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Biomedical subjects

K Sekioka

Publications and source records attributed to K Sekioka.

17 recordsLinked to original sources

[Changes in hemodynamic state and autonomic nerve function from sleeping to awaking with suggestion on the treatment of cardiovascular diseases].

Effects of sleeping and awaking on blood pressure, heart rate and heart rate variability were shown in normal and a diabetic patient using an ambulatory blood pressure monitor (ABPM), Holter recorder and an accelerometer indicating body motion and posture. From the circadian variation of blood pressure and autonomic nerve function, optimal treatments to protect cardio-vascular accidents were discussed. For the assessments of medication and selection of drugs, ABPM and Holter recording with simultaneous measurement of physical activity are useful.

Activities of Daily Living↗

MCI-154, a Ca2+ sensitizer, decreases the oxygen cost of contractility in isolated canine hearts.

An increase in the responsiveness of the contractile machinery to Ca2+ could theoretically enhance the mechanoenergetics of the heart. To clarify this unresolved issue, we studied the effects of MCI-154, a Ca2+ sensitizer, on the mechanoenergetics in terms of the left ventricular contractility index [slope of end-systolic pressure-volume relationship (Emax)] and the relationship between myocardial oxygen consumption (VO2) and left ventricular pressure-volume area in excised cross-circulated canine hearts. MCI-154 increased Emax by 42 +/- 31% (SD), although the slope of the VO2-PVA relationship (an indicator of contractile efficiency) was unchanged by MCI-154. Despite equal increases in Emax, the relative increase in unloaded VO2 (delta VO2/delta Emax) during infusion of MCI-154 was, however, significantly less than that during CaCl2 infusion (0.0016 +/- 0.0018 vs. 0.0059 +/- 0.0054; P < 0.05). By contrast, delta VO2/delta Emax for milrinone was the same as that for CaCl2 (0.0043 +/- 0.0041 vs. 0.0039 +/- 0.0045; P > 0.05). Basal metabolism in KCl-arrested hearts was unchanged by MCI-154, indicating that MCI-154 consumes less energy than CaCl2 for excitation-contraction coupling. These findings suggest that MCI-154 acts energetically as a Ca2+ sensitizer in beating canine whole hearts.

Animals↗

High speed detection of R-R intervals for universal Holter recordings.

Heart rate variability (HRV) has been gaining popularity for its potential to estimate the autonomic nerve function and prognosis of patients with cardiovascular diseases. Holter recordings have been used for the measurement of R-R intervals in out-patients and for the estimation of circadian variations of HRV. However, when the manufacturer of the Holter tape recorder is not the same as that of the Holter analyzer a correction of the tape speed error for the accurate measurement of the R-R intervals is abandoned. The simultaneous assessment of additional physical parameters recorded on the Holter recorder and R-R interval is not possible with commercial software. To overcome these problems, we developed a system to detect R-R intervals at the playback speed of a Holter analyzer 500 times real-time with the correction of tape speed error from a system clock recorded on the Holter tape. High- and low-pass filter processed ECG signals and a comparator provided digital signals representing the R-R intervals. The R-R intervals and system clock intervals (tape speed) were measured simultaneously by interrupt-driven software, using timer-counters in a personal computer. The measured R-R intervals were corrected with the system clock intervals. The power spectra of the tape speed error showed that tape speed error significantly affects the power spectra of HRV, if not corrected. This method is applicable to Holter tape recorders of any manufacturer. This system also enables the simultaneous measurement of HRV and other physical parameters to evaluate their relations.

Electrocardiography↗

Parallel recording of physical activity on commercial Holter recorders.

To accurately interpret heart rate variability (HRV) including circadian rhythm from Holter ECG, the simultaneous assessment of physical activity, which significantly affects HRV, is essential. In this study, to obtain this simultaneous assessment, the fundamental problems in implementing an accelerometer in a commercial Holter recorder were studied. In a treadmill exercise, three axial outputs of an accelerometer showed highly linear correlations with the running speed (correlation coefficient; vertical 0.94, forward-backward 0.97, sideways 0.97, three-dimensional amplitude 0.96, n = 8). The vertical acceleration showed a slightly sigmoidal increase with speed. Against a slope change, no significant increase in acceleration was observed except in the forward-backward direction. Individual calibration was found to be needed for the accurate estimation of physical load from body acceleration. A simplified calculation with the sum of the three axial absolute values correlated highly with the three-dimensional (3D) acceleration which shows the most reliable response to motions in any direction (r = 0.98, the slope of the regression line = 0.97) and, with this relation, the estimated 3D amplitude showed a sufficient degree of agreement. This substituted calculation was used in the Holter recordings. To know the posture of subjects, a piezoresistive accelerometer with the function of clinometer was used in another study. From played-back Holter recordings, the R-R interval and body acceleration were simultaneously sampled. The serial changes of both the power spectra of HRV and the body acceleration were observed over a 24 h period. Some cases with an abnormally reduced high-frequency component (HF) of HRV at night or an unusually high HF in the daytime were explained by physical conditions estimated with the accelerometer. The simultaneous assessment of patients' physical state by the present method provides the accurate interpretation of circadian rhythm in HRV.

Adult↗

Changes in calcium transient and left ventricular function during positive inotropic stimulation and myocardial ischemia in indo-1-loaded beating guinea pig heart.

To elucidate the issues such as excitation-contraction coupling and myocardial ischemia, it is necessary to measure intracellular free Ca2+ concentration and mechanical function of hearts perfused via the normal arterial circulation. For this purpose, we simultaneously measured Ca(2+)-dependent indo-1 fluorescence and left ventricular (LV) pressure on a beat-to-beat basis in Langendorff guinea-pig hearts, and investigated the changes in Ca2+ transient and LV function during inotropic stimulation and myocardial ischemia. The indo-1 fluoresence ratio and LV developed pressure increased the perfusate [Ca2+] increased from 1.6 to 3.2 mmol/L, and there was a good correlation between Ca2+ transient and LV contractility. Digoxin (10(-6) mol/L) and milrinone (10(-5) mol/L) increased LV contractility with a concomitant increase in Ca2+ transient, and the relative increase of Ca2+ transient produced by milrinone was much more than that by digoxin. The reduction of coronary perfusion pressure from 80 to 40 mm Hg decreased LV contractility with an increase in indo-1 fluorescence ratio. These results suggest that Ca2+ responsiveness of contractile apparatus declines during inotropic stimulation by milrinone and during myocardial ischemia. Thus, this experimental technique is useful to investigate the interrelation of Ca2- regulation and LV function during a variety of pharmacological and physiologic perturbations.

Animals↗

Decrease in oxygen cost of contractility during hypocapnic alkalosis in canine hearts.

Ca2+ sensitization of contractile machinery could theoretically enhance the mechanoenergetics of the heart. We studied the effects of alkalosis with Ca2+ sensitization on mechanoenergetics within the framework of the relationships of left ventricular pressure-volume area (PVA; a measure of the total mechanical energy), myocardial oxygen consumption per beat (VO2), and the contractility index [E(max) (slope of end-systolic pressure-volume relation)] in 10 excised, cross-circulated canine hearts. Alkalosis was stably maintained without hypoxia (mean pH 7.66). Alkalosis increased E(max) without changing the slope of the VO2-PVA relation, a reflected contractile efficiency. The incremental ratio of unloaded VO2 to E(max) in alkalosis was significantly lower than that in Ca2+ sensitization (0.0012 +/- 0.0010 vs. 0.0062 +/- 0.0030 ml O2 . mmHg-1 . ml . beat-1 . 100 g LV-2; P < 0.01). Basal metabolism under KCl arrest was unchanged by alkalosis, indicating the decreased energy cost of the excitation-contraction coupling by alkalosis. Compared with the control, alkalosis increased E(max) during the Ca2+ infusion of various concentrations without any further increase in unloaded VO2. Thus we demonstrated a decreased oxygen cost of contractility during alkalosis, presumably due to Ca2+ sensitization.

Alkalosis, Respiratory↗

Differential effects of EMD-53998 on calcium-pressure relationship in normal and ischemic guinea pig heart.

We investigated the effects of EMD-53998 and digoxin on Ca2+ transients and left ventricular (LV) function in indo 1-loaded Langendorff guinea pig hearts. EMD-53998 (10(-9) to 10(-5) M) and digoxin (10(-10) to 10(-6) M) increased +dP/dt and Ca2+ transients in normal hearts. The relative increase in Ca2+ transients by EMD-53998 was similar to digoxin. At 10(-5) M, EMD-53998 increased LV end-diastolic pressure. Low-flow ischemia decreased +dP/dt by 50%, while indo 1 ratio increased by 10-25%. EMD-53998 (10(-9) to 10(-6) M) effectively restored the depressed +dP/dt with little effect on indo 1 ratio, but at 10(-5) M, it markedly elevated LV end-diastolic pressure and the beneficial effect on contractile dysfunction disappeared. Digoxin (10(-10) to 10(-7) M) failed to improve LV function, but at 10(-6) M, it restored contractile dysfunction with a large increase in indo 1 ratio. The relation between indo 1 ratio and +dP/dt clearly showed that EMD-53998 restored contractile dysfunction by Ca2+ sensitization. These findings suggest that Ca2+ sensitization by EMD-53998 is an advantageous approach for ischemic contractile failure but impairs diastolic function.

Animals↗

Calcium sensitization in perfused beating guinea pig heart by a positive inotropic agent MCI-154.

We investigated the effects of MCI-154, a positive inotropic agent that increases the myofilament response to Ca++, on Ca++ transients, left ventricular (LV) function and phosphodiesterase (PDE) III activity of guinea pig heart, and compared them with the effects of pimobendan and milrinone. In Langendorff guinea pig hearts loaded with a fluorescent Ca++ probe indo-1, LV pressure and Ca++ transient were measured simultaneously. MCI-154 (10(-10)-10(-6) M) increased LV developed pressure, +dP/dt and -dP/dt with a reduction of LV end-diastolic pressure, although it did not affect coronary flow. The positive inotropic activity of MCI-154 was more potent than that of pimobendan and milrinone; EC50 values (concentrations for increasing +dP/dt by 50% from base line) were 4.31, 41.5 and 294 x 10(-9) M, respectively. The positive inotropic effect of MCI-154 was accompanied by the increase in systolic, diastolic and amplitude of indo-1 fluorescence ratio. The relative increase in Ca++ transients against the increase in LV contractility produced by MCI-154, however, was significantly less than that by increasing perfusate [Ca++], pimobendan or milrinone. MCI-154 (3 x 10(-7)-10(-4) M) inhibited the activity of PDE III isolated from guinea pig LV tissues, but the inhibitory effect of MCI-154 was less than pimobendan and milrinone; IC50 values were 10.1, 3.5 and 2.4 x 10(-6) M, respectively. These findings suggest that MCI-154 exerts a positive inotropic effect mainly through Ca(++)-sensitizing action in intact beating whole hearts.

Animals↗

Restoration of ischemic contractile failure of indo-1-loaded guinea pig heart by a calcium sensitizer, MCI-154.

We investigated the effect of a new Ca++ sensitizer, MCI-154, which is known to increase myofibrillar Ca++ sensitivity and maximal Ca(++)-activated force, on Ca++ transients and left ventricular (LV) function in indo-1-loaded Langendorff guinea plg hearts subjected to a reduction in coronary perfusion pressure from 80 to 40 mm Hg. During low-flow ischemia, LV contractility decreased by 50%, whereas systolic and diastolic indo-1 fluorescence ratios increased by 10%. The treatment with MCI-154 (10(-10) to 10(-6) M) 15 min after ischemia effectively restored the depressed LV function with little effect on indo-1 ratio. EMD 53998 (10(-9) to 10(-6) M), which also acts on maximal Ca(++)-activated force, restored LV function with a minimal impact on indo-1 ratio, but at 10(-5) M, EMD 53998 caused diastolic dysfunction, and its beneficial effect on systolic function disappeared. The relation between indo-1 ratio and LV contractility showed that MCI-154 and EMD 53998 restored ischemic contractile failure by Ca(++)-sensitizing action. It was noted that the restoration of LV dysfunction by MCI-154 or EMD 53998 was more pronounced than that by pimobendan, which acts primarily on Ca++ sensitivity. In contrast, the phosphodiesterase inhibitor milrinone restored LV function, but it doubled the increase in indo-1 ratio during ischemia. These findings suggest that a decrease in myofilament Ca++ responsiveness may be an important cause of ischemic contractile failure and that the restoration of depressed Ca++ responsiveness by intervention such as MCI-154 may be a promising approach for restoring the depressed function.

Animals↗

Sevoflurane anaesthesia for one-lung ventilation with PEEP to the dependent lung in sheep: effects on right ventricular function and oxygenation.

This study was undertaken to examine the effect of sevoflurane on right ventricular function, the safety of sevoflurane for one-lung ventilation and the effects of PEEP (positive end-expiratory pressure) to the dependent lung in this model using 12 open-chest sheep. Haemodynamic variables, including cardiac output, mean arterial blood pressure, right ventricular pressure and pulmonary arterial pressure, and right ventricular segment shortening (sonomicrometry) were measured. First, animals received 2.0, 3.0 or 4.0% sevoflurane for 20 min each, respectively, during two-lung ventilation to measure the dose-dependent haemodynamic effects of sevoflurane. Then one-lung ventilation was performed with a randomized sequence of 0 (ZEEP), 5 and 10 cm H2O PEEP to the dependent lung under 2.0% sevoflurane anaesthesia after one-hour stabilization. A decrease in systolic segment shortening along with increases in both the end-diastolic and end-systolic lengths of the right ventricle were observed at 3.0 and 4.0% sevoflurane, while global right ventricular function remained substantially unchanged during two-lung ventilation. During one-lung ventilation the PaO2 was greater with 5 cm H2O PEEP 198 mmHg (+/- 25 SEM) than with ZEEP 138 mmHg (+/- 22) or with 10 cm H2O PEEP 153 mmHg (+/- 23) (P < 0.05). No differences in haemodynamic variables or segment shortening between ZEEP and PEEPs during one-lung ventilation were observed. We conclude that although sevoflurane causes a dose-dependent depression of right ventricular function, sevoflurane anaesthesia can be safely applied to one-lung ventilation, and that 5 cm H2O PEEP to the dependent lung can improve arterial oxygenation without causing changes in right ventricular function.

Anesthesia, Inhalation↗

Does hypertension or aging modulate directional shortening of the left ventricular midwall?

It is unclear whether aging or hypertension modulates directional contractile function of the left ventricular (LV) wall. We investigated LV midwall shortening and thickening in 35 normal subjects and in 15 patients with mild-to-moderate systemic hypertension (HT) using 2-dimensional echocardiography. The normal subjects were divided into 3 subgroups according to age: 13 subjects below 30 years, 12 subjects over 31 and below 59 years, and 10 subjects over 60 years. In normal subjects of all ages, no significant difference was observed between meridional shortening (%Lm = 16.3 +/- 2.4) and circumferential shortening (%Lc = 17.1 +/- 4.0), and a significant increase in the short-axis cross-sectional area (CSA) of the LV wall at end-systole was observed (p < 0.001). No significant differences with age were found in the measurements, except that %Lc/%Lm was reduced (p < 0.05) in the elderly subgroup. In HT, all measured parameters, i.e., %Lm, %Lc, %Lc/%Lm, wall thickening, and the change in CSA, showed no difference from those of normal subjects. We conclude that the shortening of the normal LV midwall is similar in both meridional and circumferential directions, and that aging and mild-to-moderate HT do not significantly affect this characteristic, when echocardiographic measurements are taken at rest at end-diastole and end-systole. This observation may be applied to simulation analyses of basic LV mechanics, such as the finite element method.

Adolescent↗

Differences in direction-dependent shortening of the left ventricular wall in hypertrophic cardiomyopathy and in systemic hypertension.

To determine whether patients with hypertrophic cardiomyopathy (HC) have an altered mode of contraction of the left ventricular (LV) wall related to underlying myocardial abnormalities, geometric changes in the LV wall were analyzed at 2 points of the cardiac cycle (end-diastole and end-systole) using 2-dimensional echocardiography. The relations between meridional and circumferential shortening of the LV midwall, mean wall thickening, and the changes in the short-axis cross-sectional area of the LV wall at the level of chordae tendineae were determined in 18 patients with nonobstructive HC, and were compared with those in 31 normal subjects and 19 patients with essential systemic hypertension. In normal subjects, no significant difference was observed between meridional (16.3 +/- 2.4%) and circumferential (17.1 +/- 4.0%) shortening, whereas cross-sectional LV wall area increased significantly at end-systole (p < 0.001). In patients with hypertension, all measured indexes were not different from those in normal subjects. In contrast, patients with HC had significantly reduced meridional shortening (p < 0.001) and mean wall thickening (p < 0.01). Consequently, a striking difference was observed between meridional (8.9 +/- 2.4%) and circumferential (16.9 +/- 3.2%) shortening (p < 0.001). Furthermore, no increase in cross-sectional LV wall area was observed at end-systole. Thus, echocardiographic detection of direction-dependent contraction can be a useful index for distinguishing HC from systemic hypertension.

Adult↗

Right ventricular function under acute cor pulmonale.

Many investigators have reported the hemodynamics in acute cor pulmonale clinically and experimentally. However, earlier studies have not made quantitative evaluations of the effects of coronary perfusion pressure and hypoxia on right ventricular contractility. We simulated acute cor pulmonale in nine isolated canine hearts and investigated the relationship of the process to cardiac deterioration and restoration. The afterload and preload of the right ventricle were controlled with a computer-assisted load control servosystem. Coronary perfusion pressure (COPP) was also controlled at either normal or variable levels identical to products of measured cardiac output and assumed values of systemic vascular resistance. Critical state (CS) was defined as a condition with an initial decrease in peak systolic pressure despite increased afterload. Within the normal range of PaO2 (105 +/- 5.3 mmHg), CS developed at a COPP of 51 +/- 5.1 mmHg, while under low PaO2 (51 +/- 2.3 mmHg), it developed at a COPP of 59 +/- 8.8 mmHg. As long as the COPP was normal (90 mmHg), the contractility of the right ventricle did not decrease despite hypoxia (PaO2 51 +/- 2.3 mmHg). An increase in systemic vascular resistance or administration of a beta-stimulant at CS restored the contractility of the right ventricle. However, an increase in preload decreased the contractility of the right ventricle.

Acute Disease↗

Assessments of left ventricular function during exercise in patients with dilated cardiomyopathy: comparison with ischemic cardiomyopathy.

Responses to supine bicycle ergometer exercise were assessed in a study population consisting of 26 patients with dilated cardiomyopathy (DCM) and 23 patients with ischemic cardiomyopathy (ICM). Left ventricular ejection fraction (LVEF) and regional wall motion were analyzed at rest and during supine bicycle ergometer exercise with radionuclide ventriculography. Although the same degree of LVEF between DCM (23 +/- 8%) and ICM (26 +/- 4%) occurred at rest, the left ventricular regional wall motion abnormality was more prominent in DCM. LVEF during the peak exercise stage in DCM was almost unchanged (24 +/- 8%), but in ICM it decreased significantly (22 +/- 5%). Exercise-induced regional wall motion abnormalities were detected in nine patients (35%) in DCM and 13 patients (57%) in ICM. Although patients with DCM are believed to have diffuse hypokinesis of the left ventricle, severe regional wall motion abnormalities (akinesis or dyskinesis) were frequently observed. During the follow-up period of up to six years, eight patients with DCM died of congestive heart failure. In eight patients with DCM who showed decreased LVEF during exercise, five patients died. However, only three of 18 patients without decreased LVEF during exercise died. Exercise-induced left ventricular dysfunction in DCM seems to be a poor prognostic sign.

Adult↗

Estimation of ventricular source parameters and its load matching state in vivo.

Ventriculo-arterial coupling states were estimated by calculating left ventricular hydromotive pressure (Ps), source impedance (Zs) and input impedance (Zl) in 24 mongrel dogs with Fourier transforms of ventricular pressure and aortic flow immediately before and after instantaneous changes of arterial load. Calculated Ps (Psc) were compared with measured left ventricular isovolumic pressures (Psm) in various inotropic and loading states. Psc waveforms coinciding closely with those of Psm were obtained by cutting off higher frequencies within the fifth to tenth harmonics prior to the inverse Fourier transformation. The regression equation was Psc = 1.08 Psm +0.68 (r = 0.978). In control conditions, the ratio of Zs (0) / Zl (0) (function of frequency, 0 = zero Hz) was close to the ratio of ejection phase to one whole cardiac cycle, and the ratio of peak Psm to left ventricular ejection pressure was 1.85 +/- 0.25 SD. These results imply the presence of a ventriculo-arterial load matching state in control conditions.

Animals↗

[Power spectrum of heart murmurs: special reference to mitral regurgitant murmurs].

Heart murmurs, especially the mitral regurgitant murmurs of 40 patients were analyzed using the fast Fourier transformation technique. 1. Three types of frequency spectral pattern of mitral regurgitation (MR) were demonstrated: A) broad, spanning 100 to 500 Hz, B) narrow, characterized by one giant peak, and C) two peaks. The reason for these patterns was not clear, but they may be related to various hemodynamic events. 2. The mean frequency (f) in MR was 295 +/- 38 Hz and it increased in proportion to the regurgitant grade: e.g., Sellers II, 258 +/- 27 Hz; Sellers III, 294 +/- 23 Hz; and Sellers IV, 311 +/- 65 Hz. The accumulated percentage of the 200-400 Hz component decreased, while that of the 400-600 Hz component increased. 3. The f in MR of various etiologies were as follows: It was higher in ruptured chordae tendineae, rheumatic cases and mitral valve prolapse syndrome, but was lower in papillary muscle dysfunction and dilated cardiomyopathy. In the latter two, the percentage of the 0-200 Hz component was greater than in other disorders. The degree of left ventricular dysfunction and of myocardial injury may be responsible for the changes in the propagation properties. In ventricular septal defect and aortic stenosis, the f was 306 +/- 12 Hz and 230 +/- 40 Hz, respectively. The frequency spectrum of the latter was lower than that of MR, which may be derived from the difference between ejection and regurgitant murmurs; whereas, that of ventricular septal defect was similar to that of rheumatic MR. 4. The relation between the frequency spectrum and the phase of systole was studied. In dilated cardiomyopathy and papillary muscle dysfunction, the f of each phase increased in late systole; whereas, the maximum f was in mid-systole in other disorders. 5. Administration of amyl nitrite resulted in a decreased f, an increased percentage of the 0-200 Hz component, and a decreased 400-600 Hz component. The spectral distribution shifted to the lower frequency region. Results of this study suggested that significant information can be obtained from the frequency analysis of heart murmurs.

Adolescent↗