Characterization of [125I]ZM 241385 binding to adenosine A2A receptors in the pineal of sheep brain.

Adenosine is a ubiquitous neuromodulator and homeostatic regulator that exerts its physiologic actions through activation of A(1), A(2A), A(2B) and A(3) adenosine receptor subtypes. In the central nervous system, adenosine's action in neurons is manifested in its modulation of tonic inhibitory control. Adenosine released in the brain during hypoxia has critical depressant effects on breathing in fetal and newborn mammals, an action suggested to be mediated by A(2A) receptors in the posteromedial thalamus. In an effort to more accurately define the spatial distribution of adenosine A(2A) receptors in fetal sheep diencephalon, we have used a receptor autoradiographic technique utilizing an iodinated radioligand [(125)I]ZM 241385, which has greater sensitivity and resolution than the tritiated compound. The distribution of ligand binding sites in the fetal sheep diencephalon indicated that the highest levels of binding were in select thalamic nuclei, including those implicated in hypoxic depression of fetal breathing, and the pineal. Given the high density of labeled A(2A) receptors in the pineal, these sites were characterized more fully in homogenate radioligand binding assays. These data indicate that [(125)I]ZM 241385 binding sites display a pharmacological signature consistent with that of adenosine A(2A) receptors and are expressed at similar levels in fetal, lamb and adult ovine brain. The adenosine A(2A) receptor pharmacologic signature of the [(125)I]ZM 241385 binding site in pineal cell membranes generalized to the site characterized in membranes derived from other portions of the lamb thalamus, including the sector involved in hypoxic inhibition of fetal breathing. These results have important implications for the functional roles of adenosine A(2A) receptors in the thalamus and pineal of sheep brain.

Placental calcification: a metastatic process?

Placental calcification commonly increases with gestational age. The mechanism of apatite mineralization probably involves one of three known mechanisms of tissue calcification: physiological (like bone), dystrophic (ischaemia-related) or metastatic (mineralization in a supersaturated environment). This study was designed to determine the mechanism of calcification by examining (1) the mineral content of placental calcifications in comparison to other physiological and pathological apatites, and (2) the expression of bone morphogenetic proteins (BMPs), which are important in physiological calcification, across gestational age. By energy-dispersive x-ray analysis (EDXA), the Ca/P weight ratio for apatitic mineral from mature calcifications was 2.00+/-0.05 (s.e.), which is similar to that for stones formed in a metastatic, supersaturated environment and lower than that observed in physiological calcification. Biologically active BMP, which was determined by bioassay, was demonstrated in mature and postmature placentae. The BMPs PLAB, PDF and related protein INSL-4 were identified by semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR), but their mRNA expression was independent of gestational age (7-41 weeks of gestation). We conclude that (1) the identified BMPs were not related directly to placental calcification, which argues against physiological calcification, and (2) the chemical composition of the apatitic mineral was suggestive of rapid formation in a supersaturated environment, which is consistent with a metastatic mechanism of calcification.

Adenosine A(1) and A(2A) receptors modulate sleep state and breathing in fetal sheep.

This study was designed to determine the adenosine (Ado) receptor subtype that mediates the depressant effects of Ado on fetal breathing and rapid eye movements (REM). In chronically catheterized fetal sheep (>0.8 term), intra-arterial infusion of N(6)-cyclopentyladenosine (CPA), an Ado A(1)-receptor agonist, increased the incidence of high-voltage electrocortical (ECoG) activity while virtually abolishing low-voltage activity, REM, and breathing. These effects were blocked by 9-cyclopentyl-1,3-dipropylxanthine (DPCPX), an Ado A(1)-receptor antagonist. Infusion of DPCPX alone increased breath amplitude but had no significant effect on inspiratory duration, breath interval, incidence of REM, or incidence of low-voltage activity. Ado A(2A)-receptor blockade with ZM-241385 increased the incidence of low-voltage ECoG activity, REM, and breathing but had no effect on breath amplitude or respiratory cycle. Both DPCPX and ZM-241385 eliminated the inhibitory effects of Ado on REM and breathing. We conclude that 1) Ado A(1) receptors tonically inhibit fetal respiratory drive, 2) Ado A(2A) receptors tonically inhibit REM-like behavioral state, and 3) both Ado A(1) and A(2A) receptors mediate the depressant effects of Ado on REM and breathing.

Adenosine A(2A) receptors mediate cardiovascular responses to hypoxia in fetal sheep.

Nonselective adenosine (ADO) receptor antagonists block hypoxia-induced bradycardia and hypertension in fetal sheep. This study was designed to determine the ADO receptor subtype that is involved in these cardiovascular responses. In chronically catheterized fetal sheep (>0.8 term), fetal hypoxemia was induced by having the ewe breathe a hypoxic gas mixture (9% O(2)-3% CO(2)-88% N(2)) for 1 h. Intra-arterial infusion of ZM-241385, an antagonist highly selective for ADO A(2A) receptors, to eight fetuses during normoxia significantly increased mean arterial pressure (MAP) from 42.5 +/- 2.0 to 46.1 +/- 2.0 mmHg without altering heart rate (HR). Infusion of a selective antagonist of ADO A(1) receptors [1, 3-dipropyl-8-cyclopentylxanthine (DPCPX)] elevated MAP and HR only after the infusion was terminated, although administration of the vehicle for ZM-241385 or DPCPX had no effect on MAP or HR. Isocapnic hypoxia with infusion of DPCPX or the vehicle for DPCPX or ZM-241385 produced a transient fall in HR, a rise in MAP, and a decrease in plasma volume. In contrast, ADO A(2A) receptor blockade abolished the hypoxia-induced bradycardia and hypertension and blunted the decline in plasma volume. We conclude that fetal ADO A(2A) receptors: 1) modulate AP during normoxia, and 2) mediate cardiovascular responses during acute O(2) deficiency.

Thalamic lesions dissociate breathing inhibition by hypoxia and adenosine in fetal sheep.

The effects of diencephalic lesions on respiratory responses to intra-arterially infused adenosine (ADO) were determined in chronically catheterized fetal sheep (>0.8 term). These studies were designed to test the hypothesis that the inhibitory effects of ADO on fetal breathing, like those of hypoxia, are mediated by the parafascicular nuclear complex (Pf) of the posteromedial thalamus. ADO inhibited breathing [control (C): 26 +/- 2.6, ADO: 4 +/- 1 min/h] in normal fetuses and in a fetus with a lesion that virtually destroyed the thalamus but left intact most of Pf. Neuronal lesions in the diencephalon, produced by injecting ibotenic acid, abolished the inhibitory effects of ADO on breathing (C: 31 +/- 5.1, ADO: 30 +/- 4.5 min/h) when the lesions encompassed Pf or the sector immediately rostral to Pf that retained the capacity to regulate hypoxic inhibition. Smaller lesions created by the insertion of needles also eliminated the depressant effects of ADO when disruptions were within Pf or a rostral component of the thalamic cortical activating system. It is concluded that 1) a medial thalamic sector is critically involved in ADO-induced apnea and 2) ADO-dependent and ADO-independent mechanisms mediate hypoxic inhibition.

Metabolic and cardiorespiratory responses to hypoxia in fetal sheep: adenosine receptor blockade.

8-Phenyltheophylline (PT), a potent and specific inhibitor of adenosine receptors, was infused intra-arterially into unanesthetized fetal sheep to determine the role of adenosine in hypoxic inhibition of fetal breathing. PT in normoxic fetuses increased heart rate and the incidence of low-voltage electrocortical activity, rapid eye movements (REM), and breathing. Mean breath amplitude increased by 44%. Hypoxia (preductal arterial PO2 = 14 Torr) induced a metabolic acidemia, a transient bradycardia, and hypertension while virtually eliminating REM and breathing. PT administration during hypoxia enhanced the metabolic acidemia, blocked the bradycardia and hypertension, increased the incidence of REM and breathing, and elevated mean breath amplitude. The results indicate that 1) adenosine is involved in fetal glycolytic and cardiovascular responses to hypoxia, 2) activation of central adenosine receptors mediates about one-half the inhibitory effects of hypoxia on REM and breathing, and 3) the depression of breathing may critically depend on a hypoxia-induced reduction in phasic REM sleep.

Adenosine modulates corticotropin and cortisol release during hypoxia in fetal sheep.

OBJECTIVE: This study was designed to determine the role of adenosine in the hypoxic release of corticotropin in fetal sheep. STUDY DESIGN: The adenosine receptor antagonist 8-phenyltheophylline or the vehicle was infused intra-arterially to chronically catheterized fetal sheep (>0.8 term) during an hour of fetal hypoxemia (Pa O 2 congruent with 14 mm Hg). Control studies were also performed in which 8-phenyltheophylline or the vehicle was administered to normoxic fetuses. RESULTS: 8-Phenyltheophylline abolished hypoxia-induced bradycardia and hypertension and produced a nearly 5-fold greater rise in fetal plasma concentrations of corticotropin and approximately a 3-fold greater increase in plasma cortisol levels. During normoxia 8-phenyltheophylline increased plasma cortisol concentrations by 2-fold without altering corticotropin levels, mean arterial blood pressure, or heart rate. CONCLUSION: Adenosine blunts fetal corticotropin release during hypoxia, which in turn reduces cortisol secretion. At lower corticotropin concentrations, adenosine also appears to dampen the cortisol response through direct effects on the adrenals.

Thalamic locus mediates hypoxic inhibition of breathing in fetal sheep.

The effects of lesions rostral to the brain stem on breathing responses to hypoxia were determined in chronically catheterized fetal sheep (>0.8 term). These studies were designed to test the hypothesis that the diencephalon is involved in hypoxic inhibition of fetal breathing. As in normal fetuses, hypoxia inhibited breathing with transection rostral to the thalamus or transection resulting in virtual destruction of the thalamus but sparing most of the parafascicular nuclear complex. Neuronal lesions were produced in the fetal diencephalon by injecting ibotenic acid through cannulas implanted in the brain. Hypoxic inhibition of breathing was abolished when the lesions encompassed the parafascicular nuclear complex but was retained when the lesions spared the parafascicular nuclear region or when the vehicle alone was injected. A new locus has been identified immediately rostral to the midbrain, which is crucial to hypoxic inhibition of fetal breathing. This thalamic sector involves the parafascicular nuclear complex and may link central O2-sensing cells to motoneurons that inhibit breathing.

Fetal cardiovascular and breathing responses to an adenosine A2a receptor agonist in sheep.

CGS-21680 (CGS), a highly selective adenosine A2a receptor agonist, may excite the fetal carotid bodies. This study was designed to determine 1) whether CGS stimulates fetal breathing and 2) whether sinoaortic denervation abolishes CGS-induced tachycardia. In eight intact fetuses (> 0.8 term), intra-arterial CGS infusion (6 micrograms.min-1.kg estimated fetal wt-1) increased mean arterial PCO2 by 3-7 Torr, reduced fetal arterial PO2 by 2-5 Torr, and produced a mild metabolic acidemia. Heart rate increased from 154 +/- 7 (control) to 249 +/- 12 beats/min, but mean arterial pressure was not significantly affected. CGS initially increased the frequency, amplitude, and incidence of fetal breathing, but this hyperpnea was followed by prolonged respiratory depression that was not reversed with blockade of adenosine A1 receptors. Denervation of both carotid bodies together with interruption of the vagi abolished the hyperpnea without altering the respiratory depression or the maximum rise in heart rate. We conclude that CGS induces 1) tachycardia by a mechanism independent of the peripheral arterial chemoreceptors, 2) hyperpnea by stimulating peripheral adenosine A2a receptors, and 3) respiratory depression by activating central A2a receptors.

Enhancing adenosine A1 receptor binding reduces hypoxic-ischemic brain injury in newborn rats.

Hypoxia increases brain adenosine concentrations, which provides neuroprotection through activation of central adenosine A1 receptors. This study was carried out to determine whether PD 81,273, which increases adenosine's binding to A1 receptors, would reduce hypoxia-induced brain injury. PD 81,273 (3 mg/kg, i.p.) decreased by about 50% the weight loss of the left cerebral hemisphere caused by hypoxia-ischemia in neonatal rats. Thus, enhancing adenosine's binding to the A1 receptor decreases hypoxic brain damage.

Source of extracellular brain adenosine during hypoxia in fetal sheep.

Microdialysis was performed to determine whether hypoxia increases fetal brain adenosine (ADO) concentration through dephosphorylation of extracellular 5'-adenosine monophosphate (5-AMP). Hypoxia (fetal PaO2 approximately 14 Torr) increased fetal brain ADO levels approximately two-fold when the probes were perfused with synthetic cerebrospinal fluid (CSF) containing inhibitors of the nucleoside transporter but not with this solution plus a blocker of ecto-5'-nucleotidase (AOPCP). The hypoxia-induced rise in fetal brain ADO concentrations depends critically upon the hydrolysis of extracellular 5'-AMP.

Pregnancy outcomes after the Fontan repair.

OBJECTIVES: This study sought to determine risks and outcome of pregnancy and delivery after the modified Fontan operation. BACKGROUND: Increasingly, female Fontan patients reaching child-bearing years are interested in having children. To date, the number of reported pregnancies is small, and pregnancy has therefore been discouraged. METHODS: One hundred ten of 126 female patients from the Fontan registries of the Mayo Clinic and University of California Los Angeles Medical Center responded to a mailed questionnaire. An additional six patients with a reported pregnancy from other centers were identified and reviewed to assess pregnancy outcomes. RESULTS: Among the participating centers, a total of 33 pregnancies after Fontan operation for various types of univentricular heart disease were reported. There were 15 (45%) live births from 14 mothers, with 13 spontaneous abortions and 5 elective terminations. In the 14 women with live births, the median number of years between operation and pregnancy was 4 (range 2 to 14). Reported prepregnancy problems in these gravidas included atrial flutter in one patient and ventricular dysfunction, aortic regurgitation and atrioventricular valve regurgitation in another. One patient developed supraventricular tachycardia during pregnancy and had conversion to sinus rhythm. No maternal cardiac complications were reported during labor, delivery or the immediate puerperium. There were six female and nine male infants (mean gestational age 36.5 weeks; median weight 2,344 g). One infant had an atrial septal defect. At follow-up, mothers and infants were alive and well. CONCLUSIONS: Pregnancy after the Fontan operation appears to have been well tolerated in 13 to 14 gravidas. There does appear to be an increased risk of miscarriage. The tendency to routinely discourage pregnancy may need to be reconsidered.

Adenosine mediates metabolic and cardiovascular responses to hypoxia in fetal sheep.

1. In seven unanaesthetized fetal sheep (> 80% term), isocapnic hypoxia (arterial partial pressure of O2, Pa,O2, approximately 15 mmHg) was induced for 1 h by lowering maternal inspired PO2. Fetal hypoxia was also produced during intra-arterial administration of the adenosine receptor antagonist 8-(p-sulphophenyl)-theophylline (8-SPT). The fetal 8-SPT infusion was begun just prior to hypoxia and was stopped when fetal Pa,O2 was returned to normal. 2. Hypoxia induced a progressive fetal acidosis, a rise in mean arterial pressure, a transient fall in heart rate and a decrease in breathing movements. 8-SPT significantly reduced the metabolic acidosis and abolished the hypertension and bradycardia without altering hypoxic inhibition of fetal breathing. Administration of the vehicle for 8-SPT during hypoxia did not significantly affect the normal fetal metabolic and cardiovascular responses to acute O2 deprivation. 3. It is concluded that adenosine mediates the fetal bradycardia and hypertension produced by hypoxia, indicating that adenosine modulates fetal autonomic responses to acute oxygen deficiency. Secondly, adenosine contributes to fetal metabolic acidaemia, suggesting that adenosine also modulates fetal glycolytic responses to hypoxia.

Predictive value of HemoCue capillary whole blood glucose measurements in pregnancy.

OBJECTIVE: We determined the ability of capillary whole blood glucose concentrations to predict venous plasma and whole blood glucose levels. METHODS: During a standard oral glucose tolerance test in 29 pregnant women, paired capillary and venous blood samples were collected for analysis of glucose concentrations by the HemoCue photometer and by central laboratory methods. RESULTS: Glucose concentrations determined serially in a single blood sample by the HemoCue method were highly reproducible, with a coefficient of variation of 2.3%. However, glucose levels in blood from two different fingersticks from the same patient varied on average by 3 mg/dL, with a maximum difference of 14 mg/dL. Although capillary whole blood glucose results obtained by the HemoCue method correlated well with venous plasma or whole blood glucose measurements (r = 0.98 and r = 0.97, respectively) over the range investigated (60-250 mg/dL), individual capillary whole blood glucose measurements were only a fair predictor of venous values, with 95% of measured venous levels within +/- 26 mg/dL and +/- 20 mg/dL for concentrations predicted for plasma and whole blood, respectively. CONCLUSION: Sampling factors rather than measurement accuracy limit the ability of capillary whole blood glucose measurements to predict venous concentrations.

Adenosine modulates hypoxia-induced atrial natriuretic peptide release in fetal sheep.

The effects of adenosine on atrial natriuretic peptide (ANP) secretion were determined in chronically catheterized fetal sheep (> 0.8 term). Adenosine was infused into the the right jugular vein for 1 h at 8 +/- 0.4 (5 fetuses), 160 +/- 8 (6 fetuses), and 344 +/- 18 micrograms.min-1.kg estimated fetal wt-1. Fetal arterial blood gases and pH were generally unaffected by adenosine, although mean arterial CO2 tension increased transiently by 2-5 Torr and pH fell progressively during the highest rate of infusion. During the intermediate and high infusion rates, fetal hemoglobin concentrations increased by 11-13% and mean fetal heart rate rose by 18% from a control value of approximately 167 beats/min. Mean arterial pressure was not affected during adenosine infusion. Adenosine significantly increased fetal plasma ANP levels, with maximum concentrations 1.80, 2.36, and 2.51 times greater than control means (142-166 pg/ml) for the respective infusion rates of 8, 160, and 344 micrograms.min-1.kg estimated fetal wt-1. In seven fetuses, reducing fetal arterial O2 tension by approximately 9-10 Torr from a control of 23 +/- 1.3 Torr increased plasma ANP concentrations approximately 2.4 times the control mean of 176 pg/min. Adenosine-receptor blockade with 8-(p-sulfophenyl)-theophylline reduced by 50% the maximum hypoxia-induced rise in plasma ANP concentrations. It is concluded that adenosine causes a dose-dependent rise in fetal plasma ANP concentrations and modulates fetal ANP release during hypoxia.

Hypoxic inhibition of breathing in fetal sheep: relationship to brain adenosine concentrations.

Because hypoxic inhibition of fetal breathing may be caused by a rise in central adenosine levels, the effects of O2 deficiency on fetal brain adenosine concentrations were determined at levels of hypoxia that inhibited fetal breathing. Under halothane anesthesia, the brains of fetal sheep (0.8 term) were implanted with guide cannulas exteriorized through a Silastic rubber window in the uterus and flank of the ewe. At least 4 days after surgery, a microdialysis probe was inserted into a cannula with the membrane tip placed in the rostral brain stem. During 1 h of isocapnic hypoxia, mean fetal arterial PO2 was reduced from 24.0 +/- 0.9 Torr (control) to 13 +/- 0.6 Torr and arterial pH fell progressively from 7.354 +/- 0.007 to 7.273 +/- 0.023. Hypoxia decreased the incidence of fetal breathing movements from 33 +/- 5.2 to 5 +/- 2.2 min/h, with a normal incidence (29 +/- 3.5 min/h) during the hour after arterial PO2 returned to control values. Adenosine concentrations in microdialysis perfusate under control conditions averaged approximately 35 nM, increased up to 2.3-fold during the hour of O2 deficiency, and fell toward control values when normoxia was restored. We conclude that fetal brain adenosine levels are increased at levels of O2 deficiency that inhibit fetal breathing, which are results consistent with a role for adenosine in hypoxic inhibition of fetal breathing.

Adenosine mediates hypoxic release of arginine vasopressin in fetal sheep.

The effects of adenosine on plasma arginine vasopressin (AVP) concentrations were determined in chronically catheterized fetal sheep (> 0.8 term). Infusion of adenosine [0.35 +/- 0.01 (SE) mg.min-1.kg-1] into the inferior vena cava of six fetuses caused a transient fall in arterial PO2 (by approximately 3 Torr), a slight reduction in arterial pH, and a 5- to 6-mmHg decrease in diastolic pressure without significantly affecting systolic or mean arterial values. A lower rate of infusion (0.19 +/- 0.01 mg.min-1 x kg-1) in five fetuses had virtually no effect on arterial blood gases, pH, or arterial pressures. Both the low- and high-dose adenosine infusions significantly increased fetal plasma AVP concentrations (1.7 +/- 0.2 to 25 +/- 7 pg/ml and 1.6 +/- 0.1 to 54 +/- 8 pg/ml, respectively). Intravenous infusion of papaverine lowered fetal diastolic and mean arterial pressures by approximately 8 mmHg but had no significant effect on plasma levels of AVP. During an hour of isocapnic hypoxia (arterial PO2 12-13 Torr), fetal plasma AVP levels increased from 1.7 +/- 0.2 to 40 +/- 6 pg/ml. Intra-arterial infusion of the adenosine receptor antagonist 8-(p-sulfophenyl)-theophylline significantly blunted the hypoxia-induced rise in plasma AVP concentrations to a maximum mean level of 11 +/- 6 pg/ml. These results indicate that 1) adenosine causes a dose-dependent increase in plasma AVP concentrations and 2) a hypoxia-induced rise in fetal adenosine levels triggers vasopressin release.

Maternal and fetal cardiorespiratory responses to adenosine in sheep.

OBJECTIVE: We determined the cardiorespiratory effects of maternal adenosine administration on the ewe and fetus. STUDY DESIGN: Adenosine was infused intravenously to five pregnant ewes as graded (25 to 400 micrograms/min per kilogram) and constant (200 micrograms/min per kilogram) infusions and as a single injection (200 micrograms/kg). Heart rate, arterial pressure, and arterial blood gases and pH were monitored in the ewe and fetus; the data were analyzed with two-way analysis of variance with Duncan's test. RESULTS: Graded adenosine infusion produced a dose-dependent rise in maternal heart rate and hemoglobin concentration and a fall in diastolic and mean arterial pressures, effects that were maintained during 1 hour of constant infusion. Single injections transiently lowered diastolic pressure and induced a biphasic change in heart rate consisting of a bradycardia followed by a tachycardia with a return to control values. Adenosine administration to the ewe did not affect maternal arterial blood gases and systolic pressure nor alter fetal heart rate, arterial pressure, or arterial blood gases. CONCLUSION: Although adenosine causes cardiovascular changes in pregnant ewes, the effects are well tolerated and do not significantly affect the cardiorespiratory status of the fetus.

Cardiovascular responses to adenosine in fetal sheep: autonomic blockade.

The mechanism by which adenosine increases heart rate was investigated in 21 chronically catheterized fetal sheep (> 0.8 term). Intra-arterial infusion of adenosine (0.16 mg.min-1.kg fetal wt-1) for 1 h significantly increased fetal heart rate within 5 min with maximum values of approximately 68 beats/min above the control mean of 163 +/- 8 beats/min. The average diastolic blood pressure was reduced only during the first 10 min of infusion, and the average systolic and mean arterial pressures were not significantly affected. Mean venous pressure rose by approximately 48% after 20 min of adenosine infusion, but all other measurements did not differ significantly from the control value. The mean hemoglobin concentration during the last 30 min of infusion was increased by approximately 8%. Plasma concentrations of norepinephrine and epinephrine were elevated only during the first 30 min of adenosine administration, to values as high as 2.3 and 5 times the respective control mean. Adenosine significantly increased mean fetal heart rate by about 15-20 beats/min in fetuses with autonomic ganglion blockade or combined cholinergic, alpha-, and beta-adrenergic receptor blockade. Intra-arterial infusion of CGS 21680C, an A2-adenosine receptor agonist, also produced a fetal tachycardia of approximately 86 beats/min above the control mean and increased intrinsic fetal heart rate by approximately 38 beats/min. It is concluded that approximately 75% of the positive chronotropic effects of adenosine are produced by A2-receptor stimulation of the autonomic nervous system and that approximately 25% of the rise in heart rate induced by adenosine may be caused by activation of A2-receptors in myocardium.

Adenosine in the treatment of maternal paroxysmal supraventricular tachycardia.

Paroxysmal supraventricular tachycardia is the most common sustained cardiac arrhythmia in pregnant women. Because nearly 50% of these supraventricular tachyarrhythmias fail to respond to vagal maneuvers, other therapies are used, including electrocardioversion and pharmacologic agents. Propranolol, verapamil, and adenosine have Food and Drug Administration-approved labeling for acute termination of supraventricular tachycardia. Verapamil has been the most commonly used agent in the general population but it has several shortcomings, such as its potential to cause or exacerbate systemic hypotension, congestive heart failure, bradyarrhythmias, and ventricular fibrillation. In addition, verapamil readily crosses the placenta and has been shown to cause fetal bradycardia, heart block, depression of contractility, and hypotension. Adenosine has several advantages over verapamil, including rapid onset, brevity of side effects, theoretical safety, and probable lack of placental transfer. Adenosine ultimately may prove to be the preferred agent for termination of paroxysmal supraventricular tachycardia in the gravid woman.