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PubMed2005

Gap junction blockage limits intercellular spreading of astrocytic apoptosis induced by metabolic depression.

Astrocytes are highly coupled by gap junction channels, which allow transfer of intracellular signalling molecules and metabolites between connected cells. Astrocytic gap junctions remain open during ischemic conditions as previously demonstrated in vitro and in situ. In this study, we investigated the effect of gap junction blockage on iodoacetate-induced ATP depression and cell death progression in astrocytes in primary rat hippocampal cultures. We demonstrated that blockage of gap junctions during iodoacetate-induced inhibition of the glycolysis induced an earlier onset of the ATP depression. Moreover, initiation of apoptotic processes, demonstrated by binding of Annexin V, was critically dependent on the ATP levels. The apoptotic event was also shown to spread and involve neighbouring cells, a process that was inhibited by blockage of gap junction communication. Chelating intracellular calcium using BAPTA-AM decelerated the iodoacetate-induced ATP depression. The chelation also decelerated the spreading of apoptotic processes. Inhibition of caspases did not alter the expansion of cell groups being Annexin V positive. However, the proportion of Annexin V positive cells also being propidium iodide positive was increased after caspase inhibition. The results show that inhibition of gap junctions during cellular metabolic depression interferes with the metabolic status and cell death progression in astrocytes.

Adenosine Triphosphate↗
PubMed2005

Intragranular pH rapidly modulates exocytosis in adrenal chromaffin cells.

Several drugs produce rapid changes in the kinetics of exocytosis of catecholamines, as measured at the single event level with amperometry. This study is intended to unveil whether the mechanism(s) responsible for these effects involve changes in the intravesicular pH. Cell incubation with bafilomycin A1, a blocker of the vesicular proton pump, caused both a deceleration in the kinetics of exocytosis and a reduction in the catecholamine content of vesicle. These effects were also observed upon reduction of proton gradient by nigericin or NH4Cl. pH measurements using fluorescent probes (acridine orange, quinacrine or enhanced green fluorescent protein-synaptobrevin) showed a strong correlation between vesicular pH and the kinetics of exocytosis. Hence, all maneuvers tested that decelerated exocytosis also alkalinized secretory vesicles and vice versa. On the other hand, calcium entry caused a transient acidification of granules. We therefore propose that the regulation of vesicular pH is, at least partially, a necessary step in the modulation of the kinetics of exocytosis and quantal size operated by some cell signals.

Adrenal Glands↗
PubMed1994

Comparison of the haemodynamic profiles of elgodipine and nicardipine in the anaesthetized dog.

1. The haemodynamic profile of elgodipine (1-30 micrograms kg-1, i.v.), a new dihydropyridine calcium antagonist, has been compared directly with that of nicardipine (1-30 micrograms kg-1, i.v.) in chloralose-anaesthetized dogs. 2. Nicardipine produced dose-related systemic, pulmonary and coronary vasodilatation accompanied by reflex tachycardia, inotropy and increases in cardiac output and myocardial oxygen consumption (MVO2). Elgodipine had similar vasodilator and hypotensive properties to nicardipine but produced less reflex inotropy, little or no reflex tachycardia and did not increase MVO2. 3. Both calcium antagonists were retested in a separate group of anaesthetized dogs pretreated with propranolol (1 mg kg-1, i.v.) and atropine (0.3 mg kg-1, i.v.) to abolish reflex autonomic tone to the heart and thus reveal the direct cardiac effects of each compound. Under these conditions both elgodipine and nicardipine decreased heart rate and cardiac contractility and slowed atrio-ventricular conduction. Elgodipine was approximately ten times more potent than nicardipine as a decelerator agent and slightly more potent in depressing cardiac contractility and increasing PR interval duration. Elgodipine, unlike nicardipine, slightly reduced the QTc interval of the electrocardiogram. Therefore, the potent decelerator effect of elgodipine, which was present throughout the dose-range, appears to be largely responsible for the suppression of reflex tachycardia observed when the baroreflex is functional. 4. Elgodipine is a potent systemic and coronary vasodilator with more marked direct cardiac effects than nicardipine, particularly with respect to slowing of heart rate. The ability of elgodipine to increase coronary blood flow without significant reflex tachycardia or increases in MVO2 suggests that this compound will have a more favourable effect on myocardial oxygen supply/demand balance than nicardipine. The haemodynamic profile of elgodipine may be suitable for the treatment of angina.

Animals↗
PubMed1986

Face presentation.

The diagnosis, aetiology, management and outcome of face presentation were analyzed in 51 cases. Primigravidas accounted for 17.6%, multiparas for 54.9% and grand multiparas (5 deliveries or more) for 27.5%. Prematurity did not appear to be an important aetiologic factor. The position was mentum anterior in 26 patients (51%), all but one of whom were delivered vaginally. Of 12 fetuses in the mentum transverse position, 11 were delivered vaginally after spontaneous rotation to mentum anterior. Ten patients presented with mentum posterior; only 2 were delivered vaginally after spontaneous rotation. Three fetuses were diagnosed as face presentation during Caesarean section. The mean birth-weight of the infants who rotated from mentum posterior to mentum anterior was 3,425 +/- 35g, while that of those with persistent mentum posterior was 3,792 +/- 347 (p less than 0.01). Records of monitored fetal heart rate were available in 21 cases. Late decelerations and variable decelerations were recorded in 6 (28.5%). The incidence of Caesarean section was 25.5% compared to an overall incidence of 4.4% during the period of the study. Oxytocin was administered to 10 patients, and 7 of them were delivered vaginally. Early diagnosis of presentation and position, with close fetal surveillance may improve fetal outcome. In case of mento-posterior position, primary Caesarean section at term should be considered.

Adult↗
PubMedDate not supplied

Fetal heart rate patterns and chronic exposure to antiepileptic drugs.

Fetal heart rate (FHR) characteristics of fetuses exposed and not exposed to antiepileptic drugs (AEDs) were studied. FHR is considered to reflect central nervous system (CNS) integrity. Three intervals during pregnancy were investigated: 20, 32, and 38 weeks. At 32 and 38 weeks, FHR was studied in relation to quiet (C1F) and active (C2F) sleep periods. For each tracing, a baseline was determined and accelerations and decelerations were identified. To assess FHR variability, the long-term irregularity, interval difference and absolute beat-to-beat indexes, and the bandwidth were calculated for 30-s intervals between accelerations and decelerations. No marked differences were noted between study and control groups concerning basal FHR and the occurrence of accelerations. For FHR derived from the fetal ECG, all indexes of FHR variability and the bandwidth were lower for the study group as compared with the control group, although the differences did not reach statistical significance. Our study shows that chronic prenatal exposure to AEDs does not seriously interfere with modulation of fetal heart rhythm by the CNS.

Anticonvulsants↗
PubMed2000

Simultaneous kindling of the bilateral hippocampi: an advanced model for epilepsy research.

PURPOSE: To examine whether simultaneous kindling of bilateral hippocampi [bilateral kindling (BK)] could accelerate the achievement of seizures by the breakdown of kindling antagonism or decelerate the achievement of seizures by its enhancement. METHODS: The hippocampi of 17 adult rabbits were simultaneously kindled bilaterally according to Goddard's method. RESULTS: All animals developed stage 5 convulsions after a mean of 28 stimulations. Six animals showed spontaneous seizure discharges. Afterdischarge duration increased abruptly during the early period of kindling, but thereafter it gradually progressed. Chronological analyses of interictal discharges (IIDs) demonstrated that simple as well as complex types of IIDs increased their frequencies during BK. CONCLUSIONS: Compared with unilaterally kindled animals, the BK procedure significantly increased the percentage of animals that successfully kindled (100% vs. 59%; p < 0.01), whereas it significantly decelerated the kindling progression (28 days vs. 19 days; p < 0.02). We conclude that the BK procedure represents potentiation of both excitatory and inhibitory mechanisms. Although the reason why such an antagonistic relationship between them breaks down is still unknown, the BK provides an advanced animal model to study the pathogenic mechanisms of kindling and to screen anticonvulsants.

Animals↗
PubMed1976

Aging.

Aging, a wearing-out process which affects everything inanimate and animate, is accelerated by abuse of decelerated by care. The psychologic reaction of aging persons vary considerably. The concept of growing older is much more satisfactory and pleasant than the concept of being old, since the former is applicable to everyone regardless of age whereas the latter carries a finite significance as deterioration progresses. Chronologic age is much less important than biologic age. The desideratum is not longevity but rather a long, useful and meaningful life. Although heredity is of importance in longevity, it is a factor over which at present we have no control. However, we can influence the aging process according to whether we care for or abuse the body. The principal factors in accelerated aging, in order of importance, are: 1) tobacco use (particularly cigarette smoking), 2) lack of exercise, and 3) obesity. Conversely, abstinence from tobacco, exercise within tolerance, and avoidance of obesity not only decelerate aging but result in a better quality of life.

Aged↗
PubMed1987

Chronotropic response of an activity detecting pacemaker compared with the normal sinus node.

We compared the rate responsiveness of an activity-detecting multiprogrammable, single chamber pacemaker (Medtronic Activitrax) to rate responsiveness of the normal sinus node. This pacemaker changes its basic pacing rate in response to physical activity. The rate responsiveness is programmable by selecting one of three activity thresholds, and one of 10 rate response settings. The study included a group of six normal volunteers and 12 patients implanted with Activitrax to examine the similarity of the pacemaker rate to normal sinus rhythm during acceleration and deceleration. The pacemaker was set to Activity mode, at a basic rate of 60 bpm. In volunteers, the device was externally secured on the chest wall and tested at two programmed settings. When programmed at a high threshold of activity and high rate response in volunteers, there was no significant difference in maximum normal sinus rates and pacemaker rates during arm waving, jumping in place, and walking during stress testing. At a medium activity threshold, the only significant difference occurred during submaximal stress testing, when the maximum sinus rate achieved was 141 +/- 19 bpm and the maximum pacing rate was 105 +/- 8 bpm (p less than .02). The pacemaker behaved in a similar manner in patients, successfully simulating the typical fast acceleration and slow deceleration of a normal sinus node in exercise testing. There was no difference in pacer response when implanted in abdominal or infraclavicular locations. The implanted units have functioned normally over a follow-up period of nine to 22 months. Activitrax can be programmed to achieve physiologic pacing rates in response to normal daily activities with appropriate programming.

Abdomen↗
PubMed1998

Scoring method for assessing rate adaptive pacemakers: application to two different activity sensors.

To optimize programming of rate adaptive pacemakers (RAPs), we explored a new mathematical method to assess the performance of RAPs during daily-life tests, using customized Windows-based software. By stepwise discriminant analysis and linear regression, this method allows calculation of the acceleration and deceleration capacity of pacemakers and their general behavior during effort and recovery phases. Twenty-three patients (10 females and 13 males; 68 +/- 8 years) with chronic atrial fibrillation and a slow ventricular response were evaluated. They randomly received an accelerometer-controlled VVIR Dash Intermedics pacemaker (10 patients) or a vibration piezoelectric-controlled VVIR Sensolog III Siemens pacemaker (13 patients). All patients underwent the same test protocol: 6 minutes walking, 1.5 minutes climbing stairs, 1.5 minutes descending stairs, and 0.5 minutes sit-ups. By definition, the pacemaker responsiveness slope was programmed so that the heart rate response of paced patients during the walking test corresponded best to that of healthy controls. The slope was left unchanged for the other tests. We considered four scores: an acceleration score (EA score), an effort rate score (ER score), a deceleration score (RD score), and a recovery rate score (RR score). Scores ranged from -10 (hypochronotropic behavior of the pacemaker) to +10 (hyperchronotropic behavior), based on daily-life tests of 15 healthy controls (7 females and 8 males, 65 +/- 9 years). A score of 0 represented exact concordance with healthy controls. During stair descent, the Sensolog III produced excessive acceleration (EA score = +2.9 +/- 1.1) compared to: (1) stair climbing (EA score = -4.0 +/- 1.9; P = 0.01, with the same pacemakers); and (2) the Dash (+1.8 +/- 1.9; P = 0.04) and healthy controls (P = 0.02). The sit-up tests revealed a hypochronotropic response of both pacemakers compared to healthy controls, with a larger difference for the Sensolog III (EA score = -2.0 +/- 5.8; P = 0.04; RD score = -6.8 +/- 3.8' P = 0.02). We conclude that activity-driven pacemakers can accommodate brief activities, except for isovolumetric exercise such as sit-ups. During daily activities, accelerometer-driven pacemakers seem to provide a heart rate resoibse closer to that of healthy controls. Our new mathematical analysis is a simple and reproducible method for evaluating and quantifying the efficacy of any sensor-driven pacemaker.

Adaptation, Physiological↗
PubMed2004

Atrioventricular block during upright tilt table test.

Patients with a cardioinhibitory response (asystole or atrioventricular block [AVB]) during upright tilt table test (UTT) constitute a therapeutic challenge. Our present knowledge is partial and in those who experience AVB is absent. Furthermore, we ignore if there is any difference between both groups, particularly pacemaker indication. We aimed to study patients with a cardioinhibitory response during UTT and incidence of AVB during UTT, compared to asystole; plus the outcome during prolonged follow-up. Of 867 patients who underwent UTT, 172 were positive for a neurally mediated response, all with normal neurocardiovascular evaluation. Of the 172 patients, 6 (3.4%) developed AV block (group A), and 26 (15.1%) experienced asystole (group B). Group A included 6 women (100%), mean age 21 +/- 12 years. All patients in group A had sinus rate deceleration during AVB. Group B included 10 women (38%), mean age 28 +/- 17 years, and a mean pause of 15 +/- 9 seconds. We contacted 30 of 32 patients, mean follow-up of 45 +/- 38 months. Seven patients in group B had syncopal recurrences; five had 2 or more episodes. One patient from group B received a DDD pacemaker. In group A, one had one recurrence. No deaths were observed. AVB during UTT is rare, occurs in young women, and is always associated with sinus rate deceleration. Medium- to long-term prognosis is good, and equivalent to patients with asystole. There is no evidence that patients with AVB during UTT require a pacemaker implant.

Adolescent↗
PubMed2004

Differences between study-specific and subject-specific heart rate corrections of the QT interval in investigations of drug induced QTc prolongation.

A computational study was designed to investigate the differences between the so-called study-specific and subject-specific heart rate corrections of QT interval. In 53 healthy subjects (25 women, mean age 26.7 +/- 8.7 years), serial 10-second electrocardiograms (ECG) were obtained during daytime hours. In each subject, 200 ECGs were selected representative of the individual QT/RR relationship. Of the population of 53 subjects, 30,000 different subgroups of 16 subjects were considered and their data used to model drug induced QT interval prolongation by 0, 5, 10, and 20 ms combined with drug induced heart rate acceleration and deceleration. In each modeled study, QTc changes were assessed by: (1) Six study-specific heart rate corrections designed by regression modeling of the baseline QT/RR data pooled from all subjects; (2) Six subject-specific heart rate corrections designed by the same regression modeling of the baseline QT/RR data in each subject separately; (3) subject optimized correction that selected the best fitting regression model for each individual; and (4) by Bazett and Fridericia corrections. In each modeled study, the errors of the correction approaches were estimated and statistically summarized over all modeled studies. The subject-specific corrections led to maximum errors in single milliseconds (error range of 2.4, 5.7, and 2.6 ms with linear, log/log linear, and exponential models, respectively) while the study-specific corrections led to substantially greater errors (error range of 17.8, 19.4, and 16.9 ms with linear, log/log linear, and exponential models, respectively). Both Bazett and Fridericia corrections led not only to substantial errors (error range of 28.3 and 16.9 ms) but also to regular bias with systematically false negative and false positive conclusions dependent on modeled heart rate acceleration and deceleration. Thus, subjects-specific corrections should be used in the intensive and definite studies aimed at providing the final answer on the ability of a drug to prolong the QT interval.

Adolescent↗
PubMed2006

Hemodynamics and autonomic control of heart rate turbulence.

INTRODUCTION: Late heart rate deceleration parallels the increase of systolic blood pressure during heart rate turbulence (HRT) after ventricular premature complexes (VPC). This is consistent with the involvement of baroreflex mechanism. Physiological background of systolic blood pressure dynamics is not known. Enhanced sympathetic activation and nonautonomic post-VPC changes of stroke volume have been speculated on. METHODS AND RESULTS: We studied 28 subjects (aged 56 +/- 11 years; 20 males; 18 normal and 10 abnormal left ventricular (LV) function) with spontaneous occurrence of VPCs. HRT indices and baroreflex sensitivity were analyzed from the ECGs and finger arterial pressure recordings during 30 minutes of spontaneous respiration in supine position. Beat-by-beat stroke volume and peripheral vascular resistance were computed by a nonlinear, self-adaptive model of aortic input impedance (Modelflow, Finapres Medical Systems, Arnhem, The Netherlands). Indices of HRT and baroreflex sensitivity were highly correlated. In patients with preserved LV function, there was no substantial dynamics of stroke volume in the late phase after VPC, while peripheral vascular resistance increased significantly. In patients with impaired LV function, potentiated first sinus beat after VPC triggered transient hemodynamic alternans. Dynamics of peripheral vascular resistance was attenuated and stroke volume was depressed in the late phase after VPC. CONCLUSIONS: Delayed sympathetically mediated vasomotor response to VPC produces systolic blood pressure overshoot. This subsequently induces vagally mediated late heart rate deceleration. Under physiologic conditions, there is no evidence of other hemodynamic and/or mechanical effect outside the autonomic reflex arch. In patients with LV dysfunction, both depressed vagal and sympathetic modulation and, indirectly, enhanced postextrasystolic potentiation account for attenuated HRT.

Analysis of Variance↗
PubMed1990

Accuracy of Doppler ultrasound in evaluating changes of left ventricular diastolic properties.

In order to evaluate the effect of an increase in preload caused by contrast medium (Renografin-75) on Doppler echocardiographic indices of left ventricular diastolic properties, left ventricular pressure using a catheter tip micromanometer and pulsed-Doppler measurement of transmitral flow signals were measured simultaneously in 15 patients with coronary artery disease pre- and post-left ventricular angiography. After left ventricular angiography, changes in indices determined from left ventricular pressure were significant: left ventricular end-diastolic pressure increased from 17 +/- 2 mmHg to 24 +/- 2 mmHg (mean +/- SE) (P less than 0.001), maximum -dP/dt increased from 1,129 +/- 63 to 1,307 +/- 90 mmHg/sec (P less than 0.005), and time constant decreased from 73 +/- 2 to 67 +/- 1 msec (P less than 0.01). Changes in Doppler-derived indices were also significant: A/E ratio decreased from 0.99 +/- 0.08 to 0.81 +/- 0.07 (P less than 0.01), peak velocity of early diastolic filling increased from 0.61 +/- 0.03 to 0.79 +/- 0.03 M/sec (P less than 0.01), and deceleration rate increased from 3.1 +/- 0.2 to 4.6 +/- 0.2 M/sec 2 (P less than 0.01). Changes in Doppler echocardiographic indices (DR, acceleration half time, deceleration half time, and A/E ratio) were accompanied by changes in time constant and maximum -dP/dt after left ventricular angiography. However, the correlations between changes in hemodynamic indices and changes in Doppler echocardiographic indices were poor (r = 0.06 to 0.67).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1999

EMG activity of the iliopsoas muscle and leg kinetics during the soccer place kick.

The purpose of the study was to develop a method to record intramuscular electromyogram (EMG) from the iliopsoas muscle and to relate this activity to the kinetics during the soccer place kick. Seven skilled soccer players performed 3 maximal velocity place kicks. The kicks were filmed with a high-speed camera (400 Hz) and EMG recordings were obtained from 5 muscles of the kicking leg, including wire electrodes inserted into the m. iliopsoas. The EMG signals were compared to the kinetics of the kicking leg, which were calculated from the digitised film. The results showed hardly any torque reversal about the hip joint before impact. Angular deceleration of the thigh segment did not increase the angular velocity of the shank (work -3.57 to 0.0%). M. iliopsoas was active during the entire kicking motion (average EMG 65.1-100.9%), even in the period when the thigh was decelerating. Wire electrodes can successfully be applied to EMG recordings of fast unloaded movements.

Adult↗
PubMed1988

Infancy growth pattern related to growth hormone deficiency.

Linear growth during the first three years of life can be represented mathematically in terms of the "ICP-growth model", using a combination of a quickly decelerating Infancy component with the addition of a slowly decelerating Childhood component, the latter acting from the second half of the first postnatal year. The growth pattern for supine length of four children with growth hormone (GH) deficiency is related here to the first two components of this growth model. Basically, all four infants displayed a pattern in line with the exponential shape of the Infancy component to the age when GH therapy was initiated. This observation indicates the existence of the Infancy component as it has been adopted for the ICP-model, and also that it represents the part of postnatal linear growth which seems to be independent of GH. The onset of the Childhood component in healthy subjects has been observed as an abrupt increase in growth rate during the second half of the first year of life. A similar abrupt increase was observed in this study at the time of the initiation of GH therapy (16-27 months). This observation gives some further empirical support to the hypothesis that the child's age at onset of the Childhood component defines the as yet undetermined age at which GH begins to exert a significant influence on linear growth. ICP-based growth charts provide an improved instrument for early detection of GH deficiency.

Age Factors↗
PubMed1988

Longitudinal analysis of infantile growth in an urban area of Lahore, Pakistan.

Supine length has been registered longitudinally in 302 infants surviving to at least two years of age in an urban area of Lahore, Pakistan. According to the "ICP-growth model", normal linear growth can be represented during this age period by a combination of a sharply decelerating Infancy component with the addition of a slowly decelerating Childhood component, the latter acting from the second half of the first postnatal year. Between birth and 24 months of age the Pakistani children grew about 7.5 cm less than expected according to the Swedish standard. The difference in the gain was mainly related to the late onset of the Childhood component found in 56% of the infants. The onset of the Childhood component in the Pakistani children occurred on an average some 5 months later than in the Swedish controls, which explains the age-dependent reduction in the gain at about 1 year of age. Children with late onset showed no "catch-up growth" during the observation period after the onset. This might very well indicate the functional implications of stunted height in populations of developing countries.

Age Factors↗
PubMed1988

Growth, growth hormone and sex steroid secretion in girls with central precocious puberty treated with a gonadotrophin releasing hormone (GnRH) analogue.

We have treated 14 girls with central precocious puberty for a mean period of 2.3 years (range, 0.5-3.9) with intranasal (D-Ser6) GnRH analogue administered in a mean dose of 28 micrograms/kg/day (range, 15-56). With the onset of treatment there was an initial increase in sitting height compared to subischial leg length, but overall there was no significant change in height standard deviation score for bone age. In this respect our results were indistinguishable from untreated children with central precocious puberty. There was a decrease in physiological GH secretion, associated with decreased sex steroid secretion, which probably accounts for the growth deceleration which has been described during GnRH analogue therapy. The effect of this growth deceleration combined with slowing of the rate of epiphyseal maturation may explain the absence of alteration in height prognosis.

Administration, Intranasal↗
PubMed1990

Pathological heart rate responses associated with body movements in neurologically damaged infants during sleep.

Simultaneous electrocardiogram (ECG) and static charge sensitive bed (SCSB) method recordings were carried out in fifteen healthy and twenty-one neurologically damaged infants during sleep at the age of one week, one month and three months. The SCSB method allows continuous long-term recording of body movements without electrodes connected to the subject. The heart rate response to body movements was studied. Healthy newborns had clear heart rate (HR) acceleration response to body movements. A rapid HR deceleration response occurred at the end of body movements. In the neurologically damaged infants the HR response to body movements was significantly hyperactive or delayed. The abnormal heart rate acceleration-deceleration response to body movements in damaged infants can best be explained by disturbed function of the autonomic nervous system.

Autonomic Nervous System↗