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Biomedical subjects

H Suga

Publications and source records attributed to H Suga.

At least 127 records · Page 7Linked to original sources
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.

Animals↗
PubMed1994

Ejecting activation differs in energetics from ordinary positive inotropism in the canine left ventricle.

Ventricular ejection is known to have dual effects on the end-systolic pressure: the ejecting deactivation by a relatively large ejection against a low afterload versus the ejecting activation by a relatively small ejection against a high afterload. We studied how the increase in contractility index (Emax) by the ejecting activation would affect myocardial oxygen consumption (VO2). To this end, left ventricular steady-state ejecting contractions were produced with various stroke volumes from a fixed end-diastolic volume in an excised cross-circulated canine heart. The effect of the ejection-activated Emax on VO2 was assessed by the relation between VO2 and pressure-volume area (PVA). PVA is the total mechanical energy generated by ventricular contraction. In contrast to the elevation of the linear VO2-PVA relation in a parallel manner with an enhanced Emax by ordinary positive inotropic agents such as catecholamines and calcium, the ejection-activated Emax did not elevate the VO2-PVA relation. This result indicates that the ejecting activation enhances Emax in an energetically different manner from ordinary positive inotropism in the canine left ventricle.

Animals↗
PubMed1994

Energetics of the negative and positive inotropism of pentobarbitone sodium in the canine left ventricle.

OBJECTIVE: Pentobarbitone (sodium) is an anaesthetic widely used in animal experiments. It is known to be a cardiovascular depressant and a coronary dilator, but its effects on myocardial energetics in relation to its negative and positive (due to Gregg's phenomenon) inotropism have not been studied. The aim of this study was therefore to determine whether and how pentobarbitone affects cardiac mechanoenergetics compared with other negative inotropic agents for which data are already available. METHODS: The effects of graded doses of intracoronary pentobarbitone on mechanoenergetics were studied in the excised cross circulated left ventricles of 12 dogs. The framework of the Emax (a contractility index)--VO2 (myocardial oxygen consumption)--PVA (systolic pressure-volume area, a measure of total mechanical energy) relationships was fully utilised. RESULTS: Pentobarbitone increased Emax at low doses in five of the 12 hearts. In two of these five hearts, a marked coronary dilatation was found. Pentobarbitone decreased Emax dose dependently at high doses in all the hearts and lowered the VO2 intercept but not the slope (oxygen cost of PVA) of the VO2-PVA relation. There was no difference in oxygen cost of Emax between pentobarbitone and CaCl2, although they have opposite inotropism. These findings suggest that pentobarbitone depresses myocardial mechanoenergetics via suppression of total calcium handling in the excitation-contraction-relaxation coupling. CONCLUSIONS: Pentobarbitone at low doses partly acts as a positive inotropic agent, but at high doses it acts as a negative inotropic agent like beta blockers and calcium antagonists on cardiac mechanoenergetics in canine blood perfused hearts.

Animals↗
PubMed1994

Genomic heterogeneity of rice dwarf phytoreovirus field isolates and nucleotide sequences of variants of genome segment 12.

Electrophoretic profiles of the dsRNAs of field isolates of rice dwarf virus (RDV) were compared with those of an isolate maintained at Hokkaido University (RDV-H). Unexpectedly, the genomic dsRNAs of most of the field isolates showed distinct electrophoretic mobility profiles. This was the case even among isolates from the same region. Genome segment 12 (S12) from some variants migrated faster than S12 from RDV-H. These RNAs were converted to full-length cDNAs and sequenced. S12 from all the variants had the same length of 1066 nucleotides with nucleotide sequence identities of 96 to 99%. Three open reading frames previously reported were present in all the variants, and the sequence identities were 95 to 99% for P12, 98 to 100% for P12OPa, and nearly 100% for P12OPb. A comparison of the nucleotide and amino acid sequences of the variants with sequences of the RDV-H and Akita isolate showed that there are two genomic types, one represented by RDV-H and the other by the Akita isolate.

Base Sequence↗
PubMed1994

Hypercapnic acidosis increases oxygen cost of contractility in the dog left ventricle.

The effect of acidosis on left ventricular (LV) mechanoenergetics was assessed in seven excised, cross-circulated dog hearts with the use of the frameworks of the contractility index (Emax) and the relationship between myocardial oxygen consumption (VO2) and pressure-volume area (PVA; a measure of the LV total mechanical energy). Acidosis was stably maintained without hypoxia by appropriately mixing CO2 and air in a membrane oxygenator in the coronary arterial perfusion circuit. Acidosis [pH: 6.98 +/- 0.09 (SD), PCO2: 91 +/- 25 mmHg in the coronary arterial blood] decreased Emax by 45 +/- 12% (P < 0.01) and PVA by 47 +/- 12% (P < 0.01) at a fixed LV volume. When the preacidosis Emax level was restored by Ca2+ infusion during acidosis, unloaded VO2 (the VO2 intercept of the VO2-PVA relation) exceeded the control value by 19 +/- 17% (P < 0.05), indicating that acidosis required higher VO2 for nonmechanical activities at a matched Emax. Moreover, the oxygen cost of enhanced contractility (the incremental ratio of unloaded VO2 to Emax) was 1.53 +/- 0.40 times higher (P < 0.01) during acidosis than preacidosis. We conclude that acidosis results in LV contractile dysfunction accompanied by an increased oxygen cost of contractility. This increased energy cost of the excitation-contraction coupling can be accounted for by a decreased Ca2+ sensitivity of the contractile proteins during acidosis.

Acidosis↗
PubMed1994

Nucleotide sequence of rice dwarf phytoreovirus genome segment 2: completion of sequence analyses of rice dwarf virus.

The complete nucleotide sequence of rice dwarf phytoreovirus genome segment 2 (S2) was determined to be 3,512 nucleotides long with one open reading frame initiating at nucleotide 15 and terminating at nucleotide 3363. The encoded polypeptide was predicted to have 1,116 residues with a relative molecular weight of 123 kD. Comparison of S2 of two isolates showed they had identical lengths and 97 and 98.3% nucleotide and amino acid sequence identities, respectively. A search of the Swiss-Prot data base (R 22.0) failed to find any proteins with significant homology to the S2-encoded protein. Determination of the nucleotide sequence of the S2 has completed the sequence determination of the genome of rice dwarf virus. Homology searches made for proteins encoded by each of the genomic segments showed that the polypeptide encoded by S11 has similarity to histone H1 protein and VP6 of blue tongue virus, indicating it might possess nucleic acid binding properties.

Amino Acid Sequence↗
PubMed1994

Estimation of total carbon dioxide contents in canine coronary arterial and venous whole blood samples.

We examined whether total carbon dioxide content (CCO2) estimation equations for human whole blood in the literature are applicable to canine coronary arterial and venous blood samples. PCO2 of the tested blood samples covered 19-52 mmHg; PO2 19-398 mmHg. Three CCO2 estimation equations developed by Kelman, Godfrey, and Douglas et al yielded CCO2 values over a range of 26.7-54.9 vol%, where plasma CCO2 values calculated by the Henderson-Hasselbalch equation ranged over 27.7-62.2 vol%. The estimated blood CCO2 values were almost identical among the three equations. They also closely correlated with plasma CCO2 values measured after hemolysis with saponin. We conclude that the human whole blood CCO2 estimation equations are applicable to canine coronary arterial and venous blood samples. These CCO2 equations may be used for canine cardiac metabolic studies.

Animals↗
PubMed1994

Paul Dudley White International Lecture: cardiac performance as viewed through the pressure-volume window.

Viewing canine left ventricular performance through the pressure-volume (P-V) window, I proposed a new index of ventricular contractility (Emax: end-systolic P-V ratio or maximum elastance) in my doctoral thesis at the University of Tokyo in 1969. After I joined Dr. Kiichi Sagawa (deceased in 1989) at Johns Hopkins University, we firmly established the Emax concept during 1971-1978. The concept was extended to derive the systolic P-V area (PVA) as a new measure of the total mechanical energy generated by ventricular contraction in 1978. Experiments have revealed that PVA closely correlates with cardiac oxygen (O2) consumption (VO2) under various loading conditions at a constant Emax, the VO2-PVA relation changes its elevation with Emax, and the O2 costs of PVA and Emax characterize the mechanoenergetics of cardiac contraction under various normal and abnormal conditions in an innovative manner (Suga: Physiol Rev 70: 247-277, 1990). Emax and PVA can also evaluate the ventriculo-arterial hydraulic and energetic matching in normal and failing hearts. Emax and PVA have thus widely opened the P-V window to the extent that human and animal normal and failing cardiac performance can be characterized in a physiologically sound manner.

Adenosine Triphosphatases↗
PubMed1994

Significant prolongation of guinea pig heart contraction transplanted in rat after removal of anti-xeno-antibodies by whole body rinse-out (WBRO) with hemoglobin solution.

PURPOSE: In order to investigate effectiveness of removal of the anti-xeno- antibodies in xenotransplantation (xeno Tx), WBRO using pyridoxalated-human hemoglobin-polyethyleneglycol conjugate (PHP solution) was performed prior to transplantation (Tx) of a guinea pig heart in a rat. MATERIALS & METHOD: Experiment I. Removal of the immunoglobulins and the anti-guinea pig lymphocytotoxic antibody (ALA) by WBRO. Exchange transfusion with the PHP solution was done in the Tx-expected rats until a hematocrit lowered below 5% (n = 11). Experiment II. Xeno heart Txs. Guinea pig hearts were transplanted into rats without immunosuppressants 1) without (n = 8) or 2) with the WBRO (n = 8). RESULTS: Experiment I. Levels lowered to 14% in IgG, 17% in IgA and 6% in IgM, respectively, to initial values after the WBRO. An ALA titer lowered from 4 X (+) to 1 X (-) after the WBRO. Experiment II. An average heart contraction period was 10.4 +/- 1.8 minutes 1) without the WBRO in contrast to 472.5 +/- 4.8 minutes with the WBRO (p < 0.01). CONCLUSION: WBRO using PHP solution is effective in removal of the anti-xeno-antibodies and consequent prolongation of survival of the xenograft.

Animals↗
PubMed1994

[Home terminal care for terminal gastric cancer patients--case of epidural morphine injection].

Pain management at home for a terminal gastric cancer patient unable to take medications orally was made possible by a combination of serial morphine drip infusion and epidural anesthesia with morphine on a continuing basis using a disposal syringe. Before the patient was discharged, a conference was held to prepare for home care. Besides the patient and family, it was attended by the primary care doctor, ward nurse, home nurse, pharmacy staff, pain clinic doctor and hospital office personnel. The patient was duly informed of the disease by name and, thanks to fine cooperation from the medical staff, had achieved a good understanding, and spent his remaining time meaningfully. Morphine dosages upon discharge were 80 mg/day by drip infusion and 90 mg/day epidurally. For times of increased pain, the patient was instructed in how to self-administer 0.5% Mepivacaine (5 ml/time) with a syringe using an epidural catheter equipped with a 3-way stopcock. When this proved insufficient to control the pain, the patient was instructed to come for outpatient treatment on an emergency basis. With one visit per week to the hospital and home visits by a nurse once or twice a week, the patient managed at home for 82 days before increased pain resulted in rehospitalization. After the pain was brought under control and the patient was discharged, he was again hospitalized 5 days later. The pain control up until the time of death was by drip infusion of up to 1,200 mg/day morphine.

Adult↗
PubMed1994

The effects of dynamic cardiac compression on ventricular mechanics and energetics. Role of ventricular size and contractility.

The purpose of this study was to determine the role of ventricular size or contractility in the effectiveness of dynamic cardiac compression in terms of the pressure-volume relationship and myocardial oxygen consumption. In 10 isolated cross-circulated dog hearts, the ventricle was directly compressed during systole. For the volume run, measurements for slope of the end-systolic pressure-volume relation, pressure-volume area, external work, coronary blood flow, and myocardial oxygen consumption were achieved before and during a fixed amount of dynamic cardiac compression. Left ventricular volume was then increased while stroke volume was kept constant, and measurements were repeated. For the contractility run, after the control measurements were taken, left ventricular contractility was significantly increased or decreased by infusion of either dobutamine or propranolol into the coronary circulation. Measurements were repeated before and during dynamic cardiac compression at the control level of end-diastolic and stroke volumes. Dynamic cardiac compression significantly increased slope of the end-systolic pressure-volume relation, pressure-volume area, and external work (p < 0.01), whereas coronary blood flow and myocardial oxygen consumption were not affected. The increase in pressure-volume area caused by dynamic cardiac compression was greater with the larger volume. Despite the significant differences in the native left ventricular contractility, the increases in slope of the end-systolic pressure-volume relation, pressure-volume area, and external work did not differ among the three groups. We conclude that dynamic cardiac compression enhances left ventricular systolic function independent of ventricular contractility and without affecting coronary blood flow or myocardial oxygen consumption. Mechanical enhancement is more effective in the dilated heart.

Animals↗
PubMed1993

Participation in cellular prostaglandin synthesis of type-II phospholipase A2 secreted and anchored on cell-surface heparan sulfate proteoglycan.

Rat-liver-derived BRL-3A cells, which express both type-II phospholipase A2 (PLA2) and cytosolic PLA2 (cPLA2), generated prostaglandin E2 (PGE2) in the presence of fetal calf serum. When the cells were treated with tumor necrosis factor (TNF), PGE2 generation was greatly stimulated. The production of PGE2 observed in both cases was suppressed by a type-II PLA2-specific inhibitor, thielocin A1. Appreciable amounts of type-II PLA2 were released into the medium from the TNF-stimulated cells when heparin was added extracellularly. The release of type-II PLA2 from TNF-stimulated cells was also found in the presence of heparan sulfate or dextran sulfate, whereas other glycosaminoglycans showed no effects under the same conditions. These findings suggest that type-II PLA2 expressed in BRL-3A cells mostly associates with the cell surface by binding to cellular heparan sulfate proteoglycan. Removal of cell-surface-associated type-II PLA2, by either extracellular addition of heparin or by prior treatment of the BRL-3A cells with heparitinases, resulted in marked reduction of PGE2 synthesis in the cells. Exposure of BRL-3A cells to thrombin also induced the apparent secretion of type-II PLA2, and thrombin-stimulated PGE2 generation was suppressed by heparin effectively. Type-II PLA2 secreted and attached to heparan sulfate on the cell surface may therefore play an essential role in PGE2 synthesis by BRL-3A cells.

Animals↗
PubMed1993

On the solutions of Huxley-type models in cardiac muscle fiber contractions.

Huxley's sliding filament crossbridge muscle model coupled with parallel and series elastic components was simulated to examine the effect of various solution techniques in cardiac contractions. Solutions of both isometric and isotonic contraction cases showed that the force versus time curves were not significantly altered by solving the three-element Hill model with Huxley's Equation written as either an ordinary or partial differential equation (ODE or PDE), but this makes a difference in the solution time required. Various theoretical studies have used either the ODE or PDE representation. The crossbridge cycles at the end of a contraction showed approximately 25% and 15% difference in the isometric and isotonic cases when Huxley's Equation was written as either an ODE or PDE. Examination of the crossbridge distribution (distribution among states of reach) showed that assuming that the crossbridge distribution is a Gaussian function is a poor approximation since the shape changes considerably between the cardiac contracting and expanding phases, and using a technique such as a distribution moment approximation is questionable. Recent experimental studies have demonstrated that solving Huxley-type relations as ordinary differential equations gives good agreement with cardiac data, implying that as a first approximation, this can be successfully used.

Animals↗
PubMed1993

Adenosine inhibits efferent function of extrinsic capsaicin-sensitive sensory nerves in the enteric nervous system.

Capsaicin (1-3 microM) and electrical stimulation of mesenteric nerves in the presence of hexamethonium and guanethidine antidromically stimulate extrinsic sensory nerve fibers to produce a specific slow depolarizing response of myenteric neurons and a contractile response of muscles in the isolated guinea-pig ileum, mediated by release of substance P and acetylcholine. Adenosine (1-100 microM) inhibited the response to mesenteric nerve stimulation. Adenosine (10-100 microM) suppressed the contractile response to a threshold concentration of capsaicin (1 microM) while leaving the contractile response to a submaximal concentration of substance P (1 nM) and acetylcholine (0.1 microM) intact. Adenosine (1-10 microM) inhibited dose dependently the capsaicin 10 microM)-induced depolarization of myenteric neurons, but did not inhibit the depolarizing response to exogenous substance P. The adenosine P1 receptor antagonist, 8-phenyltheophylline (1-10 microM), antagonized the inhibitory effect of adenosine (1-10 microM) on the mechanical responses. We conclude that adenosine-induced prejunctional inhibition of the mechanical responses is mediated by adenosine P1 receptors.

1-Methyl-3-isobutylxanthine↗
PubMed1993

Variable crossbridge cycling-ATP coupling accounts for cardiac mechanoenergetics.

Cardiac twitch contractions were simulated by Huxley's sliding filament crossbridge muscle model. Huxley's model was extended to include cardiac twitch contractions with a model structure having parallel and series elastic components with a crossbridge contractile element. The appropriate crossbridge energetics were added based on the crossbridge cycling rate and the energy of ATP hydrolysis. The 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). Experimental studies have demonstrated that the pressure-volume area (PVA) correlates linearly with cardiac oxygen consumption and hence with the energy expenditure of a cardiac contraction. 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 crossbridge 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 crossbridge cycles. This could imply that one ATP can cause more than one crossbridge cycle at lower fiber activation levels as was proposed by Yanagida et al. (Nature, 316, 366-369, 1985). If the number of crossbridge cycles to ATP ratio is allowed to increase at lower activation levels, Huxley's model agrees with the experimental findings on FLA and PVA.

Adenosine Triphosphate↗
PubMed1993

Myocardial mechanics and the Fenn effect determined from a cardiac muscle crossbridge model.

A three-element cardiac muscle fibre model, utilising Huxley's sliding filament theory for the contractile element and coupled with parallel and series elastic components, was simulated to see if it were possible to predict the cardiac Fenn effect. The force/length energy (FLE) was computed in both isometric and isotonic contractions, as a function of muscle fibre length (preload) in the isometric case and afterload in the isotonic contraction case. Simulation results demonstrated that isotonic contractions produced a greater FLE than isometric contractions at every corresponding afterload, with the difference being equal to the work produced in the isotonic case, which is characteristic of the Fenn effect. The maximum energy utilisation was observed at maximum force isometric contractions, as has been experimentally observed in cardiac muscle. Changing the stiffness of the series elastic component did not change the Fenn-effect behaviour. Fenn-effect plots using crossbridge energy predictions showed behaviour similar to the FLE plots, but the FLE: crossbridge energy ratio declined with decreasing force even though the efficiency has been experimentally found to be constant.

Adenosine Triphosphate↗