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Biomedical subjects

E Ushioda

Publications and source records attributed to E Ushioda.

18 recordsLinked to original sources
PubMed1986

[Pharmacokinetics of adriamycin vaginal suppository in uterine cervical cancer].

Vaginal suppositories of Adriamycin (ADM, 5 mg), for reducing the capacity for repair from sublethal damage of X-ray-irradiated cells, were prepared using Wipepsol S-55 as the vehicle, and were intravaginally administered to patients with advanced uterine cervical cancer, and their pharmacokinetics and clinical effects were studied. The ADM concentration in the uterine cervical cancer tissues indicated high levels (17 to 566 micrograms/g), and migration into the cardinal ligament and regional lymph nodes was noted. However, little ADM was detected in serum (0 to 0.14 micrograms/g), probably because of its molecular weight and excellent tissue absorbance, and no side effects, such as cardiotoxicity and myelosuppression due to consecutive administration were detected. Histologically, the effect obtained when administered alone was limited, administration in combination with radiotherapy being more effective. Accordingly, radiotherapy of advanced uterine cervical cancer with concomitant administration of ADM vaginal suppositories seems to bring about a more powerful antitumoral effect with fewer systemic side effects.

Cervix Uteri↗
PubMed1985

[Fundamental and clinical studies of aztreonam in the field of obstetrics and gynecology].

Aztreonam (AZT, E-0734), a new beta-lactam antibiotic, was fundamentally and clinically studied. The following results were obtained. The serum and internal genital tissue levels for AZT after 1 g intravenous injection had been kept at more than about 20 micrograms/ml and 3.0 micrograms/g, respectively, during 1 hour. AZT was administered at 1-2 g of daily dose by intravenous injection or intravenous drip infusion to 5 patients with obstetric and gynecological infections, comprising 1 of pyometra, parametritis, Bartholin's abscess, puerperal endometritis and diffuse peritonitis. Clinical efficacy was; excellent in 1 puerperal endometritis case, good in 2 cases and poor in 2 cases. Neither side effect nor abnormal laboratory finding was observed.

Adult↗
PubMed1983

The contribution of the beta-adrenergic system to the cardiovascular response to hypovolemia.

Unanesthetized, chronically instrumented, nonpregnant sheep were studied in periods of progressive blood withdrawal, hypovolemic shock, blood reinfusion, and recovery. Hemodynamic responses were recorded during experiments with an intact beta-adrenergic system (saline solution), beta-adrenergic blockage (propranolol), and beta-adrenergic stimulation (isoxsuprine). With an intact beta-adrenergic system, stepwise bleeding produced a progressive decrease in arterial pressure, stroke volume, and cardiac output and an increase in systemic vascular resistance; heart rate increased initially but fell when hypovolemia became severe. All circulatory parameters returned toward control valves during blood reinfusion and recovery. In animals deprived of beta-adrenergic control, the hemodynamic response to progressive hypovolemia and blood reinfusion was not greatly different from that of control animals, despite abolition of tachycardia. During beta-adrenergic stimulation, arterial pressure and cardiac output fell more rapidly than in control and tachycardia was relatively small; cardiac output and stroke volume rebounded strikingly during reinfusion and recovery. These results support findings of others that the role of the beta-adrenergic system is minor during hypovolemia. When pharmacologically activated, it might play a significant role in the posthypovolemia compensatory mechanisms.

Animals↗
PubMed1982

Mixing problems in using indicators for measuring regional blood flow.

A basic requirement for using indicators for measuring blood flow is adequate mixing of the indicator with blood prior to sampling the site. This requirement has been met by depositing the indicator in the heart and sampling from an artery. Recently, authors have injected microspheres into veins and sampled from venous sites. The present studies were designed to investigate the mixing problems in sheep and rabbits by means of Cardio-Green and labeled microspheres. The indicators were injected at different points in the circulatory system, and blood was sampled at different levels of the venous and arterial systems. Results show the following. (a) When an indicator of small molecular size (Cardio-Green) is allowed to pass through the heart chambers, adequate mixing is achieved, yielding accurate and reproducible results. (b) When any indicator (Cardio-Green or microspheres) is injected into veins, and sampling is done at any point in the venous system, mixing is inadequate, yielding flow results which are inconsistent and erratic. (c) For an indicator or large molecular size (microspheres), injecting into the left side of the heart and sampling from arterial sites yield accurate and reproducible results regardless of whether blood is sampled continuously or intermittently.

Animals↗
PubMed1982

Circulatory effects of chemical sympathectomy in fetal, neonatal, and adult sheep.

Circulatory effects of chemical sympathectomy with 6-hydroxydopamine (6-HD), including changes in vascular sensitivity to neurotransmitters, were investigated in chronically instrumented unanesthetized fetal, neonatal, and adult sheep. In all animals acute response to 6-HD consisted of hypertension and tachycardia, which lasted 2-3 h. Chronic phase of sympathetic ablation then followed during which arterial pressure and heart rate of sympathectomized fetus and neonate returned to and remained at levels observed in intact animals, whereas adult sheep were slightly hypotensive throughout this period. In all animals supersensitivity of peripheral circulation to norepinephrine occurred, but only the fetus exhibited supersensitivity to acetylcholine and isoproterenol. Our conclusions are as follows: 1) acute phase of chemical sympathectomy in fetal, neonatal, and adult sheep simulates strong adrenergic stimulation; 2) absence of significant alteration in arterial pressure of fetus and neonate during the chronic phase of sympathectomy suggests a minor role for the adrenergic system in the maintenance of resting tone of peripheral circulation; and 3) on the basis of present and previous data, we postulate that the supersensitivity of fetal circulation to acetylcholine and isoproterenol may be secondary to changes occurring in pulmonary vascular bed.

Acetylcholine↗
PubMed1981

Autonomic control of the pelvic circulation: in vivo and in vitro studies in pregnant and nonpregnant sheep.

Pregnancy alters the autonomic control of the peripheral circulation. Present in vivo and in vitro studies were designed to investigate the mechanisms of these alterations. In the in vivo studies, pelvic and systemic circulatory responses to intra-arterial and intravenous injections of agonists were monitored in unanesthetized pregnant and nonpregnant ewes. In in vitro studies, a comparison was made of responses to transmural nerve stimulation (TNS) and to norepinephrine (NE) of different blood vessels obtained from pregnant and nonpregnant ewes. The results were the following: (1) Pelvic vascular response to all vasoactive stimuli was considerably more depressed during pregnancy than was systemic circulatory response. (2) In vitro reactivity to alpha-adrenergic stimulation with NE of different blood vessels obtained from pregnant animals was similar to that of vessels from nonpregnant animals. (3) The response to TNS of blood vessels obtained from pregnant ewes was less than that of vessels from nonpregnant ewes. The conclusions were that (a) probably largely related to dilution of a given dose of the stimulus in the greater blood volume and flow; and (b) the increased neurogenic tone of the peripheral circulation during pregnancy is most likely related to increased nerve firing rather than neural density in the vessel walls.

Acetylcholine↗
PubMed1981

Responses of the pelvic vascular bed to intra-arterial stimulation of beta-adrenergic and cholinergic receptors in pregnant and nonpregnant sheep.

The responses of different parts of the pelvic vascular bed to beta-adrenergic and cholinergic receptor stimulation were studied in chronically instrumented, unanesthetized pregnant and nonpregnant sheep. Isoproterenol and acetylcholine were administered intra-arterially in progressively increasing bolus injections, and dose-response curves were constructed for changes in blood flows, arterial pressure, and heart rate. Response to beta-adrenergic and cholinergic stimulation was measured before and after the agents reached the central circulation. In addition, data were obtained from the same animals before and after pharmacologic cardiac denervation. Results show: (1) Stimulation of beta-adrenergic and cholinergic receptors produced active vasodilatation in extrauterine vascular beds with minor changes in uterine blood flow of the pregnant horn; (2) the changes in uterine flow observed during beta-adrenergic and cholinergic stimulation were probably secondary and related to a shift of blood from the uterus to other vascular beds that were actively dilated; (3) the response of the pregnant animal to any given dose of the autonomic agonist was strikingly smaller to that of the nonpregnant animal. A number of physiologic factors peculiar to pregnancy may contribute to this difference; among these are: (1) dilution factor related to the greater volume flow; (2) near-maximal dilatation of some blood vessels and the presence of the two resistance system of placental circulation, and (3) the effect of progesterone on the vascular smooth muscle.

Acetylcholine↗
PubMed1981

Nitroprusside-induced hemodynamic alterations in normotensive and hypertensive pregnant sheep.

It has been suggested that sodium nitroprusside, a potent vasodilator, be used in the management of an acute hypertensive crisis during pregnancy. The present study was designed to evaluate the hemodynamic effects of this agent in the same group of chronically instrumented, unanesthetized pregnant sheep during two experimental periods: (a) normotension with intact kidneys, and (b) one-kidney hypertension. The results demonstrate that (1) nitroprusside is a potent vasodilator which lowers mean arterial pressure; (2) nitroprusside-induced tachycardia was greater in the hypertensive animal; (3) uterine blood flow decreased with the development of hypertension; (4) the hypertensive-induced reduction in uterine blood flow was increased by the infusion of nitroprusside.

Animals↗
PubMed1981

Hemodynamic responses of the pelvic vascular bed to vasoactive stimuli in pregnant sheep.

The responses of the common internal iliac artery and middle uterine artery of the pregnant horn to continuous infusions of graded doses of norepinephrine, epinephrine, dopamine, isoxsuprine, angiotensin and nitroprusside were investigated in chronically instrumental pregnant ewes. Norepinephrine progressively decreased the blood flow and increased the resistance in both vessels but the changes were more marked in the middle uterine artery. Isoxsuprine and epinephrine had an insignificant effect on the common internal iliac artery blood flow, but decreased that of the middle uterine artery. Nitroprusside decrease the flow in both vessels proportionately. Angiotensin in doses less than 0.16 micrograms/kg/min increased the flow in both arteries to the same extent, but higher doses decreased both flows. It is concluded that in the chronically instrumented pregnant ewe, the responses of contiguous vascular beds to different vasoactive agents may differ depending on the nature of the stimulus.

Angiotensin II↗
PubMed1980

Mechanisms of beat-to-beat variability in the heart rate of the neonatal lamb. I. Influence of the autonomic nervous system.

The contributions of the intrinsic, beta-adrenergic, and cholinergic systems to the mechanisms of beat-to-beat variability of the heart rate were investigated in chronically instrumented, unanesthetized newborn lambs from the first week to the eighth week of neonatal life. During this period of neonatal growth, the resting heart rate decreased spontaneously every week; the decrease was not related to alterations in the sympathetic and parasympathetic tones but rather to changes in the intrinsic mechanisms of heart rate control. Despite the weekly decrease in the resting heart rate of the neonatal lamb, the long and short-term beat-to-beat variabilities did not change significantly. This finding suggests an absence of a significant influence of the intrinsic mechanisms of heart rate control on the genesis of beat-to-beat variability. The results obtained with the various modes of adrenergic and cholinergic blockades and stimulation seem to indicate that the autonomic nervous system contributes significantly to the appearance of beat-to-beat variability. However, the influences of the adrenergic and cholinergic systems differ from week to week of neonatal growth and the patterns of changes are not the same for the long-term and short-term variabilities. The implication of these studies in terms of physiologic and hemodynamic significance of beat-to-beat variability in heart rate is discussed.

Aging↗
PubMed1980

Mechanisms of beat-to-beat variability in the heart rate of the neonatal lamb. II. Effects of hypoxia.

The effects of acute hypoxia on the resting arterial pressure as well as on heart rate and its beat-to-beat variability were studied in chronically instrumented, unanesthetized newborn lambs at 2 to 8 weeks of neonatal life. Lung ventilation with a gas mixture containing 10% oxygen and 3% carbon dioxide decreased arterial blood PO2 by about 50% in all animals regardless of age without significantly altering blood pH and PCO2. This degree of hypoxia produced a mild pressor response, accompanied by a significant tachycardia; the pattern of these changes, however, differed somewhat according to neonatal growth. The impact of hypoxia on beat-to-beat variability of the neonatal heart rate also varied with age. When the lambs were 2 to 3 weeks old, both the long- and short-term variabilities decreased progressively during hypoxia and the decrement reached a maximum at 10 minutes of oxygen deprivation. As the lambs became older, however, there was some initial and transient increase in the long- and short-term variabilities in the early period of hypoxia but thereafter the changes were inconsistent. The significance of these observations is discussed in terms of our knowledge of the pathophysiologic alterations in the cardiovascular system produced by acute hypoxia.

Aging↗
PubMed1980

Vascular reactivity to angiotensin II in the normotensive and hypertensive pregnant ewe.

The circulatory responses to progressively increasing doses of angiotensin II were studied in the same group of chronically instrumented unanesthetized pregnant sheep during three consecutive periods: a) normotensive with intact kidneys; b) normotensive with unilateral nephrectomy; and c) one-kidney hypertension. The results show that 1) the pressor response to a given dose of angiotensin was significantly greater in the normotensive than in the hypertensive condition; 2) uterine blood flow decreased markedly with the development of hypertension; 3) uterine circulatory response to angiotensin depended on the dosage; the response was less the the hypertensive than in the normotensive condition; 4) renal blood flow decreased and renal vascular resistance increased during angiotensin infusion, but the response was less in the hypertensive than in the normotensive condition; the response of the renal circulation decreased with increasing doses of angiotensin. These observations suggest a generalized vascular refractoriness to exogenous angiotensin II in the pregnant ewe with experimental renal hypertension.

Angiotensin II↗
PubMed1979

Uteroplacental blood flow and uteroplacental shunt rates in normal and prolonged pregnancies in rats.

To reveal the regulatory function in uteroplacental blood flow we measured, using the method of double tracer microspheres, the rates of uteroplacental blood flow (UPBF) and uteroplacental shunt (UP-shunt) in SD-strain rats of normal and prolonged pregnancy. (1) In the group of rats of normal pregnancy, the rate of UPBF attained a peak on the 20th day of gestation, while the UP-shunt rate was highest on the 18th day of gestation. (2) In the progesterone-induced prolonged pregnancy group, the rate of UPBF remained at an 8% level until the the 22nd day, i.e., the first day of prolonged pregnancy, and dropped to 6.6% on the 23rd day. The UP-shunt rate in the progesterone-administered group was about 27% on the 20th day, more favorable than the corresponding rate in the normal group, but thereafter rapidly decreased. The rate of increase in fetal body weight in this group became lower, showing a fetal death rate of 4.6%. (3) The decreases in placental alkaline phosphatase and leucine aminopeptidase examined as markers of placental function lagged behind the fall in the UP-shunt rate. On the 23rd day of gestation when the rates of UPBF and UP-shunt dropped, the decreases in their placental enzyme activities were remarkable.

Alkaline Phosphatase↗