentrations of Lp(a); aggregation was triggered with ADP, thrombin, and collagen. Control incubations were performed with Tyrode's solution or LDL. Thrombin- and ADP-triggered aggregations were only slightly influenced by Lp(a), but aggregation of platelets stimulated with collagen (4 micrograms/mL) was markedly inhibited. Measurable effects occurred at low concentrations (0.05 mg/mL) of total Lp(a); at 0.5 mg/mL, maximum aggregation of platelets was inhibited by 54 +/- 20%, and the aggregation rate was attenuated by 47 +/- 19% compared with platelets incubated with Tyrode's solution. Preincubation of collagen (4 micrograms/mL) with Lp(a) yielded similar results. The effect of Lp(a) on platelet aggregation was accompanied by a significant reduction of serotonin release and TXA2 formation. Higher concentrations of collagen ( > or = 10 micrograms/ mL) caused the inhibitory effect on Lp(a) on collagen-induced aggregation to disappear. In contrast, incubation of platelets with 5 mg/mL LDL led to a significant increase of aggregation rate, maximum aggregation, serotonin release, and formation of TXA2 when aggregation was induced with 4 micrograms/mL collagen. In an adhesion assay using fresh whole blood, which mimics the in vitro situation of vessel injury. Lp(a) reduced platelet adhesion at shear rates of 300 and 1600/s by 22.6% and 11.6%, respectively. In addition, Lp(a) reduced the size of platelet aggregates significantly (up to 63%); this reduction was more distant at the higher shear rate. Unlike LDL, Lp(a) is not a proaggregatory lipoprotein; rather, collagen-triggered aggregation in vitro is attenuated by Lp(a).

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.

Indirect measurement of blood pressure without a cuff.

This review covers the following topics: the palpation of the arterial pulse, the method of tonometry, the relation between blood pressure, arterial diameter and pulse wave velocity, the frequency dependence of the components of the pulse wave velocity, the influence of the state of the vascular smooth muscles on the pulse wave velocity, a special method to measure radial pulsations of the pulmonary artery, the so-called pulse transmission function and, finally, the influence of gravity on the arterial pulses.

Age, time, entropy, and biological optimality--some remarks on the general problem of biological optimization.

The purpose of this paper is to look from a very general viewpoint to the interaction of factors which contribute to the process of aging. Life time is the most significant period for an individual. Several theories try to explain the process of aging by genetic determinants, by genetic or metabolic defects, by immunologic failure or by other reasons. It is noteworthy that the duration of life is correlated to the size of the body of different animals. This fact indicates a close relation to metabolism. It can be assumed that under optimal conditions of life, defects in function or structure are repaired by special maintenance functions. During the process of aging these functions lose effectuality.

Analysis of left ventricular contractile behaviour during atrial fibrillation.

OBJECTIVES: The purpose of this study was to explore the physiology underlying the beat-to-beat variations of ventricular function during atrial fibrillation (AF). METHODS: Left ventricular pressure, and its first derivative (LVdP/dtmax, an index of contractility, and aortic blood velocity (and its integral AVI, an ejection index), were recorded using cathetermounted transducers in 15 patients with AF during cardiac catheterisation. Transfer function modelling was used to examine the influence of preceding intervals on LVdP/dtmax, and of LVdP/dtmax on AVI. The technique also allowed simulation of the behaviour of LVdP/dtmax in response to specific manipulations of interval. RESULTS: The variations in LVdP/dtmax recorded from the AF patients were shown to be dependent on up to six preceding intervals; a maximum of 91% of the variation was explicable in this way. The influences of mechanical restitution (MR, the relationship between preceding interval and contractility), postextrasystolic potentiation (PESP, the inverse relationship between pre-preceding interval and contractility) and the decay of that potentiation were all demonstrated. These influences collectively appeared to be powerful determinants of AVI. Simulations of LVdP/dtmax, following single interval perturbations, were entirely consistent with these interval force effects. CONCLUSIONS: The cardiac interval force relationship in man is an important determinant of the beat-to-beat variations of contractile and ejection function during AF: the beat-to-beat variations in contractile (or inotropic) function are independent of changes in ventricular filling or fibre-length.

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

BACKGROUND: Recent 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 RESULTS: In 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). CONCLUSIONS: It 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.

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.

Physiological tremor and control of limb position in 1 and 0 G.

Muscle and skeletal mechanoreceptors play an important role for the regulation of muscular tone and the genesis of normal Physiological Tremor (PT). For example if a big limb as the arm or leg is kept against the gravity vector, the la afferent spindle discharges continuously control the load bearing flexor in a negative feedback manner in order to compensate the gravity vector and to the stabilize arm position. This servo-like action, denoted as 'stretch reflex', not only increases static postural stability (tonic stretch reflex) but also counteracts against external disturbances by dynamically increasing the muscle tone. Muscle spindles are very sophisticated sensory organs. They have an own innervation and the endings of the nuclear bag fibres are highly sensitive for small microstretches. EMG and microneurografic studies showed their importance in the mechanism of the 8-12 Hz component for PT. In a 0 G a limb becomes position controlled. In contrast to 1g, where control of limb position is a subordinated function of force compensation in the load bearing muscle, an antagonistic control scheme is necessary in 0 G to compensate the arm against positional drifts. As a consequence there is a shift from load dependent (muscular) to position dependent (skeletal) mechanoreceptors that become involved in the neural control process. As the control process is reflected in the tremor pattern, we investigated arm tremor in a constant limb position in 1 and 0 G.

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.