Intrauterine therapy of fetal tachyarrhythmias: Intraperitoneal administration of antiarrhythmic drugs to the fetus in fetal tachyarrhythmias with severe hydrops fetalis

Gembruch, Ulrich; Hansmann, M.; Redel, D. A.; Bald, R.

doi:10.1515/jpme.1988.16.1.39

Cited by 56 publications

(27 citation statements)

References 11 publications

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“…The fact that verapamil (Gembruch et al 1988) and betamimetics (Friedman et al 1994), cross the placenta and that verapamil when combined with other medicaments reveals co-mutagenic effect was pointed out in many papers (Friedman et al 1990;Scheid et al 1991, Scheid andTraut 1993;Nesterova et al 1999;Seredenin et al 1999). Our results confirm the possibility that in modified intrauterine conditions the fetus reacts at the cell level, directly increasing MN frequencies in umbilical blood lymphocytes.…”

Section: Discussionmentioning

confidence: 98%

Treatment of Pregnant Women with a Betamimetic and Verapamil Increases the Micronuclei Frequency in Umbilical Cord Blood Lymphocytes

Grujičić

Milošević-Djordjević

Arsenijevic

et al. 2008

Tohoku J. Exp. Med.

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In prevention of preterm labor, betamimetics are used in gynecological practice mostly combined with antiarrhythmic verapamil because of their therapeutic cardiovascular side effects. The aim of this study was to investigate the influence of a betamimetic (ritodrine hydrochloride, fenoterol or hexoprenaline) and verapamil (administered to mothers) on the frequency of micronuclei (MN) in umbilical cord blood lymphocytes of neonates, using cytokinesis-block micronucleus test. The analyzed sample included 23 babies whose mothers received the therapy and 30 control babies whose mothers received no therapy. The average MN frequency was significantly higher in the neonates whose mothers received the therapy (8.13 ± 2.69 MN/1000 BN cells), in comparison with the baseline frequency in untreated controls (3.30 ± 2.63 MN/1000 BN cells), with probability p < 0.05. The highest MN frequency was found in neonates whose mothers received fenoterol and verapamil (2.8-fold i.e. 9.10 ± 3.00 MN/1000 BN cells), while ritodrine hydrochloride and hexoprenaline combined with verapamil induced 2.3-fold and 2.2-fold higher MN values than in controls (7.50 ± 3.33 MN/1000 BN cells and 7.29 ± 0.95 MN/1000 BN cells). Multiple linear regression analysis showed that MN frequency was affected only by the maternal therapeutic treatment, while the neonates' sex, maternal age, cigarette smoking, and therapeutic doses did not affect the MN frequency in umbilical lymphocytes of neonates. We conclude that the treatment of pregnant women with a betamimetic and verapamil significantly increases the MN frequency in umbilical cord blood lymphocytes of neonates, regardless to therapeutic doses.umbilical cord blood lymphocytes; micronuclei; betamimetic; verapamil.Tohoku

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Section: Discussionmentioning

confidence: 98%

Treatment of Pregnant Women with a Betamimetic and Verapamil Increases the Micronuclei Frequency in Umbilical Cord Blood Lymphocytes

Grujičić

Milošević-Djordjević

Arsenijevic

et al. 2008

Tohoku J. Exp. Med.

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“…The use of verapamil for fetal tachyar rhythmias have been reported [7,12,13]. Verapamil effects the atrioventricular node and blocks AVC.…”

Section: Discussionmentioning

confidence: 99%

Hemodynamic Changes during Cardioversion in utero: A Case Report of Supraventricular Tachycardia and Atrial Flutter

et al. 1993

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Two cases of fetal tachyarrhythmias were treated in utero. One case showed supraventricular tachycardia which was successfully treated with procainamide. The other case was an atrial flutter with 2:1 atrioventricular conduction (AVC) which was treated with digoxin and verapamil. In both cases, the blood flow in the descending aorta was observed using pulsed Doppler ultrasound during therapy. In the first case, the interval of blood flow peaks was suddenly prolonged to normal heart rate, and in the second case, the blood flow peaks appeared irregularly which indicated that (AVC) was intermittently blocked. The blood flow pattern represented the mode of cardioversion. The blood flow velocity was also measured in both cases; it decreased transiently during therapy representing a depression in cardiac function. The cause of this was thought to be the negative inotropic effects of procainamide and verapamil. In spite of these negative inotropic effects, a greater R-R interval means a greater stroke volume. This relationship has a favorable effect on the fetal circulation as a result of therapy for fetal tachyarrhythmias.

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“…Furthermore, in some cases (4,8) the dose of digoxin had to be reduced to avert maternal toxicity. Direct fetal administration of digoxin has been reported recently (12,13). Although this mode of therapy effectively converted tachycardia to normal sinus rhythm, fetal digoxin administration is impractical because it requires multiple intrafetal injections to maintain the digoxin concentration.…”

Section: Discussionmentioning

confidence: 99%

“…In another group of 14 fetuses, Because transplacental digoxin therapy is unreliable, direct administration of digoxin to the fetus has been attempted. we injected digoxin at an estimated dose of 0.3 nmol/kg fetal Recently, Gembruch et al (12) and Weiner and Thompson body wt (low dose). At the end of the study the fetuses were ( I that injecting digoxin directly into the fetal pento-weighed.…”

mentioning

confidence: 99%

Fetal Uptake of Intraamniotic Digoxin in Sheep

et al. 1990

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ABSTRACT. To explore the possibility that intraamniotic is impractical to treat tachyarrhythmia both because multiple administration of digoxin is an effective treatment regimen intrafetal injections are required and because fetal plasma digoxin for fetal tachyarrhythmia, we injected digoxin into the concentrations are difficult to control. To determine whether amniotic fluid cavity of pregnant sheep and examined the intraamniotic administration of digoxin might effectively treat time course of digoxin distribution to the fetal and maternal fetal tachyarrhythmia, we injected digoxin into the amniotic plasma compartments. Animals were studied in two groups cavity of pregnant sheep and measured the distribution of digoxin according to digoxin dosage: 0.7-1.8 nmol/kg fetal body wt from the amniotic cavity to the fetal and maternal plasma in the high-dose group (n = 6) and 0.1-0.6 nmol/kg fetal compartments. body wt in the low-dose group (n = 14). Within 1 h, plasma digoxin concentrations in the high-dose and low-dose L, and at 24 h they were 2.3 nmol/L (n = 1) and 1.8 f 1.2 gestation. Surgical techniques to implant catheters into the ewe nmol/L, respectively. Peak maternal digoxin levels were and the fetus have been described in detail previously (14). about one-tenth fetal values in the high-dose group and Briefly, after spinal anesthesia was induced in the ewe with 4 mL undetectable in the low-dose group. Fetal digoxin concen-of 1 % tetracaine hydrochloride, polyvinyl catheters were inserted trations were significantly greater in the descending aorta into a peripheral artery and vein. The ewes were given an i.v.than in the umbilical vein ( p < 0.02). Fetal arterial blood infusion of 0.9% saline during the operative procedure. Ketamine pressure and heart rate were not significantly different was administered intravenously in doses of 100 mg every 15-20 from control at any time after digoxin administration. min. Through a midline incision, the uterus was exposed and These results demonstrate that digoxin is rapidly taken up the fetal hindlimbs identified. Polyvinyl catheters were inserted into the fetal circulation from the maternal amniotic cavity. into a peripheral artery and vein of each hindlimb and advanced The exact mechanism whereby this occurs is unknown, but to the descending aorta and inferior vena cava. In seven fetuses, transplacental transfer from the maternal circulation is not an 8 F polyvinyl catheter was inserted suprapubically into the involved. Our findings suggest that intraamniotic admin-urinary bladder through a purse-string suture (15). A 3.5 F istration of digoxin may be an alternative treatment for multiple side-hole catheter was introduced into a distal cotylefetal tachyarrhythmias when direct administration of an-donary tributary of the umbilical vein and advanced proximally tiarrhythmic agents is ineffective or produces maternal toward the fetal body in 12 animals. Two catheters were also toxicity. (Pediatu Res 27: 282-285, 1990) inserted into the amniotic cavity, one near the cervix a...

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Intrauterine therapy of fetal tachyarrhythmias: Intraperitoneal administration of antiarrhythmic drugs to the fetus in fetal tachyarrhythmias with severe hydrops fetalis

Cited by 56 publications

References 11 publications

Treatment of Pregnant Women with a Betamimetic and Verapamil Increases the Micronuclei Frequency in Umbilical Cord Blood Lymphocytes

Treatment of Pregnant Women with a Betamimetic and Verapamil Increases the Micronuclei Frequency in Umbilical Cord Blood Lymphocytes

Hemodynamic Changes during Cardioversion in utero: A Case Report of Supraventricular Tachycardia and Atrial Flutter

Fetal Uptake of Intraamniotic Digoxin in Sheep

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