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Biomedical subjects

K Goto

Publications and source records attributed to K Goto.

At least 595 records · Page 33Linked to original sources
PubMed1991

External cardiac massage using a hand-powered chest compressor on dogs with ventricular fibrillation.

We devised a hand-powered portable chest compressor for external cardiac massage. The purpose of this study was to assess the efficacy and safety of this device in comparison to manual chest compression in dogs with ventricular fibrillation. Five out of 7 dogs that received manual chest compression during cardiopulmonary resuscitation (CPR) were successfully resuscitated. Seven out of 8 dogs that received mechanical chest compression with this device during CPR were successfully resuscitated. There were no differences between the two methods in maximum arterial pressure at 1 and 10 min after the initiation of CPR. There was also no difference between the two methods in pulmonary arterial pressure or arterial and mixed venous blood gases during CPR. Minimum arterial pressure during CPR was higher in dogs receiving mechanical chest compression than those receiving manual chest compression. This study reveals that the hand-powered chest compressor is equally efficient for external cardiac massage as manual cardiac massage. Moreover, this device can be useful in a situation where manual compression has to be interrupted, such as during litter transport of the patient, and so on.

Journal Article↗
PubMed1991

Structure-activity relationships of mammalian bombesin-like neuropeptides in the contraction of rat uterus.

Various peptide derivatives of the C-terminal decapeptide of gastrin releasing peptide (GRP-10) and neuromedin B (NMB), i.e., carboxyl terminal fragments, amino terminal fragments and substituted analogues, were chemically synthesized and the structure-activity relationships of the peptides were investigated by comparing their contractile activities on the rat uterus. Peptides with chain lengths of 8 and 9 amino acid residues from the C-terminus of GRP-10 and NMB, respectively, had considerable contractile activities. At position 6 of both decapeptides, Val seems to be more favourable than Thr for inducing contraction of the rat uterus. The substitution of His at position 3 and Leu at position 9 of GRP-10 by Leu and Phe, as in NMB leads to a decrease in activity. Moreover, Trp at position 4 and -Met-NH2 at the C-terminus are essential for activity. Furthermore, in order to characterize the bombesin-receptor profile of rat uterus, the inhibitory effect of two peptide antagonists, [D-Arg1, D-Pro2, D-Trp7,9, Leu11]-substance P and [Leu13-phi (CH2NH)-Leu14]-bombesin on the contraction of rat uterus were examined.

Amino Acid Sequence↗
PubMed1991

Characterization of the effect of endothelins in canine cerebral arteries.

In a few populations of endothelial cells of dog basilar arteries, endothelin (ET)-like immunoreactivity was detected to be present. ET-1, ET-2, and ET-3 caused vasoconstrictor responses but not vasodilator responses in isolated ring preparations of dog cerebral arteries in vitro. The ED50 values for the contractions were 411 pM, 478 pM, and 26.5 nM for ET-1, ET-2, and ET-3, respectively. NiCl2 (10(-3) M) attenuated the contractions induced by ET-3 (10(-8)-3 x 10(-7) M) and those to relatively low doses (10(-9) M) but not higher doses (10(-8)-10(-7) M) of ET-1 and ET-2. The contractions in response to ET-1, ET-2, and ET-3 were greatly attenuated in Ca(2+)-free solutions, although high concentrations of ET-1 and ET-2 still evoked contractions. These results suggest that the vasoconstriction induced by ET-3 and lower doses of ET-1 and ET-2 largely depends on the influx of Ca2+ ions. Furthermore, additional distinct mechanisms may contribute to the vasoconstrictor effects of high concentrations of ET-1 and ET-2. The presence of endothelin-like immunoreactivity in endothelial cells suggests that endothelin is a potential endogenous spasmogen.

Animals↗
PubMed1991

Endothelin-1 and endothelin-3 stimulate ovarian steroidogenesis.

The possible direct involvement of endothelin (ET) in preovulatory follicular steroidogenesis was investigated in vitro. Follicular development in immature rats was induced by pregnant mare's serum gonadotropin (PMS). Twenty-four and 48 h after PMS injection, ovarian follicles were incubated in vitro with or without 4 x 10(-11) to 4 x 10(-5) M endothelin-1 (ET-1) or endothelin-3 (ET-3) for 2 h, or perifused in vitro with 4 x 10(-7) M of ET-1 or ET-3 for 3 h. In the incubation study, ET-1 and ET-3 significantly stimulated progesterone, testosterone, and 17 beta-estradiol production by follicles 24 and 48 h after PMS injection. Progesterone, testosterone, and 17 beta-estradiol were increased in a dose-dependent manner by 4 x 10(-11) to 4 x 10(-6) M ET-1 or ET-3; in the case of ET-3, this increase occurred only at 24 h after PMS injection. In addition, ET-1 stimulated ovarian steroid production more effectively than ET-3. In addition to their effects on ovarian steroidogenesis, both ET-1 and ET-3 increased tissue cyclic adenosine-3',5'-monophosphate (cyclic AMP) production. The steroidogenic effect of ET-1 or ET-3 was most pronounced by follicles 48 h after PMS injection. In the perifusion experiment, ET-1 and ET-3 also stimulated progesterone, testosterone, and 17 beta-estradiol secretion. These indicate the involvement of ET-1 or ET-3 in the regulation of ovarian differentiation by stimulating steroidogenesis, at least partially through the mediation of cyclic AMP.

Animals↗
PubMed1991

Effects of endothelin-1 on coronary microcirculation in isolated beating hearts of rats.

An intravital fluorescence videomicroscope system was used to investigate the pharmacological effects of endothelin-1 (ET-1) on the coronary microcirculation in isolated beating hearts of rats. The heart was perfused by retrograde aortic steady flow with an oxygenated Krebs-Ringer solution containing FITC-dextran. Cumulative injections of ET-1 (1-30 pmol) elicited a dose-dependent increase in perfusion pressure from 52 +/- 15 mm Hg (mean +/- SEM; n = 6) before the ET-1 injection to 104 +/- 23 mm Hg at the ET-1 dose of 30 pmol. A dose-dependent narrowing of microvessels was also observed on a monitor screen. This diffuse vasoconstriction was especially prominent in small arterioles; the maximum vasoconstriction of the smaller arterioles was significantly higher than that of the larger arterioles. These findings suggest that ET-1 may have an important role in governing the coronary resistance and regulating the capillary flow in myocardium.

Animals↗
PubMed1991

Comparison of endothelin-1 concentrations in normal and complicated pregnancies.

Endothelin-1 (ET-1) may be important in regulating vascular tone in humans. To understand the role of ET-1 during pregnancy, we measured the concentrations of plasma immunoreactive ET-1 in normal, toxemic (pre-eclamptic or eclamptic), and other complicated pregnancies. There were no significant differences between ET-1 concentrations in normal pregnancy and those in toxemic pregnancy, except in one case with IgA nephropathy and severe toxemia. There also was no significant difference between the ET-1 concentrations in pure toxemia of pregnancy compared with superimposed toxemia of pregnancy. Furthermore, there was no correlation between ET-1 concentrations, blood pressure, or renal function during toxemic pregnancy. Similarly, there were no significant differences between ET-1 plasma levels in normal pregnancies and other complicated pregnancies except for two cases in which much blood was lost due to uterine atony and abruptio placenta. Thus, plasma ET-1 concentrations showed no significant relationship to blood pressure or renal function during normal or toxemic pregnancy, and were not related to the type (pure or superimposed type), grade, or severity of toxemic pregnancy.

Adult↗
PubMed1991

Plasma concentrations of endothelin-1 and endothelin-3 are altered differently in various pathophysiological conditions in humans.

Several studies have indicated that endothelin-1 (ET-1) and endothelin-3 (ET-3) are produced by different cells. Although ET-1 is produced by vascular endothelial cells, these cells do not produce ET-3. In the present study, we measured plasma concentrations of both ET-1 and ET-3 by sandwich-enzyme immunoassays which we developed recently in patients on chronic hemodialysis, age-matched normal subjects, patients with acute myocardial infarction, patients undergoing surgery, and healthy subjects before and after strenuous endurance exercise. Plasma levels of ET-1 and ET-3 were demonstrated to be altered differently in the above conditions in humans. Although the exact origin of circulating endothelins has yet to be elucidated, the different alterations of plasma levels suggest that both ET-1 and ET-3 may play different roles in physiological and/or pathophysiological responses to various conditions in humans.

Adult↗
PubMed1991

Increased plasma concentrations of endothelin-1 during and after pulmonary surgery.

We studied the involvement of endothelin-1 (ET-1) in the physiological response to surgical stress. Plasma concentrations of ET-1 were measured by a sandwich-type enzyme immunoassay. The blood samples were collected from the pulmonary artery (PA), the left atrium (LA), and the median cubital vein (MCV) in four patients who had undergone pulmonary lobectomy. The samples were collected before, during, and after surgery. Plasma ET-1 concentrations increased in the blood from all sampling sites. The highest concentration of plasma ET-1 was observed at 6 h after surgery in MCV (3.97 +/- 1.47 pg/ml, mean +/- SD) and at the end of surgery in PA (1.79 +/- 0.48 pg/ml) and in LA (1.93 +/- 0.43 pg/ml). These values returned to the baseline value within 72 h after surgery [1.21 +/- 0.19 (MCV), 1.00 +/- 0.18 (PA)]. Although the lung has a large capacity to remove ET-1 from the circulating blood, ET-1 concentrations measured in plasma samples obtained from the LA were not different from those obtained from the PA. This may suggest that the lungs have the ability to absorb and release ET-1 simultaneously during pulmonary surgery. The increase of ET-1 in MCV was greater than that in PA or in LA. This suggests the possibility of ET-1 release from the forearm.

Endothelins↗
PubMed1991

Sandwich-enzyme immunoassays for endothelin family peptides.

Sandwich-enzyme immunoassays (sandwich-EIAs) for endothelin-1 (ET-1), endothelin-3 (ET-3), big ET-1, big endothelin-2 (big ET-2), and big endothelin-3 (big ET-3) have been established using two antibodies directed against the N-terminal and C-terminal portions of each ET and big ET. These sandwich-EIAs are sensitive enough to detect 0.1-0.4 pg/well of each ET or big ET with cross-reactivity of less than 1% with other ETs and big ETs (except in the case of the EIA for ET-1, which detects immunoreactivity of ET-2 as well as ET-1). Plasma levels of immunoreactive (ir-) ET-1, big ET-1, and ET-3 in normal humans were approximately 2.0, 5.1, and 0.9 pg/ml, respectively, when corrected for recovery efficiency. In reverse-phase high-performance liquid chromatography (HPLC) analysis, immunoreactivities detected by these sandwich-EIAs were eluted at the positions of authentic ET-1, big ET-1, and ET-3, indicating that plasma levels of ET-1, big ET-1, and ET-3 were precisely measured by our methods. Levels of ir-big ET-2 and ir-big ET-3 were also detected in normal human plasma; however, further studies are needed to determine their precise values. The establishment of reliable sandwich-EIAs and the measurement of specific ETs and big ETs in normal human plasma will contribute to clarifying the biological and clinical significance of ET family peptides.

Adult↗
PubMed1991

Possible role of endothelin in the pathogenesis of cerebral vasospasm.

Since the discovery of endothelin-1 (ET-1), its involvement in cerebral vasospasm after subarachnoid hemorrhage (SAH) has been suspected. We performed various experiments, first to demonstrate the presence of ET in both patients and dogs with SAH, and second to examine the effects of ET synthesis inhibition in experimental vasospasm. Here we report that ET was present in both plasma and cerebrospinal fluid (CSF) in SAH, but did not correlate with vasospasm. However, ET was locally expressed in the vascular endothelium in vasospasm. Several therapeutic approaches causing the inhibition of ET synthesis were effective in preventing the development of vasospasm. Such approaches utilized drugs that inhibited RNA and DNA synthesis. Among them, actinomycin D treatment was most effective. We also utilized phosphoramidon, a recently found conversion inhibitor of big ET to ET. However, this product failed to ameliorate the development of vasospasm. Therefore, although we cannot yet conclude that ET is the main cause of cerebral vasospasm, it may, at least, act as one of the modifying factors in cerebral vasospasm.

Animals↗
PubMed1991

Endothelins: vasoconstrictor effects and localization in canine cerebral arteries.

1. The vascular effects of endothelin and localization of endothelin-like immunoreactivity were characterized in isolated cerebral arteries of dogs. 2. Endothelin-like immunoreactivity was detected in a few populations of endothelial cells of dog basilar artery. 3. Endothelin-1, endothelin-2 and endothelin-3 contracted isolated ring preparations of cerebral arteries in a dose-dependent manner independently of the presence of endothelium. The ED50 values (and 95% confidence intervals) for the contraction were 411 pM (242-697 pM) and 478 pM (295-776 pM) for endothelin-1 and endothelin-2, respectively. Endothelin-3 induced vascular contraction at a higher concentration (ED50 = 26.5 nM, 95% confidence interval = 15.7-45.7 nM). 4. The increases in tone induced by endothelin-1 and endothelin-2 did not return to the resting level after repeated washings, while a rinse with Krebs solution reversed the vasoconstrictor response to endothelin-3. The endothelins did not cause any vasodilator response in arteries precontracted with uridine 5'-triphosphate even in the presence of intact endothelial cells. 5. NiCl2 (1 mM) attenuated the contractions induced by endothelin-3 (10-300 nM) and those to relatively low doses (1 nM) but not higher doses (10-100 nM) of endothelin-1 and endothelin-2. The contractions in response to endothelin-1, endothelin-2 and endothelin-3 were greatly attenuated in Ca(2+)-free solutions although high concentrations of endothelin-1 and endothelin-2 still evoked contractions. 6. These results suggest that the vasoconstriction induced by endothelin-3 and lower doses of endothelin-1 and endothelin-2, largely depends on the influx of Ca2+ ions. The apparent insensitivity to Ni2+ shows that additional distinct mechanisms also operate in the vasconstrictor responses to high concentrations of endothelin-1 and endothelin-2. 7. The presence of endothelin-like immunoreactivity in endothelial cells suggests that endothelin is a potential endogenous spasmogen.

Animals↗
PubMed1991

Characteristics of binding of endothelin-1 and endothelin-3 to rat hearts. Developmental changes in mechanical responses and receptor subtypes.

Endothelin-1 (ET-1) and endothelin-3 (ET-3) produced positive inotropic effects on electrically stimulated left atria and increased the frequency of spontaneously beating right atria of adult rats. The potency of the inotropic effect of ET-1 was greater than that of ET-3, but the potencies of the chronotropic effects of ET-1 and ET-3 were not significantly different. In the neonatal atria, ET-1 and ET-3 also induced positive inotropic and chronotropic responses. ET-1 and ET-3 showed weak or no cardiotonic effects on the adult ventricles, whereas they caused marked positive inotropy in the neonatal ventricles. The characteristics of binding sites for ET-1 and ET-3 were very similar between the atria and the ventricles of the rat neonate. Saturation and competition binding experiments have shown that neonatal cardiac membranes from both atria and ventricle have two distinct binding sites for endothelin, that is, a low-affinity and a high-affinity site. ET-1 was found to bind to the low-affinity sites with a significantly lower Kd than ET-3, whereas the estimated Kd values for ET-1 and ET-3 at the high affinity sites were similar. In contrast, the binding sites in adult atria were different from those of the ventricles: only a single binding site for both ET-1 and ET-3 was detected. Adult atrial membranes, on the other hand, had two distinct binding sites similar to those of neonatal membranes.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1991

[Effect of inclusion complexation of decanoic acid with alpha-cyclodextrin on rectal absorption of cefmetazole sodium suppository in rabbits].

Inclusion complex of decanoic acid (DA) with alpha-cyclodextrin (alpha-CyD) was prepared as an additive of cefmetazole sodium (CMZ) suppository and rectally administered to rabbits. The resulting complexation was examined by the phase solubility method, differential scanning calorimetry (DSC) and X-ray diffractometry. Plasma concentration and AUC of CMZ after rectal administration of a suppository containing DA/alpha-CyD complex to rabbits increased more significantly than those with none additive.

Adjuvants, Pharmaceutic↗
PubMed1991

Endothelin-1-induced phosphorylation of the 20-kDa myosin light chain and caldesmon in porcine coronary artery smooth muscle.

Endothelin-1 (ET), a potent vasoconstrictor, induces a sustained increase in the phosphorylation level of the 20-kDa myosin light chain (MLC) in porcine coronary artery strips. ET also induces late phosphorylation of caldesmon, which is mimicked by 12-deoxyphorbol 13-isobutyrate, but not by 60 mM KCl. Nitroglycerin, a vasorelaxant, completely reverses the ET-induced phosphorylation of MLC, but not that of caldesmon. These results suggest an important regulatory role of MLC phosphorylation in ET-induced contraction.

Animals↗