Local vaginal bioelectrical impedance can predict preterm delivery in mice.

Preterm birth is a serious pregnancy complication that affects neonatal mortality, morbidity, and long-term neurological prognosis. Predicting spontaneous preterm delivery (PTD) is important for its management. While excluding the risk of PTD is important, identifying women at high risk of PTD is imperative for medical intervention. Currently used PTD prediction parameters in clinical practice have shown high negative predictive values, but low positive predictive values. We focused on sulfated and sialylated glycocalyx changes in the uterus and vagina prior to the onset of parturition and explored the potential of electrophysiological detection of these changes as a PTD prediction parameter with a high positive predictive value. In vivo local vaginal bioelectrical impedance (VZ) was measured using two different mouse PTD models. PTD was induced in ICR mice through the subcutaneous injection of mifepristone or local intrauterine injection of lipopolysaccharide (LPS). The PTD rates were 100% and 60% post-administration of mifepristone (16-20 h, n = 4) and LPS (12-24 h, n = 20), respectively. The local VZ values (15 and 10 h after mifepristone or LPS treatment, respectively) were significantly lower in the PTD group than in the non-PTD group. Receiver operator characteristic (ROC) curve analysis of VZ at 125 kHz as a predictor of PTD showed an area under the ROC curve of 1.00 and 0.77 and positive predictive values of 1.00 and 0.86, for the mifepristone and LPS models, respectively, suggesting that local VZ value can predict PTD. Histological examination of the LPS-treated model 6 h post-treatment revealed increased expression of sulfomucins and/or sulfated proteoglycans and sialomucins in the cervical epithelium, cervical stroma and vaginal stroma. In conclusion, local VZ values can determine sulfated and sialylated glycocalyx alterations within the uterus and vagina and might be a useful PTD prediction parameter.

Vaginal bioelectrical impedance determines uterine receptivity in mice.

STUDY QUESTION: Can vaginal bioelectrical impedance (VZ) electrophysiologically determine alterations of the endometrium in preparation for implantation? SUMMARY ANSWER: VZ can electrophysiologically detect the sulfation and sialylation changes in the uterine glycocalyx in preparation for implantation. WHAT IS KNOWN ALREADY: Uterine receptivity is associated with various glycosylation changes that affect negative charge density at the luminal epithelial cell surface. VZ has been used to monitor the oestrous cycle. STUDY DESIGN, SIZE, DURATION: Pathogen-free Jcl:ICR mice, aged 8-10 weeks, were used in this study. We conducted the following three steps to test our hypothesis that VZ may be used to determine uterine receptivity. First, to investigate whether VZ could determine alteration of sulfation and sialylation in the uterine glycocalyx, VZ was measured in mice with induced artificial sulfation and sialylation changes in the uterine glycocalyx (galactose-3-O-sulfotransferase 2 (GP3ST) + α(1,3/1,4) fucosyltransferase gene (FucT-III)-transferred group (n = 15) and in LacZ (encoding for ß-galactosidase)-transferred mice as a control group (n = 12)). Second, to investigate whether VZ could determine alterations of the endometrium in preparation for implantation, we measured VZ during the early stage of pregnancy (n = 12 each). Third, to investigate whether VZ could be used to evaluate uterine receptivity prospectively, VZ was measured in an implantation failure model mice. In 21 mice, local and transient suppression of signal transducer and activator of transcription-3 (Stat3) in the uterus were evaluated 1 day before implantation began, and 23 scramble decoy-transferred mice were used as a control group. PARTICIPANTS/MATERIALS, SETTING, METHODS: The VZ was measured at a frequency of 1 kHz in Jcl:ICR mice. Data were analysed using the Kruskal-Wallis test with Dunn's multiple comparisons, or the Student's t-test or Wilcoxon's rank-sum test with the Shapiro-Wilk normality test. The values of VZ were analysed using receiver operating characteristic (ROC) curve analysis to identify the optimal cut-off point to determine if this parameter predicted non-pregnancy. MAIN RESULTS AND THE ROLE OF CHANCE: Sulfation and sialylation changes induced in the luminal epithelial glycocalyx decreased the value of VZ. VZ showed a significant daily decrease during the early stage of pregnancy (Day 1.5 versus 2.5 p.c.: P < 0.005; Student's t-test, Day 2.5 versus 3.5 p.c.: P < 0.001; Wilcoxon's rank-sum test, Day 3.5 versus 4.5 p.c.: P < 0.005; Student's t-test, Day 4.5 versus 5.5 p.c.: P < 0.05; Student's t-test). One day before implantation began, VZ in the implantation failure model mice was significantly higher than in the control mice (P < 0.001, Wilcoxon's rank-sum test). The ROC curve analysis of VZ as a predictor of non-conception showed areas under the ROC curve of 0.91 (95% CI: 0.83-0.99). LIMITATIONS, REASONS FOR CAUTION: Although it is influenced by surface charge in the uterine epithelium, the mechanism whereby VZ changes during early pregnancy is still unexplained. WIDER IMPLICATIONS OF THE FINDINGS: Local bioelectrical impedance may help to prospectively evaluate uterine receptivity in women. Including the measurement of local bioelectrical impedance as part of a frozen-thawed embryo transfer strategy may improve the efficiency of ART. STUDY FUNDING/COMPETING INTEREST(S): This work was supported in part by the Japan Society for the Promotion of Science JSPS KAKENHI Grant (Nos. 19390429, 21390453, 16K11086 and 16K11087) from the Ministry of Education, Science and Culture of Japan (Tokyo, Japan) and Suzuken Memorial Foundation (Nagoya, Japan). The authors declare that they have no conflict of interest.

Prospective evaluation of uterine receptivity in mice.

In current infertility treatments it is necessary to evaluate uterine receptivity in each menstrual cycle. During the implantation period, the uterus goes through many complex orchestrated changes, including changes to the glycocalyx. The changes to the glycocalyx are due to sialylation, sulfation and fucosylation. Can the measurement of in-vivo uterine pH and/or oxidation-reduction potential (ORP) determine the alterations of uterine endometrium for implantation and evaluate prospective uterine receptivity? In the present study we assessed in vivo uterine pH and ORP during the early stages of pregnancy in naïve mice, as well as in a murine model of implantation failure created by local and transient suppression of signal transducer and activator of transcription 3. There was no change in the in vivo uterine pH between post-coitus Days 2 and 6. In vivo uterine ORP was significantly higher compared to the day before. One day before implantation began, uterine ORP was significantly decreased in the implantation failure group compared with the naïve and control groups. Receiver operator characteristic (ROC) curve analysis of uterine ORP as a predictor of non-conception showed an area under the ROC curve of 0.96 (95% confidence interval 0.92-1.00). Thus, in vivo uterine ORP could be a parameter to prospectively evaluate uterine receptivity.

Prediction of pregnancy after frozen-thawed embryo transfer via in vivo intrauterine oxidation-reduction potential measurements: a pilot study.

PURPOSE: During the implantation period, the uterus goes through many complex, orchestrated changes, including alterations of the glycocalyx that are due to sialylation, sulfation, and fucosylation. A previous mouse study showed that the in vivo intrauterine oxidation-reduction potential (ORP) aided in determining the alterations in the uterine endometrium that are suitable for implantation and for evaluating prospective uterine receptivity, while the in vivo intrauterine pH did not. It was assessed if the in vivo intrauterine ORP could be a useful parameter to predict pregnancy in women. METHODS: A prospective cohort study was conducted for patients who had received a frozen-thawed single embryo transfer in a programmed, hormonally controlled cycle. The in vivo intrauterine ORP was measured 3 times during the treatment cycle, at cycle days 9-10, 1 day before progesterone administration and immediately before the embryo transfer. RESULTS: The amount of in vivo intrauterine ORP at 9-10 days after the start of menstrual bleeding was significantly lower in the pregnant group than in the non-pregnant group. A receiver-operator characteristic curve analysis of the intrauterine ORP as a predictor of non-conception showed an area under the curve of 0.80. CONCLUSION: The in vivo intrauterine ORP could be a useful parameter to predict pregnancy for the frozen-thawed embryo transfer treatment cycle.

In utero diagnosis of long QT syndrome by magnetocardiography.

BACKGROUND: The electrophysiology of long QT syndrome (LQTS) in utero is virtually unstudied. Our goal here was to evaluate the efficacy of fetal magnetocardiography (fMCG) for diagnosis and prognosis of fetuses at risk of LQTS. METHODS AND RESULTS: We reviewed the pre/postnatal medical records of 30 fetuses referred for fMCG because of a family history of LQTS (n=17); neonatal/childhood sudden cardiac death (n=3), or presentation of prenatal LQTS rhythms (n=12): 2° atrioventricular block, ventricular tachycardia, heart rate < 3(rd) percentile. We evaluated heart rate and reactivity, cardiac time intervals, T-wave characteristics, and initiation/termination of Torsade de Pointes, and compared these with neonatal ECG findings. After birth, subjects were tested for LQTS mutations. Based on accepted clinical criteria, 21 subjects (70%; 9 KCNQ1, 5 KCNH2, 2 SCN5A, 2 other, 3 untested) had LQTS. Using a threshold of corrected QT= 490 ms, fMCG accurately identified LQTS fetuses with 89% (24/27) sensitivity and 89% (8/9) specificity in 36 sessions. Four fetuses (2 KCNH2 and 2 SCN5A), all with corrected QT ≥ 620 ms, had frequent episodes of Torsade de Pointes, which were present 22-79% of the time. Although some episodes initiated with a long-short sequence, most initiations showed QRS aberrancy and a notable lack of pause dependency. T-wave alternans was strongly associated with severe LQTS phenotype. CONCLUSIONS: Corrected QT prolongation (≥490 ms) assessed by fMCG accurately identified LQTS in utero; extreme corrected QT prolongation (≥620 ms) predicted Torsade de Pointes. FMCG can play a critical role in the diagnosis and management of fetuses at risk of LQTS.

Importance of optimal local uterine blood flow for implantation.

AIMS: The aim of this study was to determine whether uterine blood flow is an effective parameter to anticipate uterine receptivity. MATERIAL AND METHODS: The local uterine blood flow was measured in the endometrium and on the outside of the uterus in mice during the early stage of pregnancy and an implantation failure mouse model using transient and local suppression of signal transducer and activator of transcription-3 activity during implantation. RESULTS: The local uterine blood flow was dramatically increased after mating and was decreased towards the time of implantation. The local uterine blood flow at 2.5 days post-coitus in signal transducer and activator of transcription-3 decoy transferred mice was significantly higher than in control mice. However, the range of individual values was too wide to find a cut-off point. CONCLUSIONS: It is necessary to decrease local uterine blood flow after ovulation to prepare the opening implantation window. The optimal local uterine blood flow is regulated by time events during pregnancy. The range of individual values of uterine blood flow is wide using a laser Doppler blood flow meter. This parameter itself may not be an appropriate parameter to evaluate the prospect of uterine receptivity.

Effect of hypothermia on motor function of adult rats after neonatal hyperthermic hypoxic-ischemic brain insult.

Regarding therapeutic hypothermia for human neonatal hyperthermic hypoxic-ischemic encephalopathy (HIE), we investigated the motor function of a neonatal hyperthermic HIE rat model, and also performed systemic hypothermia using the model. Forty-two neonatal Wistar rats at 7-days-old were used in this study. The left common carotid artery of 34 neonatal rats was ligated under isoflurane anesthesia. We also established a sham group (S group, n = 8). After 1-h recovery, all rats were exposed to 8% oxygen at an ambient temperature (T (a)) of 40 degrees C for 15 min. Following insult, 16 rats were placed in a chamber at a T (a) of 30 degrees C (H group) and the other 18 rats at a T (a) of 37 degrees C after arterial ligation (N group), and all rats in the S group were placed in a chamber at a T (a) of 37 degrees C for 12 h. A Rota-Rod test was performed involving all rats at 8 weeks old. The rod was rotated at 5, 5, and 7 rpm on three consecutive days, respectively. Rats in the N group stayed on the rotating rod for a significantly shorter period than those in S and H groups only on the second day of measurement. The width of the insulted hemisphere in N group rats was significantly smaller than those in S and H groups. There was no significant correlation between S and H groups regarding the motor function and anatomy. These results suggest that neonatal hyperthermic hypoxic-ischemic insult impairs the motor function, which may be rescued by systemic hypothermia after insult.

Effects of a heat- and steam-generating sheet on relieving symptoms of primary dysmenorrhea in young women.

AIM: To test the efficacy of heat- and steam-generating (HSG) sheets for the relief of symptoms of primary dysmenorrhea in young women. MATERIALS & METHODS: Thirty-four female university students were enrolled in this study. HSG sheets generate moist heat to keep the attached body area at 38.5 degrees C for 8 h. Subjects attached the HSG sheet to the lower abdominal or lumbar region for 5 to 8 h once a day on the first, second and third days of menstruation. Subjects documented symptoms of dysmenorrhea (abdominal pain, lumbago and lumbar dullness) on a self-recording form using a 4-score scale of 0 (mild) to 3 (severe) just before applying and after removing the HSG sheet. Either a small (54 cm(2)) or large (164 cm(2)) HSG sheet was used for warming. RESULTS: By applying HSG sheets on the abdomen or lumbar region, 57 and 63% of subjects felt relief of abdominal pains, and 54 and 61% of subjects felt relief from lumbago on the first and second days of menstruation, respectively. Applying the HSG sheets was significantly effective to relieve symptoms compared to the control. Small and large HSG sheets were equally effective. Applying HSG sheets to the abdomen was as effective as that to the lumbar region except for cases of lumbago on the second day of menstruation. Applying HSG sheets two days prior to the onset of menstruation was more effective in relieving lumbar dullness on the second day of menstruation than those just before its onset. CONCLUSION: HSG sheets are useful as non-pharmacological methods to relieve symptoms of primary dysmenorrhea.

Post-ischemic hypothermia reduced IL-18 expression and suppressed microglial activation in the immature brain.

Inflammation is an important factor for hypoxia-ischemia (HI) brain injury. Interleukin (IL)-18 is a proinflammatory cytokine which may be a contributor to injury in the immature brain after HI. To investigate the effects of post-HI hypothermia on IL-18 in the developing brain, 7-day-old rats were subjected to left carotid artery ligation followed by 8% oxygen for 60 min and divided into a hypothermia group (rectal temperature 32 degrees C for 24 h) and a normothermia group (36 degrees C for 24 h). The IL-18 mRNA was analyzed with real-time RT-PCR, and the protein level was analyzed by Western blot, and the location and source of IL-18 were assessed by immunohistochemistry. The significant increase of the IL-18 mRNA was observed in the ipsilateral hemispheres of the normothermia group at 24 h and 72 h after HI compared with controls, but the level in the ipsilateral hemispheres of the hypothermia group was significantly reduced at both time points, compared with the normothermia group, respectively. The IL-18 protein level in the ipsilateral hemispheres of the normothermia group significantly increased at 72 h after HI compared with controls, however, the protein level of the hypothermia group was significantly decreased, compared with the normothermia group. IL-18-positive cells were observed throughout the entire cortex, corpus callosum (CC) and striatum in the ipsilateral hemispheres of normothermia group at 72 h after HI, however, little positive cells were observed in the hypothermia group. Double labeling immunostaining found that most of the IL-18-positive cells were colocalized with lectin, which is a marker of microglia. The number of ameboid microglia (AM) in the normothermia group was significantly increased in cortex and CC, compared with the number in controls, but there were very few ramified microglia (RM) in these areas. In contrast, the number of AM in the hypothermia group was significantly decreased in cortex and CC, compared with the number in the normothermia group, and there were no significant differences in the number of AM and RM between the hypothermia group and controls. In conclusion, we found that IL-18 mRNA and the protein level were attenuated by post-HI hypothermia and that post-HI hypothermia may decrease microglia activation in the developing brain.

[Fetal magnetocardiography].

The electrical activities of the heart causes weak changes of the magnetic field, which can be recorded as magnetocardiogram (MCG). Fetal cardiac magnetic activity is measured in the order of less than 10 pT. An advance of the novel technology of a superconducting quantum interference device enabled the first recording of fetal MCG (FMCG) in 1974. In Japan, FMCG instrument (MC6400, Hitachi High-Technologies Ltd) was approved as a diagnostic tool by Japanese Government in 2003 owing to the cooperative studies of Tsukuba University, National Cardiovascular Center and Hitachi Ltd. FMCG offers similar information to a fetal electrocardiogram, which is difficult to be recorded because the fetal skin is covered with fatty caseous vernix of weak electrical conductivity in the second and third trimester of pregnancy. Magnetic flux can pass through the fat layer, and thus FMCG can measure the electrical activity of the fetal heart. Besides FMCG has far higher resolutions in time domain than echocardiography does. The amplitude of FMCG signals depends on the size of fetal heart and the distance between the sensors and the fetal heart. The amplitudes of the QRS, P and T waves increases with gestational age. Since the amplitudes of P and T waves are often weak, averaging of FMCG signals is needed to improve the signal-to-noise ratio. Current-arrow map is a useful mapping technique even in FMCG. FMCG has been applied in the prenatal diagnosis of fetal arrhythmias such as bradyarrhythmia (atrioventricular block, long QT syndrome, etc), tachyarrhythmia (supraventricular tachycardia, atrial flutter, atrial fibrillation and WPW syndrome, etc) and extrasystoles. Fetal cardiomegaly with myocardial abnormalities can be also diagnosed by FMCG. Applications of FMCG for fetal heart rate monitoring using beat-to-beat variability have been also studied to obtain better information on fetal well-beings.

Effects of 3-h hypothermia after neonatal hyperthermic hypoxic-ischemic encephalopathy in rat models on behavioral prognosis and anatomical and histological features after growth.

OBJECTIVE: To clarify the effects of 3-h hypothermia on learning ability and motor function after growth, employing neonatal rat models with hyperthermic hypoxic-ischemic encephalopathy (HIE). METHODS: We divided all rats into three groups: N (adult rats after neonatal hyperthermic HIE without subsequent 3-h hypothermia), H (adult rats after neonatal hyperthermic HIE with subsequent 3-h hypothermia) and Sham (S) groups. We evaluated their malfunctions with the rota-rod test and the step-down passive avoidance test. We also analyzed the cerebrum width and the hippocampal CA1 area of the insulted hemisphere. RESULTS: In the rota-rod test, the result of the N group was significantly worse than that of the S group. In the step-down passive avoidance test, the result of the N group was significantly worse than those of the S and H groups. The longest cerebrum width and the hippocampal CA1 area of the insulted hemisphere of the N group were significantly smaller than those of the S and H groups. CONCLUSION: Neonatal hyperthermic hypoxic-ischemic insult restricts motor function and learning ability after growth, and such neuronal malfunctions can be relieved by hypothermia for 3 h soon after neonatal HIE.

Thermal regulation and comfort during a mild-cold exposure in young Japanese women complaining of unusual coldness.

We examined body core and skin temperatures and thermal comfort in young Japanese women suffering from unusual coldness (C, n = 6). They were selected by interview asking whether they often felt severe coldness even in an air-conditioned environment (20-26 degrees C) and compared with women not suffering from coldness (N, n = 6). Experiments were conducted twice for each subject: 120-min exposure at 23.5 degrees C or 29.5 degrees C after a 40-min baseline at 29.5 degrees C. Mean skin temperature decreased (P < 0.05) from 33.6 +/- 0.1 degrees C (mean +/- SE) to 31.1 +/- 0.1 degrees C and from 33.5 +/- 0.1 degrees C to 31.1 +/- 0.1 degrees C in C and N during the 23.5 degrees C exposure. Fingertip temperature in C decreased more than in N (P < 0.05; from 35.2 +/- 0.1 degrees C to 23.6 +/- 0.2 degrees C and from 35.5 +/- 0.1 degrees C to 25.6 +/- 0.6 degrees C). Those temperatures during the 29.5 degrees C exposure remained at the baseline levels. Rectal temperature during the 23.5 degrees C exposure was maintained at the baseline level in both groups (from 36.9 +/- 0.2 degrees C to 36.8 +/- 0.1 degrees C and 37.1 +/- 0.1 degrees C to 37.0 +/- 0.1 degrees C in C and N). The rating scores of cold discomfort for both the body and extremities were greater (P < 0.05) in C than in N. Thus the augmented thermal sensitivity of the body to cold and activated vasoconstriction of the extremities during cold exposure could be the mechanism for the severe coldness felt in C.

Fos expression induced by warming the preoptic area in rats.

The preoptic area (POA) occupies a crucial position among the structures participating in thermoregulation, but we know little about its efferent projections for controlling various effector responses. In this study, we used an immunohistochemical analysis of Fos expression during local warming of the preoptic area. To avoid the effects of anesthesia or stress, which are known to elicit Fos induction in various brain regions, we used a novel thermode specifically designed for chronic warming of discrete brain structures in freely moving rats. At an ambient temperature of 22 degrees C, local POA warming increased Fos immunoreactivity in the supraoptic nucleus (SON) and the periaqueductal gray matter (PAG). Exposure of animals to an ambient temperature of 5 degrees C induced Fos immunoreactivity in the magnocellular paraventricular nucleus (mPVN) and the dorsomedial region of the hypothalamus (DMH). Concurrent warming of the POA suppressed Fos expression in these areas. These findings suggest that thermal information from the preoptic area sends excitatory signals to the SON and the PAG, and inhibitory signals to the mPVN and the DMH.

Brain activation during whole body cooling in humans studied with functional magnetic resonance imaging.

Regional activation of the brain was studied in humans using functional magnetic resonance imaging during whole body cooling that produced thermal comfort/discomfort. Eight normal male subjects lay in a sleeping bag through which air was blown, exposing subjects to cold air (8 degrees C) for 22 min. Each subject scored their degree of thermal comfort and discomfort every min. As the subjects reported more discomfort the blood oxygen level dependent response in the bilateral amygdala increased. There was no activation in the thalamus, somatosensory, cingulate, or insula cortices. This result suggests that the amygdala plays a role in the genesis of thermal discomfort due to cold.

The coincidence of fetal magnetocardiography and direct electrocardiography in a case of fetal atrial flutter due to intracardiac tumor.

OBJECTIVE: To demonstrate the coincidence of fetal magnetocardiography (FMCG) and fetal direct electrocardiography (FDECG) in a case of fetal atrial flutter (AF). METHODS: FMCG and FDECG using a fetal scalp electrode were recorded in the case of fetal AF at 41 weeks' gestation. RESULTS: FMCG revealed fetal AF with 2:1 atrioventricular block, which was also documented by FDECG using a fetal scalp electrode. The prenatal diagnosis was confirmed by postnatal electrocardiogram. Neonatal echocardiography revealed an intracardiac tumor on the left atrial septum. The tumor seemed to be the cause of AF. CONCLUSION: FMCG may provide the same information as a fetal electrocardiogram in the prenatal diagnosis of fetal AF.

Fetal atrial flutter recorded prenatally by magnetocardiography.

A case of fetal atrial flutter successfully recorded by magnetocardiography (MCG) is reported. Initial ultrasonography revealed frequent fetal atrial extrasystoles at 31 weeks of gestation. Fetal MCG was recorded using a multichannel MCG system at 31, 35 and 38 weeks of gestation. A series of fluctuations in the baseline of the MCG were noted at 35 and 38 weeks of gestation, which were revealed to be atrial flutter P waves. The averaged MCG showed that the fetal arrhythmia was an atrial flutter with a 3:1 atrioventricular block. The diagnosis was confirmed by neonatal electrocardiogram. Fetal MCG may be useful for the diagnosis of fetal atrial flutter.

Prenatal diagnosis of long QT syndrome using magnetocardiography: a case report and review of the literature.

OBJECTIVES: To investigate the usefulness of magnetocardiography (MCG) in the prenatal diagnosis of fetal long QT syndrome. METHODS: Fetal MCG was recorded in a case of fetal long QT syndrome suspected in utero. The literature on the prenatal diagnosis of fetal long QT syndrome was also reviewed. RESULTS: The MCG was performed at 36 weeks' gestation because sustained fetal bradycardia of 110-120 bpm was detected by cardiotocography. The 64-channel MCG revealed a prolonged fetal corrected QT-interval of 0.57 s. The postnatal electrocardiogram coincided with prenatal MCG. CONCLUSION: An accumulation of cases of prenatally diagnosed long QT syndrome using MCG indicates that MCG may be the most reliable tool for the prenatal diagnosis of long QT syndrome.

Prenatal diagnosis of fetal complete atrioventricular block with QT prolongation and alternating ventricular pacemakers using multi-channel magnetocardiography and current-arrow maps.

We report a case of fetal complete atrioventricular block (CAVB) with QT prolongation and alternating ventricular pacemakers diagnosed by magentocardiography (MCG). Fetal bradyarrhythmia of around 60 bpm was detected at 30 weeks of gestation. Ultrasonography revealed fetal CAVB without structural cardiac anomalies. MCG was recorded at 30 weeks of gestation using a 64-channel superconducting quantum interference device (MC-6400, Hitachi, Japan). The averaged MCG revealed QT prolongation, and the current-arrow maps generated by MCG revealed alternating ventricular pacemakers. The diagnosis was confirmed by electrocardiogram after birth. A permanent pacemaker was implanted during the early neonatal period, and the infant was healthy at 6 months of follow-up. MCG may be a useful diagnostic tool for fetal CAVB with QT prolongation and alternating ventricular pacemakers.

Postischemic hyperthermia induced caspase-3 activation in the newborn rat brain after hypoxia-ischemia and exacerbated the brain damage.

The effects of postischemic hyperthermia were investigated in the newborn rat brain after hypoxia-ischemia (HI). Seven-day-old rats were subjected to left carotid artery ligation followed by 8% oxygen for 30 min, and divided into a hyperthermia group (rectal temperature at 39 degrees C for 6 h) and a normothermia group. Hyperthermia resulted in an approximately 5-fold increase in activated caspase-3 24 h after HI when compared with the normothermia group, and gross loss of brain tissue was observed only in the hyperthermia group at 7 and 30 days after HI. Our results show that postischemic hyperthermia exacerbates HI injury in immature brains, and that the mechanism is strongly associated with activation of an apoptotic pathway.

Long-term neuroprotective effects of hypothermia on neonatal hypoxic-ischemic brain injury in rats, assessed by auditory brainstem response.

A method to assess long-term neurofunctional outcome of hypothermia on immature brains has not yet been clearly established. To investigate the effects of hypothermia on long-term neurofunctional outcome, we studied brainstem function using auditory brainstem response in adult rats after neonatal hypoxic-ischemic brain injury. Seven-day-old rats underwent a combination of left common carotid artery ligation and subsequent exposure to 8% O(2) for 1 h (n = 17). The rats were divided into three groups: hypothermia group (n = 6), normothermia group (n = 6), and sham control group (n = 5). During recovery from the hypoxic-ischemic insult, body temperature was reduced to 30 degrees C for 24 h in the hypothermia group, but was kept at 37 degrees C in the normothermia and sham control group. Three months later the rats were assessed by auditory brainstem response, then killed. The normothermia group showed increased III-V latencies and wave V abnormalities. Hypothermia significantly ameliorated wave V abnormalities. Injury to the ipsilateral inferior colliculus was also reduced in the hypothermia group compared with that in the normothermia group, and the degree of damage assessed histologically correlated well with auditory brainstem response findings. The current study demonstrates that postischemic hypothermia may provide effective and long-lasting neurofunctional as well as histopathologic protection to the immature brain.