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H Suga

Publications and source records attributed to H Suga.

At least 145 records · Page 8Linked to original sources
PubMed1993

Comparison of the cardiac force-time integral with energetics using a cardiac muscle model.

Several investigators have found experimentally that the force-time integral varies non-linearly with energy expenditure over the course of a cardiac contraction. Also, recent research findings have indicated that the crossbridge cycle to ATP hydrolysis ratio in muscle fiber systems may not be coupled with a one-to-one ratio. In order to investigate these findings, Huxley's sliding filament crossbridge muscle model coupled with parallel and series elastic components was simulated to examine the behavior of the crossbridge energy utilization and force-time integral vs time. Crossbridge (CB) energy utilization was determined by considering the ATP hydrolysis for the crossbridge cycling, and this CB energy was compared with the force-length energy in a contraction. This CB energy was calculated in both isometric and isotonic contractions as a function of contraction time and compared to the force-time integral. Simulation results demonstrated that the ratio of the force-time integral to CB energy varies strongly throughout the cardiac cycle for both isometric and isotonic cases, as has been observed experimentally. Simulations also showed that using the force-length energy component of energy vs the CB energy gave a better correlation between the total energetic predictions and the force-time integral, agreeing with recent finding that the crossbridge cycle to ATP hydrolysis ratio may not be coupled one-to-one, especially at lower force levels.

Actins↗
PubMed1993

Coupling between regional myocardial oxygen consumption and contraction under altered preload and afterload.

OBJECTIVES: This study was designed to assess the relation between left ventricular regional myocardial oxygen consumption (VO2) and variables of regional myocardial contractile function under various loading conditions. BACKGROUND: Although the relation between global VO2 and global ventricular function has been extensively studied, the relation between regional VO2 and regional myocardial contraction is not fully understood. METHODS: Myocardial shortening (regional area shrinkage), regional work, regional total mechanical energy index and regional VO2 were measured under variously altered loading conditions in the isolated, blood-perfused dog left ventricle. Regional total mechanical energy per beat was quantified by wall tension-regional area area (TAA) by the analogy of left ventricular pressure-volume area. Left ventricular loading conditions were altered by changing end-diastolic volume and stroke volume with a servo pump as follows: 1) increased preload (increased end-diastolic volume and stroke volume at a constant ejection fraction), 2) decreased afterload (increased stroke volume at a constant end-diastolic volume), 3) increased preload and afterload (increased end-diastolic volume at a constant stroke volume), and 4) altered mode of contraction (ejecting vs. isovolumetric contractions). RESULTS: During increased preload, all three variables correlated positively with regional VO2 (r = 0.78 to 1.00). During decreased afterload, the correlation was negative for area shrinkage (r = -0.65 to -0.91) and variable for regional work (r = -0.55 to 0.98) but positive and highly linear for TAA (r = 0.80 to 0.99). During increased preload and afterload, the correlation was again negative for area shrinkage (r = -0.77 to -0.97) but positive for regional work (r = 0.83 to 0.93) and TAA (r = 0.95 to 0.99). During altered mode of contraction, the correlation was insignificant for area shrinkage (r = 0.24 to 0.57) and moderate for regional work (r = 0.50 to 0.79), whereas again highly linear for TAA (r = 0.95 to 0.98). Thus, only TAA correlated closely with regional VO2 under any loading conditions. Furthermore, the slope and regional VO2 intercept of the regional VO2-TAA relation was remarkably consistent among the different hearts and loading conditions. CONCLUSIONS: We conclude that there is a tight coupling between regional VO2 and regional total mechanical energy represented by TAA regardless of left ventricular afterload and preload conditions.

Animals↗
PubMed1993

Variable cross-bridge cycling-ATP coupling accounts for cardiac mechanoenergetics.

Cardiac twitch contractions were simulated by Huxley's sliding filament cross-bridge muscle model coupled with parallel and series elastic components. The energetics of the contraction were based on the ATP hydrolysis for the cross-bridge cycling. Force-length area (FLA), as a measure of the total mechanical energy, was computed for both isometric and isotonic contractions in a manner similar to the pressure-volume area (PVA) (Suga, H. Physiol. Rev. 70: 247-277, 1990). PVA correlates linearly with cardiac oxygen consumption, and since FLA is analogous to PVA, FLA should correlate with the ATP expended. Simulations comparing FLA with the cross-bridge cycling ATP usage showed that at lower muscle fiber activation levels (shorter initial fiber lengths and lower preload levels) FLA decreased more rapidly than the number of muscle fiber cross-bridge cycles in both isometric and isotonic contraction cases. This suggests that one ATP can cause more than one cross-bridge cycle at lower activation levels as was proposed by Yanagida, Arata, and Oosawa (Nature 316: 366-369, 1985). If the number of cross-bridge cycles to ATP ratio is allowed to increase at lower activation levels as suggested by Yanagida et al., Huxley's model is compatible with the experimental findings on FLA and PVA.

Adenosine Triphosphate↗
PubMed1993

Ejecting deactivation does not affect O2 consumption-pressure-volume area relation in dog hearts.

We studied the effects of ejection velocity and resistive properties of the left ventricle (LV) on myocardial oxygen consumption (VO2) in 13 excised cross-circulated dog hearts. Increases in peak ejection velocity (-dV/dt) from 4.0 +/- 1.3 (SD) end-diastolic volume (EDV)/s to 12.7 +/- 5.3 EDV/s with constant EDV and end-systolic volume (velocity run) induced systolic pressure deficit. This decreased pressure-volume area (PVA; a measure of ventricular mechanical energy) and LV end-systolic elastance (Emax) by 47 +/- 14 and 38 +/- 15%, respectively. Unchanged maximum rate of left ventricular pressure rise and time-varying elastance during the isovolumic contraction period at the same EDV indicated that these contractions started with the same contractile state although the quicker ejection caused the greater deactivation. If the PVA deficit due to systolic pressure deficit is attributable to an internal energy-dissipating resistive element, VO2 in the velocity run will not as much decrease in proportion to PVA as in the isovolumic or slowly ejecting control run. However, the decreases in PVA due to increased -dV/dt decreased VO2 to the same extent as in the control run. This result negated the possibility that the pressure and PVA deficits would be caused by a mechanical energy-losing process. The same results were obtained whether or not Emax was decreased by quick ejection. We conclude that the pressure and PVA deficits and the proportionally decreased VO2 during quick ejection are mainly attributable to suppression of a ventricular mechanical energy generation process, but not of mechanical energy-losing process, by ejecting deactivation.

Animals↗
PubMed1993

Ryanodine wastes oxygen consumption for Ca2+ handling in the dog heart. A new pathological heart model.

Ryanodine (RYA) at a low concentration (several tens of nM) is known to selectively bind to Ca2+ release channels in sarcoplasmic reticulum (SR) and to fix them open. The present study was designed to investigate the effects of the selective change in Ca2+ release channel activity on cardiac mechanoenergetics as a model of Ca(2+)-leaky SR observed in pathological hearts. We analyzed the negative inotropic effect of RYA at a low concentration (up to 30 +/- 13 nM) on left ventricular (LV) mechanoenergetics using frameworks of LV Emax (a contractility index) and the myocardial oxygen consumption (LV VO2)-systolic pressure-volume area (PVA) (a measure of total mechanical energy) relation in 11 isolated, blood-perfused dog hearts. RYA significantly decreased Emax by 42%, whereas PVA-independent VO2 remained disproportionately high (93% of control). This oxygen-wasting effect of RYA was quite different from ordinary inotropic drugs, which alter Emax and PVA-independent VO2 proportionally. The present result suggests that RYA suppresses force generation of cardiac muscle for a given amount of total sequestered Ca2+ by SR in a similar way to myocardial ischemia and stunning. We speculate about the underlying mechanism that RYA makes SR leaky for Ca2+ and thereby wastes energy for Ca2+ handling by SR.

Analysis of Variance↗
PubMed1993

Characterization of erythropoietin isolated from rat serum: biochemical comparison of rat and human erythropoietins.

We isolated erythropoietin (Epo) from anemic-rat serum with 1.3 x 10(6)-fold purification and 38% recovery using immunoaffinity chromatography. The isolated Epo migrated in SDS polyacrylamide gel with a molecular size of 37 kDa. Biological properties of rat Epo were compared with those of human Epo using target cells of primate and murine origins. When murine cells were used as target cells for assaying Epo, rat Epo stimulated proliferation of the cells with a 50% lower potency than did human Epo. The activity of rat Epo on human cells was only 25% of that of human Epo. Studies of Epo binding to the receptor indicated that rat and human Epos were not distinguishable in binding to murine cells; however, rat Epo bound to the receptor on human cells with an affinity much lower than that of human Epo. Rat Epo was digested with N-glycanase. Complete removal of N-linked sugars converted the native Epo to the deglycosylated form with 18 kDa. The in vitro activity of deglycosylated Epo was 2.5-fold higher than that of the native Epo.

Amino Acid Sequence↗
PubMed1993

Nipradilol depresses cardiac contractility and O2 consumption without decreasing coronary resistance in dogs.

Nipradilol (3,4-dihydro-8-(2-hydroxy-3-isopropylamino) propoxy-3-nitroxy-2H-1-benzopyran) is a newly synthesized chemical agent designed to possess beta-adrenoceptor blocking and vasodilating actions. Nipradilol decreased left ventricular contractility index (Emax, slope of the ventricular end-systolic pressure-volume relation), systolic pressure-volume area (PVA, a measure of ventricular total mechanical energy) and oxygen consumption in cross-circulated excised dog hearts. However, nipradilol did not decrease total coronary resistance. These results indicate that nipradilol, like propranolol, depresses myocardial mechanoenergetics and that the vasodilating action of nipradilol could not be detected in the present study.

Adrenergic beta-Antagonists↗
PubMed1993

Left ventricular ORS widening decreases Emax without lowering VO2-PVA relation in dog hearts.

We observed a few rare spontaneous cases of a suddenly widened QRS wave of left ventricular ECG associated with a simultaneous decrease in left ventricular (LV) contractility (Emax, end-systolic pressure-volume ratio) in excised cross-circulated dog heart experiments. The decreased Emax was not associated with a descent of the relation between cardiac oxygen consumption (VO2) and LV systolic pressure-volume area (PVA, a measure of total ventricular mechanical energy). This result is intriguing because ventricular VO2-PVA relation generally changes its elevation in proportion to Emax under various inotropic interventions. We suspected the unusual observation to reflect no change in myocardial contractility despite ventricular asynchrony augmented by an intraventricular conduction defect.

Animals↗
PubMed1993

Oxygen consumption for constant work is minimal at lowest working contractility in normal dog hearts.

We tested whether minimal myocardial oxygen consumption (MVO2) for a given external work would exist in the middle of a normal contractility range as previously predicted theoretically. The left ventricle of the excised cross-circulated dog heart preparation was connected to a volume servo pump. Myocardial contractility in terms of ventricular end-systolic elastance (Emax) was gradually increased from control 8.9 +/- 3.4 (mean +/- SD) to 30.0 mmHg/(ml/100 g) by epinephrine and decreased to 1.8 mmHg/(ml/100 g) by propranolol while heart rate, end-systolic pressure and stroke work were kept constant. MVO2 was determined as the product of total coronary flow and coronary arteriovenous oxygen content difference in each contractile state. We plotted MVO2 values against E(max) values in each heart. The MVO2-E(max) relation for a constant cardiac work showed that MVO2 was minimal at the low end of the covered E(max) range. We conclude that minimal MVO2 for a given cardiac work is generally obtained at the lowest working contractility in normal dog hearts. This conclusion might pose some problems in the previous theoretical prediction as to the contractility that achieves the minimal MVO2 in a given external work.

Animals↗
PubMed1993

Ventricular perspective on efficiency.

The heart has many efficiencies of different definitions, of which mechanical work efficiency is the most popular and conventional. We have proposed a method to quantify the total mechanical energy generated by ventricular contraction. This energy can be quantified as a specific area called "systolic pressure-volume area" or "PVA" in the ventricular pressure-volume diagram. In the left ventricle of excised, cross-circulated dog heart preparations, we found a closely linear relation between PVA and oxygen consumption (VO2) under various loading conditions in a stable contractile state (Emax). An enhanced contractility was accompanied by an elevation of the load-independent VO2-PVA relation in a parallel manner, where the elevation was proportional to Emax. The slope of the VO2-PVA relation represents the "oxygen cost of mechanical energy (or PVA)" and its reciprocal indicates the "contractile efficiency", i.e., the energy conversion efficiency from PVA-dependent VO2 to PVA. This efficiency was 40% on the average, independent of various inotropic interventions. The slope of the PVA-independent VO2-Emax relation represents the "oxygen cost of contractility (or Emax)". This cost was relatively constant for different inotropic interventions except for myocardial cooling and stunning. We considered the discrepancy between the stable contractile efficiency and the variable thermal economy of force generation and maintenance.

Animals↗
PubMed1993

[Physiology of cardiac performance].

We previously proposed i) Emax (end-systolic maximum elastance of the ventricle) as an index of contractility independent of preload and afterload and ii) PVA (systolic pressure-volume area of the ventricle) as a measure of the total mechanical energy generated by the ventricular contraction. Emax is defined as the slope of the end-systolic pressure-volume relation, which is relatively linear within the normal working range of the left ventricle. A working pressure-volume point starts from the end-diastolic pressure-volume curve, comes close to or slightly exceeds the end-systolic pressure-volume line, and returns to the end-diastolic curve. Thus, the end-diastolic and end-systolic pressure-volume curves envelop a family of pressure-volume trajectories of variously loaded contractions in a stable contractility. Emax increases with enhanced contractility and decreases with depressed contractility. PVA is an area between the end-diastolic and end-systolic pressure-volume curves on the origin side of the systolic pressure-volume trajectory. PVA linearly correlates with myocardial oxygen consumption regardless of ventricular loading conditions in a given Emax and this load-independent oxygen consumption-PVA relation is elevated with an enhanced Emax. Consequently, Emax and PVA have proved to be key measures and concepts in the physiology of cardiac performance.

Echocardiography↗
PubMed1993

Determinants of myocardial oxygen consumption in fibrillating dog hearts. Comparison between normothermia and hypothermia.

The purpose of the present study was to elucidate the mechanism of the difference in myocardial oxygen consumption between heating and fibrillating states during normothermia and hypothermia. In five isolated cross-circulated dog hearts, we measured left ventricular pressure at several ventricular volumes and myocardial oxygen consumption at V0 and V100, at which peak isovolumic pressures were zero and approximately 100 mm Hg, respectively, in beating and fibrillating states during normothermia and hypothermia (29 degrees C). As a measure of the total mechanical energy at V100, we obtained pressure-volume area in the beating state and equivalent pressure-volume area for fibrillation. We calculated equivalent heart rate as an estimate of the contraction frequency of individual myocytes in a fibrillating ventricle from myocardial oxygen consumption at V0 in the beating and fibrillating states. During normothermia, myocardial oxygen consumption per minute at V0 and V100 and myocardial oxygen consumption for mechanical purposes at V100 (myocardial oxygen consumption at V100-myocardial oxygen consumption at V0) were significantly higher during fibrillation than in the beating state. Equivalent pressure-volume area during fibrillation and pressure-volume area in the beating state at V100 were comparable, whereas equivalent heart rate during fibrillation was significantly higher than heart rate in the beating state. During hypothermia, myocardial oxygen consumption was comparable between beating and fibrillating states at V0, although myocardial oxygen consumption at V100 was slightly lower during fibrillation than in the beating state. Myocardial oxygen consumption for mechanical purposes during fibrillation was half of that in the beating state. Equivalent pressure-volume area was significantly smaller than pressure-volume area, whereas equivalent heart rate and heart rate were comparable. We conclude that during normothermia, higher myocardial oxygen consumption during fibrillation than in the beating state at V0 and V100 is attributable to the higher contraction frequency. During hypothermia the comparable myocardial oxygen consumption values at V0 are attributable to the comparable contraction frequencies, whereas slightly lower myocardial oxygen consumption during fibrillation at V100 is ascribed to the lower total mechanical energy.

Animals↗
PubMed1992

Nucleotide sequence of rat erythropoietin.

The cDNA for the rat erythropoietin (EPO) has been cloned and sequenced. The deduced amino acid sequence consists of 166 amino acid residues, which has a 79% and 95% homology with human and mouse EPOs, respectively. Many short stretches, highly conserved in primate and rodent EPOs, are found in the 3'-noncoding region when insertions and deletions are taken into consideration.

Amino Acid Sequence↗
PubMed1992

Possible mechanism of ruthenium red antagonism of capsaicin-induced action in the isolated guinea pig ileum.

Ruthenium red (3-5 microM) antagonism of the inhibitory effect of capsaicin (1 microM) on the contractile response to mesenteric nerve stimulation in the presence of hexamethonium (50 microM) and guanethidine (2 microM) was reversed significantly by sialic acid (2 mM) or neuraminidase (0.1 U/ml). These results suggested that ruthenium red at low concentrations inhibits the capsaicin-induced desensitization of activated Ca2+ influx into sensory nerves at least in part by binding to sialic acid residues.

Animals↗
PubMed1992

Cardiac muscle fiber force versus length determined by a cardiac muscle crossbridge model.

A mathematical model incorporating Huxley's sliding filament crossbridge muscle model coupled with parallel and series elastic components was simulated to examine force-length relations under different external calcium concentrations. Several researchers have determined experimentally in both papillary muscle preparations and in situ heart experiments that the calcium concentration (or effective concentration from inotropic agents) will affect the strength and convexity of the cardiac muscle fiber force-length relations. Simulations were performed over a several-order-of-magnitude range of calcium concentrations in isometric contractions and these showed that the force-length curve convexity was changed. Simulation results demonstrated that increasing the stiffness in the model contractile element or series elasticity element did not change the force-length convexity. Increasing the series elasticity element stiffness did slightly change the shape of the force-length curve. The model predicts that the curve convexity changes as a result of the calcium-troponin interactions.

Calcium↗
PubMed1992

Epinephrine and calcium have similar oxygen costs of contractility.

We compared the oxygen cost of increasing ventricular contractility using Emax (slope of the ventricular end-systolic pressure-volume relation) as the index of ventricular contractility. Contractility was enhanced by calcium and epinephrine in paired experiments on dog left ventricles. Firstly, we obtained left ventricular oxygen consumption (VO2) and systolic pressure-volume area (PVA, a measure of total mechanical energy) of contractions at different volumes in the control contractile state to determine a reference VO2-PVA relation. PVA was obtained as the area in the pressure-volume (P-V) diagram which was bounded by the end-systolic P-V line, end-diastolic P-V curve and systolic P-V trajectory of individual contractions. Secondly, we gradually enhanced Emax with calcium and epinephrine in two consecutive runs at a fixed ventricular volume. Both VO2 and PVA increased with enhanced Emax. From these VO2-PVA data, we calculated the PVA-independent VO2 values at the respective enhanced Emax levels and determined the oxygen cost of Emax as the slope of the relation between the PVA-independent VO2 and Emax. The cost per beat and per 100 g was 0.00158 ml O2/(mmHg/ml) for calcium and 0.00166 ml O2/(mmHg/ml) for epinephrine on average, values not significantly different from each other (P less than 0.05). We conclude that epinephrine and calcium have similar oxygen costs of contractility over a wide range of Emax despite their different pharmacological mechanisms of positive inotropism.

Animals↗
PubMed1992

Similar oxygen cost of myocardial contractility between DPI 201-106 and epinephrine despite different subcellular mechanisms of action in dog hearts.

The effects of DPI 201-106 (a novel, cyclic AMP-independent positive inotropic agent with Ca(2+)-sensitizing and Na(+)-channel agonistic mechanisms) on myocardial mechanics and energetics were assessed in the excised cross-circulated dog left ventricle. In the first protocol, the relation between left ventricular oxygen consumption (VO2) and systolic pressure-volume area (PVA) was analyzed before and during administration of DPI 201-106. The reciprocal of the slope of the VO2-PVA relation has been shown to reflect the contractile efficiency, and the VO2-intercept consists of the oxygen cost of contractility-dependent excitation-contraction coupling and basal metabolism. DPI 201-106 increased Emax (contractility index) and elevated the VO2-PVA relation in a parallel manner, i.e., the VO2-intercept increased without a change in the slope. In the second protocol, the increase in the VO2-intercept of the VO2-PVA relation for a unit increase in Emax (i.e., oxygen cost of enhanced contractility) was compared between DPI 201-106 and epinephrine in a paired manner in each heart. Epinephrine significantly abbreviated the time to end systole, whereas DPI 201-106 did not, suggesting that the mechanism of inotropic action differed between the two drugs. However, the oxygen cost of enhanced contractility was the same between the two drugs in each heart. Therefore, DPI 201-106 did not alter the contractile efficiency nor spare the oxygen cost of enhanced contractility as compared to epinephrine under the present experimental conditions. This suggests that the Ca(2+)-sensitizing effect of DPI 201-106, if any, is too small to spare the oxygen cost of contractility in the blood-perfused, non-failing dog heart.

Animals↗