Biomedical subjects

M Takaki

Publications and source records attributed to M Takaki.

At least 37 records · Page 2Linked to original sources

PubMed2000

New method for evaluating intestinal contractions in guinea pig by curve fitting.

Using a "hybrid logistic function," we attempted to develop a new approach for a quantitative and comprehensive evaluation of the force-time curve of guinea pig gut contractions. We recorded ileum twitch and proximal colon spontaneous isometric longitudinal contractions because of their high regularities. We digitized the force-time curves of both contractions and performed curve fitting to them by hybrid logistic functions with a personal computer. We found that the fitness of these functions to both contractions was excellent. The respective best-fit parameters of these functions were closely correlated with the observed mechanical indexes, all of which are physiologically meaningful. This result suggests the possibility that these parameters can characterize the magnitudes and time courses of F(t) curves of the intestinal contractions. Furthermore, it might be able to show an effect of a pharmacological agent specifically either on the contraction phase, the relaxation phase, or other parameters of each. Therefore, we insisted that the present new approach for evaluating gut motility is promising for clinical application.

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

Increase in O(2) delivery with hyperoxia does not increase O(2) uptake in tetanically contracting dog muscle.

We investigated the influence of hyperoxia on O(2) uptake in tetanically contracting canine gastrocnemius. Hyperoxia showed neither increase in O(2) uptake nor decrease in lactate release, irrespective of increased O(2) supply, venous Po(2) and vascular resistance, as compared to normoxia, suggesting that hyperoxia decreases O(2) diffusion conductance and/or effective O(2) supply probably due to arteriovenous O(2) diffusion shunt.

Anaerobic Threshold↗

PubMed2000

Correlation between erythropoietin and lactate in humans during altitude exposure.

The plasma concentrations of both immunoreactive erythropoietin (EPO) and lactate were determined in four healthy untrained subjects at sea level and on the 2nd or 3rd day at altitudes (1,300 and 3,500 m). The mean plasma EPO (18.8 +/- 1.6 mU/ml at sea level) increased significantly on the 3rd day at 1,300 m (25.5 +/- 2.0 mU/ml, p < 0. 05) and showed an almost three-fold increase on the 2nd day at 3,500 m (53.5 +/- 3.7 mU/ml, p < 0.001). Likewise, the mean plasma lactate at 3,500 m (3.98 +/- 0.27 mmol/l) was 3.6 times as high as that at sea level (1.11 +/- 0.05 mmol/l) (p < 0.001). The plasma EPO concentrations were found to correlate well with the lactate concentrations at sea level and altitudes (r = 0.86, p < 0.01). These results are consistent with the well-known EPO/lactate response to altitudes and suggest that the circulating EPO concentration as well as blood lactate concentration can be used as an index of anaerobic condition.

Adult↗

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↗

PubMed1999

Muscle venous PO2 and VO2 are linearly related in repetitive tetanic contractions of canine muscle during hypoxic hypoxia.

1. It has previously been shown that perfusion with high O2-affinity-erythrocytes decreases venous PO2 (PVO2) and decreases O2 uptake (VO2) in contracting muscle at the same O2 delivery (arterial O2 concentration x flow). A linear VO2-PVO2 relationship has been obtained with a VO2-axis intercept, suggesting that, during this type of hypoxia, VO2 is composed of a PVO2-dependent and -independent VO2. However, the VO2-PVO2 relation during hypoxic hypoxia has not been examined. 2. To clarify this relation, PVO2 and VO2 have been measured in contracting gastrocnemius (1 Hz trains of 0.2 s isometric tetani) under both normoxic and hypoxic conditions during 5 min of stimulation. 3. Venous O2 changes proportionally with O2 delivery. Each VO2-PVO2 relation was linear, with the mean described by the equation VO2 = 5.06 + 0.41 x PVO2 (n = 6, r = 0.81, P < 0.05). The VO2-axis intercept was significantly different from zero (P < 0.05). 4. These results were similar to those obtained during hypoxia induced by high O2-affinity-erythrocytes. We conclude that there is a linear relationship between PVO2 and VO2 above the VO2-axis intercept, regardless of the type of hypoxia.

Animals↗

PubMed1999

Energy expenditure by Ba(2+) contracture in rat ventricular slices derives from cross-bridge cycling.

To clarify the energy-expenditure mechanism during Ba(2+) contracture of mechanically unloaded rat left ventricular (LV) slices, we measured myocardial O(2) consumption (VO(2)) of quiescent slices in Ca(2+)-free Tyrode solution and VO(2) during Ba(2+) contracture by substituting Ca(2+) with Ba(2+). We then investigated the effects of cyclopiazonic acid (CPA) and 2,3-butanedione monoxime (BDM) on the Ba(2+) contracture VO(2). The Ca(2+)-free VO(2) corresponds to that of basal metabolism (2.32 +/- 0.53 ml O(2). min(-1). 100 g LV(-1)). Ba(2+) increased the VO(2) in a dose-dependent manner (from 0.3 to 3.0 mmol/l) from 110 to 150% of basal metabolic VO(2). Blockade of the sarcoplasmic reticulum (SR) Ca(2+) pump by CPA (10 micromol/l) did not at all decrease the Ba(2+)-activated VO(2). BDM (5 mmol/l), which specifically inhibits cross-bridge cycling, reduced the Ba(2+)activated VO(2) almost to basal metabolic VO(2). These energetic results revealed that the Ba(2+)-activated VO(2) was used for the cross-bridge cycling but not for the Ca(2+) handling by the SR Ca(2+) pump.

Animals↗

PubMed1999

Weibull distribution function for cardiac contraction: integrative analysis.

The Weibull distribution is widely used to analyze the cumulative loss of performance, i.e., breakdown, of a complex system in systems engineering. We found for the first time that the difference curve of two Weibull distribution functions almost identically fitted the isovolumically contracting left ventricular (LV) pressure-time curve [P(t)] in all 345 beats (3 beats at each of 5 volumes in 23 canine hearts; r = 0.999953 +/- 0.000027; mean +/- SD). The first derivative of the difference curve also closely fitted the first derivative of the P(t) curve. These results suggest the possibility that the LV isovolumic P(t) curve may be characterized by two counteracting cumulative breakdown systems. Of these, the first breakdown system causes a gradual pressure rise and the second breakdown system causes a gradual pressure fall. This Weibull-function model of the heart seems to give a new systems engineering or integrative physiological view of the logic underlying LV isovolumic pressure generation.

Animals↗

PubMed1999

New index for oxygen cost of contractility from curved end-systolic pressure-volume relations in cross-circulated rat hearts.

We have already reported the linear oxygen consumption per beat (VO(2))-systolic pressure-volume area (PVA) relation from the curved left ventricular (LV) end-systolic pressure-volume relation (ESPVR) in the cross-circulated rat heart. The VO(2) intercept (PVA-independent VO(2)) is primarily composed of VO(2) for Ca(2+) handling in excitation-contraction (E-C) coupling and basal metabolism. The aim of the present study was to obtain the oxygen cost of LV contractility that indicates VO(2) for Ca(2+) handling in E-C coupling per unit LV contractility change in the rat heart. Oxygen cost of LV contractility is obtainable as a slope of a linear relation between PVA-independent VO(2) and LV contractility. We obtained a composite VO(2)-PVA relation line at a mid-range LV volume (mLVV) under gradually enhanced LV contractility by stepwise increased Ca(2+) infusion and thus the gradually increased PVA-independent VO(2) values. As a LV contractility index, we could not use E(max) (ESP-V ratio; ESP/ESV) for the linear ESPVR because of the curved ESPVR in the rat LV. A PVA at a mLVV (PVA(mLVV)) has been proposed as a good index for assessing rat LV mechanoenergetics. Since the experimentally obtained PVA(mLVV) was not triangular due to the curved ESPVR, we propose an equivalent ESP-V ratio at a mLVV, (eESP/ESV)(mLVV), as a LV contractility index. This index was calculated as an ESP-V ratio of the specific virtual triangular PVA(mLVV) that is energetically equivalent to the real PVA(mLVV). The present approach enabled us to obtain a linear relation between PVA-independent VO(2) and (eESP/ESV)(mLVV) and the oxygen cost of LV contractility as the slope of this relation.

Animals↗

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

CD2-, CD4+, CD56+ agranular natural killer cell lymphoma of the skin.

We present a case of CD56-positive cutaneous lymphoma with a clinical appearance resembling angiosarcoma. The biopsy specimen showed angiocentric infiltrates of small to medium-sized cells positive for CD4, CD45, and CD56 but negative for CD2, surface and cytoplasmic CD3, CD8, CD20, and CD57. There was no detectable clonal rearrangement of either TCRbeta or TCRgamma genes and no dense core granules in the cytoplasm. Epstein-Barr virus was not detected. The patient died of an unrelated disease 20 months after initial biopsy, although there was some response to interleukin-2, radiotherapy, and VP-16. The results suggest that our case does not precisely match the recently proposed variants of CD56-positive lymphoma, namely nasal T/natural killer cell lymphoma and blastic natural killer cell lymphoma. Agranular natural killer cell lymphomas similar to our case in the immunophenotype have been reported to be indolent and occur in the skin. These lymphomas may be a distinct subtype and have a predilection for involving the skin.

Aged↗

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

Unloaded skeletal muscle O2 uptake decreases with decreased venous PO2 at high-frequency stimulation.

The aim of the present study was to clarify the effects of O2 diffusion limitation resulting from hypoxic interventions on O2 uptake (V.O2) in unloaded (that is, near-zero initial force) and loaded skeletal muscle in a high-frequency stimulation. We measured V.O2, muscle venous PO2 (PvO2) and initial force in gastrocnemius-plantaris muscle in situ of anesthetized dogs: (1) during hypoxic hypoxia at 1 Hz tetanic stimulation, and (2) during hypoxia induced by the perfusion with high O2-affinity erythrocytes (having a low value of PO2 at 50% saturation of hemoglobin (P50)) at 4 Hz twitch stimulation. Averaged unloaded V.O2 during normoxia was 10.2 ml.min-1.100 g-1 at averaged blood flow of 74 ml.min-1.100 g-1 (n = 6). Hypoxic hypoxia of a decreased O2 delivery (arterial O2 concentration x flow) significantly decreased both unloaded and loaded V.O2 with a decrease in PvO2 (p<0.05). The unloaded V.O2 was reduced to 8.5 ml.min-1.100 g-1. Low P50-hypoxia decreased V.O2 at high and low initial force conditions with a decrease in PvO2 (p<0.05) at the same O2 delivery. If these decreases in V.O2 correspond with a decrease in V.O2 at zero initial force (unloaded V.O2), the unloaded V.O2 value is calculated to be 7.57 ml.min-1.100 g-1 from V. O2-initial force data. Despite the different conditions of O2 delivery, the unloaded V.O2 decreased by both hypoxia showed similar values. Thus the decreased unloaded V.O2 does not seem to be derived from only the limited O2 delivery. Some other factors such as the limitation of O2 diffusion may contribute to the decreased V.O2.

Animals↗