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Biomedical subjects

J Kikuchi

Publications and source records attributed to J Kikuchi.

At least 19 recordsLinked to original sources
PubMed1992

Effects of mechanical vibration on left ventricular diastolic properties during global ischemia.

To examine the effect of mechanical vibration on ventricular relaxation and diastolic chamber stiffness under global ischemia, we studied eight coronary perfused, isolated, isovolumic canine left ventricles (LV). To produce varying degrees of impaired relaxation, graded coronary flow reduction and paced tachycardia were imposed. A mechanical 50-Hz, 2-mm-amplitude vibration was applied during diastole and was turned off during systole. Without diastolic vibration, the relaxation time constant of LV pressure (tau) increased with the severity of ischemia. The chamber stiffness index (K) from the diastolic pressure-volume relationship showed a slight increase during ischemia; tau decreased with diastolic vibration. The change in tau with vibration increased with ischemia and was dependent on vibration amplitude but not heart rate. The ratio of tau to the diastolic interval (DI, the time from peak negative rate of LV pressure change to end diastole) always decreased with vibration and was linearly correlated with K (r = 0.93; P less than 0.01). K decreased with vibration when tau/DI was greater than 0.3. We conclude that diastolic vibration improves impaired relaxation and chamber stiffness under myocardial ischemia.

Analysis of Variance↗
PubMed1992

Diastolic vibration improves systolic function in cases of incomplete relaxation.

BACKGROUND: Incomplete relaxation of the left ventricle (LV) affects LV filling, but the subsequent effect on LV systolic function remains unclear. We attempted to improve relaxation by applying oscillatory mechanical perturbation during diastole (diastolic vibration) and examined the extent to which systolic function improved. METHODS AND RESULTS: Using 10 open-chest canine preparations, pacing tachycardia and administration of propranolol were imposed to induce various levels of incomplete relaxation. Myocardial length perturbation was induced with an oscillator attached to the LV surface (50 Hz, 1-mm amplitude) and was restricted to the period from the beginning of isovolumic relaxation to end diastole. At resting heart rates, diastolic vibration caused an immediate decrease in the time constant (T) of LV pressure fall without any influence on heart rate, LV peak systolic pressure (peak LVP), stroke volume (SV), LV peak positive dP/dt, and total systemic vascular resistance. With pacing tachycardia, diastolic vibration increased both peak LVP and SV at 160 beats per minute (before) and 120 beats per minute (after propranolol), simultaneously decreasing both T and LV diastolic pressures and increasing end-diastolic segment length. The increase in peak LVP and SV caused by diastolic vibration correlated with the T/diastolic interval (r = 0.82), the assumed index of severity of incomplete relaxation. CONCLUSIONS: These results suggest that diastolic vibration accelerates the LV relaxation rate and that this increased relaxation improves systolic function through the Frank-Starling mechanism.

Animals↗
PubMed1992

Ventricular contractility evaluated by mechanical perturbation of the myocardium--experimental and clinical approach adopting small amplitude vibration input.

Small amplitude mechanical vibration has been reported to depress the function of the isolated left ventricle in an amplitude dependent manner. We examined, 1) contractility and preload dependency of the magnitude of functional depression (VID) by applying 50 Hz, 2 mm amplitude vibration to the epicardium of the canine left ventricle and 2) whether VID is present in the failing human ventricle. The magnitude of VID was independent of preload in the physiological range of LV volume showing peak LV pressure greater than 75 mmHg, and VID was correlated with Emax at each inotropic state. In the in-situ condition, VID appeared only in the failing condition with a sensitive increase at a mild level of heart failure. In a study during routine cardiac catheterization (n = 27), the presence of VID has been demonstrated in the human ventricle (n = 18). The magnitude of VID was correlated with ejection fraction (EF) as, VID in peak LV pressure (mmHg) = 80.6 - 110 x EF, r = 0.84, p less than 0.01 in patients with EF less than or equal to 0.7 (n = 14). Therefore, we concluded that VID could be a clinical tool for evaluation of mild heart failure.

Animals↗
PubMed1992

Bilateral Bochdalek hernias in an elderly patient diagnosed by magnetic resonance imaging.

An elderly patient with asymptomatic bilateral Bochdalek hernias is reported. The chest roentgenogram showed dome-shaped supradiaphragmatic masses about 6 cm in diameter in the posteromedial regions of both sides of the lungs. Computed tomography showed a discontinuity of the lines of diaphragmatic musculature in the left thorax, and a mass with a homogenous low density area indicative of fatty tissues in the right thorax. The magnetic resonance imaging, coronal and sagittal T1-weighted images revealed interruptions of the diaphragmatic musculature adjacent to the masses and protrusion of retroperitoneal fat into the thoracic cavity. The lesions were therefore diagnosed as bilateral Bochdalek hernias of the diaphragm.

Adipose Tissue↗
PubMed1991

Vibration analysis of the human left ventricular posterobasal wall at the moment of the first heart sound emission.

We examined whether human left ventricular (LV) wall vibration at the first heart sound emission (LVvibr) could be a potential source of information about the left ventricular physical properties, as has been demonstrated by experimental forced vibration studies. LV posterobasal wall vibration in 51 subjects characterized by functional murmur (n = 13), mitral stenosis (n = 8), hypertrophic cardiomyopathy (HCM, n = 8), ischemic heart disease with old myocardial infarction (n = 12) and without prior infarction (n = 10), was detected with a miniature intraesophageal vibration sensor. Peak frequency, sharpness and peak power of LVvibr in patients with functional murmur and mitral stenosis were linearly related to the Q-vibration interval. HCM patients showed a higher peak frequency and sharper configuration in the power spectrum. However, differing from previous reports, we found no characteristic difference in configuration of power spectrum in patients with ischemic heart disease. These results suggest that human LVvibr possibly includes information demonstrated by experimental forced vibration analysis.

Adolescent↗
PubMed1991

Structure determination of a diuretic-glutathione conjugate by mass and n.m.r. spectrometry.

1. A glutathione (GSH) conjugate of the uricosuric diuretic DBCA 6,7-dichloro-5(N,N-dimethylsulphamoyl)-2,3-dihydrobenzofuran-2-car boxylic acid, formed enzymically in rat liver 100,000g supernatant fortified with GSH, was purified by t.l.c. and h.p.l.c. 2. According to mass spectrometry the composition of the GSH-conjugate corresponded to C21H29N4O11S2Cl2. 1H- and 13C-n.m.r. studies gave the structure of the conjugate as 2-glutathionyl-3-[3,4-dichloro-5-(N,N-dimethyl sulphamoyl)2-hydroxyphenyl]-propionic acid, which indicates that GSH was bound to the chiral centre carbon and caused scission of the C-O bond in the dihydrofuran ring.

Animals↗
PubMed1991

[New method for estimating left ventricular myocardial elasticity by vibration analysis].

We solved numerical solutions of Advani-Lee's equation, which treats free vibrations of fluid-filled spherical shells, and forms the basis for non-invasive estimation of left ventricular myocardial elasticity. Numerical results showed that elasticity is approximated by E = 86.5.a2.f2 (E: elasticity (dyn/cm2), a: internal radius (cm), f: eigen-frequency (Hz)). To examine the accuracy of this theoretical equation in estimating elasticity, we made 7 spherical shells of silicone rubber, and compared the estimated elasticity by this equation with that by a standard stretch test. The elasticity calculated by Advani-Lee's equation and by stretch test proved to be nearly identical. Therefore, we concluded that we can estimate the elasticity of a spherical shell using this equation. We calculated the myocardial elasticity at the first heart sound emission in 25 normal persons with a simplified (approximated form of) Advani-Lee's equation. The mean elasticity in normal subjects was (7.04 +/- 2.46) x 10(5) dyn/cm2.

Elasticity↗
PubMed1991

[Effects of mitochondrial lipoperoxidation on liver regeneration after partial hepatectomy of the cirrhotic rat liver].

Lipoperoxide levels in mitochondrial fraction and mitochondrial respiratory activity during hepatic regeneration were studied serially in normal (N) and cirrhotic (C) rats following one-third (I) or two-third (II) partial hepatectomy. Recovery of liver weight after 14 days was about 90% in each group except C-II group, in which it was 71.3%. ATP synthetic activity (ATP-S) was always higher in N-II group than N-I which reached maximum on the first postoperative day (POD) and returned to the preoperative levels on the 14th POD. Lipoperoxide peak value of N-II group was obtained sooner than that of N-I group, in addition the peak value of N-II group was higher than that of the N-I group. ATP-S of C-II group reached maximum levels on the third POD and thereafter decreased progressively. In contrast, ATP-S of C-I group returned to preoperative level on the 14th POD. Peak lipoperoxide levels were obtained on the first POD in both groups, but that of C-II group was 1.6 times higher than that of C-I. Moreover, it was observed that inhibition of lipoperoxidation by alpha-tocopherol administration improved respiratory activity significantly. From these results it can be said that hepatectomy-induced lipoperoxidation in massive resection of the cirrhotic liver may inhibit activation of mitochondrial respiration and hepatic regeneration.

Adenosine Triphosphate↗
PubMed1991

[A case of complete remission obtained with etoposide in uterine choriocarcinoma].

A 27-year-old female was admitted to Sendai National Hospital complaining of continuous slight genital bleeding for about one and a half year after incomplete abortion. At first visit, urinary hCG was elevated to 32,000 IU/l and ultrasonography revealed a heterogeneous tumor in the uterus body. After abdominal simple total hysterectomy, the sample was diagnosed pathologically as a uterine choriocarcinoma. The patient was treated with 2 courses of MTX, but this regimen was not so effective. Because of persistent elevation of urinary hCG, 2 courses of etoposide were performed and hCG was rapidly reduced to within LH level. Etoposide (25 mg/day per os) was given to the patient for about three months since hospitalization and now complete remission has been obtained.

Administration, Oral↗
PubMed1990

Activities of newly synthesized dihydropyridines in overcoming of vincristine resistance, calcium antagonism, and inhibition of photoaffinity labeling of P-glycoprotein in rodents.

Newly synthesized 1,4-dihydropyridine derivatives (NK-compounds) were screened to determine whether they could overcome vincristine (VCR) resistance in VCR-resistant (P388/VCR) leukemia-bearing mice. Among the 57 NK-compounds examined, six compounds had strong reversing ability (Grade A), 18 partially overcame the resistance (Grade B), and 33 did not reverse the resistance (Grade C). The ability to overcome resistance varied considerably with the nature of substituents at positions 3.5 of the 1,4-dihydropyridine, and the most suitable substituents were the pyridylalkyl-including esters. Calcium antagonistic activity of NK-compounds having pyridylalkyl-including esters at positions 3.5 and dithiene ring at position 4 of the 1,4-dihydropyridine was greater than in those compounds having the dioxene ring at position 4. NK-242, which was assessed at Grade A and had no calcium antagonistic activity, improved therapeutic effects in both VCR-sensitive (P388/S) leukemia- and P388/VCR leukemia-bearing mice when combined with VCR. Fourteen NK-compounds were screened to determine whether they could inhibit photoaffinity labeling of the P-glycoprotein (Mr 170,000 glycoprotein) in a multidrug-resistant cell line by [3H]azidopine. All six compounds of Grade A and two of the three compounds of Grade B almost completely inhibited the labeling of Mr 170,000 glycoprotein at 1 to 10 microM. Thus there was a good correlation between the ability to reverse VCR resistance in vivo and the inhibition of photoaffinity labeling of Mr 170,000 glycoprotein.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1990

Reversal by two dihydropyridine compounds of resistance to multiple anticancer agents in mouse P388 leukemia in vivo and in vitro.

We investigated whether two representative 1,4-dihydropyridine derivatives, NK-250 and NK-252, could potentiate the antitumor activity of multiple anticancer agents including vincristine (VCR), vinblastine, vindesine and actinomycin D in drug-resistant tumor cells and their parental drug-sensitive tumor cells. NK-250 and NK-252 at 5-10 microM almost completely reversed VCR resistance in cultured VCR-resistant P388/VCR cells derived from the mouse drug-sensitive P388/S leukemia cell line and also potentiated the cytocidal activity of VCR in drug-sensitive P388/S cells. NK-250 and NK-252 at 1-10 microM inhibited the photoaffinity labeling by [3H]azidopine of the cell-surface 170,000-molecular-weight P-glycoprotein. In chemotherapeutic experiments with leukemia-bearing mice, NK-250 or NK-252 was orally administered in combination with different drugs of the MDR phenotype administered intraperitoneally. The antitumor activity of the various combinations was found to be augmented in mice bearing P388/S- and P388/VCR-leukemia. Among the combinations examined, the combination of NK-250 and VCR was the most effective. These two 1,4-dihydropyridines, NK-250 and NK-252, are unique compounds because they were effective not only in circumventing the drug resistance, but also in potentiating the action of antitumor drugs against drug-sensitive tumors.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1989

Analysis of structural features of dihydropyridine analogs needed to reverse multidrug resistance and to inhibit photoaffinity labeling of P-glycoprotein.

Synthetic dihydropyridine analogs were screened to determine whether they would reverse multidrug resistance of a multidrug-resistant human KB carcinoma cell line, KB-C1. Among twenty-four dihydropyridine analogs examined, thirteen almost completely overcame drug resistance (group A), nine partially overcame resistance (group B) and two did not reverse resistance (group C). The twenty-two compounds that reversed drug-resistance (groups A and B) were hydrophobic dihydropyridine derivatives. Three compounds that reversed resistance, NK-113, NK-138 and NK-194, increased the accumulation of [3H]vincristine in the resistant KB-C1 cells, but not in the parental KB cells, nor in a revertant cell line, KB-C1-R2. NK-101 (group C), which did not reverse resistance, had no effect on drug accumulation. Enhanced efflux of vincristine from the resistant cells was inhibited completely by NK-194, but NK-194 did not affect vincristine influx. Nine of the twenty-four compounds were screened to determine whether they inhibited photoaffinity labeling of the cell surface protein gp170 (P-glycoprotein) in KB-C1 cells by N-(p-azido-[3-125I]-salicyl)-N'-beta-aminoethylvindesine [( 125I]NASV). All five compounds of group A, NK-138, NK-194, NK-200, NK-203 and NK-220, inhibited the photoaffinity labeling of gp170 at less than 10-100 microM, whereas NK-113 and NK-196 of group B inhibited the labeling at 100-200 microM. By contrast, NK-101 and NK-102 of group C did not inhibit labeling even at 2000 microM. These studies confirm the relationship among reversal of multidrug resistance, decreased efflux of vincristine, and inhibition of [125I]NASV labeling of P-glycoprotein.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1989

The response of normal and failing heart to externally applied vibration in the canine open chest preparation.

We examined the left ventricular functional response to externally applied vibration using four canine open chest preparations. A sinusoidal 30 Hz vibration (2.7 mm in amplitude) was applied to the ventricular epicardium at each level of propranolol-induced myocardial depression. External vibration in control conditions induced no significant change either in peak left ventricular pressure (LVP) or in stroke volume (SV). With propranolol, 0.1 and 0.3 mg/kg, peak LVP and SV were depressed by the application of external vibration, even though there was no significant change of these values in the nonvibrating condition compared to control. We conclude that the ventricular response to vibration depends on the underlying myocardial viability.

Animals↗
PubMed1989

Effect of left ventricular volume on the magnitude of functional depression by external minute vibration.

We examined the effect of the left ventricular (LV) volume on the magnitude of the vibration induced functional depression (VID) using four canine cross-circulated isovolumically beating LV preparations. A sinusoidal, 50 Hz vibration (1.5 mm in amplitude) was applied to the ventricular anterior epicardium at different values of LV volume which was stepwisely increased by 1-2 ml from 0 to 30 ml. VID was estimated as the difference of the peak LV pressure between control and during external vibration. VID increased as an increment in LV volume when the volume was below 7-8 ml and when peak LV pressure was less than 70 mmHg. However, VID remained constant when the volume increased further. We concluded that VID was independent of LV volume at physiological range.

Animals↗
PubMed1989

The improvement of systolic function of depressed left ventricle by external vibration at diastole.

The left ventricular (LV) incomplete relaxation (IR) has been reported to play an important role in the pathophysiology of the congestive heart failure such as causing higher diastolic pressure and/or impeding the coronary perfusion during diastole. Therefore, using open chest canine preparations (n = 4), we examined 1) whether the minute external vibration during diastole could release IR and 2) what occurred to LV systolic function in this perturbation. LV failure with IR was induced by propranolol administration and, if necessary, by rapid atrial pacing up to 180 beats/min. When we applied a 50 Hz, sinusoidal vibration of 2.1 mm magnitude during diastole to the epicardium of LV with complete relaxation, there was no significant change in the ventricular function. However, the systolic functional improvement (3.8 +/- 1.1 mmHg elevation in LV systolic pressure) was observed when the vibration was applied to LV with IR. We concluded that external vibration at diastole could release IR and would be useful to improve the systolic function of the depressed heart with IR.

Animals↗
PubMed1989

Clinical demonstration of vibration-induced depression of left ventricular function.

In experimental studies, minute sinusoidal vibration has been reported to induce functional depression of the left ventricle and to be an index for evaluation of myocardial crossbridge kinetics. Therefore, to examine whether or not this vibration-induced functional depression could also be observed in the human ventricle, motion of the left ventricular (LV) wall or LV pressure was measured by echocardiography (n = 16) or by left heart catheterization (n = 4), in which 100 Hz, 2.07 mm-amplitude sinusoidal vibration was applied to the subject's precordium. In the echocardiographic study, left ventricular wall shortening did not change by vibration in nine healthy volunteers, but was depressed in two patients with aortic regurgitation (AR) and in one patient with ischemic heart disease (IHD). In measurement of LV pressure, the decrease in LV systolic pressure caused by vibration was obviously observed in two patients (AR and IHD) but was not observed in two patients with hypertrophic cardiomyopathy. These results suggest that we might be able to extend previously proposed experimental idea on early detection of the abnormality in myocardial crossbridge kinetics to the clinical setting.

Adult↗