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Biomedical subjects

H Suga

Publications and source records attributed to H Suga.

At least 181 records · Page 10Linked to original sources
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

External mechanical work during relaxation period does not affect myocardial oxygen consumption.

We assessed the effect of external mechanical work (EW) during the relaxation period (RP) on myocardial oxygen consumption (VO2) and clarified the energetic significance of the potential energy (PE) portion of the pressure-volume area (PVA) in the cross-circulated dog left ventricle. We changed the course of the relaxation segment of the pressure-volume (P-V) trajectory by increasing or decreasing EW within a given PVA without changing the end-diastolic volume (EDV) and the systolic segment of the P-V trajectory while measuring VO2. Thus the ventricle underwent ejection or filling during RP. Although the percent fraction of EW in PVA (%EW/PVA) was markedly increased from 32 +/- 12 (SD) to 93 +/- 3% in ejecting contractions (8 hearts) and from 0 to 93 +/- 5% in isovolumic contractions (3 hearts), these marked changes in %EW/PVA did not significantly affect VO2. Moreover, the VO2-PVA data during these procedures fell on the reference VO2-PVA relation line obtained by changing EDV and PVA of isovolumic contractions. We conclude that EW during RP at a constant PVA does not affect VO2 and part of PE can be converted into EW in an energetically equivalent manner.

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

Physiological interpretation of negative circumferential tension in vascular walls.

The balance of force in a cylindrical tube (Oka-Azuma equation) indicates existence of a negative circumferential tension in the wall of blood vessels in vivo. However, we conventionally consider only a positive wall tension due to a positive transmural pressure in blood vessels. In this paper, the nature of such a negative circumferential tension in the vascular wall was reconsidered. The same type of negative tension or compressive force was shown to exist in any hollow and solid biological tissues placed in the atmospheric pressure. In living tissues, which have abundant water and are incompressible to external pressure, the compressive force by atmospheric pressure is simply the internal fluid pressure. The fluid pressure is a scalar and does not produce any effective net force vector. For this reason, there is no need to consider the compressive force component produced by the environmental pressure in the balance of force in living tissues.

Atmospheric Pressure↗
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

Myocardial efficiency and economy in Huxley's 1957 crossbridge model.

In cardiac muscle and the heart, the maximum mechanical efficiency is relatively constant (15-25%) under various acute and chronic inotropic interventions, whereas the economy of isometric force development varies by 2-4 times with these interventions. We speculated about this discrepancy using Huxley's 1957 crossbridge model. Our theoretical derivation showed that the economy is proportional to the product of the thermodynamic efficiency (w/e in Huxley's notation) and the reciprocal of the rate constant of crossbridge detachment in the forward position (g1 in Huxley's notation): (w/e) (1/g1). The w/e value is the maximum limit of the mechanical efficiency. This w/e value has been assumed to be 0.75 for fast contracting skeletal muscle and 0.95 for slow contracting skeletal muscle; a 1.3-fold difference. Representative g1 values are 6/s for the fast skeletal muscle and 0.12/s for the slow skeletal muscle; a 50-fold difference. These differences in w/e and g1 between the fast and slow skeletal muscles predict that the economy would change by 65 (= 1.3 x 50) times while the efficiency changes by only 1.3 times. Extrapolation of this relation to fast and slow contracting cardiac muscles suggests that only a 4-fold change in the economy, which is the observed maximum difference between the rat or rabbit hypo- and hyperthyroid myocardium, would be associated with only a less than 10% change in the maximum mechanical efficiency.

Isometric Contraction↗
PubMed1991

[Effects of gabexate mesilate (FOY) on the gallbladder, sphincter of Oddi and duodenum of the normal and gastrectomized dogs].

FOY induced a dose-dependent inhibitory response on the gallbladder, sphincter of Oddi and duodenum of normal and gastrectomized dogs, although it induced an excitatory response in some dogs. The inhibitory response was not reduced or terminated by pretreatment with atropine, guanethidine, hexamethonium or/and proglumide. The FOY-induced inhibitory response reversed to the excitatory response in the sphincter of Oddi and duodenum by pretreatment with tetrodotoxin, but not in the gallbladder. These results suggested that the FOY-induced inhibitory response of the sphincter of Oddi and duodenum was caused by stimulation of nonadrenergic noncholinergic inhibitory neurons, not by FOY-induced cholecystokinin secretion. The excitatory response was induced by direct stimulation of their smooth muscles. The inhibitory response of the gallbladder to FOY was induced by direct stimulation of the smooth muscles.

Animals↗
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↗
PubMed1990

Solvent effects on the cooperative order-disorder transition of aqueous solutions of schizophyllan, a triple-helical polysaccharide.

A triple helical polysaccharide schizophyllan in aqueous solution exhibited a highly cooperative transition between ordered and disordered states associated with the conformation of its side chains and nearby water molecules. The transition was followed by optical rotation and calorimetry using water containing additives such as NaOH and DMSO as solvents. The ordered state was stabilized or destabilized depending on the kind and amount of the additive employed; in particular, the addition of DMSO had a remarkable stabilizing effect. This effect was analyzed by means of a statistical mechanical theory of linear cooperative transitions, where DMSO was assumed to interact favorably with the ordered side chains. A small amount of NaOH in a solvent mixture stabilized the ordered state and made the transition curve very gradual. No molecular mechanism was elucidated to account for the role of NaOH.

Calorimetry↗
PubMed1990

Force-time integral does not improve predictability of cardiac O2 consumption from pressure-volume area (PVA) in dog left ventricle.

We have proposed the systolic pressure-volume area (PVA) as a measure of the total mechanical energy generated by ventricular contraction, and we found a closely linear correlation between PVA and cardiac oxygen consumption (VO2). Although the force-time integral (FTI) has long been considered to be the most reliable correlate of cardiac oxygen consumption (VO2), we have already shown that VO2 remained constant although FTI was changed while PVA was kept constant in the excised, cross-circulated dog left ventricle. This means that PVA is superior to FTI as a predictor of VO2. In the present study, we studied whether a linear addition of FTI to PVA could improve the prediction of VO2 from PVA in isovolumic and ejecting contractions with different afterload pressures in the same type of dog left ventricle preparation. Although left ventricular VO2 was always closely correlated with either PVA (r = 0.967, mean after z-transformation) or FTI (mean r = 0.925), multiple regression analysis indicated that PVA alone accounted for as much as 94% (mean) of the variance of VO2 and that FTI linearly added to PVA accounted for an additional few percent of the variance (statistically significant in less than half the cases). We conclude that the addition of FTI to PVA does not improve the predictability of VO2 from PVA in ordinary contractions.

Animals↗
PubMed1990

Contractility to minimize oxygen consumption for constant work in dog left ventricle.

We studied whether an optimal Emax (contractility index) to minimize myocardial O2 consumption (MVo2) for a constant external work (EW) and, hence, maximize mechanical work efficiency exists as a nadir of MVo2 within the physiological range of Emax. MVo2 and Emax were measured in the left ventricles (LV) of 10 dogs. In each experiment, heart rate, cardiac output, and mean aortic pressure were kept constant by pacing, bypassing the right heart, and adjusting the inflation of an intra-aortic balloon, respectively, to maintain a constant EW. MVo2 was determined as the product of coronary arteriovenous O2 difference, and coronary blood flow drained from the right heart. Emax was obtained by an abrupt aortic occlusion method. We changed Emax over 1.4-16.1 mmHg.ml-1.100 g) by dobutamine, propranolol, and sodium pentobarbital. The obtained MVo2-Emax relationship showed that MVo2 correlated positively with Emax in 9 of the 10 dogs (correlation coefficients = 0.68-0.96). In one of the 9 dogs and the remaining dog, MVo2 slightly increased with decreases in Emax below 7-8 mmHg.ml-1.100 g. We conclude that the optimal Emax to minimize MVo2 for a constant EW does not generally exist as a nadir of MVo2 in the physiological range of Emax in dog hearts.

Animals↗