The effects of repeated administration of camphor-crataegus berry extract combination on blood pressure and on attentional performance - a randomized, placebo-controlled, double-blind study.

The present study investigated the effects of repeated administration of Korodin(®), a combination of camphor and crataegus berry extract, on blood pressure and attentional functioning. This study was conducted based on a randomized, placebo-controlled, double-blind design. 54 persons participated (33 female, 21 male) with a mean age of 24.3 years. Blood pressure and body mass index were in the normal range. Participants received 20 drops of either Korodin(®) or a placebo for four times with interjacent time intervals of about 10 min. Blood pressure was measured sphygmomanometrically before and after each administration. Attentional performance was quantified by using two paper-and-pencil tests, the d2 Test of Attention and Digit Symbol Test. Greater increases in blood pressure occurred after the four Korodin(®) administrations in comparison to the four placebo administrations. The performance in two parameters of d2 Test of Attention was consistently superior after the intake of Korodin(®). The excellent tolerability and safety of Korodin(®), even after a total consumption of 80 drops, was confirmed.

Time-locked association between rapid cerebral blood flow modulation and attentional performance.

OBJECTIVE: The study investigated relationships between rapid cerebral hemodynamic modulation and attentional performance. Based on former results on complex cognitive functioning, a specific association between the first seconds of the hemodynamic response and performance was hypothesized. METHODS: Using transcranial Doppler sonography, blood flow velocities in the middle cerebral arteries of both hemispheres were recorded in 48 healthy subjects. The applied task comprised motor reactions on a visual stimulus which was preceded by an acoustic warning signal (interstimulus interval 5s). Task-induced hemodynamic changes were assessed second-by-second, and related to reaction time using analysis of variance and linear regression. RESULTS: A right dominant blood flow response was observed. Flow velocity increase in the middle fraction of the interstimulus interval, i.e. seconds 2 and 3 after the cuing signal, significantly correlated with reaction time. This was not the case for the very early and late components of the response. CONCLUSIONS: The results suggest a time-locked association between cerebral blood flow increase and attentional performance. This is in accordance with neurophysiological studies that revealed the closest relationship between brain perfusion and cortical activity during a similar time window. SIGNIFICANCE: The study supports the assumption of a specific, relatively early time interval in which relationships between cerebral blood flow and behavior become apparent.

[Reduced drive and impaired cerebral performance: a new perspective on chronically low blood pressure]. / Antriebsschwäche und beeinträchtigte Hirnleistungen: neue Perspektiven zum chronisch niedrigen Blutdruck.

The scientific literature on mental impairment in persons with chronically low blood pressure (using WHO criteria) is systematically reviewed within its physiological context. Subjective symptoms related to hypotension, especially tiredness and listlessness have been adequately demonstrated. There are consistent findings demonstrating deficits in cognitive functions, especially in the fields of concentration and memory. Additionally, contrary to the current views, recent studies provide evidence for an impaired regulation of cerebral blood flow and reduced cerebral perfusion. The resulting deficits in brain function are also reflected in EEG findings. These findings indicate that the marginal attention paid to chronic hypotension in research and clinical practice is no longer justified.

Efficacy, tolerability and safety of nateglinide in combination with metformin. Results from a study under general practice conditions.

In a general practice observation study 11,476 patients with type 2 diabetes pretreated with oral antidiabetic drugs, mainly metformin, received an oral combination therapy of nateglinide with metformin. Mean age+/-SD of the participants was 61+/-10.3 years, range 19 to 97 years, the body mass index (mean+/-SD) was 29.4+/-4.5 kg/m2, range 14.9 to 68.7 kg/m2. The observation period lasted 3 to 4 months (mean 96 days). During this period the mean HbA1c decreased from 8.4 % to 7.2%, displaying a positive relation between initial value and degree of reduction. Postprandial glucose levels dropped from a mean of 210 to 152 mg/dl. At the beginning of the study the combination of the two target values for glucose control, HbAc <7% and postprandial glucose <180 mg/dl, was reached in only 5.8% of the participants, at the end in 44.9%. During the therapy, weight and blood pressure dropped slightly. Adverse events were reported in only 2.9% of the patients and involved a broad range of symptoms with mild gastrointestinal complaints being predominant (1.3%). This study demonstrated that the combination of nateglinide with metformin can be considered as an effective and safe option for treatment of patients with type 2 diabetes, with additional beneficial effects on body weight and blood pressure.

The heartbeat-evoked brain potential in patients suffering from diabetic neuropathy and in healthy control persons.

OBJECTIVES: Neurotransmission from the heart to the brain results in a heartbeat evoked potential (HEP). This potential appears as a positive waveform ranging from 250 to 600 ms after the onset of ventricular contraction. Only limited information exists as to what extent the HEP is sensitive to a dysfunction in cardio-afferent pathways. Thus, the HEP was studied in patients with autonomic diabetic neuropathy. METHODS: Twenty-five patients and a healthy control group of equal size participated. The HEP was obtained as the average over 1200 EEG sweeps (18 channels) sampled contingent upon the onset of ventricular contraction. A heartbeat attention task and a distraction task were employed. Patients answered a questionnaire pertaining to the frequency of subjective symptoms related to diabetic neuropathy. RESULTS: The HEP amplitude at frontal, central and temporal locations was significantly diminished in patients in the latency range of 280-330 ms. A significant correlation was found between the questionnaire score of subjective autonomic symptoms and the reduction in the HEP. CONCLUSIONS: We conclude that the HEP is sensitive to a comparably moderate abnormality in nerve function. Furthermore, we assume that the processing of subjective symptoms of the disease and the generation of the HEP share some common neuronal pathways.

Contingent negative variation and cognitive performance in hypotension.

The difference in attention and cognitive performance between 26 hypotensive (systolic blood pressure < 100 mmHg and diastolic blood pressure < 60 mmHg) and 22 normotensive female university students was assessed. Attention was examined with contingent negative variation (CNV) recorded using light and tone as S1 and S2. Cognitive performance was assessed by free recall of a list of words and two German tests of cognitive speed performance and sustained attention: Zahlen-Verbindungs-Test and d2. The hypotensive participants demonstrated a lower increase in negativity on the CNV. Moreover, in the free recall test, hypotensive individuals remembered fewer words, in comparison with normotensive subjects. Scores for hypotensive individuals on the Zahlen-Verbindungs-Test and d2 were also lower. No difference was found in reaction times to imperative stimuli (S2).

[Change in quality-of-life and mood through pacemaker implantation: a follow-up study]. / Veränderungen von Stimmung und Lebensqualität nach Herzschrittmacher-Implantation.

The study was run to investigate the changes in quality-of-life and mood after pacemaker implantation. Data assessment was performed at three points in time: immediately before the implantation, 4 weeks, and 12 weeks later. The eight-dimensional Hacettepe Quality-of-Life Questionnaire and the brief version of the Profile of Mood States (POMS) were used. The three quality-of-life dimensions "physical activities", "working performance" and "appetite" as well as the mood dimensions "depression", "fatigue" and "illhumor" showed significant improvements. Patient subgroups regarding diagnosis and types of pacemaker systems reacted differently to pacemaker implantations according to quality-of-life assessment.

Event-related brain potentials and the processing of cardiac activity.

The cortical processing of cardiac afferent input can be studied by means of event-related potentials (ERP), in which characteristic brain waves are seen to accompany rhythmic activity of the heart. In the present paper, results from three studies, investigating the heartbeat-evoked potential are summarized. These studies demonstrated that (a) cardio-afferent input is projected primarily to fronto-cortical areas; (b) typically, this activity is reflected as a broad positive wave form in a range of 300-600 ms after the EKG R-wave; (c) psychological factors such as level of attention and motivation exert influences on the heartbeat-evoked potential which are comparable to effects known from exteroceptive evoked potentials. On the basis of these data we infer that cardio-afferent input is for the most part transmitted along visceral fibers and that the cortical processing of cardiac activity is similar to the processing of external stimuli.

Symptom reporting in asthma patients and insulin-dependent diabetics.

In this paper, results from two studies are presented. (1) Sixty-eight diabetics registered their blood glucose levels both as estimated and as measured and they indicated the intensity of 20 symptoms on a symptom checklist. Data were assessed twice a day over a 30-day period. During this period, blood glucose levels decreased slightly, the accuracy of blood glucose estimation improved, and for about half of the subjects specific symptoms could be identified, which covaried closely with blood glucose levels over time. (2) Fifty-three asthmatic patients monitored their peak flow each morning and evening over a period of 30 days. Before measuring peak flow, the patients estimated their peak flow and indicated the intensity of 28 symptoms specific for asthma. For about half of the sample, symptoms were identifiable, which correlated highly with measured peak flow. A substantial increase in the accuracy of estimated peak flow could be observed over time.

[Assessment of symptoms in asthma patients]. / Symptomwahrnehmung bei Asthmapatienten.

An important prerequisite for an effective institution of the required medication in asthma patients is the correct assessment of the severity of obstruction on the basis of subjective symptoms. However, empirical data are hardly available to date on the accuracy with which symptoms are reported by asthma patients under everyday conditions. In the present study extending over 30 days entered twice daily in an asthma logbook plus the estimated and measured peak flow. Assessed and measured peak flow showed fair agreement, albeit with high interindividual variation. The accuracy of assessment improved in about one-half of the participants in the study in course of time. There was a particularly marked link between the measured peak flow and those subjective symptoms that characterise obstructive airway disease complaints.

Changes in physical symptoms, blood pressure and quality of life over 30 days.

The existence of subjective symptoms arising from high blood pressure (BP) remains controversial. Few studies have been performed which compare symptoms of hypertensives and normotensives. The results of these studies are inconsistent. The present study investigates the intensities and prevalences of symptoms of hypertensives and normotensives and the relationship between symptoms and BP for both groups. During a 30-day period, 45 patients with primary hypertension and 45 normotensive controls documented BPs and intensities of 13 symptoms daily as well as mood and life satisfaction weekly. Starting on day 3 hypertensives received beta-blocker therapy (bopindolol, 1 mg/day). The BP values of the hypertensives normalized during the study, while the BPs of the normotensives did not change. At the beginning, hypertensives showed higher prevalences and intensities of the symptoms and poorer mood and life satisfaction. After normalization of BP, hypertensives attained scores similar to those of normotensives in all measured categories. Calculating within-S correlations between symptom intensities and systolic BPs, 70% of the hypertensives, but only 27% of the normotensives, showed at least one significant correlation. The differences observed between untreated hypertensives and the normotensive control group with respect to the prevalence and intensity of symptoms provide convincing evidence that untreated hypertensives are by no means symptom-free. The within-S correlations of the present study documented well the close relationship between symptoms and actual BP for a percentage of hypertensives.

On the relation between cardiodynamics and heartbeat perception.

The mediation of heartbeat perception by cardiodynamic parameters was investigated by experimentally introducing changes in heart performance. Twenty-five subjects (14 women, 11 men) underwent bicycle ergometric exercises (0-75 W) at different tilt angles (90 degrees-0 degree). After each of the 31 tilt/exercise phases, the following measures of cardiac performance were taken using impedance cardiography: stroke volume, Heather Index (as an indicator of contractile force), heart rate, and an estimate of the momentum of the ejected blood mass. Additionally, a heartbeat perception task was performed. The different tilt/exercise combinations induced profound changes in all cardiodynamic measures. The correlation between heartbeat perception and cardiodynamic parameters was highest for "momentum" (r = .67) and for stroke volume (r = .59). From our data, we infer that intraindividually occurring changes in cardiac perception are mediated partially by characteristics of heart dynamics and that the source of these interoceptive signals lies in the heart or in its close vicinity.

Heartbeat evoked potentials (HEP): topography and influence of cardiac awareness and focus of attention.

Heartbeat evoked potentials (HEP) were recorded from good and poor heartbeat perceivers under two conditions differing in focus of attention. Under the first condition (ATT), subjects were instructed to count their heartbeats. Under the second condition (DIS), subjects were distracted from their heartbeats by having them count external tones. Electrical brain activity was recorded from 19 electrodes. EEG epochs were triggered by the R wave of the EKG. Analyses of variance yielded a significant difference for focus of attention in HEP amplitudes at central electrodes (Cz, C3, and C4) in the latency range 350-550 msec post R wave. No significant differences occurred between good and poor perceivers. The interaction between the Group and Condition factors was significant at F4, C4 and T6. The potential map of good perceivers showed a fronto-temporal positivity, which was reduced in poor perceivers. Our data suggest that paying attention to an internal event such as the heartbeat can modify the cortical evoked response associated with that event.

[The correlation between coping with stress and blood pressure reaction]. / Zum Zusammenhang zwischen Stressbewältigung und Blutdruckreaktion.

This study explored the relationship between individual strategies of coping and blood pressure responses during and after mental stress. Blood pressure behavior was measured noninvasively and continuously before, during and after a mental stress situation in 27 normotensive subjects. Coping strategies were assessed with the Stressverarbeitungsfragebogen (SVF; coping with stress inventory). Two extreme groups were formed on the basis of the scores in the SVF. Results were: (a) Individuals who used coping strategies characterized by controlling the situation directly and constructively, in contrast to probands not using these strategies, exhibited lower blood pressure during the stress situation and a faster return to baseline levels after cessation of stress. (b) Subjects using a coping behavior characterized by the use of defense mechanisms such as suppression and denial, also showed lower blood pressure during stress but a significantly delayed return to baseline levels of blood pressure after stress was concluded.

[Effect of body posture on heart rate and cardiocirculatory parameters in stress--implications for frequency-adapted pacemaker systems]. / Einfluss von Körperposition auf Herzfrequenz und kardiozirkulatorische Parameter unter Belastung--Implikationen für frequenzadaptierende Schrittmachersysteme.

In order to study the influence of body position on cardiodynamics and the consequences for the regulation of rate-adaptive pacing, we examined variations of cardiocirculatory parameters with passive graded tilt from the erect to the supine position (90 degrees, 75 degrees, 60 degrees, 45 degrees, 30 degrees, 0 degrees) in 25 healthy subjects of both sexes under resting conditions and under conditions of exercise on a bicycle ergometer. Using impedance cardiography combined with phonocardiography, it was possible to record heart rate, cardiac output, contractility (Heather index), and left-ventricular ejection time (LVET). Under the condition of rest, some parameters showed evident tilt dependency: tilting from erect to supine induced a decrease of heart rate (85.1 to 65.7 bpm), an increase of stroke volume (84.4 to 111.4 ml), and a prolongation of LVET (255.8 to 330.3 ms). Cardiac output and the index of contractility were not changed by this manipulation, however. Tilting under the condition of exercise clearly had less influence on all cardiodynamic parameters than tilting under the condition of rest. The only significant increase of heart rate (89.4 to 109.2 bpm), cardiac output (10.4 to 13.1 l/min), and Heather index (24.2 to 29.8 ohm/s2) was found between 30 degrees or 15 degrees, respectively, and the supine position. Thus, in addition to indicators of physical activity, body position respective stroke volume should be taken into consideration. Consequently, rate-adaptive pacing may guarantee optimal physiological hemodynamics.

[Atopic eczema: psychophysiological reactivity with standardized stressors]. / Atopisches Ekzem: psychophysiologische Reaktivität unter standardisierter Belastung.

In 18 atopic eczema patients with active symptomatology and 15 control subjects a comparison of reactivity to psychological stressors was made. The physiological measures were heart rate, peripheral vasomotor response, skin resistance level, spontaneous fluctuations of the skin resistance, and forearm skin temperature. In addition, self-ratings of subjective state, situational anxiety, and social anxiety were assessed. Mental arithmetic performed undisturbed and in distracting conditions, and anticipation of the latter and of having to speak in public served as stressors. The results show higher reaction values of the eczema patients for heart rate, peripheral vasomotor response, fluctuations of skin resistance and subjective tension. A subgroup of patients with extreme skin irritation (itching) reacted with an elevation of skin temperature, in contrast to control subjects and patients with less marked itching, in whom skin temperature dropped slightly. The results suggest that atopic eczema may have a psychophysiological component.

Enhancement of heartbeat-related brain potentials through cardiac awareness training.

Heartbeat synchronous potentials were found to be sensitive to differences in perceptual accuracy. Since heartbeat perception can be improved using appropriate training procedures, increased ability to perceive cardiac performance should also influence heartbeat-related potentials. In the present study, subjects in either of two groups had to press a button immediately after the occurrence of a heartbeat-feedback tone. Whereas the first group was given acoustical heartbeat-feedback throughout the entire training, the second group was provided with tone signals that became fainter during the course of the training phases. The better posttraining performance in heartbeat perception of the group receiving full-intensity feedback was also reflected in the evoked potentials. They differed markedly before and after training, especially between 250 to 400 ms (after the EKG-R-wave), the biggest effect being at Fz and F7. The findings are interpreted as the brain electrical reflection of an increased perception susceptibility to a cardiovascular signal occurring at about 200 ms after the R-wave.

[Cardiodynamic determinants of heart perception]. / Kardiodynamische Determinanten der Herzwahrnehmung.

Subjective perception of one's heartbeat is augmented by psychological factors (stress, fear) as well as by physiological influences (e.g., physical work). It is still unclear on which cardiac or circulatory parameters the "signal" for cardiac perception is based. In this study, the relation between cardiac performance and the ability to perceive one's heartbeat was investigated. Sixteen healthy subjects (8 female, 8 male, aged from 21 to 31 years) participated. Cardiac activity was varied by a combination of passive tilt and physical work on a bicycle ergometer. Subjects had to perform physical work (0, 25, 50, 75, 100 W) on the bicycle at seven different angles (90 degrees, 75 degrees, 60 degrees, 45 degrees, 30 degrees, 15 degrees, 0 degrees). A cardiac perception test was carried out after each load. The following cardiodynamic parameters were measured: stroke volume, contractility, and heart rate. The mean correlation coefficient between cardioceptive performance and cardiodynamic parameters was .62 for stroke volume, .45 for contractility, and .12 for heart rate. Obviously, a remarkable relation exists between the mass and--to a lesser degree--the velocity of ejected blood and cardiac perception. From this we infer, tentatively, that the subjectively perceivable heartbeat stimulus is generated by mechanical events that occur close to the left ventricle.

[Changes in the cardiac dynamics in passive tile to the supine position--impedance cardiography measurements]. / Veränderungen der Kardiodynamik bei passivem Kippen in die Waagrechte--Impedanzkardiographische Messungen.

Passive tilt is an effective means to manipulate cardiodynamic processes. While there is a large amount of literature available concerning cardiac function with upright tilt, passive tilt into the supine position is poorly investigated. There is evidence that adapting processes to the new position do not show analogy in both conditions. In this study we investigated cardiodynamic changes occurring with passive-graded tilt from the upright position to 20 degrees headdown tilt. Twenty healthy students of both sexes participated in the study. Using impedance cardiography combined with phonocardiography it was possible to acquire stroke volume, heart rate, Heather index, and systolic time intervals. The whole procedure was repeated to test the reliability of impedance data. There was no steady augmentation of stroke volume. Between 90 degrees and 60 degrees stroke volume remained stable and showed only little change between 60 degrees and 30 degrees. Between 30 degrees and the supine position there was a steep increase of stroke volume. Tilting into the upright position apparently has a different effect. The onset of heart rate decline preceded the increase of stroke volume. It is concluded that only little changes of stroke volume/preload are necessary to induce vagal response. In the 30 degrees position both cardiac output and Heather index were minimal; this may be due to decreased sympathetic output. Systolic time intervals showed volume dependancy. Correlations between the first and second part of the study were high for all variables.