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Biomedical subjects

M Takaki

Publications and source records attributed to M Takaki.

At least 55 records · Page 3Linked to original sources
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

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↗
PubMed1997

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

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 Emax (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 Emax, PVA, and VO2. They first obtained the VO2-PVA relationship for varied LV volumes at control Emax. 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 Emax, 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

Effect of blood blow and haematocrit on the relationship between muscle venous PO2 and oxygen uptake in dog maximally contracting gastrocnemius in situ.

1. To clarify the limiting factors for peak VO2 (VO2,peak), we measured muscle venous PO2, (PVO2) and VO2,peak under various O2 delivery conditions (arterial O2 concentration x flow) via the alteration of blood flow and haematocrit (Hct) in anaesthetized dog gastrocnemius muscle (n = 11) stimulated by 1 Hz isometrically and tetanically. 2. Two levels of flow (high and moderate) were maintained by using a pump (150 and 100 mL/min per 100 g, respectively). Haematocrit was adjusted to 45 and 30% by isovolaemic haemodilution with dextran (MW 40,000). 3. The decrease in Hct induced a 31% decrease in O2 delivery (P < 0.05), a 9-12% decrease in PVO2, a 23% decrease in VO2,peak (P < 0.05) and a 12-14% increase in O2 extraction (VO2/O2 delivery) at both flow levels. The decrease in flow induced a 24-25% decrease in O2 delivery (P < 0.05), a 15-17% decrease in PVO2 (P < 0.05), a 9% decrease in VO2,peak (P < 0.05) and a 19-22% increase in O2 extraction (P < 0.05) at both Hct levels. 4. The results suggest that the limiting factor of VO/,peak, unrelated to O2 diffusion limitation (i.e. the change in the heterogeneity of VO2 to O2 delivery ratio among capillaries), due to lowering Hct may be different from that due to lowering blood flow in maximally contracting muscle.

Animals↗
PubMed1997

New mechanoenergetic evaluation of left ventricular contractility in in situ rat hearts.

We recorded a series of ejecting left ventricular (LV) pressure (P)-volume (V) loops of in situ rat hearts during a gradual ascending aortic occlusion. The end-systolic (ES) P-V relationship (ESPVR) was upward convex curvilinear regardless of LV contractility. The ESPVR was shifted upward in an enhanced contractility by dobutamine and downward in a depressed contractility by propranolol; ESP at a midrange V of 0.1 ml/g LV on each ESPVR increased from 131 +/- 11 to 192 +/- 17 mmHg and decreased from 136 +/- 10 to 110 +/- 7 mmHg, respectively. Furthermore, we obtained an upward concave curvilinear pressure-volume area (PVA; a measure of total mechanical energy)-V (preload) relationship to assess LV work capability in each contractility. This relationship also shifted upward in enhanced contractility and downward in depressed contractility; the PVA at midrange V increased from 7.9 +/- 1.2 to 12.3 +/- 1.5 mmHg. ml.beat-1.g-1 and decreased from 8.2 +/- 0.9 to 6.4 +/- 0.8 mmHg.ml.beat-1.g-1. We conclude that the heights of the ESPVR and PVA-V relationship curves can evaluate LV contractility mechanoenergetically.

Animals↗
PubMed1997

Mechanism of constant contractile efficiency under cooling inotropy of myocardium: simulation.

We have reported that, in canine hearts, cardiac cooling to 29 degrees C enhanced left ventricular contractility but changed neither the contractile efficiency of cross-bridge (CB) cycling nor the excitation-contraction coupling energy. The mechanism of this intriguing energetics remained unknown. To get insights into this mechanism, we simulated myocardial cooling mechanoenergetics using basic Ca2+ and CB kinetics. We assumed that both adenosinetriphosphatase (ATPase)-dependent sarcoplasmic reticulum (SR) Ca2+ uptake and CB detachment decelerated with cooling. We also assumed that all the ATPase-independent SR Ca2+ release, Ca2+ binding to and dissociation from troponin, and CB attachment remained unchanged. The simulated cooling shifted the CB force-free Ca2+ concentration curve to a lower Ca2+ concentration, increasing the Ca2+ responsiveness of CB force generation, and increased the maximum Ca(2+)-activated force. The simulation most importantly showed that these cooling effects combined led to a constant contractile efficiency when Ca2+ uptake and CB detachment rate constants changed appropriately. This result seems to account for our experimentally observed constant contractile efficiency under cooling inotropy.

Adenosine Triphosphatases↗
PubMed1997

Pressure-interval relationship characterizes left ventricular irregular beat contractilities and their mean level during atrial fibrillation.

How left ventricular (LV) contractility relates to irregular RR intervals during atrial fibrillation (AF) is still unclear. We investigated the relationship between the LV contractility (Emax) of individual beats and their preceding RR intervals during AF in isovolumic contractions is excised cross-circulated canine hearts, and additionally in ejecting contractions in in situ canine hearts. Atrial high-frequency electrical stimulation induced AF. We recorded a LV electrocardiogram, volume and pressure, and calculated the Emax of every arrhythmic beat. Multiple linear regression analysis between Emax and the six preceding RR intervals of all arrhythmic beats during 1 min AF showed the preceding RR interval (RR1) and the pre-preceding interval (RR2) to be the predominant predictors of Emax. The Emax-RR1/RR2 scattergram was closely fitted by a linear regression line. We found Emax at RR1/RR2 = 1 on the regression line to be virtually identical with both mean Emax during AF and stable Emax obtained during irregular atrial pacing at the same intervals as the mean RR interval during AF. These results newly indicate that the pressure-interval relationship predominantly characterizes LV irregular beat contractilities and their mean level during AF.

Animals↗
PubMed1997

Hybrid logistic characterization of isometric twitch force-time curve of intact blood-perfused canine right ventricular papillary muscle.

We previously found that a ventricular isovolumic pressure-time curve could be well fitted by the difference between two S-shaped logistic curves for the pressure rising and falling components, and called it "hybrid logistic" function: P(t)=A/[1+exp[-(4B/A)(t-C)]]-D/[1+exp[-(4E/D)(t-F)]]+G. We reported that the parameters of this hybrid logistic function are useful to characterize left ventricular contraction and relaxation comprehensively. In this study, we investigated how well this hybrid logistic function could fit the isometric twitch force-time curves of cross-circulated right ventricular papillary muscles of 7 dogs. This function precisely fitted the isometric force curves with correlation coefficients above 0.9996, much better than another fitting function (F(t)=C(t/A)(B)exp[1-(t/A)(B)]) proposed by Nwasokwa. The present results indicate that our hybrid logistic function can also reasonably express the canine right ventricular papillary muscle isometric twitch force-time curve. We suggest the possibility that the parameters of this hybrid logistic function are also useful to comprehensively characterize right ventricular papillary muscle twitch contraction and relaxation.

Animals↗
PubMed1997

Oxygen uptake in maximally contracting muscle perfused at low flow with high O2 affinity erythrocytes.

To analyze the roles of blood flow and blood-tissue diffusion in determining oxygen (O2) availability to maximally exercising skeletal muscle, we investigated the influence of low flow on the O2 uptake (VO2)-venous PO2 (PVO2) relation with normal and high O2 affinity erythrocytes. We prepared normal and high O2 affinity erythrocytes by incubating human citrate-phosphate-dextrose-stored erythrocytes with and without cyanate. We perfused maximally contracting gastrocnemius muscle at 4-Hz isometric twitch with solutions containing normal and high O2 affinity erythrocytes for 3 min in anesthetized dogs. During stimulation, perfusion flow was maintained low at 50 ml.min-1.100 g-1 with a perfusion pressure of 50 mmHg. PVO2 for normal affinity erythrocytes (25.6 Torr) was significantly (p < 0.05) higher than that for high O2 affinity erythrocytes (15.9 Torr). Nevertheless, the VO2 for normal and high O2 affinity erythrocytes was approximately the same value, 6.5 ml.min-1.100 g-1 (p > 0.05). The O2 extraction rate was approximately 80% in normal and high O2 affinity erythrocytes. These results indicate that VO2 at low flow was independent of PVO2 in maximally contracting skeletal muscle, although PVO2 was reversely correlated with O2 affinity. We suggest that this PVO2-independency of VO2 at low flow is caused by long red-cell transit time in the capillary without diffusion-limitation and/or a 20% constant arterio-venous shunt of arterial O2 delivery.

Animals↗
PubMed1997

Ryanodine decreases internal Ca2+ recirculation fraction of the canine heart as studied by postextrasystolic transient alternans.

We tested our hypothesis that the O2 wasting of Ca2+ handling in the excitation-contraction (E-C) coupling in ryanodine-treated failing hearts could be reflected by a decrease in the internal Ca2+ recirculation fraction (RF). We have reported, using canine excised cross-circulated hearts, that intracoronary ryanodine (40 nmol/l blood) halved left ventricular contractility without decreasing myocardial O2 consumption for the E-C coupling. We previously suspected this mechanoenergetic state to manifest energy wasting of Ca2+ handling due to ryanodine causing leakage of Ca2+ from the sarcoplasmic reticulum. To test this hypothesis, we analyzed all the sporadic spontaneous cases of postextrasystolic potentiation (PESP) obtained during the ryanodine experiments. We calculated RF from the beat constant of the exponential decay component of not only the monotonic type but also the transient alternans type of PESP. Results showed that ryanodine significantly decreased the beat constant in both types of PESP from about 2 to 1.5 beats and hence RF from 0.6 to 0.5 on the average, supporting the hypothesis. This organ-level systems approach to Ca2+ handling using transient alternans PESP as well as monotonic PESP may help obtain better insights into the mechanoenergetics of failing hearts.

Animals↗
PubMed1997

No suppression of respiratory function of mitochondrial isolated from the hearts of anesthetized rats with high-dose pentobarbital sodium.

Pentobarbital sodium is a widely used anesthetic for animal experiments. We have already reported that a high dose of pentobarbital sodium (100 mg/kg i.p., twice the usual anesthetic dose) depresses myocardial mechanoenergetics in the canine heart. Furthermore, it has been reported that a high concentration of pentobarbital sodium inhibits myocardial contractility and mitochondrial electron transport and energy transfer. Therefore, we were afraid that the mitochondrial respiratory function would be impaired by pentobarbital anesthesia and that pentobarbital sodium would be an inappropriate anesthetic for cardiac mechanoenergetic studies. In this study, we investigated the respiratory function of mitochondria isolated from the hearts of anesthetized rats with high-dose pentobarbital sodium. We examined the mitochondrial respiratory function by the ADP/O ratio, respiratory control index (RCI), oxygen consumption rate in state III (State III O2) by oximetry, and membrane potential using a fluorescent dye, 3,3'-dipropylthiodicarbocyanine iodide (diS-C3-(5). The ADP/O ratio, RCI, and State III O2 values and changes in membrane potential induced by various respiratory substances were not significantly different between the rats with and without anesthesia. These results indicate that the respiratory function is not suppressed in the isolated myocardial mitochondria of rat hearts after high-dose pentobarbital anesthesia, although the pentobarbital sodium blood concentration was of the same order as that which exerts mitochondrial uncoupling in rat isolated mitochondrial preparation. Therefore, pentobarbital sodium anesthesia up to 100 mg/kg i.p. is applicable for mechanoenergetic studies of excised rat hearts, at least from the energetic aspect.

Adjuvants, Anesthesia↗
PubMed1997

Mechanoenergetics of rat left ventricles in in situ and excised blood-perfused hearts and in unloaded rat left ventricular slices.

We investigated rat left ventricular (LV) mechanoenergetics in three different preparations. We obtained an upward convex curvilinear end-systolic pressure-volume relation (ESPVR) regardless of left ventricular (LV) contractility in in situ and excised cross-circulated rat hearts. We also obtained a linear myocardial O2 consumption per beat (VO2)-end-systolic pressure-volume area (PVA; a measure of ventricular total mechanical energy) relation regardless of the curvilinear LV ESPVR in the excised cross-circulated heart. The slope and the VO2 intercept of the VO2-PVA relation was similar to those in other species. The basal metabolism obtained by KCl arrest was higher than those in other species. In the whole heart preparation, the VO2 intercept may include O2 consumption for residual crossbridge cycling as well as O2 consumption for excitation-contraction (E-C) coupling and basal metabolism. Therefore, we established a new system for measuring myocardial O2 consumption of mechanically unloaded (zero PVA) rat LV slices. The increment in O2 consumption by stimulation of the slices represents O2 consumption for E-C coupling (but not for crossbridge cycling). Most O2 consumption for E-C coupling seems consist of O2 consumption for the sarcoplasmic reticulum Ca2+ pump.

Animals↗
PubMed1996

Logistic character of myocardial twitch force curve: simulation.

We found that the isovolumic pressure-time curve of the canine left ventricle closely fitted the difference of two logistic function curves and that the isovolumic relaxation-pressure curve segment was more reliably characterized by a logistic time constant than by the conventional exponential time constant. We therefore hypothesized that the calcium (Ca) transient and the Ca-troponin (Tn) binding and crossbridge (CB) kinetics underlay the logistic character of the ventricular isovolumic pressure curve. We tested this hypothesis with a computer simulation of a simple Ca and CB kinetics model of myocardial isometric twitch force development. We assumed the instantaneous number of attached CBs that was theoretically given as the difference between the cumulative CB attachment and detachment curves. We radically changed the Ca transient, Ca-Tn binding, and CB kinetic parameters. We always found that both the cumulative CB attachment and detachment curves closely fitted logistic functions. The difference curve of these two best-fit logistic functions closely fitted the theoretical F curve with certain combinations of the Ca transient, the Ca-Tn binding, and the CB kinetic parameters. These results seem to support our hypothesis.

Animals↗
PubMed1996

Myocardial VO2 of mechanically unloaded contraction of rat ventricular slices measured by a new approach.

We instituted a new approach of measuring mechanically unloaded myocardial oxygen consumption (VO2) by using rat left ventricular (LV) slices in an air-tight chamber filled with oxygenated Tyrode solution. Myocardial slices (300 microns in thickness) freely shortened without external load by electrical field stimulation (St). VO2 without St (n = 6) was 1.69 +/- 0.41 ml O2.min-1.100 g LV-1. VO2 with St (n = 6) increased to 2.28 +/- 0.36 ml O2.min-1.100 g LV-1. VO2 in Ca(2+)-free Tyrode solution irrespective of St was nearly equal to VO2 without St in normal Tyrode solution, indicating that all these VO2 correspond to basal metabolic VO2. The increment in VO2 by St (delta VO2) increased up to twice normal with the extracellular Ca2+ concentration up to 4 times normal. Inhibition of cross-bridge cycling by 2,3-butanedione monoxime (5 and 10 mM) did not decrease delta VO2. These results suggest that delta VO2 consists of VO2 primarily for excitation-contraction coupling but not for cross-bridge cycling.

Animals↗
PubMed1996

Constancy and variability of contractile efficiency as a function of calcium and cross-bridge kinetics: simulation.

We simulated myocardial Ca2+ (Ca) and cross-bridge (CB) kinetics to get insight into the experimentally observed constancy and variability of cardiac contractile efficiency in generating total mechanical energy under various inotropic and pathological conditions. The simulation consisted of a Ca transient, Ca association and dissociation rate constants of troponin C, and CB on and off rate constants. We evaluated sarcomere isometric twitch contractions at a constant muscle length. We assumed that each CB cycle hydrolyzes one ATP and that the force-length area (FLA) quantifies the total mechanical energy generated by CB cycles in a twitch contraction. FLA is a linear version of pressure-volume area, which quantifies the total mechanical energy of cardiac twitch contraction and correlates linearly with cardiac oxygen consumption (H. Suga, Physiol. Rev. 70: 247-277, 1990). The simulation shows that the contractile efficiency varies with changes in the Ca transient and Ca and CB kinetics except when they simultaneously speed up or slow down proportionally. These results point to possible mechanisms underlying the constancy and variability of cardiac contractile efficiency.

Animals↗