Effect of partial agonist activity in beta blockers in severe angina pectoris: a double blind comparison of pindolol and atenolol.

The use of beta adrenoceptor blockade in the treatment of rest angina is controversial, and the effects on severe angina of partial agonist activity in beta blockers are unknown. Eight patients with effort angina and seven with effort and nocturnal angina and severe coronary artery disease were studied initially when they were not taking any antianginal drugs. Pindolol 5 mg thrice daily (with partial agonist activity) and atenolol 100 mg daily (without partial agonist activity) were given for five days each in a double blind randomised manner. Diaries of angina were kept and treadmill exercise testing and ambulatory ST monitoring performed during the last 48 hours of each period of treatment. Daytime and nocturnal resting heart rates and the frequency of angina were significantly reduced by atenolol compared with pindolol (p less than 0.01). The duration of exercise was significantly increased and the frequency, duration, and magnitude of daytime and nocturnal episodes of ST segment depression on ambulatory monitoring were reduced by atenolol. Reduction in resting heart rate is important in the treatment of both effort and nocturnal angina. Partial agonist activity in beta adrenoceptor antagonists may be deleterious in patients with severe angina pectoris.     

Atenolol in essential hypertension during pregnancy.

OBJECTIVE--To determine the effect of atenolol on the outcome of pregnancy in women with essential hypertension. DESIGN--Prospective, randomised, double blind, placebo controlled study. SETTING--Hospital clinic. PATIENTS--33 Women with mild essential hypertension (systolic blood pressure 140-170 mm Hg or diastolic pressure 90-110 mm Hg on two occasions at least 24 hours apart) consecutively referred to two obstetric medical clinics. Four patients in the placebo group were withdrawn from the study: control of blood pressure was inadequate in two, one developed breathlessness, and one changed her mind about participating. The mean gestation in the 29 remaining women on entry to the study was 15.9 weeks. MAIN OUTCOME MEASURES--Blood pressure and birth weight. INTERVENTION--14 Women received placebo. 15 Women received atenolol 50 mg daily initially, increasing until either the blood pressure was less than 140/90 mm Hg or a dose of 200 micrograms daily was reached. RESULTS--The mean blood pressure on entry was 148/86 mm Hg in the group given atenolol and 144/86 mm Hg in the group given placebo. During treatment the mean diastolic pressure was significantly reduced by atenolol compared with placebo (to 74 v 81 mm Hg; difference in means (95% confidence interval) 7.0 (2.9 to 10.0) mm Hg) but the effect on systolic pressure was marginal (132 v 136 mm Hg; 4.0 (-1.4 to 8.6) mm Hg). Babies in the atenolol group had a significantly lower birth weight than those in the placebo group (2620 g v 3530 g; 910 (440 to 1380)g). CONCLUSION--Atenolol given from the end of the first trimester in patients with mild hypertension is associated with intrauterine growth retardation. When taken in conjunction with the results of a previous study in which methyldopa was given these findings indicate that benefit is unlikely to result from treating mild essential hypertension in pregnancy.     

Immunoreactive endothelin concentrations in maternal and fetal blood

Immunoreactive-endothelin (ir-ET) concentrations were determined in peripheral maternal blood and in umbilical cord blood just after delivery. The concentrations in both the umbilical artery (2.83 +/- 1.36 pmol/l plasma, Mean +/- SD) and vein (3.37 +/- 1.53 pmol/l) were significantly higher than those found in maternal venous blood (1.43 +/- 1.02 pmol/l). On the other hand, ir-ET levels in maternal blood were not significantly different when compared with those found in non-pregnant women (1.50 +/- 0.83 pmol/l). No significant difference of ir-ET levels between the umbilical artery and vein was observed. A highly significant correlation (r = 0.60, p less than 0.01) of ir-ET levels between the umbilical artery and vein was observed. Also, a significant correlation (r = 0.48, p less than 0.01) between umbilical vein and maternal vein ir-ET levels with a weaker correlation (r = 0.36, p less than 0.05) between umbilical artery and maternal vein ir-ET levels was demonstrated. The present study indicates that ir-ET may be actively secreted in fetal circulation and the plasma levels in maternal and fetal circulation may have a possible relation.     

Doppler ultrasonographic assessment of maternal and fetal blood flow in abnormal canine pregnancy

The aim of this study was to describe the changes of uterine artery, umbilical artery and fetal abdominal aorta, renal and internal carotid arteries blood flow in abnormal canine pregnancy. Twenty-two, Brucella-negative pregnant bitches were retrospectively classified into abnormal (which had either interrupted their pregnancy between days 52 and 60 or had perinatal death >60% of the litter; n=11) and normal (which had delivered healthy puppies at term; n=11). In all the animals, color and pulsed-wave Doppler examinations of uterine artery were conducted every 10 days from Day 20 to 50 from estimated luteinizing hormone peak. Doppler ultrasonography was also conducted in the fetuses to assess umbilical artery, abdominal aorta, renal and internal carotid arteries from Day 40 to 60 of gestation. Throughout the study, resistance index (RI) of uterine, umbilical and fetal renal arteries decreased up to -15% compared to -36% (P<0.01), -11% compared to -23% (P<0.05) and 2% compared to -13% (P<0.05), respectively in the abnormal and normal bitches. Fetal abdominal aorta and internal carotid did not differ between groups (P>0.05). It is concluded that in dogs, uterine artery, umbilical artery and fetal renal artery RI differ between normal and abnormal gestation being useful for the prediction of adverse obstetric outcome.     

beta blockade and intermittent claudication: placebo controlled trial of atenolol and nifedipine and their combination.

OBJECTIVE--To determine the effects of the beta 1 selective adrenoceptor blocker atenolol, the dihydropyridine calcium antagonist nifedipine, and the combination of atenolol plus nifedipine on objective and subjective measures of walking performance and foot temperature in patients with intermittent claudication. DESIGN--Randomised controlled double blind four way crossover trial. SETTING--Royal Hallamshire Hospital, Sheffield. SUBJECTS--49 patients (40 men) aged 39-70 with chronic stable intermittent claudication. INTERVENTIONS--Atenolol 50 mg twice daily; slow release nifedipine 20 mg twice daily; atenolol 50 mg plus slow release nifedipine 20 mg twice daily; placebo. Each treatment was given for four weeks with no washout interval between treatments. MAIN OUTCOME MEASURES--Claudication and walking distances on treadmill; skin temperature of feet as measured by thermistor and probe; blood pressure before and after exercise; subjective assessments of walking difficulty and foot coldness with visual analogue scales. RESULTS--Atenolol did not significantly alter claudication distance (mean change -6%; 95% confidence interval 1% to -13%), walking distance (-2%; 4% to -8%), or foot temperature. Nifedipine did not alter claudication distance (-4%; 3% to -11%), walking distance (-4%; 3% to -10%), or foot temperature. Atenolol plus nifedipine did not alter claudication distance but significantly reduced walking distance (-9%; -3% to -15% (p less than 0.003)) and skin temperature of the more affected foot (-1.1 degrees C; 0 to -2.2 degrees C (p = 0.05)). These effects on walking distance and foot temperature seemed unrelated to blood pressure changes. CONCLUSIONS--There was no evidence of adverse or beneficial effects of atenolol or nifedipine, when given singly, on peripheral vascular disease. The combined treatment, however, affected walking ability and foot temperature adversely. This may have been due to beta blockade plus reduced vascular resistance, which might also explain the reported adverse effects of pindolol and labetalol on claudication.     

Comparison of monotherapy with enalapril and atenolol in mild to moderate hypertension. The Canadian Enalapril Study Group.

Therapy with 10 to 40 mg once daily of enalapril, a new angiotensin converting enzyme inhibitor, was compared with therapy with 50 to 100 mg once daily of atenolol in a double-blind randomized multicentre trial in 180 patients with a diastolic blood pressure (determined with the patient seated) of 95 to 115 mm Hg between March 1984 and April 1986. A total of 86 patients (61 men and 25 women with a mean age of 49.4 years and a mean blood pressure [and standard deviation] at entry into the trial of 155.5 [15.7]/101.0 [6.3] mm Hg) received enalapril, and 94 patients (63 men and 31 women with a mean age of 50.9 years and a mean blood pressure at entry of 156.6 [16.6]/101.2 [5.7] mm Hg) received atenolol. After a placebo run-in period the patients received increasing dosages of medication every 2 weeks until the target diastolic blood pressure of 90 mm Hg or less was achieved on two consecutive visits, the maximum dosage was reached, or the patient withdrew because of adverse effects. At 14 weeks the mean blood pressure was 141.6 (18.0)/90.1 (9.5) mm Hg in the enalapril group (61 patients) and 140.0 (17.1)/88.4 (8.7) mm Hg in the atenolol group (54 patients). The target diastolic blood pressure was achieved on completion of therapy (between weeks 10 and 14) in 67 (77%) of the patients receiving enalapril and 75 (79%) of the patients receiving atenolol. Compliance was similar in the two groups. Seven patients withdrew because of adverse effects, three in the enalapril group and four in the atenolol group. The results suggest that once-daily monotherapy with enalapril, 10 to 40 mg, is effective in the treatment of mild to moderate hypertension and is as effective as and tolerated as well as once-daily therapy with atenolol, 50 to 100 mg.     

Lactate uptake by the fetal sheep liver

Lactate is produced by the sheep placenta and is an important metabolic substrate for fetal sheep. However, lactate uptake and release by the fetal liver have not been assessed directly. We measured lactate flux across the liver in 16 fetal sheep at 129 (120-138) days gestation that had catheters chronically maintained in the fetal descending aorta, inferior vena cava, right or left hepatic vein, and umbilical vein. Lactate and hemoglobin concentrations and oxygen saturation were measured in blood drawn from all vessels. Umbilical venous, portal venous, and hepatic blood flow were measured by injecting radionuclide-labeled microspheres into the umbilical vein while obtaining a reference sample from the descending aorta. We found net hepatic uptake of lactate (5.0 +/- 4.4 mg/min per 100 g liver). A large quantity of lactate was delivered to the liver (94.2 +/- 78.1 mg/min per 100 g), so that the hepatic extraction of lactate was only 7.7 +/- 6.5%. Hepatic oxygen consumption was 3.18 +/- 3.3 ml/min per 100 g, and the hepatic lactate/oxygen quotient was 2.07 +/- 1.54. There was no significant correlation between hepatic lactate uptake and hepatic lactate or glucose delivery, hepatic oxygen consumption, hepatic blood flow, hepatic glucose flux, total body oxygen consumption, arterial pH, oxygen content, or oxygen saturation. There was, however, a significant correlation between hepatic lactate uptake and umbilical lactate uptake (r = 0.74, P less than 0.005) such that net hepatic lactate uptake was nearly equivalent to that produced across the umbilical-placental circulation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Randomised,double blind,multicentre comparison of hydrochlorothiazide,atenolol, nitrendipine,and enalapril in antihypertensive treatment: results of the HANE study. HANE Trial Research Group.

OBJECTIVE: To compare the effectiveness and tolerability of hydrochlorothiazide, atenolol, nitrendipine, and enalapril in patients with mild to moderate hypertension. DESIGN: Randomised multicentre trial over 48 weeks with double blind comparison of treatments. SETTING: 48 centres in four countries. PATIENTS: 868 patients with essential hypertension (diastolic blood pressure 95-120 mm Hg) INTERVENTIONS: Initial treatment (step 1) consisted of 12.5 mg hydrochlorothiazide (n = 215), 25 mg atenolol (n = 215), 10 mg nitrendipine (n = 218), or 5 mg enalapril (n = 220) once daily. If diastolic blood pressure was not reduced to < 90 mm Hg within four weeks, doses were increased to 25 mg, 50 mg, 20 mg, 10 mg, respectively, once daily (step 2) and after two more weeks to twice daily (step 3). The eight week titration phase was followed by an additional 40 weeks for patients who had reached the target diastolic pressure. MAIN OUTCOME MEASURES: Blood pressure by means of an automatic device with repeated measurements. RESULTS: After eight weeks the response rate for atenolol (63.7%) was significantly higher than for enalapril (50.0%), hydrochlorothiazide (44.7%), or nitrendipine (44.5%). After one year atenolol was still more effective (48.0%) than hydrochlorothiazide (35.4%) and nitrendipine (32.9%), but not significantly better than enalapril (42.7%). The treatment related dropout rate was higher (P < 0.001) in the nitrendipine group (n = 28). CONCLUSIONS: There is no evidence of superiority for antihypertensive effectiveness or tolerability of the "new" classes of antihypertensives (calcium channel blockers and angiotensin converting enzyme inhibitors). As these drugs are now widely used as treatment of first choice, our results further emphasise the need for studies confirming that they also reduce morbidity and mortality, as has been shown for diuretics and beta blockers.     

Stimulated cytokine production correlates in umbilical arterial and venous blood at delivery

BACKGROUND: Umbilical venous blood is easy to obtain after delivery, and thus has been commonly used in many studies for cytokine analysis. Our aim was to evaluate whether or not induced cytokine production differs after stimulation in umbilical artery and vein whole blood samples, using two different stimulation protocols. The effect of such stimulation on fetal and maternal blood was also evaluated. METHODS: Blood samples from umbilical artery (UA) and vein (UV), and from the mother were collected from 23 women after delivery at term. Concentrations of cytokines (IL-4, IFN-gamma, IL-6 and TNF-alpha) were measured in plasma and whole blood after PMA/ConA and PMA/ionomycin stimulation. RESULTS: Both in maternal and in fetal samples, cytokine concentrations in unstimulated plasma samples were lower than in stimulated samples, except for IL-4 after PMA/ConA stimulation. UA and UV showed similar, average cytokine levels after stimulation and the correlations were high (r=0.68-0.95). Cytokine concentrations were clearly higher in umbilical blood than in maternal blood after stimulation, but not in plasma. Correlations between maternal and umbilical samples after stimulation were generally low (r<0.41). IFN-gamma was not detectable in unstimulated plasma samples. The production of IL-4 and IFN-gamma was more intense after PMA/ionomycin stimulation than after PMA/ConA stimulation. INTERPRETATION OF THE RESULTS: Concentrations of the cytokines examined are similar in blood from the UA and UV. For IL-4 and IFN-gamma, the stimulant used has a significant effect on the level of cytokine expression, and interestingly, the effect is more pronounced on the fetal than on the maternal side.     

Cardiac two-dimensional imaging and reference values for blood flow velocities in the ovine fetus.

Since the ovine model is the most commonly used for foetal haemodynamic investigation it was felt important 1) to investigate the technical difficulties involved with ultrasound fetal cardiac imaging in this species and 2) to establish normal reference values for ovine cardiac and umbilical blood flow velocity measurements. Both two-dimensional and pulsed Doppler techniques were used for this assessment in 25 unsedated ewes. All morphological features described in human features to identify the ventricular cavities could be found in the ovine fetus with the two-dimensional echocardiogram. Specific differences included a flatten thorax as visualized from the lateral position, the mesocardial position of the heart, and a large left azygos vein behind the left atrium draining blood into a dilated coronary sinus. The mean peak velocities (cm/sec) of the early diastolic wave (E) and the atrial wave (A), along with their calculated ratio, were not statistically different between the two atrio-ventricular valves (E: 30.6 +/- 6.6, 31.2 +/- 6.1; A: 43.0 +/- 8.3, 41.6 +/- 8.0; E/A: .72, .76 for mitral and tricuspid valves respectively). A significant difference was observed between the acceleration times of the blood ejected into the aorta and the pulmonary artery, with the time interval being shorter in the pulmonary artery (Aorta: 0.052 +/- 0.011; Pulmonary artery: 0.037 +/- 0.009 s). A mean pulsatility index of the umbilical artery of 0.89 was recorded. The data recorded in this study should serve as a reference base for further non-invasive studies of the ovine foetal circulatory system using the ultrasound technique.     

Demonstration of beta 1-adrenoceptor mediating relaxation of porcine coronary artery by radioligand binding and pharmacological methods

beta-adrenoceptors in the porcine coronary artery were characterized by a radioligand binding assay using (-)-[3H]dihydroalprenolol (DHA) and also by measuring the relaxant response of isolated coronary artery to norepinephrine. Specific (-)-[3H]DHA binding in the porcine coronary artery was saturable, reversible and of high affinity (Kd = 1.6 nM) with a maximal number of binding sites of 63 fmol/mg protein, and it showed a pharmacological specificity as well as stereoselectivity which characterized beta-adrenoceptors. The Hofstee analysis of inhibition of (-)-[3H]DHA binding by atenolol, practolol and ICI 118551 has shown that the averaged concentration of beta 1 and beta 2-adrenoceptors in this tissue was 68% and 32% respectively. The relaxant response of isolated coronary artery to norepinephrine was competitively antagonized by (-)propranolol, (+)propranolol, atenolol, practolol and ICI 118551. The pA2 values of these adrenoceptor antagonists were significantly correlated with the Ki values for beta 1 but not beta 2-adrenoceptors determined by the (-)-[3H]DHA binding assay. Thus, the present study demonstrates that the relaxant response of porcine coronary artery to norepinephrine is predominantly mediated through the stimulation of beta 1-adrenoceptors on vascular smooth muscles.     

Study of the development of uteroplacental and fetal feline circulation by triplex Doppler

The objective was to evaluate blood flow in fetal and maternal vessels by Triplex Doppler and its association with development of blood vessels during gestation in the domestic cat. Ten queens were examined weekly from 14 to 63 d after mating. Peak systolic velocity (PSV), end diastolic velocity (EDV), resistance index (RI) and pulsatility index (PI) of uteroplacental, aorta and umbilical fetal arteries and caudal vena cava of the fetus were evaluated. Throughout pregnancy, there was an increase in PSV and EDV in the aorta and umbilical arteries. In the caudal vena cava, there was an increase in PSV, whereas the EDV was constant, with a significant increase on Day 63. Peak systolic velocity and EDV of the uteroplacental artery reduced significantly on Day 63. Resistance index of the umbilical artery progressively decreased. In the aorta, this reduction was detected only on Day 42, with no defined pattern in the caudal vena cava and uteroplacental artery. Pulsatility index of the aorta varied. Although pulsatility increased in the caudal vena cava on Day 35 and remained elevated, pulsatility was significantly reduced in the umbilical artery by Day 63. The pulsatility index of the uteroplacental artery was constant (increased only on Day 63). Triplex Doppler evaluation could be a useful adjunct for prenatal care of pregnant queens, including assessment of vascular gestational development and prediction of gestational age.     

Ambulatory blood pressure during once-daily randomised double-blind administration of atenolol,metoprolol, pindolol,and slow-release propranolol

Intra-arterial ambulatory blood pressure was measured over 24 hours, in 34 patients with newly diagnosed hypertension, both before and after double-blind randomisation to treatment with atenolol (n=9), metoprolol (n=9), pindolol (n=9), or propranolol in its slow-release form (n=7). The dosage of each drug was adjusted at monthly clinic visits until satisfactory control of blood pressure was achieved (140/90 mm Hg or less by cuff) or the maximum dose in the study protocol was reached. A second intra-arterial recording was made after these drugs had been taken once daily at 0800 for three to eight months (mean 5·0±SD 1·4) and was started four hours after the last dose.At the end of the 24-hour recordings blood pressure was significantly lower with all four drugs. The extent to which the drugs reduced blood pressure, however, differed over the 24 hours. Atenolol lowered mean arterial pressure significantly throughout all 24 recorded hours, metoprolol for 12 hours, pindolol for 15 hours, and slow-release propranolol for 22 hours. Neither metoprolol nor pindolol lowered blood pressure during sleep. A significant reduction in heart rate was observed over 20 hours with atenolol, 20 hours with metoprolol, 10 hours with pindolol, and 24 hours with slow-release propranolol. Atenolol, metoprolol, and slow-release propranolol continued to slow the heart rate 24 hours after the last tablet was taken; this effect on heart rate, however, was not sustained throughout the second morning in those patients taking atenolol. Pindolol, the only drug studied that has intrinsic sympathomimetic activity, increased heart rate and did not lower blood pressure during sleep.Atenolol and slow-release propranolol are effective as antihypertensive agents over 24 hours when taken once daily, whereas metoprolol and pindolol may need to be taken more frequently. At times of low sympathetic tone, however, such as during sleep, beta-blockers with intrinsic sympathomimetic activity may raise heart rate and attenuate the fall in blood pressure with treatment.     

Serum prolactin level changes in the maternal and fetal circulation between the 28th-40th weeks of pregnancy

Serum prolactin concentration was determined in blood samples taken from the maternal cubital vein, the umbilical vein and artery between the 28th-40th weeks of pregnancy from 108 parturients, of whom 74 gave birth prematurely and 34 gave birth at term. Results indicated that during this period the prolactin level rose in the umbilical vein and artery but not in the maternal vein. Correlative analysis showed a significant positive correlation between gestational age and the serum prolactin concentration of umbilical arterial and venous blood, but no correlation was found in the case of maternal blood. During the 28th-32nd weeks the prolactin level of maternal blood was found to be higher than that of umbilical blood while during the 33rd-36th weeks and at the 40th week the prolactin level was higher in the umbilical vein and artery. No correlation was found between the prolactin concentration of maternal and umbilical blood. On the basis of these results the authors conclude that fetal prolactin concentration changes occur independently of the maternal organism and increases during the 28th-40th weeks of pregnancy.     

Effects of chronic instrumentation on fetal growth

Chronically-instrumented fetal sheep are a commonly used animal model for the study of fetal growth and metabolism. In the current study, we wanted to test the hypothesis that instrumentation alone would alter fetal growth patterns. Thirty-two animals in three groups were used: (i) non-instrumented animals (n = 10); (ii) instrumented with catheters in the maternal and fetal femoral artery and vein and electromagnetic flow probes on the main uterine arteries (n = 10): (iii) animals instrumented as group 2, but with the addition of a doppler flow probe on the common umbilical artery and a common umbilical vein catheter (n = 12). Animals in group 2 and 3 were monitored until 137 to 140 days of gestation, at which time they were sacrificed for fetal morphometric measurements. Instrumentation significantly (P less than 0.05) decreased fetal body weight, length, and thymus weights. Liver-to-body ratios increased (P less than 0.05) in both surgically-instrumented groups. The addition of the umbilical artery doppler flow probe and an umbilical venous catheter did not lead to any further alterations in fetal growth. The current study demonstrates that surgical instrumentation alone can lead to significant alterations in fetal growth.     

Enantioselectivity in the steady-state pharmacokinetics and transplacental distribution of pindolol at delivery in pregnancy-induced hypertension

Nine patients taking oral doses of 10 mg/12 h rac-pindolol as part of their treatment for hypertension in pregnancy were recruited for the study. Maternal and fetal gestational age ranged from 20-38 years and 28-41 weeks, respectively. Blood was collected from the umbilical cord vein and from the mother from zero to 12 h after drug administration. Urine was collected for 12 h after rac-pindolol administration at the following intervals: 0-3, 3-6, 6-9, and 9-12 h. Plasma and urine concentrations of the pindolol enantiomers were determined by HPLC using a Chiralpak AD chiral column and fluorescence detection. The data were fitted to a one-compartment model and differences between (+)-R and (-)-S enantiomers were compared by the paired t-test (P < 0.05). Mean results are reported. The disposition of pindolol in maternal plasma was stereoselective, with higher AUC(SS)0-12 (84.34 vs. 95.69 ng.h/ml) and Cl(R) values (9.16 vs. 10.85 L/h) and lower Vd/f (251.38 vs. 225.17 L) and Cl/f (62.48 vs. 55.74 L/h) for the (+)-R pindolol. The transplacental distribution of pindolol was not stereoselective. Cord, plasma, and presumably fetal, concentrations of the pindolol enantiomers were 56% of the maternal plasma concentrations up to 6 h after the last dose.     

Measurement of human fetal blood flow.

Real-time B-mode ultrasonography was combined with a pulsed Doppler ultrasound technique for transcutaneous measurement of human fetal blood flow in the aorta and intra-abdominal part of the umbilical vein. The target vessel was located and its diameter measured in the two-dimensional real-time image. The pulsed Doppler transducer was attached to the real-time transducer at a fixed angle. By processing the Doppler shift signals the instrument estimated the mean and maximum blood velocities and the integral under the velocity curves. This permitted calculation of the blood flow. The method was applied to 26 fetuses in normal late pregnancies. Mean blood flow in the descending part of the fetal aorta based on maximum velocity was 191 ml/kg/min. Mean flow in the intra-abdominal part of the umbilical vein was 110 ml/kg/min. This method of measurement is non-invasive and opens new perspectives in studying fetal haemodynamics.     

The effects of prostacyclin and thromboxane analogue (U46619) on the fetal circulation and umbilical flow velocity waveforms

In placental insufficiency and pre-eclampsia the relative production rates of prostacyclin and thromboxane by the placenta and umbilical vessels are altered and the Doppler umbilical flow velocity waveform shows a high resistance pattern. To investigate the control of umbilical placental blood flow by those eicosanoids either prostacyclin (10 micrograms/min), or the thromboxane analogue U46619 (10 ng/min) was infused into the distal aorta of 12 chronically catheterized fetal lambs at day 125. Thromboxane produced a rise in mean arterial pressure and a rise in the systolic diastolic ratio of the umbilical artery flow waveform (2.6 to 3.1; P less than 0.05). Umbilical blood flow did not change and there was no evidence of altered flow to other organs. Prostacyclin caused a fall in fetal mean arterial pressure and a decrease in the umbilical artery systolic diastolic ratio (2.9 to 2.4; P less than 0.05). Prostacyclin produced a three-fold increase in lung perfusion (and the onset of fetal breathing movements) and this was associated with a 90% reduction in muscle blood flow (hindlimb muscle flow reduced from 12.5 to 1.1 ml.min-1 100g-1; P less than 0.01). We conclude that the local release of thromboxane in the fetal placental vascular bed could account for the rise in systolic diastolic ratio seen in umbilical placental insufficiency.     

Blood collection from the tail of a rat

Techniques for blood collection from the rat include puncture of the heart, retro-orbital plexus, jugular vein, saphenous vein, tail blood vessels, carotid artery, abdominal aorta, and vena cava. Most techniques (except saphenous vein and tail blood vessel puncture) require anesthesia. The following discussion focuses on two methods of blood collection - ventral tail artery puncture and dorsal or lateral tail vein puncture.     

Community care compared with hospital outpatient care for hypertensive patients.

Three hundred and seventy-six patients with treated diastolic blood pressures of less than 105 mm Hg and no history of accelerated hypertension or renal failure were selected from among those attending the Hammersmith Hospital hypertension clinic. Their average lying treated blood pressure was 146 mm Hg systolic and 90 mm Hg diastolic and average age 56 years; 18% were black, 6% Asian, and 76% white. The patients were mostly having multiple treatment, 90% receiving a diuretic, 35% methyldopa, 33% propranolol, 18% atenolol, 9% hydrallazine, and 7% bethanidine. They were randomly allocated to either two years of further hospital outpatient care or referred back to their general practitioners. During the two years 19 (10%) of the 187 patients followed up in hospital defaulted and three had their treatment discontinued. Twelve (6%) of the 189 followed up by their general practitioners defaulted from follow-up and nine had their treatment discontinued. At the end of the trial the average lying blood pressure was 148 mm Hg systolic and 88 mm Hg diastolic in the hospital group and 149 mm Hg systolic and 90 mm Hg diastolic in the general practice group. The change in blood pressure was calculated for each individual and showed an average fall of 1.6 mm Hg in standing diastolic pressure in the hospital group and a rise of 1.4 mm Hg in the general practice group (p less than 0.05). The 90% confidence limits for a difference in standing diastolic pressure between the groups were 1 and 5 mm Hg with the pressure lower in the hospital group. General practice care was not quite as effective in controlling blood pressure as continued specialist supervision over two years in this selected group of treated outpatients with mild or moderate hypertension, but these results show that the discharge back to general practitioners of patients who are well controlled after hospital treatment is a sensible policy.