The purpose of our study was to examine the feasibility of long-term extrauterine incubation of an isolated premature fetus in artificial amniotic fluid with arteriovenous extracorporeal circulation. Two premature goat fetuses (age 120 and 128 days) were incubated in an isothermal artificial amniotic fluid incubator with arteriovenous extracorporeal membrane oxygenation via the umbilical vessels. We administered pancuronium bromide to suppress fetal movement and swallowing because movement and swallowing have been implicated in fetal deterioration during extrauterine fetal incubation. The fetuses maintained stable circulatory and respiratory parameters. The total incubation time was 494 and 543 h. The animals were then removed from the incubator and stimulated to initiate lung respiration. With ventilator support, both animals maintained stable blood-gas exchange and survived for more than 1 week. These results clearly indicate that umbilical arteriovenous extracorporeal membrane can effectively support extended extrauterine incubation of an isolated premature fetus.

Background. This study aimed to determine the perioperative change in serum double-strand DNA (dsDNA) as a marker potentially reflecting neutrophil extracellular trap concentration in samples from patients undergoing cardiac surgery and to analyze a relationship between serum dsDNA concentrations and perioperative renal dysfunction. Methods. Serum dsDNA concentrations in samples that were collected during a previously conducted, prospective, multicenter, observational study were measured. Eighty patients undergoing elective cardiac surgery were studied. Serum samples were collected at baseline, immediately after surgery, and the day after surgery (POD-1). Results. Serum dsDNA concentration was significantly increased from baseline (median, 398 ng/mL [interquartile range, 372–475 ng/mL]) to immediately after surgery (median, 540 ng/mL [437–682 ng/mL], p < 0.001), and they were reduced by POD-1 (median, 323 ng/mL [256–436 ng/mL]). The difference in serum creatinine concentration between baseline and POD-1 was correlated with dsDNA concentration on POD-1 (r s = 0.61, p < 0.001). Conclusions. In patients undergoing cardiac surgery, serum dsDNA concentration is elevated postoperatively. Prolonged elevation in dsDNA concentration is correlated with perioperative renal dysfunction. Further large-scale studies are needed to determine the relationship between serum concentration of circulating dsDNA and perioperative renal dysfunction.

SUMMARY The mechanism by which excessive sodium chloride intake raises blood pressure has not been fully clarified. The present study was therefore undertaken in patients with essential hypertension to investigate the possible role of an intracellular calcium-dependent mechanism in salt sensitivity. The difference in mean blood pressure between a week of low sodium chloride diet (3 g/day) and a week of high sodium chloride diet (20 g/day) was studied in relation to the intracellular free calcium concentration in lymphocytes and an acute hypotensive response to a 10-mg sublingual dose of nifedipine in 12 inpatients. Sodium chloride loading induced significant increases in mean blood pressure (from 111 ± 12 to 122 ± 1 1 mm Hg; p<0.01), intracellular free calcium in lymphocytes (from 133 ± 13 to 145 ± 9 nmol/L; /K0.01), and the hypotensive response to nifedipine (from 19 ± 6 to 31 ± 10 mm Hg; /X0.01). In addition, serum total calcium concentration was decreased while urinary calcium excretion was increased. The elevation of mean blood pressure was closely and positively correlated with the increase in intracellular free calcium concentration (r=0.71, p<0.05) and the increase in the hypotensive effect of nifedipine (r=0.91, p<0.01) after sodium chloride loading. However, changes in these values had no relation to the change in serum concentration or urinary excretion of calcium. These data suggest that change in the cellular calcium-dependent vasoconstriction mechanism may be associated with salt sensitivity of patients with essential hypertension. (Hypertension 11: 703-707, 1988) KEY WORDS concentration salt sensitivity lymphocytes essential hypertension nifedipine intracellular free calcium S ODIUM chloride is well known to be an important factor in the pathogenesis and development of essential hypertension. However, excessive sodium chloride intake does not always raise blood pressure, as several reports have shown marked interindividual differences in response of blood pressure to changes in dietary salt intake (i.e., salt sensitivity) in patients with essential hypertension. 1 The actual mechanism underlying the differences in salt sensitivity has not been fully clarified, although expansion of fluid volume, 1 inappropriate response of the humoral factors, 2 and enhanced vascular response to pressor substances 3 have been proposed to explain the mechanism.Since the importance of intracellular free calcium influx with relative selectivity for vascular smooth muscle, were determined in 12 inpatients with essential hypertension during intake of low sodium chloride diet and intake of high sodium chloride diet. Patients and MethodsTwelve Japanese inpatients with mild to moderate essential hypertension (7 men and 5 women) with a mean age of 54.5 years (range, 42-63 years) were studied. All the patients gave informed consent to this study. The presence of hypertension was defined as a blood pressure level of greater than 160/95 mm Hg in the sitting position on at least three different occasions in the outpatient cl...

No abstract

PurposePropofol infusion syndrome (PRIS) is a lethal condition caused by propofol overdose. Previous studies suggest that pathophysiological mechanisms underlying PRIS involve mitochondrial dysfunction; however, these mechanisms have not been fully elucidated. This study aimed to establish an experimental model of propofol-induced cytotoxicity using cultured human induced pluripotent stem cell (iPSC)-derived cardiomyocytes to determine the mechanisms behind propofol-induced mitochondrial dysfunction, and to evaluate the protective effects of coenzyme Q10 (CoQ10).MethodsHuman iPSC-derived cardiomyocytes were exposed to propofol (0, 2, 10, or 50 µg/ml) with or without 5 µM CoQ10. Mitochondrial function was assessed by measuring intracellular ATP, lactate concentrations in culture media, NAD+/NADH ratio, and the mitochondrial membrane potential. Propofol-induced cytotoxicity was evaluated by analysis of cell viability. Expression levels of genes associated with mitochondrial energy metabolism were determined by PCR. Intracellular morphological changes were analyzed by confocal microscopy.ResultsTreatment with 50 µg/ml propofol for 48 h reduced cell viability. High concentrations of propofol (≥ 10 µg/ml) induced mitochondrial dysfunction accompanied by downregulation of gene expression of PGC-1alpha and its downstream targets (NDUFS8 and SDHB, which are involved in the respiratory chain reaction; and CPT1B, which regulates beta-oxidation). Cardiomyocytes co-treated with 5 µM CoQ10 exhibited resistance to propofol-induced toxicity through recovery of gene expression.ConclusionsPropofol-induced cytotoxicity in human iPSC-derived cardiomyocytes may be associated with mitochondrial dysfunction via downregulation of PGC-1alpha-regulated genes associated with mitochondrial energy metabolism. Co-treatment with CoQ10 protected cardiomyocytes from propofol-induced cytotoxicity.