Possible Neuroprotective Role of Exogenous Growth Hormone on Hypoxic-Ischemic Brain Injury in Neonatal Rats / 소아과

PURPOSE: This study was performed to evaluate the possible neuroprotective effect of exogenous growth hormone on hypoxic-ischemic brain injury in neonatal rats. METHODS: After ligation of the right common carotid artery, seven-day old Sprague-Dawley rats(n= 75) were exposed to 8% oxygen for two hours. In a growth hormone(GH)-treated group(n=25), each animal was subcutanously injected by GH(50 mg/kg, Grotrpin, Dong-Ah Pharmacy Co. KOREA) just before exposing to 8% oxygen, and then injected for the next two consecutive days by the same method. In a saline-treated group(n=25), the same amounts of saline were injected instead of GH. Other twenty five animals were sham-operated without hypoxia as a sham control group. The gross morphologic changes of extracted brains at three and seven days after injury were observed, and the ratios of wet and dry weight of each cerebral hemisphere ipsilateral and contralateral to hy poxic-ischemic injury were compared among three groups for evaluating the severity of brain edema. Also, the microscopic changes of cerebral cortex on coronal sections of paraffin-embedded brains were observed at three days after injury by light microscopy. RESULTS: The GH injection reduced the severities of gross changes at seven days after HI injury. The brain edemas of ipsilateral cerebral hemispheres to the site of ligation of the right common carotid artery were significantly decreased in GH-treated animals at three days after HI injury, compared to those in saline-treated animals(P<0.05). On light microscopic examination, neurons with pyknosis of nucleus were remarkably reduced on cerebral cortex at three days after hypoxic-ischemic injury by GH treatment. CONCLUSION: Exogenous GH might have a some neuroprotective role in hypoxic-ischemic brain injury of newborn rats.

Changes in the Levels of Eicosanoids and Isoprostane (8-iso-PGF2alpha) in the Newborn Rat Brain after Hypoxic-Ischemic Injury

PURPOSE: The changes in the levels of eicosanoids and isoprostane (8-iso-PGF2alpha) were investigated in brain tissue of 7 day-old rats after hypoxic-ischemic (HI) injury. METHODS: The 7 day-old newborn rats underwent right unilateral common carotid artery ligation followed by exposure to hypoxia with 8% oxygen for 150 minutes. There after, the pups were decapitated during reoxygenation 21% period of 0, 1, 6, 24, and 72 hours and their cerebral hemisheres were dissected through sagittal plane. Ipsilateral and contralateral cerebral hemesheres to common carotid artery ligation were used to determine the water content for estimation of severity of brain edema (n=5) and to measure the levels of eicosanoid and isoprostane (n=7). The levels of 6-keto-PGF1alpha, TXB2, and PGE2 were measured by RP-HPLC (reversed-phase high-performance liquid chromatography) and the levels of isoprostane (8-iso-PGF2alpha) were measured by enzyme immunoassay. The changes of eicosanoid and isoprostane levels during reoxygenation period were observed and comparisons between ipsilateral and contralateral hemispheres were done. RESULTS: The edema of ipsilateral cerebral hemesheres to common carotid artery ligation was more severe than that of contralateral cerebral hemisheres (P<0.05). The levels of 6-keto-PGF1alpha, TXB2, and PGE2 were found to increase during the early period of reoxygenation after HI insult, peak at 1 hour, and then decrease to the control levels at 72 hour (P<0.05). But, the levels of 8-iso-PGF2alpha did not significantly increase during the period of reoxygenation. The levels of 6-keto-PGF1alpha, TXB2, and PGE2 of ipsilateral hemispheres had a tendency to be higher than those of contralateral hemispheres during the initial 6 hour reoxygenation period, but the levels of 8-iso-PGF2alpha of ipsilateral hemispheres were significantly higher than those of contralateral hemispheres during the relatively later reoxygenation period (P<0.05). CONCLUSION: Reoxygenation after hypoxic-ischemic injury increased the levels of 6-keto-PGF1alpha, TXB2, and PGE2 in 7 day-old rat brain during the early period of reoxygenation, but the levels of isoprostane (8-iso-PGF2alpha) were not significantly increased during the reoxygenation period after HI injury.

Treatment of Persistent Pulmonary Hypertension of the Newborn with Magnesium Sulphate

PURPOSE: MgSO4 was used to evaluate the clinical effects in the treatment of severe persistent pulmonary hypertension of the newborn(PPHN). METHODS: Seven newborn infants with severe PPHN, and a persistent elevation of AaDO2(Alveolar-arterial oxygen tension difference) above 610 mmHg for more than 8 hours despite the aggressive conventional therapy were included. A loading dose of 200 mg/kg MgSO4 was given intravenously over 20-30 minutes, followed by continuous infusion of 20-50 mg/kg/hour. Vital signs, arterial blood gases, serum electrolytes, calcium and magnesium, and ventilatory setting were measured and recorded before MgSO4 was given and periodically thereafter. Severity of impairment of gas exchange was evaluated by AaDO2 and oxygenation index(OI). RESULTS: Mean gestational age and birth weight of seven infants were 38+5 weeks and 2,949844 grams, and one of them was a premature infant with gestational age of 27 weeks, and birth weight of 1,096 grams. There were six males and one female. Four infants were outborn. Four infants were presented with meconium aspiration syndrome, one with birth asphyxia, one with respiratory distress syndrome, and one with subdural hemorrhage. Before the start of the MgSO4 treatment, the mean AaDO2 and OI of seven infants were 638.8+/-10.8 mmHg and 43.811.2, respectively. During the treatment AaDO2 and OI significantly decreased to 538.4+/-114.5 mmHg and 13.4+/-9.4 within 24 hours(P< 0.05). Hypermagnesemia was noted in 7 infants, hypocalcemia in three, bradycardia in five, and hypotension in two. Only one infant was discharged against medical advice, and remaining six survived. CONCLUSION: MgSO4 may be considered as an alternative treatment of severe PPHN when other conventional treatments fail, are contraindicated, or not available.

Incidence of Hypercalcemia in Dialysis Patients: HD vs. CAPD / 대한신장학회잡지

Oral phosphate binders and high calcium dialysate have been used as standard therapies for dialysis patients to prevent renal osteodystrophy. Calcium containing phosphate binders are used to prevent intestinal absorption of dietary phosphate and to avoid aluminum loading by using aluminum containing phosphate binders. The use of calcium products resulted in hypercalcemia in a substantial portion of dialysis population. Calcium carbonate as a phophate binder is widely used in Korea. However, the incidence of hypercalcemia in Korean dialysis patients has not been reported to date. In this study we evaluated the incidence of hypercalcemia in dialysis patients. Patients with associated diseases that may influence serum calcium level were excluded from the study. A total of 180dialysis patients (116 HD patients and 64 CAPD patients) maintained at Soon Chun Hyang University Hospital were included. Three consecutive 2 monthly measurements of serum calcium, phosphate, albumin, alkaline phosphatase, bicarbonate in HD and two consecutive measurements in 3 month interval in CAPD patients were retrospectively evaluated. Ionized calcium and intact parathyroid hormone (N-terminal) were measured every 6 months. Serum total calcium level was corrected by serum albumin level. Three HD patients(2.5%) were hypercalcemic pre-HD while 50(43.1%) hypercalcemic postdialysis. 5 CAPD patients(7.8%) were hypercalcemic. Pre-HD calcium level did not differ from the value in CAPD patients. An average value of pre-and post-HD calcium, and serum albumin levels were significantly higher in HD patients than those values in CAPD patients(p<0.01). Ionized calcium (p<0.01) and serum PTH(p<0.05) levels were significantly higher, while serum bicarbonate level (p<0.01) was significantly lower in HD patients than in CAPD patients. The amount of calcium carbonate used were 2.2g in HD and 2.8g in CAPD. In conclusion, the incidence of hypercalcemia is low in pre-HD (2.5%) and in CAPD patients(7.8%). However, the high incidence of post-HD hypercalcemia observed in this study advocates a future study to evaluate the effect of low calcium dialyste on calcium-phosphate metabolism.