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H Suga

Publications and source records attributed to H Suga.

At least 73 records · Page 4Linked to original sources
PubMed1998

Sarcoplasmic reticulum Ca2+ pump blockade decreases O2 use of unloaded contracting rat heart slices: thapsigargin and cyclopiazonic acid.

We previously established a new measuring method of the myocardial O2 consumption of mechanically unloaded rat left-ventricular slices. O 2 consumption of unstimulated myocardium corresponds to basal metabolism. We have found O2 consumption of stimulated myocardium to include basal metabolism and O 2 consumption for Ca2+ handling in the excitation-contraction coupling, but not for crossbridge cycling. Thus, O2 consumption for the excitation-contraction coupling is obtained by subtracting basal metabolism from O2 consumption of the stimulated myocardium. We have shown that O2 consumption for the excitation-contraction coupling corresponds to 40% of basal metabolism. The purpose of the present study was to analyse the component of myocardial O2 consumption for the excitation-contraction coupling by this method. Blockade of the sarcoplasmic reticulum Ca2+ pump by thapsigargin (0.1-1 micro mol/l), or by cycloplazonic acid (10 micro mol/l), significantly reduced O2 consumption for the excitation-contraction coupling by 40 or 70% of the respective controls. Neither thapsigargin nor cyclopliazonic acid reduced basal metabolism O2 consumption. The magnitude of free shortening of the unloaded myocardial slices, quantified by slice surface area reduction, was small (about 1.5%) because of the lack of external preload. Thapsigargin (1 micro mol/l) and cycloplazonic acid (10 micro mol/l) markedly attenuated the already reduced free shortening. 2,3-butanedione monoxime (5 mmol/l) also largely suppressed the free shortening, although this agent did not alter the O2 consumption of either unstimulated or stimulated myocardium. Some residual cross-bridge cycling may occur without detectable O2 consumption. Our present energetic results revealed that the O2 consumption of myocardial slices for the Ca2+ handling in the excitation-contraction coupling was mainly used for the sarcoplasmic reticulum Ca2+ pump.

Animals↗
PubMed1998

Effects of thapsigargin and KCl on the O2 use of the excised blood-perfused rat heart.

We have already reported a curvilinear end-systolic pressure-volume relation and a linear oxygen consumption per beat (Vo2)-systolic pressure-volume area (PVA) relation of the left ventricle in the rat blood-perfused whole heart preparation. Recently, we have proposed that a PVA at an appropriate left-ventricular end-diastolic volume (0.15 ml/g), such as PVA0.15 and the Vo2 intercept (minimally loaded Vo2) of the Vo2-PVA relation, can be good indexes for assessing rat left-ventricular mechanoenergetics. The minimally-loaded Vo2 would mainly consist of Vo2 for Ca 2+ handling in the excitation-contraction (E-C) coupling and basal metabolism. However, the fraction of the Vo2 by the sarcoplasmic reticulum (SR) Ca2+-ATPase in the total Ca2+ handling Vo2 has not yet been examined. To study this for the first time, we investigated the effects of thapsigargin and KCl on left-ventricular mechanoenergetics. Blockade of the SR Ca2+ pump by thapsigargin (2.5 micromol/l) decreased PVA 0. 15 by 65% and decreased the Vo2 intercept by 40% without a change in the slope of the Vo2-PVA relation. We measured the basal metabolic Vo2 by intracoronary KCl and found a 75% decrease in the Vo2 intercept. We conclude that the minimally-loaded Vo2 mainly consists of Vo2 for Ca2+ handling in the E-C coupling (at least 40% is consumed by the SR Ca2+ ATPase) and basal metabolism (25%).

Animals↗
PubMed1998

Ventricular pressure-volume area (PVA) accounts for cardiac energy consumption of work production and absorption.

We briefly review that ventricular systolic pressure-volume area (PVA) can predict changes in myocardial O2 consumption (VO2) associated with cardiac work production (positive work) and absorption (negative work). PVA represents the total mechanical energy of cardiac contraction as it is an integral of mechanical energy generated during systole in the cardiac chamber. We have shown that PVA linearly correlates with VO2 under varied pre- and afterload conditions in the left ventricle of the excised cross-circulated canine heart preparation as well as other heart preparations of different species. PVA is the sum of external mechanical work (EW) and mechanical potential energy (PE) which is almost fully convertible to mechanical work without affecting VO2. To compare the energetic effects of cardiac work production and absorption, we varied the timing of the servo pump motion relative to left ventricular (LV) contraction. When the pump fills the LV during diastole and sucks (allows ejection) during systole, cardiac work is produced by the heart, and hence EW > 0. When the pump fills the LV during systole and sucks during diastole, work is absorbed by the heart, and hence EW < 0. The pressure-volume loop rotates counterclockwise when EW > 0. It rotates clockwise when EW < 0. As the result, PVA (= PE + EW) > PE when EW > 0; PVA < PE when EW < 0. We found that VO2 always linearly correlated with PVA regardless of the polarity of EW. Therefore, PVA is the unique determinant of VO2 in a cardiac chamber in a stable contractility.

Animals↗
PubMed1998

Oxygen consumption and motility of mechanically unloaded myocardial slices.

We have recently established a new measurement system of myocardial O2 consumption per min (mVO2) of mechanically unloaded rat left ventricular (LV) slices (Yasuhara et al.: Am. J. Physiol. 270: H1063-H1070, 1996). Using this system, we have revealed that an increment in O2 consumption (delta mVO2) by electrical stimulation primarily represents mVO2 for Ca2+ handling in the excitation-contraction (E-C) coupling, though much smaller than that in the whole heart preparation. The much smaller delta mVO2 in the sliced myocardium than that in the whole heart is due to the much lower frequency of stimulation (60 bpm against 300 bpm). We consider that delta mVO2 does not contain mVO2 for residual crossbridge cycling from the results showing no effect of 2,3-butanedione monoxime on delta mVO2 despite the large decrease in mechanically unloaded contraction, which is expressed by the motility index. We also revealed that mVO2 without stimulation represents basal metabolism. The basal metabolism in rat myocardial slices, which is much higher than in other mammalian hearts, corresponds to that in the rat whole heart preparation. We finally obtained the results showing that sarcoplasmic reticulum (SR) Ca2+ pump blockers, thapsigargin and cyclopiazonic acid, did not reduce basal metabolic mVO2 but both of them reduced delta mVO2 maximally by 50-70% of control and markedly reduced the motility index. We conclude that myocardial O2 consumption (VO2) is composed of VO2 for E-C coupling and basal metabolism and does not contain VO2 for residual crossbridge cycling. Basal metabolic VO2 does not include VO2 for the SR Ca2+ pump, and at least two-thirds of VO2 for E-C coupling represents VO2 for the SR Ca2+ pump.

Animals↗
PubMed1998

Sponge Pax cDNA related to Pax-2/5/8 and ancient gene duplications in the Pax family.

Members of the Pax gene family encode transcription factors containing a DNA-binding paired domain which is involved in developmental control and the formation of the central nervous system (CNS). The family members are classified into six classes or subfamilies, depending on the presence or absence of paired-type homeobox and octapeptide. To obtain rough estimates of times when the different classes of the Pax family diverged by gene duplication, we cloned and sequenced a Pax-related cDNA, sPax-2/5/8, from Ephydatia fluviatilis, a freshwater sponge, which encodes a paired-type homeobox and an octapeptide, in addition to a paired domain. A phylogenetic tree based on the paired domain sequences suggest that sPax-2/5/8 is a homologue of vertebrate Pax-2/5/8. It was also suggested that the majority of gene duplications that gave rise to distinct classes has been completed in the very early evolution of animals before the parazoan-eumetazoan split. Long after the ancient gene duplications, further gene duplications that gave rise to members in each subfamily occurred on the chordate lineages and completed before the fish-tetrapod split. This suggests that the major classes of the Pax genes involved in the formation of CNS characteristic of triploblasts had already existed long before the Cambrian explosion of triploblasts, and there is no direct link between the creation of new genes with novel functions and the Cambrian explosion. The pattern of gene diversification found in the Pax family is similar to those in five gene families involved in the signal transduction analyzed by us. Furthermore, the evolutionary rates of the Pax proteins have been shown to decrease with increasing organismal complexity during animal evolution.

Amino Acid Sequence↗
PubMed1998

Long-term follow-up of primary anterior chamber intraocular lens implantation.

PURPOSE: To evaluate the long-term outcome in eyes having primary anterior chamber intraocular lens (AC IOL) implantation. SETTING: Kimura Eye and Internal Medicine Hospital, Hiroshima, Japan. METHODS: Primary AC IOL implantation was performed in 171 eyes from 1983 to 1988. Two lenses were implanted: the open C-loop Simcoe lens and the 4-point fixation Kelman lens. In 86 eyes that had a mean follow-up of 9 years 7 months, visual acuity, corneal endothelial cell density, pupil shape, and the presence of associated complications were examined. RESULTS: Although the final visual acuity was 0.5 or better in 60 eyes (69%), corneal endothelial cell density was less than 2000 cells/mm2 in 46 eyes (57%). Postoperative complications included a deformed pupil in 48 eyes (56%) and bullous keratopathy in 12 eyes (14%). In 14 eyes the AC IOL was explanted; 11 of these were the open C-loop Simcoe lens. CONCLUSION: Although our findings show that the open C-loop AC IOL (Simcoe) is contraindicated, implantation of the 4-point fixation AC IOL may be acceptable in selected cases.

Aged↗
PubMed1998

Ventricular contractility in atrial fibrillation is predictable by mechanical restitution and potentiation.

We recently found that contractility (Emax) of an individual irregularly arrhythmic beat in electrically induced atrial fibrillation (AF) is reasonably predictable from the ratio of the preceding beat interval (RR1) to the beat interval immediately preceding RR1 (RR2) in the canine left ventricle. Moreover, the monotonically increasing relation between Emax and the RR1-to-RR2 ratio (RR1/RR2) passed through or by the mean arrhythmic beat Emax as well as the regular beat Emax at RR1/RR2 = 1. We hypothesized that this Emax-RR1/RR2 relation during irregular arrhythmia could be attributed to the basic characteristics of the mechanical restitution and potentiation. To test this, we adopted a known comprehensive equation describing the force restitution and potentiation as a function of two preceding beat intervals and simulated contractilities of irregular arrhythmic beats with randomized beat intervals on a computer. The simulated Emax-RR1/RR2 relation reasonably resembled the one that we recently observed experimentally, supporting our hypothesis. We therefore conclude that the primary mechanism underlying the varying contractilities of irregular beats in AF is mechanical restitution and potentiation.

Animals↗
PubMed1998

A new integrative method to quantify total Ca2+ handling and futile Ca2+ cycling in failing hearts.

Ca2+ handling in excitation-contraction coupling requires considerable O2 consumption (VO2) in cardiac contraction. We have developed an integrative method to quantify total Ca2+ handling in normal hearts. However, its direct application to failing hearts, where futile Ca2+ cycling via the Ca2+-leaky sarcoplasmic reticulum (SR) required an increased Ca2+ handling VO2, was not legitimate. To quantify total Ca2+ handling even in such failing hearts, we combined futile Ca2+ cycling with Ca2+ handling VO2 and the internal Ca2+ recirculation fraction via the SR. We applied this method to the canine heart mechanoenergetics before and after intracoronary ryanodine at nanomolar concentrations. We found that total Ca2+ handling per beat was halved after the ryanodine treatment from approximately 60 micromol/kg left ventricle before ryanodine. We also found that futile Ca2+ cycling via the SR increased to >1 cycle/beat after ryanodine from presumably zero before ryanodine. These results support the applicability of the present method to the failing hearts with futile Ca2+ cycling via the SR.

Animals↗
PubMed1998

Effects of Ca2+ and epinephrine on Ca2+ recirculation fraction and total Ca2+ handling in canine left ventricles.

We investigated the effects of intracoronary Ca2+ and epinephrine on the intracellular Ca2+ recirculation fraction (RF) and total Ca2+ handling in the left ventricle (LV) of the excised cross-circulated canine heart preparation. We analyzed LV postextrasystolic potentiation (PESP) following a spontaneous extrasystole that occurred sporadically under constant atrial pacing. All PESPs decayed in alternans and none decayed monotonically. We extracted an exponential decay component from the alternans PESP, determined its beat constant (taue), and calculated RF = exp(-1/taue). Increased intracoronary Ca2+ slightly increased taue and RF, but epinephrine did not change them, although both agents enhanced LV contractility 2-3 times. Neither Ca2+ nor epinephrine affected the sinusoidal decay of the alternans PESP. These results indicate that RF via the sarcoplasmic reticulum was slightly augmented by Ca2+, but not by epinephrine. We combined these RF data with LV Ca2+ handling O2 consumption data and obtained 40-110 micromol/kg as the total amount of Ca2+ handled in one cardiac cycle in the control and enhanced contractile states. These results indicate that this new LV-level approach seems to better the understanding of the Ca2+ mass dynamics responsible for the mechanoenergetics enhanced by inotropic interventions.

Animals↗
PubMed1998

Linear O2 use-pressure-volume area relation from curved end-systolic pressure-volume relation of the blood-perfused rat left ventricle.

We measured rat left ventricular pressure, volume, and oxygen consumption ( = arteriovenous oxygen content differencexcoronary flow) to establish a new evaluation of its mechanoenergetics in the whole heart preparation by using the cross-circulation method. We obtained a curved end-systolic pressure-volume relation in contrast to a linear end-systolic pressure-volume relation in dogs, rabbits, and humans. However, we obtained a linear oxygen consumption per beat (VO2)-systolic pressure-volume area (PVA, a measure of left ventricular total mechanical energy per beat) relation as in other species. Thus PVA can be a good index for assessing rat left ventricular mechanoenergetics. The VO2 intercept and slope of the linear VO2-PVA relation correspond to those in other species. Intracoronary calcium elevated the curved end-systolic pressure-volume relation and significantly increased PVA at 0.15 ml/g of left ventricular end-diastolic volume (PVA0.15) by 50%. Calcium also significantly increased the VO2 intercept of the VO2-PVA relation by 30% without a change in its slope. We conclude that the rat left ventricular end-systolic pressure-volume relation is curved, but the VO2-PVA relation is linear, and that the VO2 intercept is mainly composed of PVA-independent VO2, presumably VO2 for Ca2+ handling in the excitation-contraction coupling and basal metabolism. Therefore we propose PVA at an appropriate left ventricular volume and the VO2 intercept as good rat left ventricular mechanoenergetic indexes despite the nonlinearity of the end-systolic pressure-volume relation.

Animals↗
PubMed1998

Effects of intracoronary caffeine on left ventricular mechanoenergetics in Ca2+ overload failing rat hearts.

How different the effects of caffeine on cardiac mechanoenergetics in failing hearts are from those of normal hearts remains to be fully elucidated. First we successfully instituted a new experimental model of acute mild heart failure in the rat by 0.005 mM Ca2+ Tyrode perfusion. These failing hearts neither decreased left ventricular end-systolic pressure nor increased left ventricular end-diastolic pressure, indicating unchanged left ventricular mechanics. However, their myocardial mitochondrial respiratory function examined by respiratory control index (RCI) and oxygen consumption rate in state III (State III O2) was significantly depressed compared with normal hearts. From these results, we judged that this Ca2+ protocol could make mild Ca2+ overload acute failing hearts and that this model would be appropriate for comparing the effects of caffeine on cardiac mechanoenergetics between normal hearts and these failing hearts. We investigated the effects of caffeine on cardiac mechanoenergetics above a concentration of 0.05 mM that corresponds to the maximum blood concentration after a healthy human subject drinks a cup of coffee or tea. We obtained results indicating that caffeine depressed left ventricular systolic and diastolic functions and decreased a measure of total mechanical energy per beat in terms of systolic pressure-volume area (PVA) more severely in these failing hearts at concentrations (20-fold higher than the concentration in a cup of coffee) lower than those in normal hearts. This result implies that these acute failing hearts are Ca2+ overloaded.

Animals↗
PubMed1998

Effects of myosin isozyme shift on curvilinearity of the left ventricular end-systolic pressure-volume relation of In situ rat hearts.

Recently we have shown that the left ventricular end-systolic pressure-volume relation (ESPVR) of in situ rat hearts is an upward convex curve in contrast to the linear left ventricular ESPVR in dog and human hearts. Within the smaller left ventricular volume range, the left ventricular end-systolic pressure rose steeply with increases in left ventricular volume, but it gradually reached a plateau at the larger left ventricular volumes. In adult rat hearts, the myosin isozyme is V1, unlike V3 in dog and human hearts. To investigate whether myosin isozyme affects the curvilinearity of the left ventricular ESPVR, we evaluated the left ventricular ESPVR in hypothyroid rats in which the left ventricular myosin isozyme had been shifted to V3. In the hypothyroid rats, the left ventricular contractility was depressed and the ESPVR became closer to linear. However, after dobutamine administration the ESPVR returned to curvilinear. In nor-mal rats the curvilinearity of the left ventricular ESPVR was decreased by negative inotropic agents such as adrenergic blockers. These results indicate that the depressed left ventricular contractility in the hypothyroidism make ESPVR linear and that the enhanced left ventricular contractility from dobutamine make it curvilinear. We concluded that the curvilinearity of the rat left ventricular ESPVR is not determined by myosin isozyme per se, but by the left ventricular contractility.

Animals↗
PubMed1997

Intermittent divergence of the protein tyrosine kinase family during animal evolution.

The protein tyrosine kinases (PTKs) are a large protein family consisting of many subfamilies with a variety of domain structures. The basic functions are thought to differ for different subfamilies. To know the dates at which the subfamilies diverged by gene duplications, a phylogenetic tree of the PTKs was inferred by comparing sequences from a wide range of species covering diploblasts and triploblasts. The PTK tree revealed that almost all of the gene duplications that gave rise to different subfamilies occurred rapidly before the diploblast-triploblast split, accompanying with rapid amino acid substitutions. This type of gene duplication was, however, rarely observed after that split. Long after the subfamily divergence, another type of gene duplication that gave rise to diverse tissue-specific genes occurred in each subfamily on the chordate lineage since the separation from arthropods. This type of gene duplication occurred frequently before the fish-tetrapod split, accompanying with rapid amino acid substitutions. In contrast, both the frequency of gene duplications and the rate of the amino acid substitutions were considerably reduced after that split. These results strongly suggest that the PTKs diverged intermittently, but not gradually, during animal evolution.

Amino Acids↗
PubMed1997

Calcium equally increases the internal calcium recirculation fraction before and after beta-blockade in canine left ventricles.

We studied whether intracoronary Ca administration after beta-blockade would increase the internal Ca recirculation fraction (RF) analogously to the Ca administration before beta-blockade. This was performed in excised cross-circulated canine hearts. We analyzed the exponential decay component of the postextrasystolic potentiation (PESP) following a spontaneous extrasystole. All the PESPs decayed in alternans with atrial pacing at a constant rate. We obtained the time constant (tau(e)) of the monoexponential decay component of the alternans PESP. An increment of intracoronary Ca by 1.5 mmol/l enhanced the left ventricular contractility index Emax (end-systolic maximum elastance) by 2.5 times before and after beta-blockade with propranolol. The intracoronary Ca after beta-blockade slightly but significantly increased tau(e), and hence increased RF calculated from tau(e) by RF = exp(-1/tau(e)). This was analogous to the slightly increased tau(e) and RF with Ca before beta-blockade. We speculate that the myocardial cyclic AMP-dependent phosphorylation level would not significantly alter the effect of intracoronarily administered Ca on myocardial Ca handling, in terms of tau(e) and RF.

Adenosine Monophosphate↗
PubMed1997

Dynamic cardiac compression improves contractile efficiency of the heart.

The effect of dynamic cardiac compression on left ventricular contractile efficiency was assessed in terms of the pressure-volume relationship and myocardial oxygen consumption. In 11 excised cross-circulated dog hearts, the ventricle was directly compressed during systole (dynamic cardiac compression). Measurements for pressure-volume area (a measure of total mechanical energy), external work, and myocardial oxygen consumption were done before and during dynamic cardiac compression. Dynamic cardiac compression increased pressure-volume area by 28% +/- 17% (mean plus or minus the standard deviation) and external work by 24% +/- 20% (p = 0.0000185 and 0.0000212, respectively) at given end-diastolic and stroke volumes without affecting myocardial oxygen consumption. As a result, the oxygen cost of pressure-volume area, that is, the slope of the myocardial oxygen consumption-pressure-volume area relationship, significantly decreased by 16% +/- 13% (p = 0.0000135) whereas the pressure-volume area-independent myocardial oxygen consumption was unchanged. Then, contractile efficiency, that is, the reciprocal of the slope of the myocardial oxygen consumption-pressure-volume area relationship in joules significantly improved from 45% +/- 8% to 53% +/- 13% (p = 0.0000437). When the native myocardial oxygen consumption-pressure-volume area relationship was assessed by subtracting the dynamic cardiac compression pressure applied to the heart, the slope of the myocardial oxygen comsumption-pressure-volume area relationship returned to the control level. This indicates that the contractile efficiency of the native heart was not affected by dynamic cardiac compression. We conclude that dynamic cardiac compression enhances left ventricular pump function by improving the contractile efficiency of the overall heart leaving the energetics of the native heart unchanged.

Animals↗
PubMed1997

Effects of intracoronary fentanyl on left ventricular mechanoenergetics in the excised cross-circulated canine heart.

BACKGROUND: It is still unclear whether fentanyl directly alters left ventricular (LV) contractility and oxygen consumption. This is because of the difficulty in defining and evaluating contractility and energy use independently of ventricular loading conditions and heart rate in beating whole hearts. METHODS: This study was conducted to clarify the mechanoenergetic effects of intracoronary fentanyl in six excised cross-circulated canine hearts. The authors used the framework of the E(max) (a contractility index)-PVA (systolic pressure-volume area, a measure of total mechanical energy)-VO2 (myocardial oxygen consumption per beat) relationship practically independent of ventricular loading conditions. The authors measured LV pressure, volume, coronary flow, and arteriovenous oxygen content difference to calculate E(max), PVA, and VO2. They first obtained the VO2-PVA relationship for varied LV volumes at control E(max). The authors then obtained the VO2-PVA relationship at a constant LV volume, whereas coronary blood fentanyl concentration was increased in steps up to 240 ng/ml. Finally, they obtained the VO2-PVA relationship for varied LV volumes at the final dose of fentanyl. RESULTS: Fentanyl at any concentrations did not significantly change E(max), PVA, and VO2 from the control. The linear end-systolic pressure-volume relations and their slopes were virtually the same between the control and fentanyl volume loading in each heart. Further, either the slope (oxygen cost of PVA) or the VO2 intercept (unloaded VO2) of the linear VO2-PVA relationship remained unchanged by fentanyl. CONCLUSIONS: These results indicate that intracoronary fentanyl produces virtually no effects on LV mechanoenergetics for a wide range of its blood concentration.

Anesthetics, Intravenous↗
PubMed1997

Mechanoenergetics of the negative inotropism of isoflurane in the canine left ventricle. No O2 wasting effect.

BACKGROUND: The mechanisms underlying the negative inotropic effects of isoflurane are incompletely understood. One suggested mechanism is that isoflurane may decrease Ca2+ sensitivity of contractile proteins. If so, more free calcium would be needed to activate contractile proteins to the same degree, which would impose a greater requirement for myocardial oxygen consumption used in the cycling of calcium. In this study, the authors use the excised, cross-circulated, canine heart model and the volume servopump technique to measure the effects of isoflurane on Emax (a contractile index) and on the relationship between pressure-volume area (PVA, a measure of total mechanical energy) and myocardial oxygen consumption per beat (VO2). METHODS: Effects of intracoronary isoflurane infused via a precoronary oxygenator on myocardial mechanoenergetics were studied during isovolumic contractions. The authors measured left ventricular (LV) pressure, LV volume, coronary flow, and arteriovenous oxygen content difference and computed Emax, VO2 and PVA at 0, 1.0, 1.5, and 2.0% isoflurane. From these data, the authors obtained oxygen costs of PVA and Emax in control subjects and in those receiving 2.0% isoflurane. RESULTS: Emax, PVA, and VO2 dose-dependently decreased by similar degrees (P < 0.05). Isoflurane did not change the oxygen costs at 1.5% and 2.0% concentration (P < 0.05). CONCLUSIONS: These mechanoenergetic findings suggest that the primary method by which isoflurane decreases contractility is not by decreasing Ca2+ sensitivity of contractile proteins but mainly by decreasing Ca2+ handling in the excitation-contraction coupling without myocardial oxygen wasting effect.

Anesthetics, Inhalation↗