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S Futaki

Publications and source records attributed to S Futaki.

At least 73 records · Page 4Linked to original sources
PubMed1992

Myocardial oxygen consumption of fibrillating ventricle in hypothermia. Successful account by new mechanical indexes--equivalent pressure-volume area and equivalent heart rate.

We studied the effects of cardiac hypothermia on myocardial oxygen consumption of a fibrillating ventricle and evaluated whether myocardial oxygen consumption of a fibrillating ventricle in hypothermia can be accounted for by new mechanical indexes: equivalent pressure-volume area and equivalent heart rate in the isolated cross-circulated canine heart preparation. Equivalent pressure-volume area is the area that is surrounded by a horizontal pressure-volume line at the pressure of a fibrillating ventricle and the end-systolic and end-diastolic pressure-volume relations in the beating state in the pressure-volume diagram. Equivalent pressure-volume area is an analog of the pressure-volume area of a beating heart and has been proposed to be a measure of the total mechanical energy of a fibrillating ventricle. Equivalent heart rate was calculated from myocardial oxygen consumption per minute in both beating and fibrillating states under unloaded conditions as an estimate of the frequency of contractions of individual myocytes on the assumption that individual myocytes during ventricular fibrillation have the same contractility as that in the beating state. We estimated myocardial oxygen consumption per minute of the fibrillating ventricle at various ventricular volumes as a function of both equivalent pressure-volume area and equivalent heart rate. The myocardial oxygen consumption-equivalent pressure-volume area relation during ventricular fibrillation in hypothermia was highly linear, with a correlation coefficient of 0.90 (mean). The relation between estimated and directly measured myocardial oxygen consumption values of a fibrillating ventricle in hypothermia was highly linear (r = 0.98), and the regression line (y = 0.80x + 0.48) was close to the identity line in the working range. Therefore we conclude that equivalent pressure-volume area is the primary determinant of myocardial oxygen consumption during ventricular fibrillation in hypothermia, and myocardial oxygen consumption of a fibrillating ventricle in hypothermia can be accounted for by the combination of equivalent pressure-volume area and equivalent heart rate as in normothermia.

Animals↗
PubMed1992

Energetics of the fibrillating ventricle.

We have proposed a new mechanical index, equivalent pressure-volume area (ePVA), as a measure of the total mechanical energy of a fibrillating ventricle. ePVA is an analogue of the pressure-volume area (PVA) of a contracting ventricle and the specific area surrounded by the horizontal pressure-volume line at the pressure of ventricular fibrillation (VF) and the end-systolic and end-diastolic pressure-volume relations in the beating state in the pressure-volume diagram. In the isolated, cross-circulated heart preparation, we obtained myocardial oxygen consumption (VO2) during VF and ePVA at various left ventricular volumes in the control, epinephrine, propranolol and hypothermia runs. ePVA was highly linearly correlated with VO2 in all runs (r = 0.95, 0.98, 0.96 and 0.90, respectively). We also determined equivalent heart rate (eHR) as an estimate of the contraction frequency of individual myocytes in a fibrillating ventricle from mechanically unloaded VO2 in beating and fibrillating states. Using both ePVA and eHR, VO2 during VF was estimated and correlated with directly measured VO2. Estimated VO2 almost agreed with measured VO2 in all runs. We conclude that ePVA is a primary determinant of VO2 during VF, and that VO2 of a fibrillating ventricle can be reasonably accounted for by the combination of ePVA and eHR. This paper is a review of our previous studies on the energetics of a fibrillating ventricle.

Animals↗
PubMed1992

Ventricular fibrillation does not depress postfibrillatory contractility in blood-perfused dog hearts.

We studied whether ventricular fibrillation depresses ventricular contractility in a blood-perfused heart. In 12 excised, cross-circulated dog hearts, we measured left ventricular pressure and myocardial oxygen consumption at a middle left ventricular volume as control and induced ventricular fibrillation electrically. Six hearts were subjected to 20 minutes of ventricular fibrillation (group A), and the other six hearts were subjected to 40 minutes of ventricular fibrillation (group B). Then we defibrillated the heart with direct current shock and measured left ventricular pressure, left ventricular volume, and myocardial oxygen consumption immediately, 10 minutes, 20 minutes, and 30 minutes after the defibrillation. Coronary perfusion pressure was maintained normal (around 100 mm Hg) by the arterial pressure of the support dog throughout each experiment. Ventricular contractility was quantified by the maximum value for the instantaneous pressure/volume ratio (Emax). Pooled data of both groups A and B showed that Emax immediately after defibrillation increased to 116% +/- 28% (p less than 0.05) of control level and Emax 10 minutes after defibrillation decreased to 84% +/- 17% (p less than 0.05) of control level. Then Emax recovered to the control level: 95% +/- 18% (p greater than 0.05) of control level at 20 minutes and 100% +/- 20% (p greater than 0.05) of control level at 30 minutes after defibrillation. Emax of group A was not different from that of group B at comparable measurement times after defibrillation. Changes in myocardial oxygen consumption per beat were in proportion to the changes in Emax. We conclude that ventricular fibrillation per se for 20 to 40 minutes does not depress postfibrillatory contractility when coronary blood perfusion is maintained normal in the dog left ventricle.

Animals↗
PubMed1992

Mechanical enhancement and myocardial oxygen saving by synchronized dynamic left ventricular compression.

Dynamic cardiomyoplasty with synchronously paced skeletal muscle grafts has recently been developed to augment the performance of impaired myocardium. This method has been reported effective to improve patients' general status and some hemodynamic parameters. It is unknown, however, how a systolic dynamic cardiac compression, as in dynamic cardiomyoplasty, affects left ventricular energetics. The purpose of this study was to characterize the effects of dynamic cardiac compression on the ventricle in terms of the pressure-volume relationship and myocardial oxygen consumption. In an isolated cross-circulated dog heart model, a dynamic cardiac compression device was set to directly compress the ventricle during systole. End-systolic pressure, contractility index (Emax), pressure-volume area, external mechanical work, coronary blood flow, and myocardial oxygen consumption were determined before and during dynamic cardiac compression. Dynamic cardiac compression significantly increased Emax. When end-diastolic and stroke volumes were fixed, end-systolic pressure, pressure-volume area, and external mechanical work significantly increased during dynamic cardiac compression while coronary blood flow and myocardial oxygen consumption remained unchanged. When end-systolic pressure was matched with the pre-dynamic cardiac compression control level by decreasing end-diastolic volume at a constant stroke volume so that external mechanical work under dynamic cardiac compression returned to the control level, both pressure-volume area and myocardial oxygen consumption significantly decreased. In contrast to a marked increase in myocardial oxygen consumption for a given increase in external mechanical work by either volume loading or dobutamine, dynamic cardiac compression did not increase myocardial oxygen consumption for the same increase in external mechanical work. Thus dynamic cardiac compression augments left ventricular pump function without increasing myocardial oxygen demand or compromising coronary blood flow.

Animals↗
PubMed1991

Effect of substitution of a lysyl residue that binds pyridoxal phosphate in thermostable D-amino acid aminotransferase by arginine and alanine.

Lys-145 of the thermostable D-amino acid aminotransferase, which binds pyridoxal phosphate, was replaced by Ala or Arg by site-directed mutagenesis. Both mutant enzymes were purified to homogeneity; their absorption spectra indicated that both mutant enzymes contained pyridoxal phosphate bound non-covalently. Even though the standard assay method did not indicate any activity with either mutant, addition of an amino donor, D-alanine, to the Arg-145 mutant enzyme led to a slow decrease in absorption at 392 nm with a concomitant increase in absorption at 333 nm. This result suggests that the enzyme was converted into the pyridoxamine phosphate form. The amount of pyruvate formed was almost equivalent to that of the reactive pyridoxal phosphate in the mutant enzyme. Thus, the Arg-145 mutant enzyme is able to catalyze slowly the half-reaction of transamination. Exogenous amines, such as methylamine, had no effect on the half-reaction with the Arg-145 mutant enzyme. In contrast, the Ala-145 mutant enzyme neither underwent the spectral change by addition of D-alanine nor catalyzed pyruvate formation, in the absence of added amine. However, the Ala-145 mutant enzyme catalyzed the half-reaction significantly in the presence of added amine. These findings suggest that a basic amino acid residue, such as lysine or arginine, is required at position 145 for catalysis of the half-reaction. The role of the exogenous amines differs with various active-site mutant enzymes.

Alanine↗
PubMed1991

Systolic pressure-volume area (PVA) as the energy of contraction in Starling's law of the heart.

We have theoretically proposed "systolic pressure-volume area" (PVA) as a measure of total mechanical energy generated by ventricular contraction. We then experimentally showed that PVA closely correlates with left ventricular oxygen consumption (Vo2) regardless of ventricular loading conditions in a stable contractile state. Although Starling's law of the heart has been generally considered to describe the relation between ventricular preload as the input and the "energy of contraction" as the output, the energy of cardiac contraction has been variously identified with cardiac output, external work, contractile element work, tension-time index, etc., by different investigators. However, none of these variables has been unanimously accepted as the total mechanical energy of contraction because they do not consistently correlate with Vo2 which represents the total energy utilization for contraction. Considering the nature of PVA which has been revealed over the last decade, we now confidently propose that PVA is the most likely expression of the total mechanical energy of contraction that has been pursued for many years as the energy of contraction in Starling's law of the heart.

Blood Pressure↗
PubMed1991

Hyperthyroid dog left ventricle has the same oxygen consumption versus pressure-volume area (PVA) relation as euthyroid dog.

We studied the effects of hyperthyroidism on the relation between O2 consumption (Vo2) and the pressure-volume area (PVA) of the left ventricle (LV) in dogs. PVA is a measure of the total mechanical energy generated per beat of LV. Dogs were treated by daily intramuscular injection of 0.3 or 1.0 mg/kg L-thyroxine over 2-5 weeks. Hyperthyroid dogs had a 40 times higher serum T4, a 40% higher sinus heart rate, and a 35% higher LV Emax (an index of ventricular contractility) than euthyroid dogs. Hyperthyroid dog hearts had linear Vo2-PVA relations like euthyroid dog hearts. The regression line was Vo2 = A x PVA + B, where A was 2.30 (dimensionless) and B was 0.53 J/beat per 100 g LV. B was significantly increased with dobutamine and decreased with propranolol, whereas A was not significantly changed by them. These A and B values were comparable to euthyroid data. Hyperthyroidism did not significantly affect myosin Ca-ATPase activity and V3-type myosin predominance, but increased the speed of the force transient response to length perturbation by 20%-70%, suggesting similar increases in crossbridge cycling rate. We conclude that in spite of accelerated crossbridge cycling rate the Vo2-PVA relation was not altered by hyperthyroidism in dogs.

Animals↗
PubMed1991

Intrathecal injections of galanin and its antiserum affect nociceptive response of rat to mechanical, but not thermal, stimuli.

To ascertain the involvement of galanin in nociceptive transmission in the spinal dorsal horn, we examined the effects of intrathecal injections of porcine galanin and its antiserum on behavioral nociceptive responses of the rat, using the paw-pressure and paw-radiant heat tests. An intrathecal injection of antiserum against porcine galanin reversed the decreased nociceptive threshold for mechanical, but not thermal, stimulation of the carrageenin-treated hind paw of rat, with no effect on the nociceptive threshold of the non-inflamed hind paw. Rat galanin as well as porcine galanin suppressed the binding of [125I]porcine galanin to the antiserum, a finding suggesting that the antiserum can bind rat galanin. An intrathecal injection of porcine galanin (0.1 and 1 nmol, but not 0.01 nmol) decreased the mechanical nociceptive threshold of the rat hind paw with no effect on thermal nociception. These results suggest that galanin present in the dorsal horn is involved in the facilitation of mechanical, but not thermal, nociceptive transmission.

Animals↗
PubMed1991

Alterations of intracellular calcium homeostasis and myocardial energetics in acute adriamycin-induced heart failure.

To elucidate the mechanism of acute contractile failure induced by adriamycin, the intracellular concentrations of free calcium ([Ca2+]i) and energy-related phosphate compounds were determined in isolated ferret hearts. The time-averaged [Ca2+]i was measured at 10 min resolution using fluorine nuclear magnetic resonance (NMR) spectroscopy and the NMR-sensitive Ca2+ indicator 5F-BAPTA. [Ca2+]i significantly increased from a control of 381 +/- 66 nM (mean +/- SEM, N = 5) to 789 +/- 171 nM during 30 min of perfusion with adriamycin (30 mg/L), and remained elevated for at least 30 min after washout. The isovolumic LV pressure decreased to 80.7 +/- 8.9% of control (N = 12, p less than 0.05) and did not recover after washout. Intramyocardial contents of energy-related phosphates were determined by phosphorus NMR spectroscopy in seven other hearts. No significant change in myocardial energy metabolism was observed during adriamycin exposure and after washout; inorganic phosphate did not increase, and phosphocreatine and ATP did not decrease. These results indicate that Ca overload induced by adriamycin is associated with acute contractile failure. Adriamycin has been reported to inhibit Na-Ca exchange and to affect the gating of Ca2+ release channels in sarcoplasmic reticulum. Whatever the cause of the calcium overload, the fact that dysfunction persists as an aftereffect of adriamycin is consistent with the hypothesis that calcium overload, in the absence of ischemia, can leave behind long-lasting contractile dysfunction.

Adenosine Triphosphate↗
PubMed1991

Multicompartment model for mechanics and energetics of fibrillating ventricle.

We propose a new mechanical model of a fibrillating ventricle to interrelate ventricular mechanics and energetics during fibrillation. The model consists of multiple asynchronously contracting compartments with identical time-varying elastances but with different contraction phase lags. Pressures in all compartments are common, and volumes of all compartments change, keeping their sum constant in the model. We evaluated the mechanical behavior of each compartment by simulating this model on a personal computer. Results showed that each compartment contracts quasi-isobarically. We calculated the pressure-volume area (PVAc) of each compartment as a measure of the total mechanical energy generated by a contraction of the compartment. We found that the sum of PVAcs of all compartments agreed with the area (equivalent PVA; ePVA) surrounded by the end-systolic and end-diastolic pressure-volume relations and the isobaric line at the mean pressure of the fibrillating ventricle. We conclude that ePVA represents the total mechanical energy of the fibrillating ventricle model. The multicompartment model is useful for insight into the interrelation between ventricular mechanics and energetics during ventricular fibrillation.

Animals↗
PubMed1991

Sensitivities of cardiac O2 consumption and contractility to catecholamines in dogs.

We studied the effects of plasma catecholamines from the adrenal gland on systolic pressure-volume area (PVA)-independent O2 consumption (VO2) and contractility index (Emax) in the left ventricle of excised cross-circulated dog hearts. PVA is a measure of the total mechanical energy of contraction. Under baseline conditions, the PVA-independent VO2 correlated with plasma catecholamine level in the hearts (r = 0.84). Plasma epinephrine and norepinephrine levels increased gradually from 0.3 and 0.4 ng/ml to 10.3 and 2.7 ng/ml on average during adrenal sympathetic nerve stimulation of support dogs. Simultaneously, Emax and PVA-independent VO2 increased by 240 +/- 127 (SD) and 75 +/- 24%. Although their increases were monotonic in a given heart, their sensitivities to catecholamines were considerably variable among hearts. However, these two sensitivities were correlated (r = 0.96) with each other in the hearts, and the interheart variation of the sensitivity of the PVA-independent VO2 to Emax (i.e., oxygen cost of Emax) was smaller. We conclude that the oxygen cost of Emax is less variable among hearts despite large interheart variations of Emax and VO2 responses to plasma catecholamines.

Animals↗
PubMed1991

Positive inotropism in hypothermia partially depends on an increase in maximal Ca(2+)-activated force.

We investigated the contribution of maximal Ca(2+)-activated force to the positive inotropism induced by mild hypothermia. Phosphorus-31 nuclear magnetic resonance spectroscopy revealed that neither energy-related phosphorus compounds in myocardium nor intracellular pH was responsible for the change in contractility. Maximal Ca(2+)-activated pressure (MCAP), the intact-heart correlate of maximal Ca(2+)-activated force, was determined in isolated perfused rabbit hearts by measuring isovolumic left ventricular pressure during tetani at extracellular Ca2+ concentrations greater than or equal to 10 mM. Tetani were elicited by rapid pacing after exposure to ryanodine. MCAP increased by 2.17 +/- 0.28% (mean +/- SE, P less than 0.001, n = 19) for each degree of myocardial cooling between 30 and 38 degrees C. Our results indicate that a primary change in myofilament Ca2+ responsiveness underlies the positive inotropism in hypothermia. The increase in maximal Ca(2+)-activated force may explain the observation of positive inotropism without an upward shift in the relation between oxygen consumption and pressure-volume area, as previously reported for cooled whole hearts.

Animals↗
PubMed1991

Equivalent pressure-volume area accounts for oxygen consumption of fibrillating heart.

We attempted to find cardiac mechanical parameters to account for myocardial O2 consumption (VO2) during ventricular fibrillation (VF). We fully utilized the concept of pressure-volume (P-V) area (PVA), which is equivalent to the total mechanical energy generated by a ventricular contraction. We also utilized a multicompartment model consisting of multiple asynchronously contracting compartments, which we previously proposed to simulate the mechanics of a fibrillating ventricle. The model analysis had already validated the application of PVA to VF in terms of "equivalent PVA" (ePVA). ePVA is the area surrounded by the end-systolic and end-diastolic P-V relations in beating state and the isobaric P-V line at the VF pressure. ePVA is supposed to represent the total mechanical energy generated by single contractions of each compartment (or myocyte) in a fibrillating ventricle. We determined ePVA and correlated it with measured VO2 per minute (mVO2) at various ventricular volumes in electrically induced fibrillating left ventricles of the excised cross-circulated canine heart preparation. Correlation coefficient (r) of the mVO2-ePVA relation during VF was high (r = 0.95, P less than 0.01). Comparing mVO2 during VF with that in beating state at an unloaded ventricular volume, we calculated equivalent heart rate (eHR) as an estimate of the frequency of contractions of individual compartments (myocytes). With the use of both ePVA and eHR, mVO2 during VF at various ventricular volumes was estimated. The relation between estimated mVO2 and directly measured mVO2 was highly linear (r = 0.88, P less than 0.01), and the regression line almost agreed with the identity line (regression coefficient = 1.05). We conclude that the new ePVA and eHR concepts can reasonably account for VO2 during VF.

Animals↗
PubMed1991

Increased oxygen cost of contractility in stunned myocardium of dog.

Recent studies have shown that myocardial oxygen consumption does not proportionally decrease with the deterioration of contractile function in stunned myocardium. To investigate this disproportion, we studied the end-systolic pressure-volume relation and the relation between oxygen consumption per beat (VO2) and systolic pressure-volume area (PVA, a measure of total mechanical energy) in stunned hearts. In the VO2-PVA relation, VO2 can be divided into PVA-dependent and PVA-independent fractions. In excised cross-circulated dog left ventricles, a 15-minute normothermic global ischemia followed by 60-120 minutes of reperfusion significantly decreased the ventricular contractility index (Emax) by approximately 40%, but the PVA-independent VO2 did not significantly decrease. Oxygen cost of PVA, defined as the slope of the VO2-PVA relation, was slightly decreased in stunned hearts. Restoration of the depressed Emax to the preischemic control level by calcium infusion increased the PVA-independent VO2 to 137 +/- 27% of control level (p less than 0.01). Oxygen cost of contractility, defined as the slope of the relation between PVA-independent VO2 and Emax, increased from 0.0011 +/- 0.0003 to 0.0023 +/- 0.0005 ml O2.ml.mm Hg-1.beat-1 per 100 g myocardium in control and stunned hearts, respectively (p less than 0.01). From these new finding, we conclude that the unchanged VO2, despite the depressed contractility in stunned myocardium, is mainly due to the increased oxygen cost of contractility.

Animals↗
PubMed1991

Denopamine (beta 1-selective adrenergic receptor agonist) and isoproterenol (non-selective beta-adrenergic receptor agonist) equally increase heart rate and myocardial oxygen consumption in dog heart.

The effects of denopamine (a beta 1-selective adrenergic receptor agonist) and isoproterenol (a non-selective beta-adrenergic receptor agonist) on heart rate, left ventricular contractility, and left ventricular oxygen consumption (VO2) at the same left ventricular volume were compared in excised cross-circulated dog hearts. Denopamine and isoproterenol increased heart rate and VO2 to a comparable extent at a comparably increased contractility. Moreover, the oxygen cost of contractility which quantifies VO2 for excitation-contraction coupling was the same between the two agents. These findings contradict the previously reported smaller increases in heart rate and VO2 by denopamine than by isoproterenol in open-chest dog hearts, which have been mainly attributed to the beta 1-selectivity of denopamine. Our results suggest that in isolated and denervated hearts, the degree of beta 1-selectivity of a beta-agonistic agent does not directly determine the relative potencies of its inotropic and chronotropic effects and the oxygen cost of contractility.

Adrenergic beta-Agonists↗
PubMed1991

Calcium kinetics and energetics in myocardium. Simulation study.

We carried out a simulation study to obtain insight into the relation between calcium (Ca2+) transients and energy for handling Ca2+ in excitation-contraction (EC) coupling. The simulation incorporated basic Ca2+ kinetics among total released Ca2+ from sarcoplasmic reticulum (SR), myoplasmic free Ca2+ ion concentration, and troponin (Tn)-Ca complex concentration ([TnCa]). The total Ca2+ released from the SR was arbitrarily set as an impulse and three rate constants were used for Ca2+ binding to Tn, Ca2+ dissociation from Tn, and Ca2+ uptake by SR. The results showed that the peak Ca2+ transient varies widely as a reciprocal of the Ca2+ sensitivity of the contractile machinery, despite constant total released Ca2+ and hence, a constant energy for Ca2+ handling. This result suggests a disproportate relationship between the magnitude of Ca2+ transients and the energy for Ca2+ handling when the Ca2+ sensitivity of contractile machinery changes.

Calcium↗
PubMed1991

Equivalent heart rate during ventricular fibrillation in the dog heart: mechanoenergetic analysis.

We propose equivalent heart rate (eHR) as an estimate of the frequency of contractions of individual myocytes in a fibrillating ventricle by analyzing mechanics and energetics of the ventricle. Using the isolated, cross-circulated dog heart preparation, we determined eHR in two different ways. First, we obtained eHR (eHR1) from myocardial O2 consumption (Vo2)-equivalent pressure-volume area (ePVA) data points during ventricular fibrillation (VF) by utilizing the Vo2-pressure-volume area (PVA) relation in the beating state. PVA is the area surrounded by the end-systolic and end-diastolic pressure-volume relations and the systolic pressure-volume trajectory in the pressure-volume diagram. PVA has been shown to represent the total mechanical energy generated by each contraction. We have recently proposed ePVA as a measure of the total mechanical energy generated by single contractions of all individual asynchronously contracting myocytes in a fibrillating ventricle. ePVA is the area surrounded by the horizontal line at the VF pressure and the end-systolic and end-diastolic pressure-volume relations in the beating state. Second, we measured Vo2 in beating state at various heart rates and Vo2 during VF under a mechanically unloaded condition. By comparing these fibrillating and beating Vo2 values, we determined eHR (eHR2) for the fibrillating state. eHR1 was 216 +/- 27 beats/min and eHR2 was 223 +/- 26 beats/min. These two values were not significantly different. We conclude that the average frequency of contractions of individual myocytes in a fibrillating ventricle is equivalent approximately to 220 beats/min in terms of ventricular energetics.

Animals↗