Forskolin dilates the maternal ovine placental vascular bed

We have examined the placental vascular responses to forskolin in 8 near-term sheep. The drug was administered for 5 min at 1 ml/min of 10(-3) M forskolin via a retrograde uterine arterial catheter. Blood flows were measured with radioactive microspheres. Forskolin increased the nonplacental uterine blood flow from 0.318 +/- 0.031 (SEM) to 0.738 +/- 0.071 ml/min per g of tissue, P less than 0.001. The nonplacental uterine vascular resistance decreased from 308 +/- 26 to 132 +/- 12 mmHg/ml/min per g, P less than 0.001. Forskolin increased the placental blood flow from 1.8 +/- 0.18 to 2.08 +/- 0.16 ml/min per g of tissue, P less than 0.05. The placental vascular resistance decreased from 54.7 +/- 5.1 to 45.9 +/- 3.7 mmHg/ml/min per g, P less than 0.03. In the same animals we then infused angiotensin II at 5 micrograms/min via the jugular vein to induce placental vasoconstriction. In this series, the forskolin increased the nonplacental uterine blood flow from 0.141 +/- 0.016 to 0.485 +/- 0.079 ml/min per g of tissue, P less than 0.001, and the uterine vascular resistance decreased from 968 +/- 104 to 283 +/- 36 mmHg/ml/min per g, P less than 0.001. The placental blood flow increased from 2.08 +/- 0.012 to 2.69 +/- 0.17 ml/min per g of tissue, P less than 0.01 and placental vascular resistance decreased from 61.9 +/- 4.4 to 46.0 +/- 3.7 mmHg/ml/min per g, P less than 0.001.(ABSTRACT TRUNCATED AT 250 WORDS)     

Studies on the growth of the fetal sheep. Effects of surgical reduction in placental size, or experimental manipulation of uterine blood flow on plasma sulphation promoting activity and on the concentration of insulin-like growth factors I and II

The effect of long- and short-term manipulations of uterine blood flow on fetal plasma levels of IGF-I and -II have been studied in sheep at days 125-139 of pregnancy and compared with those in near term rats and guinea pig. The primary objective is to show that both long- and short-term reduction of uterine blood flow is associated with increase in the fetal plasma concentration of IGF-II while that of IGF-I falls. In the pregnant sheep long-term depression of utero-placental blood flow was caused by surgical reduction in placental mass (carunclectomy) prior to conception. This reduced fetal weight to 2.42 +/- 0.49 kg (SD) compared with 3.41 +/- 0.46 in controls; the respective values for uterine blood flow being 1694 +/- 558 and 913 +/- 324 ml/min respectively. This was associated with a fall in fetal plasma IGF-I concentration from 22.6 +/- 3.4 ng/ml to 14.9 +/- 1.31 ng/ml and a rise in IGF-II from 1952 +/- 284 ng/ml to 3360 +/- 914 ng/ml respectively. Similar changes in the plasma concentrations of IGF peptides were observed in fetal rats and guinea pigs in response to uterine artery ligation. Short-term reduction (60 min) of the uterine blood flow was caused either by compression of the common uterine artery to depress flow from 1491 +/- 375 to 648 +/- 216 ml/min or through intraarterial infusion of adrenaline at 35 ug/min to lower flow from 1628 +/- 339 to 1195 +/- 128 ml/min. Such falls in uterine blood flow had no significant effect on fetal plasma IGF-I levels but increased IGF-II levels by 30 to 60%.     

Effect of reduced uterine blood flow on fetal and maternal cortisol

We have measured the changes in fetal and maternal plasma concentrations of cortisol in relation to blood gases and percent oxygen saturation during 2- and 4-h episodes of reversibly reduced uterine blood flow in sheep between 120 days gestation and term. During that period of reduced uterine blood flow there was a significant decrease in fetal arterial percent oxygen saturation (SaO2), PO2 and pH. Fetal SaO2 decreased from 59.5 +/- 3.2% to 31.8% +/- 2.8% by 15 min, 32.9 +/- 2.9% by 60 min, and 33.5 +/- 2.9% by 120 min. Fetal PO2 decreased from 3.2 +/- 0.1 KPa to 2.0 +/- 0.2 KPa by 15 min, 2.2 +/- 0.2 KPa by 60 min and 2.3 +/- 0.1 KPa by 120 min. Fetal pH decreased from 7.36 +/- 0.01 to 7.30 +/- 0.03 by 15 min, 7.27 +/- 0.02 by 60 min and 7.25 +/- 0.03 by 120 min. During the period of reduced uterine blood flow, fetal plasma concentrations of cortisol increased from 37.1 +/- 10.8 nmol/l to 53.3 +/- 9.2 nmol/l by 15 min, 49.2 +/- 11.4 nmol/l by 60 min and 43.3 +/- 9.0 nmol/l by 120 min. The greatest percentage increase in fetal plasma concentrations of cortisol occurred in fetuses of 126-139 days gestation. There was no significant change in maternal blood gases, SaO2 or plasma concentrations of cortisol. These experiments demonstrate that there is a significant increase in fetal plasma concentrations of cortisol in response to reductions in uterine blood flow from as early as 120 days gestation.     

Uterine blood flow, oxygen and glucose uptakes at mid-gestation in the sheep

In early ovine fetal development, the placenta grows more rapidly than the fetus so that at mid-gestation the aggregate weight of placental cotyledons exceeds fetal weight. The purpose of this study was to compare two separate methods of measuring uterine blood flow and glucose and oxygen uptakes in seven mid-gestation ewes, each carrying a single fetus. Uterine blood flow to both uterine horns was measured by microsphere and by tritiated water steady-state diffusion methodology. Calculations of tritiated water blood flows and oxygen and glucose uptakes were based on measurements of arteriovenous concentration differences across each uterine horn. The distribution of blood flow and oxygen uptake between the two uterine horns was strongly correlated with placental mass distribution. The two methods gave comparable results for uterine blood flow (457 +/- 35 vs 476 +/- 35 ml/min), oxygen uptake (457 +/- 35 vs 476 +/- 35 mumol/min), and glucose uptake (63 +/- 8 vs 64 +/- 6 mumol/min). Uterine blood flow was approximately 38% of the late gestation value and 56.1 +/- 1 times higher than umbilical blood flow. Uteroplacental oxygen consumption was about 58% of late gestation measurements and 3.9 +/- 0.5 times higher than fetal oxygen uptake. We confirm that the large placental mass of mid-gestation is associated with high levels of maternal placental blood flow and placental oxidative metabolism.     

Capillary blood flow in the endometrium and myometrium of conscious sheep: effect of catheterization of uterine arteries

Measures of capillary blood flow in the uterine tissues of conscious ewes were obtained by the use of microspheres. Total uterine capillary blood flow was significantly greater (P less than 0.01) at oestrus than at day 8 of the oestrous cycle [69.5 +/- (s.e.m.) 11.9, cf. 15.3 +/- 1.2 ml min-1, n = 7], reflecting increases of a similar order in both the endometrium and the myometrium. At these stages of the oestrous cycle, endometrial capillary blood flow constituted 83.6 and 80.5%, respectively, of the total uterine capillary flow. Following the placement of indwelling catheters in each middle uterine artery there was a decrease in the ratio of endometrial to myometrial capillary blood flow for 3-5 days.     

The effect of labour on uterine blood flow in the pregnant ewe.

The effect of labour on cardiac output and uterine blood flow was measured in pregnant ewes at a mean gestation of 124 days using radioactive microspheres labelled with 169Yb and 85Sr. Labour was induced by a continuous infusion of ACTH into the foetal circulation. Cardiac ouput measured before ACTH infusion in seven ewes was 5234 +/- 175-9 ml./min (mean +/- S.E.) and total uterine blood flow was 732 +/- 57-9 ml./min (mean +/- S.E.). Measurements during labour in six ewes showed a significant increase in cardiac output to 6175 +/- 149-6 ml./min (P less than 0-005) but no significant change in uterine blood flow. However, the partition of blood flow was altered; thus myometrial flow increased by 67% from 114 +/- 15-4 ml./min to 190 +/- 13-2 ml./min (P less than 0-005) while placental blood flow decreased, although not significantly, from 618 +/- 55-9 ml./min to 575 +/- 40-7 ml./min. Similar changes were observed in one ewe in spontaneous labour at term and in another ewe receiving an infusion of 4 mg oestradiol 17beta over a 24 hr period. It is concluded that labour is not associated with any major alternation in total uterine blood flow although myometrial blood flow is increased. It is not known whether this is due to the rise in circulating oestrogens which occurs prior to parturition in the ewe, or to other factors such as the work of uterine muscle during labour.     

Systemic hemodynamic and regional blood flow changes in response to chronic reductions in uterine perfusion pressure in pregnant rats

Preeclampsia (PE) is associated with increased total peripheral resistance (TPR), reduced cardiac output (CO), and diminished uterine and placental blood flow. We have developed an animal model that employs chronic reductions in uterine perfusion pressure (RUPP) in pregnant rats to generate a "preeclamptic-like" state during late gestation that is characterized by hypertension, proteinuria, and endothelial dysfunction. Although this animal model has many characteristics of human PE, the systemic hemodynamic and regional changes in blood flow that occur in response to chronic RUPP remains unknown. Therefore, we hypothesized that RUPP would decrease uteroplacental blood flow and CO, and increase TPR. Mean arterial pressure (MAP), CO, cardiac index (CI), TPR, and regional blood flow to various tissues were measured using radiolabeled microspheres in the following two groups of conscious rats: normal pregnant rats (NP; n = 8) and RUPP rats (n = 8). MAP was increased (132 +/- 4 vs. 99 +/- 3 mmHg) in the RUPP rats compared with the NP dams. The hypertension in RUPP rats was associated with increased TPR (2.15 +/- 0.02 vs. 0.98 +/- 0.08 mmHg x ml(-1) x min(-1)) and decreased CI (246 +/- 20 vs. 348 +/- 19 ml x min(-1) x kg(-1), P < 0.002) when contrasted with NP dams. Furthermore, uterine (0.16 +/- 0.03 vs. 0.38 +/- 0.09 ml x min(-1) x g tissue(-1)) and placental blood flow (0.30 +/- 0.08 vs. 0.70 +/- 0.10 ml x min(-1) x g tissue(-1)) were decreased in RUPP compared with the NP dams. These data demonstrate that the RUPP model of pregnancy-induced hypertension has systemic hemodynamic and regional blood flow alterations that are strikingly similar to those observed in women with PE.     

The effect of exogenous estradiol benzoate and altrenogest on uterine and ovarian blood flow during the estrous cycle in mares

In recent years, a positive relationship between genital perfusion and fertility has been established; in species other than horses, uterine and ovarian perfusion was improved by exogenous estrogen but impaired by exogenous progestin. The goal of the present study was to investigate the effect of exogenous estrogen and progestin on uterine and ovarian blood flow in cycling mares. Five Trotter mares were examined daily during three estrous cycles. Mares were given no treatment, altrenogest (0.044 mg/kg BW) orally from Day 0 (ovulation) to Day 14 and estradiol benzoate (5mg i.m.) on Days 0, 5, and 10, in three cycles, respectively. There was no difference ( P > 0.05 ) in the length of untreated versus estrogen-treated cycles ( 22.8 +/-1.3 days and 23.2 +/= 1.5 days, respectively), but cycle length was increased (P < 0.05) in progestin-treated cycles (26.0 +/- 1.2). To facilitate comparisons among cycles with different lengths, data from Days 0 to 15 (diestrus) and from Days -6 to -1 (estrus) were analyzed. Transrectal Doppler sonography was used to evaluate blood flow in both uterine arteries and in the ovarian artery ipsilateral to the preovulatory follicle during estrus and ipsilateral to the corpus luteum during diestrus. Blood flow was assessed semiquantitatively using the pulsatility index (PI); high PI values indicated high resistance and a low perfusion and vice versa. An immediate effect of treatments occurred only after the administration of estradiol benzoate on Day 0; uterine PI values decreased (P < 0.05) between Days 0 and 1 and estrogen-treated mares but increased (P < 0.05) at the corresponding time in untreated cycles. Mean PI values for the uterine and ovarian arteries during both diestrus and estrus were higher (P < 0.05) in estrogen-treated versus untreated mares. Furthermore, mean uterine PI values during diestrus and estrus were higher (P< 0.05) in altrenogest-treated versus untreated mares. Neither estrogen nor altrenogest treatments had a significant immediate effect on ovarian PI values. Compared to untreated cycles, mean ovarian PI values were elevated (P < 0.05) only in the estrus following altrenogest administration. In conclusion, exogenous estrogen and progestin both decreased genital perfusion in cycling mares.     

The effect on fetal development and utero-placental blood flow of ligating a uterine artery in the rat near term

The uterine artery of one horn of 13 rats was ligated on day 18 of gestation; the remaining horn was used as a control. The effect, four days later, on blood flow to the reproductive tract, was measured with radioactive microspheres and compared to the effect on fetal and placental weights. Fetal survival in the ligated horns, 41 percent, was significantly lower (P less than 0.05) than that in the control horns, 98 percent. Fetal and placental weights of the survivors in the ligated horns, 3.159 +/- 0.133 g (SE) and 450 +/- 18 mg respectively, were similarly lower than those in the control horns, 3.814 +/- 0.111 g and 529 +/- 27 mg respectively. Maternal placental blood flow closely reflected the weight of tissue being supplied and was similar in the ligated and control horns, 129 +/- 21 and 130 +/- 18 ml.min(-1). 100g(-1), respectively. Myometrial blood flow was again similar in the ligated and control horns, 34 +/- 5 and 37 +/- 4 ml.min(-1). 100 g(-1), respectively, and in the ovarian, middle and cervical sections of each horn. These results are compatible with the view that ligation causes only a temporary reduction in uterine blood flow which permanently checks placental and fetal, or placental thus fetal, growth. Blood flow then returns to normal levels compatible with the reduced weights of tissues being supplied.     

Ultrasonic transit-time measurement of blood flow in the umbilical arteries and veins in the bovine fetus during stage II of labor

The vitality of the bovine fetus during parturition depends on an intact umbilical circulation to supply adequate amounts of oxygen and nutrients to the fetus. The goal of the present study was to measure the blood flow in the umbilical vessels during stage II of labor and to determine when blood flow ceases in the umbilical cord. In 20 cows, ultrasonographic transducers were placed on one umbilical vein and one umbilical artery after rupture of the allantochorionic sac, and the blood flow volume per unit time was measured. At the same time, a pressure transducer was placed into the uterus to measure uterine pressure. Parturition was spontaneous in all 20 cows. In 20 live calves born, pH, base excess and lactate concentration were measured in the blood immediately after birth. During the last 90 min before birth the mean total umbilical blood flow (artery and vein combined) was 1.186+/-0.028 L/min. Calves with a blood pH> or =7.2 (n=13) had a higher mean total blood flow than calves with a pH<7.2 (n=7; 1.243+/-0.038 versus 1.095+/-0.038 L/min). In calves with a blood pH<7.2, the mean total blood flow decreased from 1.178+/-0.134 at 20 min before birth to 0.959+/-0.126 L/min at the end of stage II of labor. During this time period, the arterial blood flow did not differ between calves with a blood pH> or =7.2 and<7.2, but venous blood flow decreased significantly in calves with a blood pH<7.2. During uterine contractions, the total umbilical blood flow decreased significantly by 0.22 L/min. The blood flow in the umbilical artery and vein ceased before the calves were completely born.     

Serotonin-induced disruption of implantation in the rat: I. Serum progesterone, implantation site blood flow, and intrauterine pO2

Serotonin, administered on the day after the initiation of implantation, promptly terminates pregnancy in the rat. Consequently, the effects of serotonin on serum progesterone levels, implantation site blood flow, and intrauterine oxygen tension were determined to see whether the disruption of implantation is related to altered corpus luteum and/or uterine vascular function. Animals received a subcutaneous injection of physiological saline (C: control) or serotonin (S: 20 mg/kg) on Day 5 of pregnancy. Serotonin did not alter the number of blastocysts implanting (C: 6.02 +/- 0.52 vs. S: 6.29 +/- 0.46, sites/cornu) but did cause subsequent implantation site resorption (C: 0.08 +/- 0.07 vs. S: 5.46 +/- 0.44/cornu; P less than 0.001). Progesterone levels in serotonin-treated rats did not differ from those of controls at 6 h postinjection or on Days 6 through 10 of pregnancy. Implantation site blood flow was reduced at 30 min (C: 0.76 +/- 0.12 vs. S: 0.25 +/- 0.02 ml/min per g; P less than 0.01) and remained suppressed at 2 h after serotonin injection. A prompt and sustained reduction in intrauterine oxygen tension (C: 48.9 +/- 3.7 vs. S: 25.9 +/- 4.5 mmHg; P less than 0.005; 120 min) accompanied the reduced uterine perfusion. Thus, disruption of implantation is not a result of impaired corpus luteum function but is associated with marked and protracted reductions in uterine blood flow and intraluminal oxygen availability.     

Uterine and ovarian blood flow during the estrous cycle in mares

Uterine and ovarian blood flow was investigated in four mares during two consecutive estrous cycles using transrectal color Doppler sonography. The uterine and ovarian arteries of both sides were scanned to obtain waves of blood flow velocity. The pulsatility index (PI) reflected blood flow. There were significant time trends in PI values of all uterine and ovarian blood vessels during the estrous cycle (P < 0.05). PI values did not differ between the uterine arteries ipsi- and contralateral to the corpus luteum or the ovulatory follicle. PI values of the uterine arteries showed a wave shaped profile throughout the estrous cycle. The highest PI values occurred on Days 0 and 1 (Day 0 = ovulation) and around Day 11, and the lowest PI values were measured around Days 5 and -2 of the estrous cycle. During diestrus (Days 0-15) PI values of the ovarian artery ipsilateral to the corpus luteum were significantly lower than PI values of the contralateral ovarian artery (P < 0.0001). No differences (P > 0.05) in resistance to ovarian blood flow occurred between sides during estrus (Days -6 to -1). In this cycle stage PI values decreased in both ovarian vessels (P < 0.05). During diestrus, high PI values of the ovarian artery ipsilateral to the corpus luteum were measured between Days 0 and 2, followed by a decline until Day 6 (P < 0.05). From this time on, the resistance to blood flow increased continuously until Day 15 (P < 0.05). The cyclic blood flow pattern in the contralateral ovarian artery was similar to that in the uterine arteries (r = 0.68; P < 0.0001). No correlations occurred between the diameter of the corpus luteum and the PI values of the ipsilateral ovarian artery (P > 0.05) during diestrus. During estrus, there was a negative relationship between growth of the diameter of the ovulatory follicle and changes in PI values of the dominant ovarian artery (r = -0.41; P < 0.05). PI values of the uterine arteries and of the ovarian artery ipsilateral to the ovulatory follicle were negatively related to estrogen (E) levels in plasma during estrus (uterine arteries: r = -0.21; P < 0.05; dominant ovarian artery: r = -0.35; P < 0.05). In diestrus, PI values of the dominant ovarian artery were negatively related to plasma progesterone levels (r = -0.38; P < 0.0001), but not the PI values of the uterine arteries (P > 0.05). The findings of this study show that there are characteristic changes in blood supply of the uterus and the ovaries throughout the equine estrous cycle. There are negative correlations between resistance to blood flow in the uterine and ovarian arteries and the plasma estrogen levels during estrus. In diestrus, there is a negative relationship between the resistance to ovarian blood flow and the progesterone levels.     

Serotonin-induced disruption of implantation in the rat: II. Suppression of decidualization

Subcutaneous injection of serotonin (20 mg/kg) on Day 5 of pregnancy disrupts implantation in the rat as indicated by the reduction in number of live fetuses/cornu present on Day 19 (0.9 vs. 6.1, treated vs. control). Such disruption of implantation possibly results from impaired decidualization. To test for suppression of decidualization, serotonin was administered to pseudopregnant rats on the day before, on (Day 4) or after artificial induction of the decidual cell reaction. Relative to saline-treated controls (C), serotonin (S) reduced decidualization when injected either before [C: 1987 +/- 130 vs. S: 1085 +/- 155 mg (Day 3); P less than 0.005] or after [C: 1987 +/- 130 vs. S: 173 +/- 8 mg (Day 5); P less than 0.001] administration of the deciduogenic stimulus. In addition, serotonin markedly decreased uterine blood flow (C: 0.47 +/- 0.05 vs. S: 0.25 +/- 0.06 ml/min per g; P less than 0.01) during pseudopregnancy. However, serotonin altered neither the duration of luteal function in pseudopregnant rats (C: 15.3 vs. S: 14.3 days) nor serum progesterone levels (C: 74-91 vs. S: 53-82 ng/ml) in pregnant animals. It is concluded that serotonin may disrupt implantation, in part, by suppression of decidualization. The loss of endometrial competence to undergo decidualization appears to be a consequence of serotonin-induced uterine ischemia rather than impaired corpus luteum activity.     

The effects of ethanol on pancreatic blood flow in awake and anesthetized dogs

The pathophysiology of alcohol-induced acute pancreatitis is not clear. Ischemic injury has been suggested as a possible mechanism. To examine the effects of ethanol on pancreatic and splanchnic blood flow, measurements were made in fasted, conditioned awake dogs before and after iv infusion of ethanol (1.7 g/kg). At 30 min blood ethanol concentration ranged between 60 and 150 mg/dl and at 60 min between 166 and 350 mg/dl. Although cardiac output, aortic pressure, left atrial pressure, and arterial pH did not change, pancreatic flow declined by 39 +/- 12 ml/min/100 g, P less than 0.05 (from 173 +/- 10 ml/min/100 g) at 30 min and was still depressed (by 27 +/- 12 ml/min/100 g, P less than 0.05) at 60 min. Concomitantly, hepatic arterial flow increased. While hepatic and pancreatic flow changed inversely, the correlation (r = -0.17) of these changes was not significant. At comparable blood ethanol concentrations in pentobarbital-anesthetized dogs hepatic arterial flow increased by 11 +/- 3 ml/min/100 g, P less than 0.01 (from 24 +/- 5 ml/min/100 g), but pancreatic flow did not change. Thus, in the awake dog at blood levels that would produce mild to moderate alcoholic intoxication in man, ethanol reduces pancreatic flow. Although hepatic flow increases concomitantly, the relationship of these changes appears to be independent.     

Oxygen consumption is maintained in fetal sheep during prolonged hypoxaemia.

Experiments were conducted in 12 chronically-catheterized pregnant sheep to examine the effect of prolonged hypoxaemia secondary to the restriction of uterine blood flow on fetal oxygen consumption. Surgery was performed at 115 days gestation to place a teflon vascular occluder around the maternal common internal iliac artery and for insertion of vascular catheters. Following a 5-day recovery period, uterine blood flow was reduced in 6 animals for 24 hours and in 6 animals, the occluder was not adjusted. Fetal arterial PO2 decreased from 19.9 +/- 2.0 mmHg to 12.8 +/- 2.0 mmHg and 11.0 +/- 2.0 mmHg at 1 and 24 hours respectively in the experimental group and did not change the control group. Fetal pH decreased from 7.34 +/- 0.01 to 7.25 +/- 0.03 and 7.29 +/- 0.02 at 1 and 24 hours of hypoxaemia respectively. Fetal arterial lactate concentrations remained elevated throughout the experimental period with maximum concentrations of 6.6 +/- 2.1 mmol/l being present at 4 hours compared to 1.3 +/- 0.2 mmol/l during the control period. Umbilical blood flow increased from 186 +/- 19 ml/min/kg to 251 +/- 39 ml/min/kg at 1 h of hypoxaemia and returned to 191 +/- 21 ml/min/kg at 24 h. In association with the progressive fall in oxygen delivery to the fetus, oxygen extraction increased from 0.33 +/- 0.04 to 0.43 +/- 0.04 and 0.54 +/- 0.05 at 1 and 24 hours, respectively. Overall oxygen consumption by the fetus remained unchanged from control values.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of atrial natriuretic factor on maternal ovine vascular resistance

Atrial natriuretic factor (ANF) is a potent endogenous vaso-dilator and diuretic peptide of uncertain physiologic relevance. In this study, the effects of ANF on normal and angiotensin II constricted placental, uterine and renal vessels were examined in pregnant sheep. Ewes were equipped with catheters to monitor vascular pressures, infuse drugs and measure blood flow by the microsphere technique. An electromagnetic flow sensor was placed around the middle uterine artery and electromyogram electrodes were attached to the uterus. ANF was administered into a branch of the uterine artery to minimize its systemic effects. The experiment included two protocols. First, blood flows and pressures were measured after a 5-min period of saline infusion into the uterine artery. These measurements were repeated at the end of a 5-min infusion of ANF (6.25 micrograms.min-1) into the uterine artery. During the second protocol, angiotensin II (AII) was infused via the jugular vein at 5 micrograms.min-1 for 10 min and ANF (6.25 micrograms.min-1) was infused through the uterine artery during the second half of the AII infusion. In the absence of AII, ANF lowered blood pressure from 97 +/- 6 to 90 +/- 6 mmHg (P less than 0.05); and placental resistance from 67.8 +/- 11.3 to 57.3 +/- 10.4 mmHg.min.ml-1 per g (P less than 0.01). Uterine resistance did not change.(ABSTRACT TRUNCATED AT 250 WORDS)     

Exercise responses in pregnant sheep: oxygen consumption, uterine blood flow, and blood volume

In an attempt to explore the acute maternal responses to exercise we measured oxygen consumption, uterine blood flow, and blood volume in 13 chronically catheterized pregnant sheep at rest and while exercising on a treadmill. With maximal exercise O2 consumption increased 5.6 times, from a resting value of 5.8 +/- 0.3 (SE) to 32.1 +/- 2.8 ml X min -1 X kg -1, cardiac output increased 2.7 times, from 149 +/- 8 to 404 +/- 32 ml X min -1 X kg -1, and arteriovenous oxygen content difference increased 2.1 times, from 3.9 +/- 0.2 to 8.0 +/- 0.4 ml X dl -1. Total uterine blood flow decreased from a mean resting value of 292 +/- 6 to 222 +/- 19 ml X min -1 X kg fetus -1 near exhaustion during prolonged (40 min) exercise at 70% maximal oxygen consumption. Maternal blood volume decreased 14% (P less than 0.01) from 67.5 +/- 3.7 to 57.8 +/- 3.6 ml X kg -1 during this exercise period, with a 20% decrease in plasma volume without a change in red cell volume. We conclude that uterine blood flow decreases during maternal exercise. However, hemoconcentration helps to maintain a relatively constant oxygen delivery to the uterus.     

Dose-dependent effect of bradykinin on muscular blood flow and glucose uptake in man

Using the forearm technique, the effect of bradykinin on muscular blood flow and glucose uptake in healthy man in the postabsorptive state (n = 8) was studied at different doses of an intra-arterial infusion of bradykinin (2.5-150 ng/min). The blood flow of the forearm was increased dose-dependently from basal 2.8 +/- 0.3 up to 14.7 +/- 2.8 ml/(100 g X min). At lower bradykinin concentrations (2.5-25 ng/min), muscular glucose uptake was raised parallel to the increased blood flow from basal 0.71 +/- 0.30 to 2.93 +/- 0.50 mumol/(100 g X min). However, at higher doses (50-150 ng/min) glucose uptake was decreased again. Thus, the greatest metabolic effect of bradykinin was seen at a calculated bradykinin concentration of approximately 1 X 10(-9)M in the blood.     

Effects of chronic reduction in uterine blood flow on fetal and placental growth in the sheep

Pregnancy is associated with a significant increase in uteroplacental blood flow (UBF), which is responsible for delivering adequate nutrients and oxygen for fetal and placental growth. The present study was designed to determine the effects of vascular insufficiency on fetal and placental growth. Thirty-nine late-term pregnant ewes were instrumented to investigate the effects of chronic UBF reduction. Animals were split into three groups based on uterine blood flow, and all animals were killed on gestational day 138. UBF, which began at 851 +/- 74 ml/min (n = 39), increased in controls (C) to 1,409 +/- 98 ml/min (day 138 of gestation) and in the moderately restricted (R(M)) group to 986 +/- 69 ml/min. In the severely restricted (R(S)) group, UBF was only 779 +/- 79 ml/min on gestational day 138. This reduction in UBF significantly affected fetal body weight with R(M) fetuses weighing 3,685 +/- 178 g and R(S) fetuses weighing 2,920 +/- 164 g compared with C fetal weights of 4,318 +/- 208 g. Fetal brain weight was not affected, whereas ponderal index was significantly reduced in R(M) (2.94 +/- 0.09) and R(S) fetuses (2.49 +/- 0.08) compared with the value of the C fetuses (3.31 +/- 0.08). Placental weight was also significantly reduced in the R(M) group, being 302 +/- 24 g, whereas the R(S) group placenta weighed 274 +/- 61 g compared with the C values of 414 +/- 57 g. Fetal heart, liver, lung, and thymus were all significantly smaller in the R(S) group. Thus the present study shows a clear relationship between the level of UBF and both fetal and placental size. Furthermore, the observation that fetal brain weight was not affected, whereas fetal body weight was significantly reduced suggests that this experimental preparation may provide a useful model in which to study asymmetric fetal growth restriction.     

Transrectal Doppler sonography of uterine and umbilical blood flow during pregnancy in mares

Transrectal color Doppler sonography was used to investigate uterine and umbilical blood flow during pregnancy (duration, 46-48 weeks) in four mares. The resistance index (RI) and blood flow volume (VOL) of the uterine arteries ipsilateral and contralateral to the conceptus, and the presence of an early diastolic notch in the Doppler wave, were evaluated every 4 week throughout pregnancy. Fetal blood flow was calculated semiquantitatively every 2 week (from 20 to 40 weeks), using the RI of the umbilical arteries. During the entire period of investigation, there were no significant individual variations in uterine RI and VOL nor differences between the two uterine arteries. Mean RI decreased by more than half during pregnancy from 0.89 +/- 0.01 to 0.39 +/- 0.03, and mean VOL increased almost 400-fold from 69 +/- 37 to 27,467 +/- 8851 ml/min. There were relationships (P<0.0001) between week of pregnancy (x) and RI as well as VOL. These were described by the equations RI=0.938-0.150 ln(x) and VOL (ml/min)=7.621x(2.157). Log transformed total estrogen (TE) were related to RI (r=-0.879; P<0.05) as well as to VOL (r=0.888; P<0.05). The notch in the Doppler wave of the uterine artery disappeared between 18 and 26 weeks. There was a correlation (P<0.0001) between week of gestation (x) and RI values of the umbilical arteries; this was described by the equation RI=1.763-0.071x+0.001x2. Further studies are needed to determine whether transrectal color Doppler sonography could be used to identify mares at risk of abortion.