Toru Kanzaki

Evaluation of the Preload Condition of the Fetus by Inferior Vena Caval Blood Flow Pattern

Using pulsed Doppler ultrasound, blood flow in the inferior vena cava (IVC) was studied in 47 normal fetuses from 24 to 40 weeks of gestation and 35 abnormal fetuses, with the exception of those with arrhythmias. The abnormal fetuses were divided into 4 groups according to diagnosis, i.e., 6 cases of heart disease with hydrops (group 1), 9 cases of heart disease without hydrops (group 2), 11 cases of hydrops without heart disease (group 3), and 9 cases of other fetal diseases (group 4). By measuring the velocity of IVC blood flow, we defined a new index, the change in parallel with reverse flow velocity, and called it the preload index (PLI). In normal fetuses, PLI values ranged from 0 to 0.37 and had no relation with gestational age. The PLI was significantly higher in groups 1-3 than in normal fetuses. In group 1, the PLI was also higher than in group 2. In group 3, the PLI values in 4 cases of chylothorax, 1 of chyloascites and 1 of cytomegalovirus infection were significantly lower than in the remaining 5 cases where the cause of hydrops was undetermined. The PLI was normal in 9 fetuses with other diseases and no hydrops. The PLI was increased in conditions in which excessive preload, tricuspid regurgitation, or some kind of structural heart disease were present.

Post-ischemic hypothermia blocks caspase-3 activation in the newborn rat brain after hypoxia–ischemia

The effects of hypothermia on caspase-3 activation were investigated in the newborn rat brain after hypoxia-ischemia (HI). Intense caspase-3 activation was observed in the control brains after HI, but this activation was significantly reduced by postischemic hypothermia. These findings suggest that the inhibition of caspase-3 activation may be an interventional point underlying the neuroprotective effect of hypothermia in neonates.

Effects of neonatal hypoxic–ischemic brain injury on skilled motor tasks and brainstem function in adult rats

In an attempt to establish more sensitive long-term neurofunctional measurements for neonatal hypoxic-ischemic brain injury, we examined skilled motor task and brainstem functions in adult rats after neonatal cerebral hypoxia-ischemia (H-I), using a staircase test and auditory brainstem response (ABR), respectively. Seven-day-old rats underwent a combination of left common carotid artery ligation and exposure to 8% O(2) for 1 h (n=16). The control animals only received sham operation (n=16). At 3 months of age, the staircase test and ABR were performed. In the staircase test, H-I animals showed marked impairment of skilled forelimb use in the side contralateral to the occluded artery, and the degree of brain damage correlated significantly to skilled forelimb use. In the ABR, H-I animals showed brainstem dysfunction assessed by measuring interpeak latencies for waves III-V and I-V. We also examined the brainstem with antibodies specific for activated caspase-3, a protein involved in initiation of apoptosis, and observed that caspase-3 was activated in the ipsilateral inferior colliculus at 24 h after H-I. The present study shows that both the staircase test and ABR are sensitive and objective long-term neurofunctional measurements that can be used in future studies to assess therapeutic intervention in this neonatal cerebral H-I model.

CHANGES IN VENOUS FLOW AND INTRA TRACHEAL FLOW IN FETAL BREATHING MOVEMENTS

Using pulsed Doppler ultrasound combined with a real-time B-mode image, changes in the central venous blood flow and tracheal fluid flow were recognized during fetal breathing movements. The blood flow in the umbilical vein was increased with fetal inspiration in which the abdominal wall of fetus moved inward, and decreased with expiration in which the abdominal wall moved outward. Velocity in the fetal vena cava revealed a complex blood flow, in accordance with both fetal cardiac motions and breathing movements. The tracheal flow velocity during fetal breathing was measured at a maximum of 40 cm s-1 and the flow volume was estimated at a maximum of 6 ml breath-1 in the matured fetus.

Effects of hypothermia on neonatal hypoxic-ischemic brain injury in the rat: phosphorylation of Akt, activation of caspase-3-like protease

Neuroprotective mechanisms of hypothermia have not been clearly established especially in the immature brain. To investigate the effect of hypothermia on cell death and cell survival signal pathways, we studied caspase-3-like activity and activation of Akt in a rat model of neonatal hypoxic-ischemic (H-I) brain injury. Seven-day-old rats underwent a combination of left common carotid artery ligation and exposure to 8% O(2) for 1-h (n=32). During recovery, the body temperature was reduced to 30 degrees C for 24 h in 16 animals, but was kept at 37 degrees C in 16 animals. Post-ischemic hypothermia was shown to diminish the caspase-3-like activity compared to normothermia at 6 and 24 h after H-I. Phospho-Akt was increased during the early reperfusion period after H-I in the normothermia group, but hypothermia rather decreased this enhanced phosphorylation of Akt following H-I. These results indicated that hypothermia may have some depressant effects on both cell death and cell survival signal pathways, and that Akt conceivably may not play a major role in the neuroprotective effect of hypothermia in the immature brain.

Prediction of postpartum onset of rheumatoid arthritis

OBJECTIVE To investigate the prediction of the postpartum onset of rheumatoid arthritis (RA). METHODS Two thousand five hundred and forty seven healthy pregnant subjects were examined prospectively and the relation between serum rheumatoid factors (RF) and postpartum onset of RA was observed. Rheumatoid factors were measured in early pregnancy by the antihuman IgG latex agglutination test (Latex test) and antirabbit IgG haemagglutination test (RAHA test). RESULTS Latex test and RAHA test were positive in 26 (1.0%) and 64 (2.5%) pregnant subjects, respectively. Four hundred and ten subjects of 2547 pregnant women could be followed up for one year after delivery. None of 401 subjects without RF, or with only one RF on either Latex test or RAHA test, developed RA after delivery. Two (22.2%) of nine subjects with both RFs developed RA at one and three months postpartum, respectively. Transient arthralgia was found within 12 months postpartum in three of nine (33.3%) subjects with both RFs and this prevalence was significantly higher than that in RF negative subjects (8.1%). CONCLUSION Postpartum onset of RA was found in at least 2 of 2547 healthy subjects (0.08%) and onset was predicted by positive test for rheumatoid factors.

Evaluation of fetal structural heart disease using color flow mapping.

The technique of color flow mapping was used to diagnose 19 cases of fetal structural heart disease from a study group of 104 fetuses. Color flow mapping was 76% effective in detecting the presence of fetal structural heart disease. The colored views of a single stream in the atrioventricular canal were most impressive in cases of complete atrioventricular canal, hypoplastic left heart syndrome, mitral atresia, and tricuspid atresia. The colored views of tricuspid regurgitation were also clear in cases of endocardial fibroelastosis, pulmonary atresia with intact ventricular septum, and Ebsteins anomaly. The use of this technique resulted in the in-utero diagnoses coinciding more closely with the final diagnoses, which were made after birth. This was particularly important in those cases which required immediate management after birth.

Apoptosis and Related Proteins in Placenta of Intrauterine Fetal Death in Prostaglandin F Receptor-Deficient Mice

Abstract The present study investigated whether the increase of apoptosis in the placenta is associated with intrauterine fetal death in prostaglandin F receptor-deficient mice. Apoptosis was demonstrated within placental and decidual tissue by the TUNEL method. The majority of apoptosis was found in syncytiotrophoblast tissues. Enhanced TUNEL-positive staining in the syncytiotrophoblast layer was scattered in the placental tissues in clusters of apoptotic cells in the death group. Marked TUNEL-positive cells were identified in decidua of both groups. The rate of apoptosis in the placenta and decidua in the death group was higher than that in the survival group (P < 0.05). Immunohistochemical analysis showed that the level of active caspase-3 protein expression in the placenta in the death group was much higher than that in the survival group. The level of Bcl-2 protein expression in the placenta in the death group was much lower than that in the survival group. Western blot analysis demonstrated that increased expression of the active form of caspase-3 was detected in the placenta and decidua in the death group compared with that in the survival group. In contrast, a decrease in the expression of Bcl-2 was detected in the placenta and decidua in the death group compared with that in the survival group. Enhanced expression of Bax:Bcl-2 ratio was detected in placenta and decidua in the death group compared with that in the survival group. Thus, significantly increased apoptosis in the mouse placenta and decidua might be involved in the pathophysiologic mechanism of intrauterine fetal death.

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°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.

Quantitative Analysis of Cardiac Function in Non-Immunological Hydrops fetalis

The present study was designed to quantitatively evaluate fetal cardiac dysfunction in fetal congestive heart failure associated with cardiogenic hydrops fetalis. Thirty-seven cases of non-immunological hydrops fetalis and/or fetal heart disease were assigned to four groups: (1) hydrops fetalis with structural heart disease; (2) hydrops fetalis without heart disease; (3) structural heart diseases without hydrops, and (4) complete A-V block without hydrops. One hundred and ten control fetuses were also studied. The ejection fraction in the first and third groups was significantly lower than that in the control. In the first group, systolic flow velocity in the descending aorta normalized but gestational age was significantly lower than that in the controls. Compensation of fetal cardiac function in the fourth group (complete A-V block) was noted on the basis of higher flow velocity and higher contractility. The cardiothoracic area ratios of the pathological and control groups were also evaluated.