Effect of captopril on uterine blood flow and prostaglandin E synthesis in the pregnant rabbit

Captopril, 5 mg/kg, administered to pregnant rabbits caused a reduction in mean arterial pressure (MAP) from 106±2 to 87±2 mmHg (P<0.01) without change in cardiac output or renal blood flow. Uterine blood flow fell from 31.9±2.5 to 21.3±3.4 ml/min (P<0.01) as uterine vein prostaglandin E series level (PGE) decreased from 127±23 ng/ml to 26±8 ng/ml (P<0.01). Saralasin also caused a reduction in MAP from 110±5 to 92±4.3 (P<0.01), a reduction in uterine blood flow from 28.8±1.6 to 21.8±1.7 ml/min (P<0.01) as uterine vein PGE decreased from 121.3±14.4 to 63.5±14.2 ng/ml (P<0.01). Plasma renin activity (PRA) was higher in the uterine vein, 11±3 ng/ml per h, than peripheral vein, 6±1.6 ng/ml per h, (P<0.05), before Captopril and rose in the uterine vein to 90±19 ng/ml per h (P<0.01) as peripheral vein PRA rose to 62±15 ng/ml per h (P<0.05) after Captopril. After saralasin uterine vein PRA rose from 4.6±1.5 to 14.8±6.3 ng/ml per h (P<0.05) and peripheral vein PRA rose from 3.7±1 to 6.5±2.1 (P<0.05).     

Uterine prostaglandin E secretion and uterine blood flow in the pregnant rabbit.

Studies were performed in pregnant rabbits to assess the effect of inhibition of prostaglandin synthesis on uterine blood flow. Cardiac output and uteroplacental blood flow (UPBF) were measured using radiolabeled microspheres. Prostaglandin E (PGE) concentration was measured by radioimmunoassay in the uterine vein and peripheral artery of the pregnant nephrectomized rabbit. Either meclofenamate or indomethacin 2 mg/kg were utilized to inhibit prostaglandin synthesis. Systemic arterial pressure increased from 86 mm Hg to 98 mm Hg (P less than0.0001) after prostaglandin inhibition. Cardiac output was unchanged after the inhibition of prostaglandin synthesis, 326 ml/min to 7.8 ml/min. Uterine vein PGE concentration was extremely high, 172.4 ng/ml, with concomitant peripheral arterial PGE 2.1 NG/ML. Intravenous administration of either meclofenamate or indomethacin reduced uterine vein PGE to 23 ng/ml (P less than 0.01) and arterial PGE to 1.0 ng/ml (P less than 0.05). Male and nonpregnant female rabbits had lower arterial PGE, 0.37 ng/ml (P less 0.05). Studies in non-nephrectomized pregnant animals demonstrated that uteroplacental secretion of PGE was greater than five times renal secretion. These studies demonstrate that the rabbit uteroplacental unit is a rich source of PGE and suggest that production of the vasoactive lipid may have a key role in regulating UPBF during pregnancy.     

Effect of vasoactive agents on intestinal oxygen consumption and blood flow in dogs.

A comparison study of several vasoconstrictor and vasodilator agents was conducted measuring changes in intestinal blood flow and oxygen consumption during 10-min periods of intra-arterial infusion. Blood flow was measured in a branch of the superior mesenteric artery of anesthetized dogs with an electromagnetic blood flow meter, and the arteriovenous oxygen content difference across the gut segment was determined photometrically. Vasopressin (4 x 10(-3) and 7x 10(-4) U/kg-min) diminished blood flow 60 and 28% and reduced oxygen consumption 54 and 22%, respectively (all P less than 0.001). In a dose which did not lower blood flow, vasopressin still caused a decline in oxygen consumption (P less than 0.01). Epinephrine (5 x 10(-2) mug/kg-min) decreased blood flow 19% (P less than 0.001) but did not reduce oxygen consumption. After beta-adrenergic blockade, however, the same dose of epinephrine decreased blood flow 41% and oxygen consumption 33% (both P less than 0.001). Responses to angiotension II, calcium chloride, and prostaglandin F2alpha resembled effects of vasopressin rather than those of epinephrine, namely decreased blood flow and decreased oxygen consumption. The vasodilator agents, prostaglandin E1, is isoproterenol, and histamine, increased (P less than 0.001) both blood flow (130, 80, and 98%, respectively) and oxygen consumption (98, 64, and 70%, respectively). Vasopressin, angiotensin II, calcium chloride, and prostaglandin F2alpha appear to contract arteriolar and precapillary sphincteric smooth muscle indiscriminately to evoke both intestinal ischemia and hypoxia. Epinephrine is the exceptional constrictor in this case, producing diminished blood flow without a reduction in oxygen uptake.     

Cardiac output, oxygen consumption and renal blood flow in essential hypertension

Cardiac output, oxygen consumption, total blood volume and mean circulatory transit time were investigated at rest in men with sustained essential hypertension in comparison with normal subjects of the same age and sex. In normal subjects and in patients with hypertension, oxygen consumption was positively correlated to cardiac output. In hypertensives, the slope of the curve was significantly shallower with an increase in arteriovenous oxygen difference. Oxygen consumption in both populations was negatively correlated with mean circulatory transit time but not with total blood volume. In normal subjects, mean circulatory transit time and arteriovenous oxygen difference were positively correlated. The correlation was not significant in hypertensive patients. The study suggests important abnormalities in the transport and cost of energy in erythrocytes of patients with sustained essential hypertension.     

Impaired uterine arterial blood flow in pregnant women with recurrent pregnancy loss.

OBJECTIVE: This study was undertaken to evaluate uterine perfusion, which regulates uterine receptivity, in women with recurrent pregnancy loss. METHODS: We evaluated the blood flow resistance in the uterine arteries of 104 pregnant women at 4 to 5 weeks' gestation by transvaginal pulsed Doppler ultrasonography (control group, n = 52; and recurrent pregnancy loss group, n = 52). Blood tests for antinuclear and antiphospholipid antibodies were also performed. RESULTS: The uterine arterial pulsatility index in the recurrent pregnancy loss group was significantly higher than that in the control group. Women with antinuclear or antiphospholipid antibodies had an elevated pulsatility index in the uterine artery, which is prominent in women with recurrent pregnancy loss. Coagulopathy and vascular dysfunction caused by autoantibodies may impair uterine perfusion. However, the uterine arterial pulsatility index in the recurrent pregnancy loss group was significantly higher than that in the control group even among women without antinuclear antibodies or among women without antiphospholipid antibodies. This observation strongly suggests that the uterine artery pulsatility index may be an independent index for recurrent pregnancy loss. CONCLUSIONS: The introduction of pulsed Doppler ultrasonography has provided the means for noninvasive evaluation of uterine impedance and may identify patients with recurrent pregnancy loss associated with impaired uterine perfusion.     

Catecholamine-mediated reduction in uterine blood flow after nicotine infusion in the pregnant ewe.

The effect of nicotine on uterine blood flow, uterine vascular resistance, and plasma catecholamine concentration was studied in chronically catheterized pregnant sheep equipped with electromagnetic flow probes. The systemic administration of nicotine (14--32 micrograms/kg body wt per min) resulted in a 44% reduction in uterine blood flow (P less than 0.001) and a 203% increase in uterine vascular resistance. Both responses were inhibited by pretreatment with the alpha blocker, phentolamine. Arterial plasma concentrations of norepinephrine and epinephrine, measured by a single isotopic radioenzymatic assay, rose (from 117.9 +/- 6.7 to 201.8 +/- 13.3 pg/ml, P less than 0.001; and from 71.6 +/- 4.5 to 124.1 +/- 8.4 pg/ml, P less than 0.001, respectively) during nicotine infusion. The findings suggest that nicotine exerts a deleterious effect on uterine blood flow mediated through the release of catecholamines.     

Trial-by-trial relationship between neural activity, oxygen consumption, and blood flow responses

Trial-by-trial variability in local field potential (LFP), tissue partial pressure of oxygen (PO2), cerebral blood flow (CBF), and deoxyhemoglobin-weighted optical imaging of intrinsic signals (OIS) were tested in the rat somatosensory cortex while fixed electrical forepaw stimulation (1.0-ms pulses with amplitude of 1.2 mA at a frequency of 6 Hz) was repeatedly applied. The changes in the cerebral metabolic rate of oxygen (CMRO2) were also evaluated using a hypotension condition established by our group based on the administration of a vasodilator. Under normal conditions, CBF, PO2, and OIS showed positive signal changes (48%, 32%, and 0.42%, respectively) following stimulation. Over multiple trials, the CBF responses were well correlated with the integral of the LFP amplitudes (sigmaLFP) (Rmean=0.78), whereas a lower correlation was found between PO2 and sigmaLFP (Rmean=0.60) and between OIS and sigmaLFP (Rmean=0.54). Under the hypotension condition the LFP responses were preserved, but the CBF responses were suppressed and the PO2 and OIS changes were negative (-12% and -0.28%, respectively). In this condition, the trial-by-trial variations in PO2 and OIS were well correlated with the variability in sigmaLFPs (Rmean= -0.77 and -0.76, respectively), indicating a single trial coupling between CMRO2 changes and sigmaLFP. These findings show that CBF and CMRO2 signals are more directly correlated with neural activity compared to blood oxygen-sensitive methods such as OIS and BOLD fMRI.     

The effect of changes in perfusion pressure on uteroplacental blood flow in the pregnant rabbit.

The effect of perfusion pressure on uteroplacental blood flow was determined in pregnant rabbits utilizing the radioactive microsphere method. Control mean arterial pressure, 93 mm Hg +/- 2.6 SEM, was raised by carotid ligation to 109 +/- 4.1 mm Hg and then reduced with antihypertensive drugs to 74 +/- 1.3 mm Hg. Over this range of pressure there was no significant change in cardiac output, 605 +/- 36, 523 +/- 37, and 540 +/- 39 ml/min; or uteroplacental blood flow, 30 +/- 3.2, 27 +/- 5.2, and 29 +/- 4.5 ml/min, respectively. When prostaglandin synthesis was inhibited with either indomethacin or meclofenamate (2 mg/kg), uterine vascular resistance was higher but maintenance of uteroplacental flow occurred over a perfusion pressure of 89 +/- 6.7-115 +/- 9.3 mm Hg. With more severe hypotension induced with trimethaphan, control arterial pressure fell from 92 +/- 2.4 to 39 +/- 0.9 mm Hg, cardiac output fell from 514 +/- 17 to 407 +/- 22 ml/min (P less than 0.025) and uteroplacental blood flow fell from 6.1 +/- 0.9 to 2.5 +/- 0.9% of cardiac output (P less than 0.05), which represented an absolute fall from 32.4 +/- 5 to 10.6 +/- 3 ml/min (P less than 0.025). There was no significant change in renal blood flow expressed as percentage of cardiac output, 14.9 +/- 2 and 13 +/- 1.5%, or in absolute flow, 75 +/- 7.7 and 54 +/- 7 ml/min with trimethaphan-induced hypotension. These studies indicate that uteroplacental blood flow is maintained relatively constant over a range of perfusion pressure of 60-140 mm Hg in both normal and prostaglandin-inhibited pregnant rabbits. However, with reduction in pressure to 36-42 mm Hg, uteroplacental blood flow falls, expressed as a percentage of cardiac output and in absolute flow.     

Effects of mannitol alone and mannitol plus furosemide on renal oxygen consumption,blood flow and glomerular filtration after cardiac surgery

Objective

Imbalance of the renal medullary oxygen supply/demand relationship can cause hypoxic medullary damage and ischaemic acute renal failure (ARF). The use of mannitol for prophylaxis/treatment of clinical ischaemic ARF is controversial and the effect of mannitol on renal oxygenation in man has not yet been investigated. We evaluated the effects of mannitol on renal oxygen consumption (RVO₂)_, renal blood flow (RBF) and glomerular filtration rate (GFR) in postoperative patients.

Design

Prospective interventional study.

Setting

University hospital cardiothoracic ICU.

Patients

Ten uncomplicated mechanically ventilated and sedated postcardiac surgery patients with preoperatively normal renal function.

Interventions

Mannitol infusion (225 mg/kg + 75 mg/kg/h) and combined mannitol and furosemide infusion (0.25 mg/kg + 0.25 mg/kg/h).

Measurements and results

Systemic haemodynamics were evaluated by a pulmonary artery catheter. RBF and GFR were measured by the renal vein thermodilution technique and by renal extraction of ⁵¹Cr–EDTA, respectively. Mannitol increased urine flow (60%), GFR (20%) and filtration fraction (FF) (20%) with no change in RBF. This was accompanied by an increase in renal sodium reabsorption (18%), RVO₂ (19%) and renal oxygen extraction (21%). When combined with mannitol, furosemide normalised sodium reabsorption, RVO₂, renal oxygen extraction with no change in RBF, while GFR and FF were still elevated compared to control.

Conclusions

In patients with normal renal function, mannitol increases GFR, which increases tubular sodium load, sodium reabsorption and RVO₂ after cardiac surgery. The lack of effect on RBF, indicates that mannitol impairs the renal oxygen supply/demand relationship. Furosemide normalised renal oxygenation when combined with mannitol.

     

胎盘生长因子、血小板参数及子宫动脉血流参数预测子痫前期的临床意义

目的 探讨胎盘生长因子(PLGF)、血小板参数及子宫动脉血流参数预测子痫前期的临床意义.方法 回顾性选取2019年1月至2020年8月在东莞市长安医院和东莞市人民医院产检过程中确诊为子痫前期的60例孕妇为研究组,并选择同时期在两家医院分娩的60例正常孕妇为对照组.收集并分析两组孕妇妊娠早期的PLGF、血小板计数(PLT...     

Experimental validation of uterine artery volume blood flow measurement by Doppler ultrasonography in pregnant sheep.

OBJECTIVE: To test the hypothesis that Doppler-derived (calculated) uterine artery volume blood flow (cQ(UtA)) reflects accurately volume blood flow measured directly (mQ(UtA)) in an experimental setting. METHODS: Five pregnant sheep were instrumented at 122-130 days of gestation under general anesthesia. After a 4-day recovery period, maternal hemodynamics were varied by administering to the sheep under general anesthesia noradrenaline, beta-blocker, low oxygen gas mixture, epidural bupivacaine and ephedrine, consecutively. The central venous pressure was obtained with the help of a thermodilution catheter. The mean arterial pressure and acid-base status were monitored using a 16-gauge polyurethane catheter inserted into the descending aorta via a femoral artery. A 6-mm transit-time ultrasonic perivascular flow probe was used to measure the mQ(UtA). Doppler ultrasonography of the uterine artery was performed and volume blood flow was obtained simultaneously by the transit-time ultrasonic perivascular flow probe during each phase of the experiment. RESULTS: A total of 31 observations were made. The mQ(UtA) varied between 90 and 800 (mean +/- SD, 419 +/- 206) mL/min during the experiments. The corresponding values for the cQ(UtA) were 110 and 900 (mean +/- SD, 459 +/- 211) mL/min. There was a significant correlation (R = 0.76; P < 0.0001) between mQ(UtA) and cQ(UtA). The mQ(UtA) correlated positively with Doppler-derived uterine artery absolute velocities, i.e. peak systolic (R = 0.50; P = 0.004), end-diastolic (R = 0.53; P = 0.002) and time-averaged maximum (R = 0.69; P < 0.0001) and time-averaged intensity weighted mean (R = 0.75; P < 0.0001) velocities. CONCLUSION: cQ(UtA) correlates well with volume blood flow measured directly. Doppler-derived uterine artery absolute blood flow velocities reflect uteroplacental volume blood flow in pregnant sheep. Published by John Wiley & Sons, Ltd.     

Cerebral blood flow and cerebral oxygen consumption in patients with COPD on mechanical ventilation

Objective To investigate the effect of PaCO₂ on cerebral blood flow (CBF) in chronic obstructive pulmonary disease (COPD).Design Before-after trial.Setting General ICU in a regional hospital.Patients 7 patients undergoing mechanical ventilation because of an exacerbation of COPD.Intervention CBF and cerebral metabolic rate of oxygen (CMRO₂) of COPD were measured before and after hyperventilation and were compaired by those of normal patients. CBF was measured by the Kety-Schmidt technique using 15% N₂O.Measurements/results Hyperventilation produced a significant reduction in CBF in COPD with no concomitant change in CMRO₂. CMRO₂ in COPD was significantly lower than those in normal patients. The regression equation was shifted significantly more to the right in COPD.Conclusion The sensitivity of CBF in CO₂ remained but CMRO₂ was reduced markedly in COPD patients.     

Myocardial blood flow and oxygen consumption during positive end-expiratory pressure ventilation at different levels of cardiac inotropy and frequency

Effects of PEEP on cardiac function, myocardial blood flow (MBF) and myocardial oxygen consumption (mVO2) were studied in eight mongrel dogs anesthetized with pentobarbital. Myocardial oxygen demand was increased by isoproterenol infusion or atrial pacing, or decreased by beta-receptor blockade. PEEP was set to 15 cm H2O in all groups. The greatest reduction in cardiac output due to PEEP was seen during isoproterenol infusion (44%), and the smallest during beta-receptor blockade (18%). This is attributed to increased sensitivity to the reduced left ventricular (LV) preload induced by PEEP, when cardiac inotropy is augmented by isoproterenol, compared to normal and reduced cardiac inotropy. PEEP decreased MBF similarly and significantly in all groups. However, myocardial oxygen extraction did not increase, and reduction in MBF caused by PEEP was closely related to concomitant reduction in mVO2. A significant correlation was also observed between reductions in LV work and reduction in mVO2 when PEEP was applied in all groups. We conclude that the reduced MBF observed with use of PEEP was probably due to reduced myocardial oxygen demand.