Biomedical subjects

D Inoue

Publications and source records attributed to D Inoue.

At least 91 records · Page 5Linked to original sources

PubMed1992

Acute and subacute effects of doxorubicin on postextrasystolic potentiation in guinea pig papillary muscles.

To investigate the effects of doxorubicin on postextrasystolic potentiation (PESP), isolated guinea pig papillary muscles were field-stimulated and the resulting isometric force was recorded. Postextrasystolic contraction was evoked following trains of 37 regular stimulations. The effects of acute doses of doxorubicin (0.2 mM) on regular contractions and postextrasystolic contractions were examined for 2 hr. The effects of subacute doses of doxorubicin (total dose 5 mg/kg intraperitoneally) on the relationship between %PESP (postextrasystolic/regular contraction) and both the extra-stimulus coupling interval and the postextrasystolic interval were examined. Acute administration of doxorubicin decreased the amplitude of postextrasystolic contractions more than that of regular contractions. Thus, %PESP in the doxorubicin-treated group decreased significantly over time. There was no similar decrease in the control papillary muscles. Both the extra-stimulus coupling interval and the postextrasystolic interval had less of an effect on %PESP in doxorubicin-treated animals than in control animals. Since PESP depends upon sarcoplasmic reticulum activity, our results indicate that acute and subacute exposure to doxorubicin impairs the activity of the sarcoplasmic reticulum of guinea pig papillary muscles.

Animals↗

PubMed1992

Effects of reduction of contractile work on mechanical function in post-hypoxic guinea pig papillary muscles and on myocardial energy metabolism in post-ischemic rat hearts.

This study was designed to investigate effects of quiescence by cessation of electrical stimulation during the first stage of reoxygenation on recovery of mechanical function from hypoxia-induced contractile dysfunction in papillary muscles and effects of the absence of cardiac output on myocardial energetic metabolism of post-ischemic hearts. (1) Regular contractions and postextrasystolic contraction were evoked. After 120 min hypoxia, muscles were reoxygenated. In muscles of quiescence during the first 30 min reoxygenation, the recovery of regular contractions was better than that in muscles in which programmed stimulation was continued. However, the quiescence had no effect on the recovery of post-extrasystolic contractions from hypoxia-induced contractile dysfunction. (2) Isolated hearts were perfused either according to Langendorff technique or as working heart preparations. After 40 min ischemia, hearts were reperfused for 25 min. Although there was no difference in energy charge of myocardium between 2 modes of reperfusion, % incidence of sustained ventricular fibrillation in muscles in which non-working mode was maintained for the first step of reperfusion was lower than that in which working mode was continued. We presume that the reduction of contractile work during the initial step of reperfusion is of value for cardio-protection.

Animals↗

PubMed1992

Effects of hypoxia and reoxygenation on steady-state and potentiated contractions in papillary muscle of guinea pigs.

We studied the effects of hypoxia and reoxygenation on steady-state contractions and potentiated contractions of papillary muscles of guinea pigs. Isometric tension was measured while 120 min periods of hypoxia and reoxygenation were repeated twice. Reoxygenation after the first period of hypoxia induced a gradual recovery in steady-state contractions and a rapid recovery in potentiated contractions from the first hypoxia-induced contractile depression. After the second period of hypoxia, steady-state and potentiated contractions decreased progressively. During the second period of reoxygenation, the recovery of steady-state and potentiated contractions was very poor and the marked elevation of diastolic tension did not decrease. There were no good correlations between hypoxic depression just before reoxygenation and the recovery of both potentiated contraction and steady-state contraction at 120 min of reoxygenation. The recovery from the hypoxia-induced depression was poor in the preparations with marked elevation in diastolic tension. From these findings, we conclude that hypoxia-induced depression is progressively worsened by an additional episode of hypoxia and that diastolic tension is one of the determinants of the low contractile level achieved by steady-state and potentiated contractions in the severely hypoxic state. The degree of hypoxia-induced depression does not determine redevelopment of force with reoxygenation.

Animals↗

PubMed1992

Hypomagnesemia with increased metabolism of parathyroid hormone and reduced responsiveness to calcitropic hormones.

A patient with severe hypomagnesemia due to chronic alcoholism is presented who repeatedly exhibited marked hypocalcemia with a dissociation between radioimmunoassay findings for mid region of parathyroid hormone (PTH-M) and immunoradiometric assay findings of serum intact PTH (PTH-intact). Serum PTH-M was moderately elevated whereas serum PTH-intact was in a low normal range every time when her serum magnesium (Mg) concentration was markedly reduced. There was also a marked reduction in serum osteocalcin concentration. Supplementation of Mg resulted in a sharp increase in serum PTH level with a rapid disappearance of the dissociation between the two immunoassays of PTH. Shortly after serum PTH and 1,25(OH)2D levels reached their peak, serum osteocalcin started to increase, and was elevated into a supranormal level with normalization of serum Ca concentration. Mg is thought to act as a mimic/antagonist of calcium (Ca), and high extracellular Ca is shown to cause an inhibition of secretion with a stimulation of degradation of PTH. Thus, these observations are consistent with the hypothesis that Mg deficiency causes an increase in the metabolism of PTH and a reduction in the secretion of bioactive intact PTH by increasing the sensitivity of parathyroid cells to Ca. In addition, the fact that hypocalcemia disappeared concomitant with a marked increase of serum osteocalcin from undetectable levels suggest that refractoriness of bone to calcitropic hormones is present which plays a significant role in the development of hypocalcemia under hypomagnesemia, and that serum osteocalcin can be a good marker for the assessment of the responsiveness of bone to calcitropic hormones in these patients.

Alcoholism↗

PubMed1992

[Electrophysiologic effects of flecainide on guinea pig atrium].

We investigated the effects of flecainide on guinea pig atrial muscle. Using Langendorff's method, the whole heart of a guinea pig was perfused with Tyrode's solution containing acetylcholine (3 x 10(-7) M). Then, with right atrial extrastimulus and high frequency pacing method, the following values were measured before and after administration of flecainide (10(-7)-10(-5) M). A) Effective refractory period (ERP); the longest coupling interval which failed to produce right atrial activity at premature stimulus. B) Interatrial conduction time (ACT); After right atrial stimuli by trains at PCL 200 ms for 5 min the interval from the stimulation to the first deflection of the left atrial activity. C) Atrial fibrillation threshold (AFT); the minimal amount of current required to induce atrial fibrillation lasting for more than 30 sec by 50 Hz high frequency stimulation. Flecainide lengthened ERP (> or = 3 x 10(-5) M) and ACT (> or = 10(-7) M). Flecainide (10(-5) M) significantly increased AFT which correlated well with ERP (r = 0.81, p < 0.002) and ACT (r = 0.84, p < 0.002). In conclusion these effects of flecainide on guinea pig atrium might explain in part the clinical effectiveness of the drug on paroxysmal atrial fibrillation.

Animals↗

PubMed1992

[Electrophysiologic study of cibenzoline in patients with paroxysmal atrial fibrillation with special reference to atrial fibrillation threshold].

Electrophysiologic effects of cibenzoline were studied in 7 patients (6 males and one female) aged from 40 to 69 years (mean +/- SD; 52 +/- 10) with paroxysmal atrial fibrillation which was documented by 12 leads ECG or by 24 hours Holter monitoring. No organic heart diseases were found except in one patient with dilated cardiomyopathy and sick sinus syndrome (SSS). Cibenzoline (200mg) given orally increased P wave duration, PR interval and QRS duration significantly. The duration of P wave was gradually increased as the pacing frequency was increased. Neither sinus cycle length, nor sinus node recovery time (SRT), nor Wenkebach cycle length, nor atrial effective refractory period, nor QT interval was changed by the drug. One patient with SSS showed increase in SRT from 2,303 msec to 5,150 msec. The minimum current which was required to induce atrial fibrillation by rapid atrial stimulation (50 Hz, 1 sec) lasting more than 30 sec was defined as atrial fibrillation threshold (AFT). The AFT was 4.0 +/- 2.2 mA at the baseline state in 7 patients. After the oral administration of cibenzoline, 5 patients showed increase in AFT, while 1 patient showed decrease and another patient showed no change in AFT. Statistically, AFT was significantly increased to 7.3 +/- 3.4 mA in 7 patients. The results suggest that cibenzoline might be effective to prevent paroxysmal atrial fibrillation in patients without organic heart diseases.

Administration, Oral↗

PubMed1992

[Repeated blackout in a patient with accelerated idioventricular rhythm].

There has been no report that Accelerated Idioventricular rhythm (AIVR) causes a syncope attack. The patient described in this report is very rare because AIVR chronic without any heart diseases has been observed for 13 years, and because it is considered that AIVR is closely associated with his repeated blackouts. A 62-year-old male was admitted to our hospital because of repeated syncopal attacks. He reported that he occasionally felt lightheaded after strenuous lifting and pushing or pulling against resistance. We found that AIVR could produce a remarkable arterial pressure drop partly because of ventricular asynergy and loss of timed atrial contribution. Furthermore, we observed syncopal attacks during Valsalva maneuver and found abnormalities of baroreceptor reflex (Lack of reflex tachycardia and weakened evershoot phenomenon). It is concluded that AIVR is not a benign arrhythmia in this patient because it has been a possible cause of syncope attack due to systemic arterial pressure drop and baroreceptor abnormalities.

Accelerated Idioventricular Rhythm↗

PubMed1991

A synthetic oligopeptide derived from human thyrotropin receptor sequence binds to Graves' immunoglobulin and inhibits thyroid stimulating antibody activity but lacks interactions with TSH.

An 11-residue oligopeptide, P-195, was synthesized to match human thyrotropin (TSH) receptor structure from No. 333 to 343 of amino acid sequence. Preincubation of 5 Graves' IgGs with P-195 up to 10 micrograms resulted in dose-dependent reductions of thyroid stimulating antibody (TSAb) activity. [125I] labeled P-195 was found to bind Graves' IgG. The bound radioactivity correlated significantly with their TSAb activity (N = 25, r = 0.587, p less than 0.01). A peptide having a completely reverse sequence as P-195 did not show such biological activity. The peptide did not affect TSH and thyrotropin binding inhibitor immunoglobulin (TBII) on their receptor binding nor biological activities. P-195 was concluded to have a part of TSAb binding sites.

Amino Acid Sequence↗

PubMed1991

Prolonged atrial activity due to delayed conduction in the atrium of patients with paroxysmal atrial fibrillation.

We investigated the relationship between the duration of electrical atrial activity and intra-atrial conduction time to determine whether the prolonged atrial activity was due to delayed conduction in the human atrium. The study included 15 patients with paroxysmal atrial fibrillation (PAF) and 15 control patients. The duration of atrial electrical activity was measured by selecting a minimum electrographic amplitude of 50 microV. In patients with PAF, the duration of atrial activity was prolonged in proportion to the delay of interatrial conduction time from the high right atrium to the coronary sinus as the coupling interval of premature extrastimuli was decreased. Both the fragmented atrial activity zone and the interatrial conduction delay zone were wider in patients with PAF than in control patients. It is concluded that assessment of the duration of atrial activity with a minimum amplitude of 50 microV is useful in evaluating human atrial vulnerability since it reflects the atrial conduction delay in patients with PAF.

Adolescent↗

PubMed1991

Genetic differences shown by HLA typing among Japanese patients with euthyroid Graves' ophthalmopathy, Graves' disease and Hashimoto's thyroiditis: genetic characteristics of euthyroid Graves' ophthalmopathy.

Euthyroid Graves' ophthalmopathy (EO) is an ophthalmic disorder without persistent hyperthyroidism. To elucidate genetic differences among EO, Graves' disease (Gr) and Hashimoto's thyroiditis (H), we analysed HLA-A, B, C, DR, DQ, D and DP types in 23 Japanese EO patients, 88 Gr patients, 46 H patients and 186 control subjects utilizing assays of lymphocyte cytotoxicity and restriction fragment length polymorphism (RFLP). When compared with the control subjects, EO patients showed significant associations with HLA B40 (w61), DR9, DQw3, and Dw15 (P less than 0.01) and with HLA B12 and Cw1 (P less than 0.05). When allowance was made for the number of antigens tested, only DQw3 was significant. Significant differences were found between EO and Gr (DPw2), and between EO and H (Cw1) even after correction of P values. Comparisons between EO and related subgroups of Gr confirmed the heterogeneity of EO again. It is concluded from these results that EO is associated with different HLA types from Gr and H.

Adult↗

PubMed1991

Effect of cardiac sympathetic nerve stimulation on acutely ischemic myocardium--a comparison with the response to exogenous noradrenaline.

To assess the integrity of an adrenergic nervous function in acute myocardial ischemia, the contractile response of the ischemic region to cardiac sympathetic nervous stimulation (CSNS) was measured in comparison that with to exogenous noradrenaline (NA) infusion. In 13 anesthetized open chest mongrel dogs, haemodynamic changes, segmental wall motion, and the concentration of NA in the efferent coronary vein were measured. CSNS was performed by electrically stimulating the left ansa subclavia. Data concerning baseline values, values during CSNS, and those obtained during NA infusion both before and up to 5 h after coronary occlusion were compared. Regional myocardial blood flow of the ischemic region was also measured using the H+ clearance method. Systolic expansion with coronary occlusion was not changed or augmented by CSNS. However, improvement was observed in all experiments when NA infusion was used. The percent change of systolic shortening, indicating the response of segmental wall motion to CSNS, decreased soon after occlusion, recovered temporarily within 30 min after occlusion, but did not improve throughout the period after 60 min. The decrease of NA overflow into the efferent vein by CSNS showed a biphasic pattern; reduction occurring immediately after occlusion and again 3-5h after occlusion. Throughout these experimental studies it was considered that the preserved responses to the exogenous injected NA represented the contribution of presynaptic factor.

Animals↗

PubMed1991

Effects of hypoxia and reoxygenation on regular contractions and postrest contraction in rat papillary muscles.

The effects of hypoxia and reoxygenation on regular contractions and postrest contractions (PRC) of papillary muscle of rats were studied. Isometric tension was measured during two cycles of hypoxia and reoxygenation. Trains of 80 externally continuous stimulations at 40/min were applied. PRCs were evoked by a stimulus train after a 60 sec resting interval. After 90 min of hypoxia (the first hypoxia period), regular contractions and PRCs decreased to 5.6 +/- 2.0% and 23.4 +/- 2.4% of baseline values, respectively (p less than 0.001; n = 18). After 90 min of reoxygenation, the recovery of the PRCs (44.4 +/- 3.4%) was better than that of the regular contractions (23.3 +/- 3.3%) (p less than 0.01; n = 18). After 30 min of hypoxia (the second hypoxic period), regular contractions and PRCs decreased to 2.2 +/- 0.6% and 13.6 +/- 1.6% of baseline values, respectively (p less than 0.001; n = 18). However, the recovery from the second hypoxic injury was not significant for either regular contractions or PRCs. The % diastolic tension, which was normalized to the baseline for regular contractions, increased to 113.2 +/- 6.9% and 133.6 +/- 8.4% at the end of the first and the second hypoxic periods, respectively. There was statistically significant correlation between the % diastolic tension and the % hypoxic injury of PRCs (p less than 0.002; n = 18). There was no significant relationship between % diastolic tension and % hypoxic injury of regular contractions. There was no statistically significant correlation between % diastolic tension and % recovery from the hypoxic injury of either regular contractions or PRCs.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Electrophysiological effects of sodium channel blockers on guinea pig left atrium.

The electrophysiological effects of five sodium channel blockers (mexiletine, lidocaine, disopyramide, aprindine and flecainide) on the guinea pig left atrium were investigated by recording the action potential and its maximum rate of rise (Vmax). The onset and offset kinetics of use-dependent block of Vmax were analyzed. Lidocaine, aprindine and flecainide were classified clearly as fast, intermediate and slow, respectively. Mexiletine and disopyramide had two components in onset and offset of use-dependent block. Mexiletine showed fast and intermediate kinetics, whereas disopyramide showed intermediate and slow kinetics. Action potential duration at 90% repolarization (APD) was prolonged by disopyramide and mexiletine. The other drugs did not change the action potential duration. Effective refractory period was prolonged by all drugs with relative potency in the following order: disopyramide greater than mexiletine greater than lidocaine greater than aprindine = flecainide. In conclusion, the modes of actions of sodium channel blockers on the atrium were disclosed to be different from those on the ventricle. The pharmacological therapy for atrial arrhythmias should be based on the electrophysiological effects of the drugs on the atrium, not on the ventricle.

Action Potentials↗

PubMed1991

[Electrophysiological effect of verapamil on human atrium].

To investigate the effect of verapamil on atrial vulnerability, the following measurements were performed before and after the intravenous administration of verapamil (0.15 mg/kg) in 10 subjects with paroxysmal atrial fibrillation (Paf), and 10 subjects without Paf (non-Paf). During the sinus rhythm, 1) intra-/interatrial conduction time (Intra-/Inter- ACT); the initial deflection of high right atrium (HRA) to that of His bundel/coronary sinus were measured. After 8 consecutive HRA stimuli (A1), premature stimulus (A2) was introduced by shortening the coupling interval (A1A2) and we measured 2) conduction delay zone (CDZ); the zone of A1A2 with the prolongation of Inter-ACT, 3) % maximum atrial fragmentation (%MAF); % maximum value of the ratio of HRA activity width at A2 (Awt) against that at A1 (Awc), 4) fragmented atrial activity zone (FAZ); the zone of A1A2 with % value of Awt/Awc more than 150%,5) repetitive atrial response (RAR); more than 2 atrial activities which occur in response to A2. (6) right atrial effective refractory period (RAERP). Verapamil significantly shortened CDZ and %MFA, slightly lengthened RAERP, and had RAR disappear in Paf, while it did not effect any indices significantly in non-Paf. We concluded that verapamil could reduce atrial vulnerability in Paf due to blocking of atrial conduction delay mediated by slow response fibers.

Adolescent↗

PubMed1991

[Effects of ouabain, caffeine, and diltiazem, on spontaneous cyclic Ca2+ release from sarcoplasmic reticulum in the skinned papillary muscles of guinea pigs].

The aim of this study was to assess whether ouabain has a direct action on the sarcoplasmic reticulum (SR) sufficient to be responsible for the mechanism of the inotropic action, and whether caffeine and diltiazem, which inhibit ouabain-induced afterpotential and after-contraction, can inhibit the effects of ouabain on the SR. As one of the functions of SR, spontaneous cyclic contractions (cyclic Ca2+ release from the SR) in saponin-treated skinned fibers of guinea pig papillary muscles were used. Ouabain 10(-9)-10(-7) M increased the frequency of cyclic contractions and induced an incomplete muscle relaxation. Caffeine 1-5 mM and diltiazem 1-5 mM induced a sustained tension. In the fibers treated with ouabain, caffeine and diltiazem induced a sustained tension. In Brij-58 treated skinned fibers, 10(-9) M ouabain did not change the Ca2+ sensitivity of the contractile system. It is now known that ouabain increases intracellular calcium transients. An incomplete muscle relaxation of cyclic contractions seems to be due to both increased SR Ca2+ release and decreased Ca2+ reuptake by SR. Thus, we suppose that ouabain-induced increase in intracellular calcium transients is due to increased intracellular Ca2+, which may be one of the mechanisms in the inotropic action. The masking effects of caffeine and diltiazem on the ouabain-induced increase in cyclic contractions seem to be responsible for the inhibitory effects of drugs on digitalis-induced afterpotential and after contraction.

Animals↗

PubMed1990

Possible binding site of thyrotropin binding inhibitor immunoglobulin (TBII) on the thyrotropin (TSH) receptor, which is different from TSH binding site.

A synthetic decapeptide, P-194, which has the sequence No. 103 to 111 of hTSH receptor structure with an additional N-terminal tyrosine, did not bind TSH nor affected its receptor binding and thyroid stimulating activity. Preincubation of P-194 with sera from thyroid patients caused a significant decrease in TBII activity in almost all 12 TBII positive sera and an increase of thyroid stimulating activity in 3 of 7 Graves' IgG studied. In addition, [125I] P-194 bound to serum IgG fraction from thyroid patients with a positive correlation with TBII (N = 35, r = 0.509, p less than 0.01). The P-194 portion may be, at least a part of, TBII binding site distinct from the TSH binding site on the TSH receptor.

Animals↗

PubMed1990

Establishment of a human undifferentiated thyroid cancer cell line producing several growth factors and cytokines.

A cell line was established from undifferentiated giant cell carcinoma of the thyroid. The authors obtained cells from a 44-year-old patient admitted because of a rapidly growing anterior neck mass. The patient had significant leukocytosis and hypercalcemia shortly before her death. An autopsy revealed epidermoid metaplasia of the tumor cells. The cells (HTC/C3) had lost most of their differentiated functions. However, their thyroid nature was shown by peroxidase staining and by enzyme-linked immunostaining with Hashimoto patients' sera. The tumor extract was found to contain parathyroid (PTH)-like activity. Significant amounts of colony stimulating factor (CSF), which was further defined to be GM-CSF, and interleukin-1 alpha (IL-1 alpha) were detected in the conditioned media. Epidermal growth factor (EGF) binding to the HTC/C3 showed rich EGF receptors. Furthermore, the conditioned medium inhibited the binding of 125I-mEGF to HeLa cells, and transforming growth factor (TGF) was found repeatedly in the media.

Adult↗

PubMed1990

Effect of diltiazem on spontaneous cyclic Ca2+ release from sarcoplasmic reticulum.

We used saponin-treated skinned fibers isolated from papillary muscles of the right ventricle of guinea pigs to compare the effects of diltiazem on the spontaneous cyclic Ca2+ release from the sarcoplasmic reticulum (SR) of cardiac muscle with the effects of caffeine. Both diltiazem and caffeine increased the frequency of cyclic contractions in EGTA (ethyleneglycol-bis-(beta-aminoethylether) N,N,N',N'-tetra-acetate)-free solution and induced an incomplete, concentration-dependent relaxation of the muscle. The results suggest that the spectrum of the pharmacological effects of diltiazem on the SR is similar to that for caffeine, that is diltiazem accelerates the spontaneous Ca2+ release from the SR and suppresses Ca2+ reuptake by the SR, and that diltiazem as well as caffeine may act on the SR in vivo in a specific condition.

Animals↗