Biomedical subjects

H Suga

Publications and source records attributed to H Suga.

At least 37 records · Page 2Linked to original sources

PubMed2001

Preparation of new nitrogen-bridged heterocycles. 51. Syntheses and structures of compounds having two indolizine nuclei in a molecule.

New compounds having two indolizine nuclei in a molecule were prepared in low to moderate yields from the reactions of potassium 2-indolizinethiolates with 1,omega-dihalides such as 1,2-diiodoethane, 1,3-dibromopropane, 1,4-dibromobutane, alpha,alpha'-dichloro-o-xylene, and alpha,alpha'-dichloro-p-xylene. Most of the products had the conformation in which the two indolizine rings in the molecule are as remote as possible, but only 1,2-bis[[(2-indolizinyl)thio]methyl]benzene derivatives, prepared from potassium 2-indolizinethiolates and alpha,alpha'-dichloro-o-xylene, showed a weak attractive interaction between the two indolizine nuclei in the X-ray analysis and the nuclear Overhauser and exchange spectroscopy (NOESY) spectrum.

Heterocyclic Compounds, Bridged-Ring↗

PubMed2001

New calculation of internal Ca(2+) recirculation fraction from alternans decay of postextrasystolic potentiation.

In our previous studies, we calculated the internal Ca(2+) recirculation fraction (RF) after obtaining the beat decay constant (tau(e)) of the monoexponential component in the postextrasystolic potentiation (PESP) of the alternans decay by curve fitting. However, this method sometimes suffers from the sensitive variation of tau(e) with small noises in the measured contractilities of the 5th and 6th postextrasystolic (PES) beats in the tail of the exponential component. We now succeeded in preventing this problem by a new method to calculate RF without obtaining tau(e). The equation for the calculation in the new method expresses an alternans decay of PESP as a recurrence formula of PESP. It can calculate RF directly from the contractilities of the 1st through the 4th PES beats without any fitting procedure. To evaluate the reliability of the new method, we calculated RF from the alternans decay of PESP of the left ventricle (LV) of the canine excised cross-circulated heart preparation by both the original fitting and the new method. Although there was no significant difference in the mean value of the obtained RF between these two methods, the variance of RF was smaller with the new method than with the original method. Thus the new method proved useful and more reliable than the original fitting method.

Animals↗

PubMed2001

Cardiovascular beneficial effects of electroacupuncture at Neiguan (PC-6) acupoint in anesthetized open-chest dog.

Neiguan (PC-6) is a traditional acupoint in the bilateral forearms, overlying the median nerve trunk. Neiguan electroacupuncture (EA) has been believed to affect cardiovascular function and used in traditional Chinese medicine to improve or treat a wide range of health conditions and diseases, including angina pectoris, myocardial infarction, hypertension, and hypotension. However, few physiological studies have assessed the beneficial effects of Neiguan EA on the cardiovascular function. In the present study, we investigated its effects on the cardiovascular function in normal open-chest dogs under pentobarbital and fentanyl anesthesia. We also obtained left ventricular (LV) pressure-volume (P-V) data with a micromanometer catheter and a volumetric conductance catheter. Mean arterial pressure, end-diastolic volume, heart rate, stroke volume, cardiac output, and end-systolic pressure gradually decreased by 5 to 10% over 1.5 h without Neiguan EA. Neiguan EA at 40 Hz, however, increased these cardiovascular variables by 10 to 15%, especially end-systolic elastance (Ees) by 40% (p<0.05) over 15 to 60 min. After Neiguan EA was stopped at 1 h, these facilitated cardiovascular variables decreased below the pre-EA level. This beneficial effect of electroacupuncture may contribute to the effectiveness of the acupuncture in Chinese medicine.

Adjuvants, Anesthesia↗

PubMed2001

Frank-Starling mechanism retains recirculation fraction of myocardial Ca(2+) in the beating heart.

Myocardial Ca(2+) handling in excitation-contraction coupling is the second primary determinant of energy or O(2) demand in a working heart. The intracellular and extracellular routes remove myocardial Ca(2+) that was released into the sarcoplasma with different Ca(2+): ATP stoichiometries. The intracellular route is twice as economical as the extracellular route. Therefore the fraction of total Ca(2+) removed via the sarcoplasmic reticulum, i.e., the recirculation fraction of intracellular Ca(2+) (RF), determines the economy of myocardial Ca(2+) handling. RF has conventionally been estimated as the exponential decay rate of postextrasystolic potentiation (PESP). However, we have found that PESP usually decays in alternans, but not exponentially in the canine left ventricle beating above 100 beats/min. We have succeeded in estimating RF from the exponential decay component of an alternans PESP. We previously found that the Frank-Starling mechanism or varied ventricular preload did not affect the economy of myocardial Ca(2+) handling. Then, to account for this important finding, we hypothesized that the Frank-Starling mechanism would not affect RF at a constant heart rate. We tested this hypothesis and found its supportive evidence in 11 canine left ventricles. We conclude that RF at a constant heart rate would remain constant, independent of the Frank-Starling mechanism.

Action Potentials↗

PubMed2001

Total Ca2+ handling for E-C coupling in the whole heart: an integrative analysis.

We assessed total Ca2+ handling (transport, flux) in excitation-contraction (E-C) coupling in a beating left ventricle (LV). We developed a new integrative analysis method that utilizes the internal Ca2+ recirculation fraction (RF), O2 consumption (V(O2)) for Ca2+ handling, and O2 cost of Emax (contractility index) of the LV. We obtained the RF from the beat constant of the exponential decay component of the postextrasystolic potentiation, and the O2 cost of Emax from V(O2) measured at different Emax. Our equation calculated the unknown total Ca2+ handling, futile Ca2+ cycling, and Ca2+ reactivity of Emax from the RF and Ca2+ handling V(O2). The calculated total Ca2+ handling fell between 30 and 110 micromol/kg, depending on Emax and pathological conditions. Our method also allowed an assessment of futile Ca2+ cycling and Ca2+ reactivity of Emax in a beating LV. These data are not available using conventional methods. Our method can be used to better understand the pathophysiology of total Ca2+ handling in a beating heart.

Animals↗

PubMed2001

Concurrent molecular recognition of the amino acid and tRNA by a ribozyme.

We have recently reported an in vitro-evolved precursor tRNA (pre-tRNA) that is able to catalyze aminoacylation on its own 3'-hydroxyl group. This catalytic pre-tRNA is susceptible to RNase P RNA, generating the 5'-leader ribozyme and mature tRNA. The 5'-leader ribozyme is also capable of aminoacylating the tRNA in trans, thus acting as an aminoacyl-tRNA synthetase-like ribozyme (ARS-like ribozyme). Here we report its structural characterization that reveals the essential catalytic core. The ribozyme consists of three stem-loops connected by two junction regions. The chemical probing analyses show that a U-rich region (U59-U62 in J2a/3 and U67-U68 in L3) of the ribozyme is responsible for the recognition of the phenylalanine substrate. Moreover, a GGU-motif (G70-U72) of the ribozyme, adjacent to the U-rich region, forms base pairs with the tRNA 3' terminus. Our demonstration shows that simple RNA motifs can recognize both the amino acid and tRNA simultaneously, thus aminoacylating the 3' terminus of tRNA in trans.

Amino Acids↗

PubMed2000

Stereocontrol in rare earth metal triflate-catalyzed 1,3-dipolar cycloaddition reaction of 2-benzopyrylium-4-olate with aldehydes

Exo-cycloadduct was obtained with high stereoselectivity by the addition of ytterbium triflate (Yb(OTf)(3)) (10 mol %) in the rhodium(II) acetate (Rh(2)(OAc)(4))-catalyzed decomposition of o-(methoxycarbonyl)-alpha-diazoacetophenone in the presence of benzaldehyde. In the reaction in the absence of Yb(OTf)(3), almost no selectivity was obtained. Stereoselectivity in the reactions with p-nitrobenzaldehyde, p-anisaldehyde, and benzyloxyacetaldehyde could be also controlled to high exo preference by the addition of Yb(OTf)(3).

Journal Article↗

PubMed2000

Protein tyrosine phosphatases from amphioxus, hagfish, and ray: divergence of tissue-specific isoform genes in the early evolution of vertebrates.

Since separation from fungi and plants, multicellular animals evolved a variety of gene families involved in cell-cell communication from a limited number of ancestral precursors by gene duplications in two separate periods of animal evolution. In the very early evolution of animals before the separation of parazoans and eumetazoans, animals underwent extensive gene duplications by which different subtypes (subfamilies) with distinct functions diverged. The multiplicity of members (isoforms) in the same subtype increased by further gene duplications (isoform duplications) in the first half of chordate evolution before the fish-tetrapod split; different isoforms are virtually identical in structure and function but differ in tissue distribution. From cloning and phylogenetic analyses of four subfamilies of the protein tyrosine kinase (PTK) family, we recently showed extensive isoform duplications in a limited period around or just before the cyclostome-gnathostome split. To obtain a reliable estimate for the divergence time of vertebrate isoforms, we have conducted isolation of cDNAs encoding the protein tyrosine phosphatases (PTPs) from Branchiostoma belcheri, an amphioxus, Eptatretus burgeri, a hagfish, and Potamotrygon motoro, a ray. We obtained 33 different cDNAs in total, most of which belong to known PTP subfamilies. The phylogenetic analyses of five subfamilies based on the maximum likelihood method revealed frequent isoform duplications in a period around or just before the gnathostome-cyclostome split. An evolutionary implication was discussed in relation to the Cambrian explosion.

Animals↗

PubMed2000

Ribozyme-catalyzed tRNA aminoacylation.

The RNA world hypothesis implies that coded protein synthesis evolved from a set of ribozyme catalyzed acyl-transfer reactions, including those of aminoacyl-tRNA synthetase ribozymes. We report here that a bifunctional ribozyme generated by directed in vitro evolution can specifically recognize an activated glutaminyl ester and aminoacylate a targeted tRNA, via a covalent aminoacyl-ribozyme intermediate. The ribozyme consists of two distinct catalytic domains; one domain recognizes the glutamine substrate and self-aminoacylates its own 5'-hydroxyl group, and the other recognizes the tRNA and transfers the aminoacyl group to the 3'-end. The interaction of these domains results in a unique pseudoknotted structure, and the ribozyme requires a change in conformation to perform the sequential aminoacylation reactions. Our result supports the idea that aminoacyl-tRNA synthetase ribozymes could have played a key role in the evolution of the genetic code and RNA-directed translation.

Acylation↗

PubMed2000

Energy-wasteful total Ca(2+) handling underlies increased O(2) cost of contractility in canine stunned heart.

Postischemic myocardial stunning halved left ventricular contractility [end-systolic maximum elastance (E(max))] and doubled the O(2) cost of E(max) in excised cross-circulated canine heart. We hypothesized that this increased O(2) cost derived from energy-wasteful myocardial Ca(2+) handling consisting of a decreased internal Ca(2+) recirculation, some futile Ca(2+) cycling, and a depressed Ca(2+) reactivity of E(max). We first calculated the internal Ca(2+) recirculation fraction (RF) from the exponential decay component of postextrasystolic potentiation. Stunning significantly accelerated the decay and decreased RF from 0.63 to 0. 43 on average. We then combined the decreased RF with the halved E(max) and its doubled O(2) cost and analyzed total Ca(2+) handling using our recently developed integrative method. We found a decreased total Ca(2+) transport and a considerable shift of the relation between futile Ca(2+) cycling and Ca(2+) reactivity in an energy-wasteful direction in the stunned heart. These changes in total Ca(2+) handling reasonably account for the doubled O(2) cost of E(max) in stunning, supporting the hypothesis.

Animals↗

PubMed2000

Postextrasystolic contractile decay always contains exponential and alternans components in canine heart.

In isolated, blood-perfused canine hearts, postextrasystolic potentiation (PESP) decays monotonically after a noncompensatory pause following a spontaneous extrasystole (ES). The monotonic PESP decay yields myocardial internal Ca(2+) recirculation fraction (RF). We have found that after a compensatory pause (CP), PESP decays in alternans, consisting of an exponential and a sinusoidal decay component. We have proposed that this exponential component also yields RF. In the present study, we examined the reliability of this alternative method by widely changing the ES coupling interval (ESI), CP, and heart rate in the canine excised, cross-circulated left ventricle. We found that all PESP decays consisted of the sum of an exponential and a sinusoidal decay component of variable magnitudes whether a CP existed or not. Their decay constants as well as the calculated RF were independent of the ESI and CP. This confirmed the utility of our alternative RF determination method regardless of the ESI, CP, and heart rate. Direct experimental evidence of Ca(2+) dynamics supportive of this alternative method, however, remains to be obtained.

Animals↗

PubMed2000

Negative inotropism of hyperthermia increases oxygen cost of contractility in canine hearts.

Heart temperature affects left ventricular (LV) function and myocardial metabolism. However, how and whether increasing heart temperature affects LV mechanoenergetics remain unclear. We designed the present study to investigate effects of increased temperature by 5 degrees C from 36 degrees C on LV contractility and energetics. We analyzed the LV contractility index (E(max)) and the relation between the myocardial oxygen consumption (MVO(2)) and the pressure-volume area (PVA; a measure of LV total mechanical energy) in isovolumically contracting isolated canine hearts during normothermia (NT) and hyperthermia (HT). HT reduced E(max) by 38% (P < 0.01) and shortened time to E(max) by 20% (P < 0.05). HT, however, altered neither the slope nor the unloaded MVO(2) of the MVO(2)-PVA relation. HT increased the oxygen cost of contractility (the incremental ratio of unloaded MVO(2) to E(max)) by 49%. When Ca(2+) infusion restored the reduced LV contractility during HT to the NT baseline level, the unloaded MVO(2) in HT exceeded the NT value by 36%. We conclude that HT-induced negative inotropism accompanies an increase in the oxygen cost of contractility.

Animals↗

PubMed2000

[Consultation and survey for drug interaction in outpatients taking the medicines potentially interact with St. John's Wort].

Ministry Health Welfare of Japan announced the caution for drug interaction of St. John's Wort (SJW), a herbal supplement occasionally used for depression, on May, 2000. Immediately after the announcement, we conducted drug consultation for outpatients prescribed the medicines potentially interacting with SJW. We provided information concerning possible drug interaction with SJW for 741 outpatients (except for pediatrics) during the period of May 22-June 16, 2000. The potential drugs prescribed frequently were warfarin (28.0%), theophylline (19.7%), digitalis (18.4%), carbamazepine (7.2%), disopyramide (6.9%) and cyclosporin (6.3%). Of the patients, 401 subjects were surveyed by collecting the questionnaires to clarify the background of SJW drug interaction. Twenty-two subjects (5.5%) have known commercially available SJW products, 5 subjects (1.2%) have ever taken SJW products before and 2 subjects (0.5%) have taken SJW products concomitant with prescribed medicines. Gender difference was observed in paying attention to SJW products; female subjects (8.6%) tended to have more interest in SJW products than male subjects (2.8%). Two subjects taking SJW have realized for the first time that the supplements they took were SJW products when their package photographs were shown at the consultation. Showing the package photographs might be helpful for making the patients easy to identify the SJW products, because most patients do not pay attention to whether the supplements contain SJW or not. It is recommended that drug consultation should be provided to avoid serious drug interaction with SJW while the outpatients are taking potential medicines prescribed.

Adult↗

PubMed2000

Effect of high amniotic fluid pressure on fetal circulation.

The purpose of this study was to investigate the effects of high amniotic fluid pressure (AFP) created by amnioinfusion on fetal circulation. Five pregnant goats whose fetuses had a mean gestational age of 131 +/- 2 days (term 145 days) were used. After a 30 minute control period, 1500 ml of warm saline was infused to the amniotic cavity over a period of 30 minutes. The AFP gradually increased during amnioinfusion and remained 2-3 mmHg above the control level for 3 hours after amnioinfusion. Fetal arterial pH (FpH) tended to decrease, and there was a significant negative correlation between the FpH and AFP (r = -0.723). Fetal arterial pO2 also tended to decrease and negatively correlated to the AFP (r = -0.59). On the other hand, fetal arterial pCO2 tended to increase and positively correlated with the AFP (r = 0.75). Although amnioinfusion is useful for improving the status of a distressed fetus, the fetal condition may be jeopardized at the same time. Therefore, careful monitoring of the AFP and fetal status is recommended during amnioinfusion.

Amniotic Fluid↗

PubMed2000

Mechanoenergetics characterizing oxygen wasting effect of caffeine in canine left ventricle.

Caffeine causes a considerable O(2) waste for positive inotropism in myocardium by complex pharmacological mechanisms. However, no quantitative study has yet characterized the mechanoenergetics of caffeine, particularly its O(2) cost of contractility in the E(max)-PVA-VO(2) framework. Here, E(max) is an index of ventricular contractility, PVA is a measure of total mechanical energy generated by ventricular contraction, and VO(2) is O(2) consumption of ventricular contraction. The E(max)-PVA-VO(2) framework proved to be powerful in cardiac mechanoenergetics. We therefore studied the effects of intracoronary caffeine at concentrations lower than 1 mmol/l on left ventricular (LV) E(max) and VO(2) for excitation-contraction (E-C) coupling in the excised cross-circulated canine heart. We enhanced LV E(max) by intracoronary infusion of caffeine after beta-blockade with propranolol and compared this effect with that of calcium. We obtained the relation between LV VO(2) and PVA with E(max) as a parameter. We then calculated the VO(2) for the E-C coupling by subtracting VO(2) under KCl arrest from the PVA-independent (or zero-PVA) VO(2) and the O(2) cost of E(max) as the slope of the E-C coupling VO(2)-E(max) relation. We found that this cost was 40% greater on average for caffeine than for calcium. This result, for the first time, characterized integratively cardiac mechanoenergetics of the O(2) wasting effect of the complex inotropic mechanisms of intracoronary caffeine at concentrations lower than 1 mmol/l in a beating whole heart.

Animals↗

PubMed2000

Logistic time constant of isometric relaxation force curve of ferret ventricular papillary muscle: reliable index of lusitropism.

We have found that a logistic function fits the left ventricular isovolumic relaxation pressure curve in the canine excised, cross-circulated heart more precisely than a monoexponential function. On this basis, we have proposed a logistic time constant (tau(L)) as a better index of ventricular isovolumic lusitropism than the conventional monoexponential time constant (tau(E)). We hypothesize in the present study that this tau(L) would also be a better index of myocardial isometric lusitropism than the conventional tau(E). We tested this hypothesis by analyzing the isometric relaxation force curve of 114 twitches of eight ferret isolated right ventricular papillary muscles. The muscle length was changed between 82 and 100% L(max) and extracellular Ca(2+) concentrations ([Ca(2+)](o)) between 0.2 and 8 mmol/l. We found that the logistic function always fitted the isometric relaxation force curve much more precisely than the monoexponential function at any muscle length and [Ca(2+)](o) level. We also found that tau(L) was independent of the choice of the end of isometric relaxation but tau(E) was considerably dependent on it as in ventricular relaxation. These results validated our present hypothesis. We conclude that tau(L) is a more reliable, though still empirical, index of lusitropism than conventional tau(E) in the myocardium as in the ventricle.

Animals↗

PubMed2000

2,3-Butanedione monoxime suppresses primarily total calcium handling in canine heart.

Whether 2,3-butanedione monoxime (BDM, < or = 5mmol/l) suppresses primarily crossbridge cycling or total Ca(2+) handling in the blood-perfused whole heart remains controversial. Although BDM seems to suppress primarily total Ca(2+) handling in canine hearts, more evidence is lacking. We therefore analyzed the cardiac mechanoenergetics, namely, E(max) (contractility), PVA (total mechanical energy), and O(2) consumption of canine BDM-treated hearts by our recently developed integrative method to assess myocardial total Ca(2+) handling. This method additionally required the internal Ca(2+) recirculation fraction. We obtained this from the beat constant of the exponential decay component of the postextrasystolic potentiation. Our analysis indicated significant decreases in both internal Ca(2+) recirculation fraction and total Ca(2+) handling in the BDM-treated heart, but virtually no change in the reactivity of E(max) to total Ca(2+) handling. This result corroborates the view that BDM suppresses primarily total Ca(2+) handling rather than crossbridge cycling in the canine blood-perfused heart.

Animals↗

PubMed2000

Effective arterial elastance of irregular beats during atrial fibrillation in canine left ventricle.

Effective arterial elastance (E(a)) was originally defined as the end-systolic pressure (ESP)/stroke volume (SV) ratio of the left ventricle (LV). E(a) combined with LV contractility (E(max)), E(a)/E(max), proved to be powerful in analyzing the ventriculo-arterial coupling of normal and failing hearts in regular beats. However, E(a) sensitively changes with LV E(max), preload, and afterload widely changing among irregular beats. This has discouraged the use of E(a) during arrhythmia. However, we hypothesized that E(a) could serve as the effective afterload (not always arterial) elastance against ventricular ejection under arrhythmia. We tested this hypothesis by analyzing beat-to-beat changes in E(a) of irregular beats during electrically induced atrial fibrillation (AF) in normal canine in situ hearts. We newly found that during AF in each heart: 1) E(a) changed widely among irregular beats and became markedly high in weak beats with small SVs; 2) E(a) and E(a)/E(max) distributed non-normally with large skewness but 1/E(a) distributed more normally; 3) 1/E(a) correlated closely with end-diastolic volume, E(max) and preceding beat intervals; and 4) the reciprocal of mean 1/E(a) closely correlated with mean ESP/mean SV. These results support our hypothesis that E(a) can serve as the effective afterload elastance against ventricular ejection on a per-beat basis during AF. E(a)/E(max) can also quantify the ventriculo-afterload (not arterial) coupling on a per-beat basis. This study, however, warns that mean E(a) and mean E(a)/E(max) of irregular beats cannot necessarily represent their averages during AF.

Animals↗