The redistribution of the blood flow under nifedipine treatment in the sheep foetuses.

The Ca(++)-antagonist nifedipine has been successfully employed in the treatment of non-gravid hypertension, and was found to inhibit uterine contractions in the perimenstrual period, as well as during premature labour in animal models. The use of antihypertensive drugs in pregnancy introduces the possibility of iatrogenic foetal distress. It has been established that nifedipine crosses the placental barrier in the sheep and causes a fall in mean arterial pressure and tachycardia in both the ewe and the foetus. This paper examines the effects of nifedipine on the foetus when administered to the pregnant ewe. Catheters and electrodes were implanted by surgical procedures in 15 ewes and foetal lambs between days 118 and 122 of gestation. The redistribution of foetal blood flow was measured by the radioactive microsphere injection technique. The infusion of nifedipine caused a 9% increase in the combined ventricular output (CVO) from 446 to 509 ml/min/kg in the foetus. Foetal lung blood flow increased from 29 +/- 6 to 69 +/- 14 ml/min/kg while figures for the skeletal muscle flow were 109 +/- 34 and 141 +/- 41.6 ml/min/kg. Heart and brain blood flow, expressed as percentages of CVO showed variations of 4.3 and 5.6 percent, respectively. Blood flow in the gut, placental membranes, skin, kidney and spleen was reduced. The present results show that nifedipine, in addition to its known effects causes a redistribution of the foetal circulation.

Effects of prostaglandin E2 on the newborn respiratory system.

To test the hypothesis that prostaglandin (PG) E2 is a respiratory depressant in the newborn lamb, 12 chronically catheterized, unanesthetized lambs (age 2 to 6 days) were infused with progressively increasing doses of PGE2 (0.1, 0.5, 1.0 and 5.0 ug/kg/min: 30 min for each dose) into the ascending aorta. PGE2 caused significant, progressive decrease in ventilation (due to decreased tidal volume and breathing rate) heart rate, blood pressure and percent of the time spent in low voltage electrocortical activity (LVA). PGE2 also caused respiratory acidosis, hypoxemia and increased frequency and duration of apneic events (greater than 3 sec). During the infusion, there was a dose related increase in plasma concentration of PGE2. At 30 min post-infusion, all measured variables showed recovery, although arterial pH carbon dioxide tension and plasma PGE2 remained significantly different from control values and the percent time in LVA was even higher than during control. Infusion of the vehicle alone (n = 5) caused no significant changes in any of the measured variables. The results, taken in combination with previous fetal studies, indicate that PGE2 has marked inhibitory effects on breathing movements both before and after birth.

Effects of ethanol infusion on foetal EEG and breathing movements.

Ethanol (0.3 g/kg and 0.5 g/kg administered over 2 hours) was infused intravenously into 15 chronically instrumented pregnant ewes between 128 to 135 days of gestation (0.85 to 0.92 gestation time, term 147 days). Brainstem dissection above the pons was made in 7 foetuses. Foetal breathing movements were suppressed for 7 hours following a 30 ml ethanol infusion. Low voltage foetal electrocortical activity was suppressed or replaced by an intermediate voltage electrocortical activity for 5 and 3 hours following the 60 ml and 30 ml ethanol infusions, respectively. In brainstem dissected foetuses the effects of ethanol infusion on the foetal EEG were similar. Foetal blood gases and pH were not altered. These data suggest that ethanol moves across the foetal blood-brain barrier and suppresses foetal breathing movements by a direct central mechanism.

Effects of calcium channel-blocker tokolysis on the foetal circulation.

The Ca++-antagonist nifedipine has been successfully employed in the treatment of non-gravid hypertension, and was found to inhibit uterine contractions in the perimenstrual period, as well as during premature labour in animal models. The use of antihypertensive drugs in pregnancy introduces the possibility of iatrogenic foetal distress. It has been established that nifedipine crosses the placental barrier in the sheep and causes a fall in mean arterial pressure and tachycardia in both the ewe and the foetus. This paper examines the effects of nifedipine on the foetus when administered to the pregnant ewe. Catheters and electrodes were implanted by surgical procedures in 15 ewes and foetal lambs between days 118 and 122 of gestation. The redistribution of foetal blood flow was measured by the radioactive microsphere injection technique. The infusion of nifedipine caused a 9% increase in the combined ventricular output (CVO) from 446 to 509 ml/min/kg in the foetus. Foetal lung blood flow increased from 29 +/- 6 to 69 +/- 14 ml/min/kg while figures for the skeletal muscle flow were 109 +/- 34 and 141 +/- 41.6 ml/min/kg. Heart and brain blood flow, expressed as percentages of CVO showed variations of 4.3 and 5.6 per cent, respectively. Blood flow in the gut, placental membranes, skin, kidney and spleen was reduced. The present results show that nifedipine, in addition to its known effects causes a redistribution of the foetal circulation.

Cardiorespiratory effects of nifedipine in pregnant sheep.

Four concentrations of nifedipine (AdalatR, Bayer) were infused into 25 pregnant sheep of 123-140 days of gestation (term, 147 days) and the effects on the ewe and the foetus have been studied. At all doses of nifedipine infused, maternal diastolic pressure fell by about 15% and maternal heart rate increased by 33%. There was no change in blood gases or pH. Uterine activity, as measured by uterine electromyographic recordings, was reduced due to an increase in the interval between periods of activity. The duration of a burst of activity remained unaffected. The effects of nifedipine on the foetus, were similar. Mean foetal arterial pressure fell by 4-5 mmHg and heart rate rose by 15 to 50%, both changes being maintained for the duration of the infusion and the increased heart rate for longer. The electrocorticogram of the foetal sheep was unaffected by nifedipine. The effects on foetal breathing movements were small. At the concentration of 5 micrograms/kg/min for either 2 or 4 hours the breathing pattern changed so that the episodes of breathing were shorter and more frequent. The total amount of breathing per hour was unaffected. Control infusion of ethanol had little effect on the ewe except for a significant increase in lactate production. In the foetus breathing was reduced at the highest concentration used.

Blood flow redistribution during isocapnic hypoxia in foetal lamb.

Circulatory responses to hypoxaemia were studied in 16 foetal lambs in 120-129 and 135-145 days of gestation (term: 147 days). Under general anaesthesia catheters were inserted into the foetal vessels and the umbilical blood was measured during antipyrine infusion by the Fick steady-state diffusion method. The combined ventricular output and actual organ blood flows were calculated from injections of radionuclide-labelled microspheres into a forelimb and a hindlimb vein. Isocapnic hypoxia was produced by giving the ewe a breathing gas mixture of 9% O2 and 3% CO2 in N2 for 30 min. A significant increase was found in the blood flow of the myocardium, the lungs, the brain and in the combined ventricular output between 0.80 and 0.95 gestation times. Under isocapnic hypoxaemia blood flow increased to the brain, heart and adrenals, whilst it decreased to the lungs, kidneys, gut and carcass. The observed changes were different at the two measurement times. Under hypoxia, depending on the gestation time, the blood flow increased in the diencephalon, midbrain, hypophysis and in the cervical cord. In the cerebral, cerebellar and lumbosacral cord it remained unchanged, while decreasing in the chorioid plexus and in the hippocampus. In the gestation period under examination the foetal circulation undergoes significant redistribution.

Effects of a beta-sympathomimetic drug on the foetal and maternal cardiovascular system in a chronic sheep model.

The effects of the beta-sympathomimetic agent terbutalin (1-/3.5 dihydroxyphenyl/-allilaminoethane sulphonate) on maternal and foetal circulation were studied in 11 ewe at 110-130 days of pregnancy. None of them exhibited uterine contractions. Catheters were implanted in the carotid artery and jugular vein, together with four stainless steel electrodes on the limbs. Terbutalin was added intravenously in Ringer-lactate (5%) infusion (1 ml/min). The following maternal and foetal parameters were measured simultaneously: heart rate, central arterial pressure, blood glucose levels, ECG. Intravenous administration of 100 micrograms terbutalin resulted in a 19% increase of maternal and 10% enhancement of foetal heart rate. Maternal systolic blood pressure rose by 9%, whereas diastolic blood pressure fell by 7%. Maternal and foetal blood glucose levels was fairly constant during the entire experiment. In further six experiments terbutalin was administered into the foetal circulation (1 ml/3 min). The same effects on foetal heart rate and pulse pressure were observed as after injecting into the maternal circulation, however but the time necessary for the maximum action to develop was significantly shorter.

Distribution of cholinesterases of rabbit skeletal muscle.

Two cholinesterase (ChE) fractions were extracted from homogenates of rabbit skeletal muscle. One of them the sarcoplasmic ChE could be dissolved quantitatively with solution A. Following the extraction with solution B the myofibrillar ChE fraction could be recovered. The ChE-activity of the sarcoplasmic extract was about 38% and the activity of myofibrillar extract was about 50% of the ChE-activity of muscle homogenates. According to our calculations about 10-12% of the total ChE-activity is insoluble. By the aid of PAGE seven zones of ChE-activity could be distinguished in the sarcoplasmic extract. The activity of myofibrillar ChE-fraction was obtained by chromatographic purification of LMM. The LMM1 proved to be inhomogeneous with PAGE, however, only one fraction displayed ChE-activity. Immune-serum produced against myosin did not give reaction with purified sarcoplasmic ChE, only with the myofibrillar fraction. Our results suggest that the heterogeneous distribution of muscle ChE-es in different molecular forms is not an artifact.