Beat-to-beat QT interval variability in children: normal and physiologic data.

BACKGROUND: QT interval variability provides information on ventricular vulnerability. However, QT interval variability in children has not been adequately evaluated. METHODS: One hundred seventy-three consecutive nursing infants and children (male-female, 106:67) up to school age with no intrinsic cardiac disease were included in this study, and they were categorized into 6 age-related groups. The QT variability index (QTVI) was calculated based on an electrocardiogram; and age-specific standard values, sex-specific classification, and a standard growth curve covering 0 to 7 years were constructed. RESULTS: The QTVI decreased in an age-dependent manner, reached constant values after school age, and exhibited no sex-specific differences in 6 age-related groups. CONCLUSIONS: Based on the age-dependent standardized QTVI values, it is possible to estimate the instability of ventricular repolarization in pediatric patients with better accuracy.

Targeted heavy-ion microbeam irradiation of the embryo but not yolk in the diapause-terminated egg of the silkworm, bombyx mori, induces the somatic mutation.

Using heavy-ion microbeam, we report target irradiation of selected compartments within the diapause-terminated egg and its mutational consequences in the silkworm, Bombyx mori. On one hand, carbon-ion exposure of embryo to 0.5-6 Gy increased the somatic mutation frequency, suggesting targeted radiation effects. On the other, such increases were not observed when yolk was targeted, suggesting a lack of nontargeted bystander effect.

Detection of DNA damage induced by space radiation in Mir and space shuttle.

Although physical monitoring of space radiation has been accomplished, we aim to measure exact DNA damage as caused by space radiation. If DNA damage is caused by space radiation, we can detect DNA damage dependent on the length of the space flight periods by using post-labeling methods. To detect DNA damage caused by space radiation, we placed fixed human cervical carcinoma (HeLa) cells in the Russian Mir space station for 40 days and in an American space shuttle for 9 days. After landing, we labeled space-radiation-induced DNA strand breaks by enzymatic incorporation of [3H]-dATP with terminal deoxyribo-nucleotidyl transferase (TdT). We detected DNA damage as many grains on fixed silver emulsion resulting from beta-rays emitted from 3H-atoms in the nuclei of the cells placed in the Mir-station (J/Mir mission, STS-89), but detected hardly any in the ground control sample. In the space shuttle samples (S/MM-8), the number of cells having many grains was lower than that in the J/Mir mission samples. These results suggest that DNA damage is caused by space radiation and that it is dependent on the length of the space flight.

Somatic mutation in larvae of the silkworm, Bombyx mori, induced by heavy ion irradiation to diapause eggs.

In order to investigate whether eggs of the black-striped strain (P(S)) of the silkworm, Bombyx mori, represent an appropriate model for estimating the biological effect of cosmic radiation, radiosensitivity of the eggs against X-rays and heavy ion particles was examined as ground-based experiments. The exposure of diapause eggs to X-rays or heavy ion particles resulted in somatic mutations appearing as a white spot on the black integument during larval stage. Irradiation of non-diapause eggs with X-rays demonstrated a significant difference in frequency of the mutation between fractionated and single administration doses, but no difference was observed in diapause eggs. Incidence of the mutation as induced by carbon ion beams for 15-day old eggs was higher for eggs that had been kept at 15 degrees C than those kept at 25 degrees C. Neon beam irradiation of diapause eggs displayed dose- and linear energy transfer (LET)-dependent effects, causing a maximal rate of the mutation at 150 keV/microm. These results confirm that B. mori eggs represent valid models for estimating the biological effects of cosmic radiation.

Dose equivalents inside the MIR Space Station measured by the combination of CR-39 plates and TLDs and their comparison with those on Space Shuttle STS-79, -84 and -91 missions.

In 1997, four dosimeter packages, each of which contains two CR-39 plates and 18 TLDs (Mg2SiO4:Tb), were placed inside the MIR Space Station and flew on an orbit with an inclination angle of 51.6 degrees and an altitude of approximately 400 km for 40 days. We estimated the absorbed doses, dose equivalents and effective quality factors during the flight by combining CR-39 data and TLD data. We then compared these results to those obtained with the same analysis method from the dosimeter packages on board Space Shuttle missions STS-79, -84 and -91 that flew along the same orbit. Finally, the differences between our results and those obtained by another group using passive dosimeters on the MIR are discussed.

Effects of low dose particle radiation to mouse neonatal neurons in culture.

To investigate effects of low dose heavy particle radiation to CNS system, we adopted mouse neonatal brain cells in culture being exposed to heavy ions generated by HIMAC at NIRS and BNL. The applied dose varied from 0.05 Gy up to 2.0 Gy. The subsequent biological effects were evaluated by an induction of apoptosis focusing on the dependencies of (1) the animal strains with different radiation sensitivities, and (2) LET with different nuclei. Of the three mouse strains, SCID, B6 and C3H, used for brain cell culture, SCID was the most sensitive and C3H the least sensitive to both X-ray and carbon ion ( 290 MeV/n) as evaluated by 10% apoptotic criterion. However, the sensitivity differences among the strains were much smaller in case of carbon ion comparing to that of X-ray. Regarding the LET dependency, the sensitivity was compared with using C3H and B6 cells between the carbon (13 keV/micrometers) and neon (70 keV/micrometers) ions. Carbon (290 MeV/n) did not give a detectable LET dependency from the criterion whereas the neon (400 MeV/n) showed 1.4 fold difference for both C3H and B6 cells. Although a LET dependency was examined by using the most sensitive SCID cells, no significant difference was detected.

Nitrate toxicity on visceral organs of Medaka fish, Oryzias latipes: aiming to raise fish from egg to egg in space.

Histological survey was made to determine nitrate toxicity on the Medaka fish, Oryzias latipes. In order to investigate the effects of short-term exposure to nitrate, one-month-old Medaka fish was exposed to NaNO3 at concentrations of 100 and 125 mg NO3-N l-1 for 96 hours. At the end of the exposure period, survival rate was found to be 30% and 10%, for the 100 and 125 mg NO3-N l-1 exposure concentrations, respectively. Histological examination of the organs showed that disruption of cell alignment was a common feature in the gills, intestinal ampulla, liver and kidney. A long-term exposure experiment was also carried out, whereby Medaka fish was exposed to NaNO3 (100 and 125 mg NO3-N l-1) for three months from its egg stage. Eggs treated with NaNO3 hatched within 10 days after fertilization. At the end of the exposure period, survival rate in the 100 and 125 mg NO3-N l-1 treatments were 40% and 30%, respectively. Fibrosis of the hepatic cells and curved spinal column were observed in the juveniles subjected to long-term nitrate exposure. The results of our experiments suggest that the high mortality resulting from short-term acute exposure to nitrate is caused by general dysfunction throughout the whole body. The chronic toxic effects attributed to nitrate, following long-term exposure, were likely to have resulted from nutrient deficiency caused by hepatic dysfunction.

Effects of heavy ion to the primary [correction of rimary] culture of mouse brain cells.

To investigate effects of low dose heavy particle radiation to CNS system, we adopted mouse neonatal brain cells in culture being exposed to heavy ions by HIMAC at NIRS and NSRL at BNL. The applied dose varied from 0.05 Gy up to 2.0 Gy. The subsequent biological effects were evaluated by an induction of apoptosis and neuron survival focusing on the dependencies of the animal strains, SCID, B6, B6C3F1, C3H, used for brain cell culture, SCID was the most sensitive and C3H the least sensitive to particle radiation as evaluated by 10% apoptotic criterion. The LET dependency was compared with using SCID and B6 cells exposing to different ions (H, C, Ne, Si, Ar, and Fe). Although no detectable LET dependency was observed in the high LET (55-200 keV/micrometers) and low dose (<0.5 Gy) regions. The survivability profiles of the neurons were different in the mouse strains and ions. In this report, a result of memory and learning function to adult mice after whole-body and brain local irradiation at carbon ion and iron ion.

Evaluation of respiratory modulation on the pulse wave amplitude in low-birth-weight neonate.

A slow oscillation of sympathetic vasoconstriction (Mayer waves) which is affected by the respiratory movements seems to appear as the fluctuation of pulse wave amplitude (PPG.P-P) in the frequency domain (0.1 Hz). Whether the vasomotor in low frequency has appeared in the pulse wave of the neonate and whether Mayer waves appear as the pulse wave oscillation of the immature low-birth-weight neonate are not fully understood from the point of autonomic nerve regulation mechanism. We therefore analyzed the frequency characteristics of PPG.P-P, respiration wave and its amplitude (RW.P-P) together with the heart rate variability (HRV) to examine the relationships between the frequency spectra.

Comparative physiology of postnatal developments of cardiopulmonary reflex.

We analyzed and compared the frequency components of the heart rate variability in human neonate, rat, white chicken, turtle, and frog during the developments. Frequency analysis with autocorrelation-FFT method was applied to the heart rate and respiration waves to calculate the respiration induced frequency component in the power spectra. The comparative analysis of the cardiopulmonary reflex in human and rat neonates resulted in a similar developmental progress. In case of human immature neonate, respiration induced frequency component in the heart rate variability was negligible at day-old 0, and significantly increased at postnatal 1 month. The rat neonates also showed no or negligible respiration induced components until days 8 and it became significant approximately postnatal 1 month. The white chicken also indicated negligible respiration induced component before and a few days after hatching, and became significant after 38 days-old (17 days post hatching). However the frog and the turtle indicated no clear response in entire periods of the development even in adult. The results strongly suggested that gravity may be a possible essential factor of the appearance of the post natal development of the cardiopulmonary reflex.

Effects of space flight on the histological characteristics of the aortic depressor nerve in the adult rat: electron microscopic analysis.

The effects of microgravity on the histological characteristics of the aortic depressor nerve, which is the afferent of the aortic baroreflex arc, were determined in 10 female adult rats. The rats were assigned for nursing neonates in the Space Shuttle Columbia or in the animal facility on the ground (NASA Neurolab, STS-90), and were housed for 16 days under microgravity in space (microg, n=5) or under one force of gravity on Earth (one-g, n=5). In the Schwann cell unit in which the axons of unmyelinated fibers are surrounded by one Schwann cell, the average number of axons per unit in the microg group was 2.1 +/- 1.6 (mean +/- SD, n=312) and significantly less than that in the one-g group (3.0 +/- 2.9, n=397, p<0.05). The proportion of unmyelinated fibers in the aortic depressor nerve in the microg group was 64.5 +/- 4.4% and significantly less than that in the one-g group (74.0 +/- 7.3%, p<0.05). These results show that there is a decrease in the number of high-threshold unmyelinated fibers in the aortic depressor nerve in adult rats flown on the Shuttle Orbiter, suggesting that the aortic baroreflex is depressed under microgravity during space flight.

Autonomic modulation of sinus and atrioventricular nodes in premature low-birth-weight infants.

Respiratory vagal activity is expressed by heart rate variability (HRV) at approximately 1 month of age in premature low-birth-weight infants (PLBWI). However, the autonomic inputs into the sinus node (SAN) and atrioventricular node (AVN) in PLBWI are unclear. We evaluated the variability in PP and PR intervals at day zero (day 0) and 1 month (1 month) after birth in 16 PLBWI (gestation 32.3 +/- 1.3 weeks, birth weight 1.578 +/- 257 g). The polygraph was recorded during sleep on day 0 and at 1 month. PP and PR intervals and the number of respiratory cycles were measured, and frequency analysis was performed by auto-correlation fast Fourier transforms. Power spectral density (PSD: ms(2)) was calculated for the low frequency domain (LF: 0.036 approximately 0.146 Hz), high frequency domain (HF: 0.146 approximately 0.390 Hz), total frequency (TF: 0.036 approximately 2.000 Hz), and respiratory sinus arrhythmia (RSA: frequency bandwidth of 0.3 Hz with peak respiratory frequency as median), and the PSD ratio in the PP and PR intervals (LF/HF, RSA/TF) were compared. Compared with day 0, a decrease in the LF/HF ratio and an increase in the RSA/TF ratio in PP intervals were observed at 1 month, consistent with expression of respiratory vagal activity. For PR intervals, on the other hand, the LF/HF ratio increased, indicative of accentuated sympathetic activity. However, the respiratory vagal input was weak, and the RSA/TF ratio remained unchanged. These observations suggest that, in PLBWI at 1 month, AVN conduction was not predominatly influenced by respiratory-related vagal activity, but was controlled by autonomic regulation, independent of the SAN.

Succinate dehydrogenase activity in rat dorsolateral ventral horn motoneurons at L6 after spaceflight and recovery.

Succinate dehydrogenase (SDH) activity levels of motoneurons in the rostral, middle, and caudal portions of the dorsolateral region of the ventral horn of the 6th lumbar (L6) segment of the rat spinal cord were determined after 14 days of spaceflight and after 9 days of recovery on Earth. The mean SDH activity of motoneurons with cell body sizes between 500 and 800 micrometers2 located in the rostral portion of the L6 segment was lower in spaceflight than in age-matched control rats. The decrease in motoneuron SDH activity persisted for at least 9 days of recovery on Earth. In contrast, the mean SDH activity of motoneurons located in the middle and caudal portions of the L6 segment were unaffected by spaceflight and recovery on Earth. The motoneurons in the rostral portion of the L6 segment presumably innervate both high- and low-oxidative fibers in hindlimb muscles, whereas those in the middle and caudal portions presumably innervate perineal muscles that are comprised only of low-oxidative fibers. These data indicate that moderate-sized motoneurons, most likely innervating fibers in high-oxidative muscles, are responsive to the microgravity environment.