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H Suga

Publications and source records attributed to H Suga.

At least 19 recordsLinked to original sources
PubMed1996

Mechanoenergetics of negative inotropism of ventricular wall vibration in dog heart.

Mechanical vibration depresses cardiac contractility. We studied the mechanoenergetic effects of this negative inotropism in the left ventricle (LV) of an isolated, cross-circulated dog heart preparation. We took full advantage of the mechanoenergetic relationship among the LV end-systolic elastance (Emax, contractility index), systolic pressure-volume area (PVA), and myocardial oxygen consumption (VO2). PVA is a measure of the total mechanical energy that cardiac contraction generates. PVA correlates closely with VO2. The VO2 intercept of the VO2-PVA relation reflects the VO2 component for excitation-contraction (E-C) coupling plus basal metabolism (PVA-independent VO2). VO2 above the PVA-independent VO2 reflects the VO2 component for mechanical contraction (PVA-dependent VO2). When we applied 70-Hz vibration of 2-mm amplitude to a LV wall region, it instantly decreased Emax and PVA by 20%, followed by a 10% decrease in VO2 at a fixed volume. However, the vibration neither lowered the VO2-PVA relation obtained at different LV volumes, unlike ordinary negative inotropism, nor changed its slope (1.88 +/- 0.23 vs. 1.86 +/- 0.23 x 10(-5) ml O2.mmHg-1.ml-1). The virtually zero delta PVA-independent VO2/delta Emax with vibration indicates a much smaller O2 cost of Emax than that seen with calcium and propranolol inotropism. These mechanoenergetics support the hypothesis that mechanical vibration primarily suppresses cardiac contractility without suppressing E-C coupling.

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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.

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PubMed1995

Logistic time constant of isovolumic relaxation pressure-time curve in the canine left ventricle. Better alternative to exponential time constant.

BACKGROUND: The time constant of left ventricular (LV) relaxation derived from a monoexponential model has been widely used as an index of LV relaxation rate or lusitropism, although this model has several well-recognized problems. In the present study, we proposed a logistic model and derived a "logistic" time constant (TL) as a better alternative to the conventional "exponential" time constant (TE). METHODS AND RESULTS: A total of 189 beats (147 isovolumic and 42 ejecting beats) were investigated in seven canine excised cross-circulated heart preparations. We found that the logistic model fitted much more precisely all the observed LV isovolumic relaxation pressure-time [P(t)] curves than the monoexponential model (P < .05). The logistic model also fitted well both the time curve of the first derivative of the observed P(t) (dP/dt) and the dP/dt-P(t) phase-plane curve. Like TE, TL indicated that volume loading depressed LV lusitropism and that increasing heart rate and ejection fraction augmented it. TL was independent of the choice of cutoff point defining the end of isovolumic relaxation; TE was dependent on that choice. CONCLUSIONS: We conclude that the logistic model better fits LV isovolumic relaxation P(t) than the monoexponential model in the present heart preparation. We therefore propose TL as a better alternative to TE for evaluating LV lusitropism.

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PubMed1995

Heterogeneity of rice ragged stunt oryzavirus genome segment 9 and its segregation by insect vector transmission.

Genomic heterogeneity of genome segment 9 (S9) of rice ragged stunt virus (RRSV) was investigated and a point mutation was found to be responsible for an electrophoretic mobility shift of S9 on polyacrylamide gel electrophoresis (PAGE). A new form of S9 (S9L) which migrated slightly faster than natural S9 (S9U) had the same length with A-->C transversion at nt 843. Synthetic S9 with a C:G pair at nt 843 migrated slightly faster than that with an A:U pair. Therefore, we conclude that the single point mutation shifts the electrophoretic mobility. Using polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP), we could detect S9U and S9L alone or mixture in insect vectors after acquisition as well as in infected rice plants.

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PubMed1995

Cardiodynamic conditions for the linearity of preload recruitable stroke work.

Studies reported in the literature show that the stroke work (SW) versus end-diastolic volume (Ved) relationship, namely, the preload recruitable stroke work relation (PRSW), is experimentally linear in closed-chest dog hearts and its slope reflects left ventricular contractility. We considered the theoretical cardiodynamic conditions necessary for the linearity of the SW-Ved relation by utilizing ventricular end-systolic elastance, Emax (ventricular contractility), and effective arterial elastance, Ea (arterial afterload). We simulated the SW-Ved relation, using four theoretical models of the left ventricle, as follows: Ea is constant and the end-systolic pressure-volume relation (ESPVR) is linear (model 1), or nonlinear (model 2), and Ea is variable and ESPVR is linear (model 3), or nonlinear (model 4). The results show that the SW-Ved relation can be linear in both linear and nonlinear ESPVR models (models 3 and 4) only when Ea is variable. In these models, end-systolic pressure (Pes) and Ea should gradually fall, maintaining the stroke volume (SV) relatively constant with decreases in Ved until the low end of the physiological Ved range. Then, Ea should rise sharply so that Pes does not fall below the critical level. These results suggest that the autoregulation mechanisms of an intact animal operate to adapt the arterial afterload against acute changes in LV preload, maintaining cardiac output and coronary artery pressure. Such mechanisms may thus produce a linear SW-Ved relation over a wide range of conditions.

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PubMed1995

Suppression of myocardial mitochondrial respiratory function in acute failing hearts made by a short-term Ca2+ free, high Ca2+ coronary perfusion.

We made acute cardiac failure in excised cross-circulated canine hearts by a new coronary perfusion protocol consisting of Ca2+ free Tyrode perfusion for the first 10 min, high Ca2+ (16 mmol/l) Tyrode perfusion for the next 5 min, and normal Tyrode perfusion for the last 5 min interrupting blood cross circulation. After 50 min from the blood recirculation, left ventricular contractility was stably depressed to 60% of control. We studied mechanoenergetics of these acute failing hearts for the next 1-3 h. Then, we prepared mitochondria from these excised failing hearts and the support dogs' normal hearts to examine their mitochondrial respiratory function by the respiratory control index (RCI) and the oxygen consumption rate in state III (State III O2). RCI and State III O2 were significantly smaller in the failing hearts than in the normal hearts. However, sham protocol consisting of normal Tyrode coronary perfusion for 20 min did not affect RCI and State III O2. These results revealed that the mitochondrial respiratory function was moderately impaired in these acute failing hearts made by the new short-term Ca2+ intervention. However, no ultrastructural injuries of mitochondria were detected in these failing hearts.

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PubMed1995

Exogenous type-II phospholipase A2 stimulates prostaglandin synthesis in rat liver-derived BRL-3A cells in the presence of tumor necrosis factor alpha.

The effect of extracellular type-II phospholipase A2 (PLA2) on prostaglandin (PG) synthesis has been studied using rat liver-derived BRL-3A cells. The addition of type-II PLA2 to the medium of BRL-3A cells resulted in a marked decrease in the enzymatic activity in the medium. An immunochemical study involving an anti-(type-II PLA2) antibody revealed that a significant amount of PLA2 was attached to the surface of type-II PLA2-treated BRL-3A cells. Heparin inhibited the binding of PLA2 almost completely. Only modest release of PGE2 over the control value was observed when cells were treated with PLA2 alone or tumor necrosis factor alpha (TNF alpha) alone, whereas PGE2 production as well as arachidonic acid release from phospholipids was augmented more than additively in the presence of both type-II PLA2 and TNF alpha. Furthermore, pretreatment of cells with type-II PLA2 followed by subsequent stimulation by TNF alpha caused an appreciable increase in PGE2 production. Thus, type-II PLA2 bound to cell-surface heparin-like molecules may exert its activity and participate in eicosanoid generation only in the presence of TNF alpha.

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PubMed1995

The effect of total blood exchange with PHP solution on cardiac xenotransplantation.

Prevention of hyperacute rejection is a difficult and unsolved problem in xenotransplantation. Natural antibodies and complement activation have been known to play an important role in the xenotransplantation between discordant species pairs. In the present study, total blood exchange (TBE) was performed with pyridoxalated-hemoglobin-polyoxyethylene conjugate (PHP) solution (Ajinomoto Co., Inc., Kawasaki, Japan) before cardiac xenotransplantation in order to remove the immunoglobulins and prolong xenograft survival time. Guinea pigs and rats were used as the discordant species combination for donor and recipient. Two groups were established: Group 1, untreated control (n = 8) and Group 2, TBT with PHP solution (n = 8). The exchange blood transfusion was carried out at the rate of 15-20 ml/h utilizing PHP solution using a blood pump. After the blood exchange was processed, hematocrit (Ht) levels dropped to 4 or 5%, and a cardiac xenotransplantation was performed within 24 h. The levels of serum IgA, IgM, and IgG were decreased to less than 25, 25, and 10% of the base line, respectively, after blood exchange. A mean xenograft survival time in Group 2 was prolonged to 472 +/- 74 min and to 10.4 +/- 1.8 min in Group 1 (p < 0.01). A titer of the anti-guinea pig lymphocytotoxic antibody in rat serum was decreased to almost nil. The data from this study suggest that total blood exchange with PHP solution may be useful in preoperative removal of xenograft antibodies in xenotransplantation.

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PubMed1995

Canine skeletal muscle ventricles: functional assessment using the pressure-volume plane.

In five dogs, skeletal muscle ventricles (SMVs) were constructed from the latissimus dorsi muscle, and placed within the thoracic cavity. After a 3-week delay period, SMVs were electrically preconditioned with 2-Hz continuous stimulation for 6 weeks. At a second procedure, SMVs were connected to a mock-circulation system, and performance was evaluated according to pressure-volume relationships at three different SMV contraction rates (33, 54, and 97 per min) and three stimulation protocols (25, 43, and 85 Hz) under varying loading conditions. Under appropriate conditions of afterload, the end-diastolic pressure-volume relation of SMVs was comparable with that of the cardiac ventricles, although SMVs were less compliant. At higher burst stimulation frequencies, SMV compliance was increased. Compliance was not affected by varying the rate of SMV contraction. End-systolic elastance, a reflection of contractility, appeared to be constant for each SMV, in contrast to cardiac ventricles, and was not influenced by changes in burst stimulation frequency or contraction rate. In this study, SMVs were capable of a level of stroke work 180% of that of the native right ventricle (RV) at rest (0.397 +/- 0.047 x 10(6) ergs) and 37% of that of the left ventricle (LV) at rest (0.298 +/- 0.61 x 10(6) ergs), at 33 contractions per minute (CPM), 25-Hz burst frequency, and physiological preload, but this level could not be sustained at higher contraction rates. Nevertheless, power output (SMV stroke work x contraction rate) was maximal at 97 CPM. These findings demonstrate important function differences between pumping chambers constructed from conditioned skeletal muscle, and those composed of cardiac muscle, which must be considered when using skeletal muscle ventricles for cardiac support or replacement.

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PubMed1995

Ca(2+)-free, high-Ca2+ coronary perfusion suppresses contractility and excitation-contraction coupling energy.

We studied the mechanoenergetic effects of a short-term Ca(2+)-free, high-Ca2+ Tyrode solution coronary perfusion in eight excised, cross-circulated canine hearts. The perfusion protocol consisted of coronary perfusion with Ca(2+)-free Tyrode solution for 10 min followed by high-Ca2+ (16 mM) Tyrode solution for 5 min. This new protocol successfully induced acute contractile failure in seven hearts, without myocardial ultrastructural changes. We studied the end-systolic pressure-volume relation (slope = Emax, a contractility index) and the relation between oxygen consumption per beat (VO2) and systolic pressure-volume area (PVA) in these failing hearts. These hearts had no increase in end-diastolic pressure at a given volume, a 40% decrease in Emax and a proportional decrease in the PVA-independent VO2 for 1-4 h, but no decrease in the oxygen cost of PVA, defined as the slope of the VO2-PVA relation. The oxygen cost of Emax for Ca2+ handling, defined as the slope of the relation between PVA-independent VO2 and Emax, was unchanged in the failing hearts. We conclude that the present protocol induced left ventricular contractile failure, primarily involving the suppression of Ca2+ handling energy for excitation-contraction coupling.

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PubMed1995

Cardiac quick-release contraction mechanoenergetics analysis using a cardiac muscle cross-bridge model.

Huxley's sliding filament cross-bridge muscle model coupled with parallel and series elastic components was simulated to examine the conflicting reports on the amount of energy saved by quick release at the peak contraction time. Cross-bridge energy utilization was determined by considering the ATP hydrolysis for the cross-bridge cycling. The quick-release cases were simulated by letting the muscle fiber suddenly shorten to the resting fiber length at peak systole, and then the contraction was allowed to continue at the resting length. Simulation results demonstrated that, using realistic parameter values, typically approximately 15% of the muscle fiber energy is used after peak systole (and approximately 30% of the cross-bridge energy), but this is also a function of the muscle fiber properties characterized by cross-bridge association and dissociation rate constants. Increasing the kinetic rate constants, the series elasticity, the initial fiber length, or the time of peak intracellular calcium will increase the amount of energy left, which may explain some of the discrepancies in the literature. Cardiac muscle hypertrophy will increase the fraction of muscle fiber energy left after peak systole to approximately 30%. The strongest indicator of the percent energy left at peak systole was the time the fiber reached peak systole, and as the fiber reached peak systole faster, the amount of energy saved by quick release increased.

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PubMed1995

Logistic characterization of left ventricular isovolumic pressure-time curve.

Although some investigators have attempted to express the left ventricular pressure-time curve by mathematical functions such as exponential and sinusoidal functions, none of them reasonably fits the left ventricular pressure-time curve. In the present study, we hypothesized that a ventricular isovolumic pressure-time curve could be expressed as the difference between two S-shaped curves for pressure rising and falling, and proposed a new "hybrid logistic" function to express the left ventricular isovolumic pressure-time curve. We investigated how well this hybrid logistic function fits left ventricular isovolumic pressure curves experimentally observed under physiological preload and contractility in the excised cross-circulated left ventricles of 10 dogs. The new function precisely fitted the isovolumic pressure curves regardless of preload and contractility with correlation coefficients above 0.9996, much better than the previously proposed functions. The observed values characterizing the magnitude and time course of the isovolumic pressure curve such as peak +/- dP/dt also closely correlated with the corresponding theoretical values calculated by the present best-fit function. We conclude that our new hybrid logistic function reasonably characterizes the canine left ventricular isovolumic pressure-time curve within physiological ranges of preload and contractility. The present results indicate that this hybrid logistic function is useful to evaluate left ventricular contraction and relaxation comprehensively.

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PubMed1995

Sinusoidal and exponential decays of postextrasystolic transient alternans in excised blood-perfused canine hearts.

We have recently reported that the postextrasystolic contractile potentiation decays in alternans after a compensatory pause in canine left ventricles even under normal coronary and contractile conditions. The transient alternans appears to consist primarily of a small-magnitude exponential decay and a large-magnitude sinusoidal decay. We, therefore, hypothesized that the contractility (y) of the postextrasystolic alternans beats (beat number x) could be expressed as y = a x exp[-(x-1)/b] + c x exp[-(x-1)/d] x sin[pi(x-0.5)] + yo, where a and c are the normalized magnitudes (relative to the preceding regular beat) of the two exponential terms in the first postextrasystolic beat, b and d are their time constants, and yo is the normalized magnitude of the post-alternans regular beat (approximately 1). The first exponential term represents the monotonic decay. The sine term multiplied by the second exponential term represents the alternating decay. Mathematical curve-fitting indicated: 1) the above equation very closely fitted the alternans data with a squared correlation coefficient of 0.9996 on average, 2) c was 7 times on average greater than a, indicating dominance of the sine component, 3) b and d were 2.5 and 1.0 beats on average, indicating a faster decay of the sine component, and 4) this b was comparable to the time constant of the exponential decay of the postextrasystolic potentiation after no compensatory pause. This study suggests that myocardium has a mechanism to switch the postextrasystolic potentiation between the exponential and alternans decays depending on the first postextrasystolic interval.

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PubMed1995

Left ventricular mechanoenergetics under altered coronary perfusion in guinea pig hearts.

Coronary perfusion pressure (CPP) is well known to affect left ventricular (LV) mechanoenergetics (Gregg's phenomenon). The garden hose effect via the Frank-Starling mechanism caused by coronary distension has long been considered to be the underlying mechanism of this phenomenon. However, recent studies have revealed a close correlation between CPP and the excitation-contraction coupling in myocytes. The aim of this study was to investigate the mechanoenergetic aspects of Gregg's phenomenon by the ventricular contractility (Emax) dependency of the myocardial oxygen consumption (VO2)-total mechanical energy (PVA, systolic pressure-volume area) relationship. Experiments were performed in the excised, cross-circulated guinea pig heart preparation. The protocol consisted of LV volume loading (VOL run), changing coronary perfusion pressure at a fixed LV volume (CPP run) and intracoronary calcium (Ca) infusion also at the same LV volume (Ca run). In all seven hearts, we obtained a linear VO2-PVA relation in VOL run. The VO2-PVA relations in CPP and Ca runs, which equally enhanced Emax, were highly linear and had no significant difference in their slopes, both significantly steeper than in VOL run. These findings suggest no significant difference in the oxygen cost of Emax between CPP and Ca runs. The enhanced LV mechanoenergetics under increasing CPP is characterized by increases in the VO2 component primarily for the excitation-contraction coupling to a greater degree than expected from the mechanical (garden hose) effect.

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PubMed1994

Effects of capsaicin on mechanoenergetics of excised cross-circulated canine left ventricle and coronary artery.

Capsaicin selectively acts on sensory nerve endings in cardiac muscles and coronary arterial smooth muscles. Capsaicin at high doses has cell-nonselective effects including both inhibition of cardiac muscle exciteability and enhancement of vascular smooth muscle tone. We studied whether and how intracoronary infusion of capsaicin affects mechanoenergetics of the excised blood-perfused canine heart and coronary vascular resistance. We found that capsaicin at low concentrations increased Emax (a contracility index) and oxygen consumption (VO2) possibly due to a specific action on capsaicin-sensitive sensory nerves in left ventricular muscles, though in a small number of hearts (3/10). This result coincides with the reported histochemical observations that the distribution of capsaicin-sensitive sensory nerves in the canine left ventricle is not dense. Capsaicin at high doses dose-dependently decreased Emax and proportionally decreased coronary flow. It also lowered the linear VO2-PVA (pressure-volume area; total mechanical energy) relationship without a change in the slope, decreasing unloaded VO2 (VO2 intercept of the VO2-PVA relation). These effects of high-dose capsaicin seem to be direct negative inotropic action on cardiac muscles associated with enhancement of coronary arterial smooth muscle tone, since these effects were not desensitized. No morphological changes of myocardial cells or mitochondria were detected. Therefore, the negative inotropic action is not due to the toxic effect of capsaicin.

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PubMed1994

Postextrasystolic transient contractile alternans in canine hearts.

We found that postextrasystolic potentiated contractility after a spontaneous extrasystole most frequently decayed as a transient alternans over several beats in excised, cross-circulated, atrially paced canine hearts. This type of heart preparation; which we have been using consistently in mechanoenergetic studies, had normal coronary blood perfusion pressure as well as flow and mechanoenergetic performance. Spontaneous atrial and ventricular extrasystoles occurred occasionally in every heart. Arrhythmic changes in left ventricular (LV) pressure at a fixed volume reflected corresponding changes in contractility. We analyzed nearly 3,600 cases of postextrasystolic potentiation in 68 hearts; 84% decayed as transient alternans, 6% decayed exponentially, and 10% belonged to neither type. We found that a postextrasystolic compensatory pause always preceded the transient alternans after either an atrial or ventricular extrasystole at any constant atrial pacing rate (85-188 beats/min). The decay was either exponential or nonalternating when the pause did not exist after an atrial extrasystole during occasional pacing failure. Therefore, the compensatory pause after either an atrial or ventricular extrasystole seems essential for the postextrasystolic transient alternans of LV contractility in the type of canine heart preparation we have been using.

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