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Changes in primary muscle spindle ending excitability induced by a ramp-and-hold stretch.

36 primary (Ia) muscle spindle afferents from the tibial anterior muscle of the cat were subjected to a ramp-and-hold stretch (stretch rate 10 mm/s, stretch amplitude 5 or 8.5 mm) of the muscle, on which a sinusoidal stretch (50 Hz) of four different amplitudes (25, 50, 250 and 500 microns) was superimposed. In 54 discharge patterns a Ia afferent subjected to a ramp-and-hold stretch with a sinusoidal stretch superimposed responded only to the superimposed sinusoidal stretch. In 25 of the cases the Ia afferent responded with an one-to-one driven action potential (AP) and in 29 of the cases with two APs per sinusoidal stretch. For these 54 discharge patterns the phase of the sinusoidal cycle was determined at which each AP occurred. Where the Ia afferent responded with one AP per cycle an accelerating phase advance was observed during the ramp stage of the underlying ramp-and-hold stretch and a decelerating phase advance during the plateau. This phase shift means that the excitability of the site generating the AP increased during the ramp stage and decreased during the plateau. If the Ia afferent responded with two APs per superimposed cycle, the second AP per cycle evinced a decelerating phase advance during the ramp and an accelerating phase advance during the plateau. The phase of the second AP per cycle showed a second, contrary change in excitability at the AP generating site. The excitability decreased during the ramp and increased during the plateau. The first kind of excitability change is interpreted as a consequence of an inward current at the AP generating site. The second, contrary type of excitability points to an interplay between an inward and an outward current. An increasing outward current lowers the excitability for the second AP per cycle during the ramp. A decreasing outward current raises the excitability during the plateau.

Action Potentials↗

Electroporation of extraneous proteins into CHO cells: increased efficacy by utilizing centrifugal force and microsecond electrical pulses.

A novel electroporation system employing an oscillating electric pulse and centrifugal force was used to introduce extraneous proteins into CHO cells. Following the electrical pulse, the compression and subsequent rebound induced by the centrifugal acceleration and deceleration, respectively, enhanced protein uptake, presumably by a hydrodynamic pumping of extracellular solutions through the permeabilized membrane. Protein uptake was quantitated by measuring the amount of radiolabeled, extraneous, CHO proteins introduced into unlabeled CHO cells. The amount of protein introduced into electroporated CHO cells was enhanced up to four-fold by a combination of electric pulse and centrifugal force compared to that introduced by electric pulse only. The optimum gradient of centrifugal force (GCF, temporal change of centrifugal force) was 590 and -470 g/s during acceleration and deceleration, respectively. The optimum electric field was 5 kV/cm with a 30-microsecond pulse length. At this optimum electroporation condition, approximately 5 pg of proteins (up to 200 kDa molecular weight) were introduced per CHO cell. These same settings also permitted electroporation of other membrane impermeable substances including propidium iodide and ethidium bromide. Introduction of extraneous materials into the cytoplasm during electroporation was confirmed by the ability of anti alpha-tubulin to stain the microtubules and propidium iodide and ethidium bromide to stain the nuclei. Cells electroporated with optimum device settings exhibited no significant decrease in clonogenic survival.

Animals↗

Changes in antepartum heart rate patterns with progressive deterioration of the fetal condition.

In this paper changes in antepartum fetal heart rate (FHR) patterns are described, that occur with progressive deterioration of the fetal condition. The data on the relationship between heart rate patterns and fetal blood gas and pH values are reviewed. A possible rank ordering is presented in which changes in FHR pattern, body movements and blood flow velocity wave form patterns occur with progressive deterioration of the fetal condition. It is concluded that in small-for-date fetuses changes in heart rate and movement patterns are rather late signs of impairment, coinciding with fetal hypoxaemia. In general, heart rate variation falls below the norm at the same time as decelerations occur; there are, however, large inter-fetal differences. In general, abnormal Doppler velocity wave form patterns precede the occurrence of heart rate decelerations. Their impact on the timing of delivery is, however, still uncertain. The advantages of a numerical analysis of FHR patterns include identification of fetuses with low FHR variation, precision of the actual fetal condition and (at early gestation) longitudinal follow-up of fetuses with abnormal heart rate patterns.

Animals↗

Quantitative analysis of fetal rate: its application in antepartum clinical monitoring and behavioural pattern recognition.

A system based on an IBM compatible personal computer is described for the computerized analysis of the cardiotocograms. The system performs a quantification of both fetal heart rate and uterine contractions providing automatically several variables including heart rate baseline; number, duration and area of accelerations and decelerations; latency time between decelerations and uterine contractions; uterine resting tone; number, duration and area of contractions. The computerized description was compared to the visual analysis of the cardiotocogram and a good agreement was evidenced. This system was applied to the analysis of heart rate variability in order to recognize the different patterns characterizing fetal behavioral states. Up to now, however, the results obtained in this latter application are not sufficiently accurate and do not allow a reliable automatic recognition of heart rate patterns.

Cardiotocography↗

Poor prognostic value of the basal fetal heart rate as observed during antenatal monitoring.

The basal fetal heart rate, accelerations, decelerations and amplitude and frequency of variation were scored in positive stress tests of 146 and in suspicious recordings of 296 patients. Positive tests scored lower for accelerations, decelerations and amplitude and frequency of variation but not for the basal heart rate. When the outcome was poor, as characterized by low 5-min Apgar score and intrauterine growth retardation, it was reflected by all parameters of the fetal heart rate pattern except for the basal heart rate.

Bradycardia↗

Electronic fetal heart rate monitoring during cesarean section.

Fetal heart rate (FHR) response to cesarean section was studied in 65 patients. Induction of anesthesia, skin, fascial, peritoneal and bladder flap incisions were not associated with a change in FHR. Abdominal preparation was associated with FHR decelerations in 15% of cases. Myometrial incision was followed by FHR deceleration in 11% of cases. No correlation between the incision/delivery (I-D) interval and FHR changes was seen.

Anesthesia, Epidural↗

Axial flow velocity patterns in a normal human pulmonary artery model: pulsatile in vitro studies.

It has been clinically observed that the flow velocity patterns in the pulmonary artery are directly modified by disease. The present study addresses the hypothesis that altered velocity patterns relate to the severity of various diseases in the pulmonary artery. This paper lays a foundation for that analysis by providing a detailed description of flow velocity patterns in the normal pulmonary artery, using flow visualization and laser Doppler anemometry techniques. The studies were conducted in an in vitro rigid model in a right heart pulse duplicator system. In the main pulmonary artery, a broad central flow field was observed throughout systole. The maximum axial velocity (150 cm s-1) was measured at peak systole. In the left pulmonary artery, the axial velocities were approximately evenly distributed in the perpendicular plane. However, in the bifurcation plane, they were slightly skewed toward the inner wall at peak systole and during the deceleration phase. In the right pulmonary artery, the axial velocity in the perpendicular plane had a very marked M-shaped profile at peak systole and during the deceleration phase, due to a pair of strong secondary flows. In the bifurcation plane, higher axial velocities were observed along the inner wall, while lower axial velocities were observed along the outer wall and in the center. Overall, relatively low levels of turbulence were observed in all the branches during systole. The maximum turbulence intensity measured was at the boundary of the broad central flow field in the main pulmonary artery at peak systole.

Blood Flow Velocity↗

Analysis of the axial flow field in stenosed carotid artery bifurcation models--LDA experiments.

Laser Doppler anemometer (LDA) experiments were performed to gain quantitative information on the differences between the large-scale flow phenomena in a non-stenosed and a stenosed model of the carotid artery bifurcation. The influence of the presence of the stenosis was compared to the effect of flow pulse variation to evaluate the feasibility of early detection of stenosis in clinical practice. Three-dimensional Plexiglass models of a non-stenosed and a 25% stenosed carotid artery bifurcation were perfused with a Newtonian fluid. The flow conditions approximated physiological flow. The results of the velocity measurements in the non-stenosed model agreed with the results from previous hydrogen-bubble visualization. A shear layer separated the low-velocity area near the non-divider wall from the high-velocity area near the divider wall. In this shear layer, vortex formation occurred during the deceleration phase of the flow pulse. The instability of this shear layer dictated the flow disturbances. The influences of the mild stenosis, located at the non-divider wall, was mainly limited to the stability of the shear layer. No disturbances were found downstream of the stenosis near the non-divider wall. Using a pulse wave with an increased systolic deceleration time, the velocity distribution showed an extended region with reversed flow, a more pronounced shear layer and increased vortex strength. From these measurements it is obvious that the influence of the presence of a mild stenosis, mainly limited to the stability of the shear layer, can hardly be distinguished from the effects of a variation of the flow pulse. From this it can be concluded that methods for detection of mild stenosis, using solely the large-scale flow phenomena, as can be measured by ultrasound or MRI techniques, will hardly have any clinical relevance.

Blood Flow Velocity↗

Effects of sound frequency on behavioral and cardiac orienting in newborn and five-month-old infants.

Alert newborn and 5-month-old infants' responsivity to variations in spectral composition of a rattle sound was examined. Each child received four stimulus conditions: low-, mid-, and high-frequency bandpass-filtered rattles and an unfiltered broadband rattle. Stimuli were played through a single loudspeaker laterally positioned, and head orientation and cardiac responses to sound were recorded. Compared to other stimuli, the low-frequency sound elicited less head turning in both age groups, with this effect exaggerated in younger infants. Head orientation toward the mid-frequency, high-frequency, and broadband stimuli did not differ with age. For all conditions, latency and duration of newborns' head turning was longer than that of 5-month-olds. Newborns responded with cardiac deceleration only on trials when they failed to turn. When head turns occurred, an acceleratory cardiac response was obtained. Five-month-olds responded with reliable cardiac deceleration irrespective of head turning toward the sound. Heart rate change did not vary as a function of frequency at either age, suggesting that all stimuli were equally effective in eliciting the infant's attention.

Arousal↗

The eta-globin gene. Its long evolutionary history in the beta-globin gene family of mammals.

In phylogenetic reconstructions by the parsimony method, utilizing 62 sequenced globin genes and pseudogenes (including 34 of the beta-globin gene family from eutherian orders Primates, Lagomorpha, Artiodactyla and Rodentia), the branch of primate psi beta pseudogenes and the goat embryonically expressed epsilon II gene group monophyletically together as orthologues of a common ancestral gene (labelled eta) distinct from orthologues of epsilon, gamma, delta and beta. This primate psi eta-goat eta branch is cladistically closer to epsilon and gamma than to delta and beta branches. In each eutherian order gene conversions replaced portions of delta by beta sequences, whereas in descent of Primates epsilon, gamma and eta mostly retained their separate ancient identities predating the radiation of Eutheria in all their exons and non-coding regions. The loci of the ancestral beta-globin gene cluster in basal eutherians and proto-primates, as deduced from beta-clusters representing the four eutherian orders, were linked 5'-epsilon-gamma-eta-delta-beta-3' with epsilon, gamma and eta being embryonically expressed genes, and delta and beta ontogenetically later expressed genes. Through deletions gamma was lost in artiodactyl evolution, eta in lagomorph and rodent evolution, and all DNA between exon 2 3' boundaries of eta and delta in prosimian lemuriform evolution (lemur having the hybrid pseudogene psi eta delta). Simian primates retained intact the five loci of the ancestral cluster. Not only did eta, after it became a pseudogene in the basal primates, persist intact in descent to present-day simians but in the line to hominoids it evolved during the last 40 million years at the decelerated rate of 1 X 10(-9) substitutions/site per year which is one-fifth the expected neutral rate. The possibility is suggested that the psi eta locus situated between fetal and adult chromosomal domains of the simian beta-globin gene cluster might play some role in a mechanism for ontogenetic switches of globin gene expression. However, not enough sequence data on genes and intergenic regions in DNA of species of primates and other mammals as yet exist to know if the slow rate of 1 X 10(-9) reflects the rate of a conserved functional gene or primarily reflects a decelerated neutral rate of hominoid DNA evolution, conceivably from enhanced DNA repair and longer generation times in hominoids. The further possibility is raised that gene correction (repair of damaged DNA that prevents emergence of new alleles) and gene conversion both more often involve strand copying of conserved than of rapidly evolving DNA.

Animals↗

Skeletal turnover and total body elemental composition during extended calcitonin treatment of Paget's disease.

Twenty patients with generalized symptomatic Paget's disease had serial measurements of radiocalcium turnover and/or total body elemental composition by in vivo neutron activation analysis during long-term calcitonin therapy. Despite maintained clinical improvement, seven of 15 patients showed partial or total loss of the initial decelerating effect of calcitonin on skeletal turnover, whereas the remaining eight patients maintained the calcitonin-induced deceleration. The changes in skeletal turnover were roughly proportional to the induced changes in serum alkaline phosphatase and urinary hydroxyproline. However, disparities in the magnitude of the changes among the three parameters were not uncommon. Total body calcium was increased by a mean of 22% above predicted prior to calcitonin and decreased significantly by 4% during long-term calcitonin treatment. Total body phosphorus, nitrogen, and sodium also decreased. The phosphorus and sodium losses appeared to be mostly from the skeleton. These data confirm histologic evidence of the disappearance of pagetic bone, resumption of normal lamelar bone formation, and radiographic evidence of a decrease in bone volume during calcitonin treatment and incidate the relative magnitude of this effect. The action of calcitonin in this regard possibly represents a specific effect on Paget's disease beyond its general skeletal effect of reduce cellular activity.

Alkaline Phosphatase↗

Dual effects of histamine on spontaneous activity in isolated bovine mesenteric lymphatics.

The mode of action of histamine on spontaneous contractions is isolated bovine mesenteric lymphatics was investigated by recording isometric tensions. Histamine at lower concentrations between about 5 x 10(-8) and 10(-6) M caused a dose-dependent deceleration of the rhythm of spontaneous contractions. Higher concentrations of histamine (more than about 5 x 10(-6) M) produced a dose-related acceleration of the rhythm in association with a slight elevation of basal tone in 115 of 173 preparations. In 58 of 173 lymphatic preparations, histamine at concentrations ranging from about 5 x 10(-8) to 10(-5) M caused only the positive chronotropic effect. The histamine-induced positive and negative chronotropic effects were unaltered by pretreatment with alpha- and beta-adrenergic antagonists but were dose-dependently antagonized by pretreatment with H1- or H2-blockers (diphenhydramine or cimetidine). The specific H1- and H2-agonists, 2-pyridylethylamine (2PEA) and dimaprit caused dose-related positive and negative chronotropic effects, respectively, on spontaneous contractions of isolated bovine mesenteric lymphatics. The effect of 2PEA was significantly blocked by pretreatment with 10(-6) M diphenhydramine, whereas the effect of dimaprit was suppressed by 10(-6) M cimetidine. These results suggest that both H1- and H2-receptors are located on the plasma membrane of smooth muscle cells in bovine mesenteric lymphatics, and that the excitations of H1- and H2-receptors respectively produce an acceleration and a deceleration of the rhythm of spontaneous contractions in lymphatic smooth muscles.

Animals↗

Pressure in the hydrocephalic fetal head during the first stage of labor.

Intraamniotic pressure was studied in the 30th week of amenorrhea in relationship with fetal intracranial pressure with open-tip catheters. The fetus had a severe hydrocephalus (echoscopy 16 cm) due to a teratologic malformation of the cerebrum. Clinically nonoperative treatment was indicated. Intracranial pressure (X) was invariably higher than intraamniotic pressure (Y) between contractions: Y = 2.04 + 0.54 X, and during contractions: Y = 5.30 + 0.55 X. There was no definite relationship between intrauterine and intracranial pressure, and the fetal tachogram. A definite relationship was established with the supine position of the patient and decelerations in the fetal tachogram. It is suggested that when fetal cardiac decelerations are seen during the first stage of labor it seems advisable to look for factors such as umbilical cord compression and decrease of materno-placental perfusion rather than fetal head compression.

Amniotic Fluid↗

Combined (stressed and non-stressed) antenatal fetal heart rate monitoring.

Acceleration patterns of the fetal heart rate, or a normal heart rate during spontaneous contractions, were used as a short weekly screening test to evaluate fetal well-being in 1102 high-risk pregnancies. When accelerations or contractions were absent during the initial screening, oxytocin was administered to stimulate uterine contractions. The mean duration of the antenatal monitoring was 18.5 min when the initial antenatal monitoring was normal, but 38.8 min when the initial results were uncertain. Oxytocin was administered to 38% of patients. This reduced the number of occasions where the diagnosis was uncertain from 46.6% to 12%. Patients with uncertain antenatal fetal monitoring had significantly more late decelerations during labor as well as newborns with low Apgar scores when compared to those with normal antenatal monitoring. Patients with abnormal antenatal monitoring (positive stress test) had significantly more low 5-min Apgar scores, late decelerations during labor and growth-retarded infants than the patients with normal antenatal fetal monitoring. Only 1 intrauterine death occurred within 7 days of a normal antenatal heart rate recording. No preventable fetal deaths occurred when antenatal monitoring demonstrated an acceleration pattern of the fetal heart rate.

Female↗

Thrombosis of the right umbilical artery, presumably related to the shortness of the umbilical cord: an unusual cause of fetal distress.

This case report concerns a late pregnancy complication, clinically apparent as severe variable decelerations in the first stage of labor. Emergency cesarean section delivered a mildly asphyxiated full-term newborn infant. Examination of the umbilical cord revealed a thrombus of the right umbilical artery, near the fetal side, confirmed by histological examination. The total length of the umbilical cord, only 30 cm, was below the limit necessary for uncomplicated delivery of the fetus near term. Transient stretching during fetal descent is thought to be responsible for constriction of the umbilical arteries, blood flow sludging and thrombosis. Although only a few cases have been reported, thrombosis of the umbilical vessels has to be considered whenever the fetal heart rate pattern shows unexplained variable decelerations.

Adult↗

Fetal heart rate and neonatal condition related to epidural analgesia in women reaching the second stage of labour.

The relationship between epidural analgesia and a number of labour and delivery factors, relevant to fetal and neonatal condition, was considered in a prospective study of 200 labours reaching the second stage of labour. The group was representative of the hospital population with regard to the proportion of nulliparous women, the incidence of instrumental vaginal deliveries and the incidence of epidural analgesia (37%). The 8% of labours requiring fetal blood sampling during the first stage, and the labours with fetal heart rate (FHR) decelerations in the hour prior to second stage (25%) and during pushing (50%) were significantly more likely to have been given an epidural. Nulliparity (55%), induced labour (34%), a first stage longer than eight hours (37%), a second stage longer than 60 min (43%), maternal pushing for longer than 36 min (50%), forceps delivery (28%) and a 1 min Apgar score less than 7 (12%) were also factors associated with significantly higher rates of epidural analgesia whereas meconium (15%), a small baby (16%) and umbilical arterial metabolic acidaemia (13%) were not. FHR decelerations in labours reaching the second stage with an epidural reflect adjustments to fetal cardiovascular control and not acidaemia.

Adult↗

Doppler velocimetry in twin pregnancy.

The flow velocity waveform profile in the umbilical artery was measured in 50 pairs of twins during the last week before birth. A significant association was found between high resistance indicies and occurrence of late fetal heart rate decelerations; the higher the resistance, the more frequent the decelerations. Further, the connection between high resistance in the circulation of the umbilical artery and low birth weight was confirmed. Flow velocity measurements in the umbilical artery seem to be a valuable tool in identifying twin fetuses suffering from placental insufficiency.

Adolescent↗

Interobserver variation in the assessment of fetal heart rate recordings.

Electronic fetal heart rate monitoring (EFM) has not fulfilled its expectations. To improve its validity various attempts were made to standardize terminology and assessment of fetal heart rate (FHR) recordings. In a multinational study, 21 experienced obstetricians were asked to segment and classify FHR patterns, recorded in 13 obstetric cases. In addition, the referees were asked to give their interpretation of the FHR pattern, to assess the fetal condition and to propose obstetric management. The kappa statistic showed fair agreement among the obstetricians for the classification of accelerations, baseline segments and decelerations. Poor agreement was found when the referees had to classify baseline variability or the type of deceleration. Also, the clinical assessment of fetal condition and proposals for obstetric management showed poor agreement among the referees. We conclude there is still a lack of unequivocal terminology and definitions in the assessment of FHR recordings.

Cardiotocography↗