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Biomedical subjects

M Sugimachi

Publications and source records attributed to M Sugimachi.

At least 55 records · Page 3Linked to original sources
PubMed1998

Liquid chromatographic determination of myocardial interstitial epinephrine.

This study describes a high-performance liquid chromatographic method with electrochemical detection (HPLC-ED) for monitoring of epinephrine (Epi) in the myocardial interstitial space. The in vitro detection limit for Epi was 200 fg in a 50-microl injection. Using a cardiac dialysis technique, 60-microl dialysates were sampled from the myocardial interstitial space (6-min fractions). After an alumina procedure, the dialysate Epi concentration was measured using the HPLC-ED system. Although the basal Epi concentration was undetectable, local administration of desipramine increased Epi concentration of the dialysate to 38.1+/-18.5 pg/ml. This system affords a new possibility for estimating myocardial interstitial Epi level.

Animals↗
PubMed1998

Transient oxygen uptake response to exercise characterizes functional capacity of the cardiocirculatory system in patients with chronic heart failure: a random stimulus approach.

The transient response of oxygen uptake (VO2) to submaximal exercise, known to be abnormal in patients with cardiovascular disorders, can be useful in assessing the functional status of the cardiocirculatory system, however, a method for evaluating it accurately has not yet been established. As an alternative approach to the conventional test at constant exercise intensity, we applied a random stimulus technique that has been shown to provide relatively noise immune responses of system being investigated. In 27 patients with heart failure and 24 age-matched control subjects, we imposed cycle exercise at 50 W intermittently according to a pseudo-random binary (exercise-rest) sequence, while measuring breath-by-breath VO2. After determining the transfer function relating exercise intensity (W) to VO2 and attenuating the high frequency ranges (> 6 exercise-rest cycles x min(-1)), we computed the high resolution band-limited (0-6 cycles x min(-1)) VO2 response (0-120 s) to a hypothetical step exercise. The VO2 response showed a longer time constant in the patients than in the control subjects [47 (SD 37) and 31 (SD 8) s, respectively, P < 0.05]. Furthermore, the amplitude of the VO2 response after the initial response was shown to be significantly smaller in the patients than in the control subjects [176 (SD 50) and 267 (SD 54) ml x min(-1) at 120 s]. The average amplitude over 120 s correlated well with peak VO2 (r = 0.73) and deltaVO2/deltaW (r = 0.70), both of which are well-established indexes of exercise tolerance. The data indicated that our band-limited VO2 step response using random exercise was more markedly attenuated and delayed in the patients with heart failure than in the normal controls and that it could be useful in quantifying the overall functional status of the cardiocirculatory system.

Adult↗
PubMed1998

Noninvasive differential diagnosis between chronic pulmonary thromboembolism and primary pulmonary hypertension by means of Doppler ultrasound measurement.

OBJECTIVES: The purpose of this investigation was to differentiate chronic pulmonary thromboembolism (CPTE) from primary pulmonary hypertension (PPH) by using noninvasive Doppler ultrasound techniques. BACKGROUND: A recent investigation in our laboratory has indicated that the pulmonary artery (PA) pressure waveform conveys significant information that can be used to differentiate CPTE from PPH. Pulse pressure was markedly larger in CPTE than in PPH, indicating that the major occlusive site is central in CPTE and peripheral in PPH. METHODS: In 19 patients with CPTE and 16 patients with PPH, we estimated PA systolic pressure and diastolic pressure from the velocities of tricuspid regurgitation and pulmonary regurgitation, respectively. RESULTS: Estimated systolic pressure was not significantly different between CPTE and PPH (mean [+/-SD] 81+/-20 and 79+/-21 mm Hg, respectively, p=NS). Pulse pressure normalized by systolic pressure was higher in CPTE than in PPH (0.82+/-0.05 vs. 0.63+/-0.10, respectively, p < 0.01). Pulse pressure normalized by mean pressure was also higher in CPTE than in PPH (1.65+/-0.30 vs. 0.94+/-0.25, respectively, p < 0.01). Receiver operating characteristic analysis indicated that pulse pressure normalized by systolic pressure separated CPTE from PPH, with a sensitivity of 0.95 and a specificity of 1.00. Pulse pressure normalized by mean pressure also separated them, with a sensitivity of 0.95 and a specificity of 1.00. CONCLUSIONS: Normalized pulse pressures estimated from Doppler ultrasound measurements enable us to noninvasively differentiate between CPTE and PPH.

Adult↗
PubMed1998

The brain is a possible target for an angiotensin-converting enzyme inhibitor in the treatment of chronic heart failure.

BACKGROUND: Although many lines of evidence have shown beneficial effects of angiotensin-converting enzyme (ACE) inhibitors on patients with chronic heart failure (CHF) after myocardial infarction (MI), the target of ACE inhibitors still remains unclear. The objectives of the present study were to evaluate the dipsogenic response to centrally administered angiotensin and to examine the effect of central administration of an ACE inhibitor on cardiac remodeling in rats with CHF after large MI. METHODS AND RESULTS: The drinking responses to intracerebroventricular (i.c.v.) injections of saline and angiotensin I (100 ng) were measured in 22 male Sprague-Dawley rats with or without CHF at 2-5 weeks after the ligation of the left coronary artery. The dipsogenic responses to i.c.v. angiotensin I were significantly larger in rats with CHF and large MI (infarct size > 30%) than in sham-operated rats. Pretreatment with losartan abolished the significant difference between the two groups. Left ventricular (LV) weights of 32 surviving rats with CHF were measured after the 3-week subcutaneous infusions of vehicle (s.c.-VEH) and captopril (1 mg x kg(-1) x h(-1), s.c.-CAP) or the 3-week i.c.v. infusions of vehicle (i.c.v.-VEH) and captopril (50 microg x kg(-1) x h(-1), i.c.v.-CAP). The LV weights normalized by body weights of s.c.-CAP rats were significantly smaller than those of s.c.-VEH rats (1.73 +/- 0.04 vs 2.08 +/- 0.09 g x kg(-1); P < .01); those of i.c.v.-CAP rats were also significantly smaller than those of i.c.v.-VEH rats (1.84 +/- 0.08 vs 2.1 +/- 0.10 g x kg(-1); P < .05). CONCLUSIONS: These results suggest that the brain is a possible target for ACE inhibitors in the treatment of CHF after MI.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1998

Dynamic transduction properties of in situ baroreceptors of rabbit aortic depressor nerve.

We developed a new method for isolating in situ baroreceptor regions of the rabbit aortic depressor nerve (ADN) and estimated the transfer function from pressure to afferent nerve activity in the frequency range of 0.01-5 Hz by a white noise technique. Complete isolation of the baroreceptor area of the right ADN was made in situ by ligation of the innominate artery and the right subclavian and common carotid arteries. We altered the pressure in the isolated baroreceptor area according to a binary quasi-white noise between 80 and 100 mmHg in 12 urethan-anesthetized rabbits. The gain increased two to three times as the frequency of pressure perturbation increased from 0.01 to 2 Hz and then decreased at higher frequencies. The phase slightly led below 0.2 Hz. The squared coherence value was > 0.8 in the frequency range of 0.01-4 Hz. The step responses estimated from the transfer function were indistinguishable from those actually observed. We conclude that the baroreceptor transduction of the ADN is governed by linear dynamics under the physiological operating pressure range.

Afferent Pathways↗
PubMed1998

A new method to measure regional myocardial time-varying elastance using minute vibration.

We developed a new technique to evaluate regional myocardial elastance using minute vibration. In 13 isolated cross-circulated canine hearts, we applied small sinusoidal vibrations of displacement to the left ventricular surface at various frequencies (50-100 Hz). Using the measured displacement and force between the vibrator head and myocardium, we derived myocardial elastance on the basis of the equation of motion for a given moment of the cardiac cycle. Simultaneous solution of the equations of motion at different frequencies yielded a unique value of elastance. Time-varying myocardial elastance increased from diastole (0.028 +/- 0.211 x 10(6) dyn/cm) to systole (0.833 +/- 0.391 x 10(6) dyn/cm). The end-systolic elastance (ees) linearly correlated with end-systolic left ventricular elastance (r = 0.717, P < 0.001) and also with the end-systolic Young's modulus (r = 0.874, P < 0.0001). We also measured ees at both ischemic and nonischemic regions during coronary occlusion. Young's modulus, estimated by normalizing ees by the wall thickness and by the estimated mass, did not change significantly at the nonischemic regions, whereas it decreased significantly from 2.303 +/- 0.556 to 1.173 +/- 0.370 x 10(6) dyn/cm2 at the ischemic region after coronary occlusion (P < 0.005). We conclude that this technique is useful for the quantitative assessment of regional myocardial elastance.

Animals↗
PubMed1998

ESPVR of in situ rat left ventricle shows contractility-dependent curvilinearity.

We developed a miniaturized conductance catheter for in situ rat left ventricular (LV) volumetry. After the validation study of the conductance volumetry in 11 rats, we characterized the end-systolic pressure-volume relationship (ESPVR) in 24 sinoaortic-denervated, vagotomized and urethan-anesthetized rats. Stroke volume (SV) measured with the conductance catheter correlated closely with that measured by electromagnetic flowmetry (r > 0.95). No significant difference was found between the in situ LV end-diastolic volumes measured by conductance volumetry and postmortem morphometry; a linear regression analysis indicated that the correlation coefficient was 0.934, that the slope was not significantly different from 1, and that the intercept was not significantly different from 0. During cardiac sympathotonic conditions, the ESPVR was curvilinear. The estimated slope of ESPVR (end-systolic elastance, Ees) by quadratic curve fitting at end-systolic pressure of 100 mmHg was 2,647 +/- 846 mmHg/ml. Bilateral cervical and stellate ganglionectomy depressed contractility and made the ESPVR linear; a quadratic equation did not improve the fit. Ees was 946 +/- 55 mmHg/ml with the volume-axis (V0) intercept of 0.076 +/- 0.007 ml. Administration of propranolol (1 mg/kg) further reduced Ees (573 +/- 61 mmHg/ml, P < 0.001) and increased V0 slightly (0.091 +/- 0.011 ml). We conclude that the conductance catheter method is useful for the assessment of the ESPVR of the in situ rat left ventricle and that the ESPVR displays contractility-dependent curvilinearity.

Animals↗
PubMed1998

Dynamic sympathetic regulation of left ventricular contractility studied in the isolated canine heart.

We investigated the dynamic sympathetic regulation of left ventricular end-systolic elastance (Ees) using an isolated canine ventricular preparation with functioning sympathetic nerves intact. We estimated the transfer function from both stellate ganglion stimulation to Ees and ganglion stimulation to heart rate (HR) for both left and right ganglia by means of the white noise approach and transformed those transfer functions into corresponding step responses. The HR response was much larger with right sympathetic stimulation than with left sympathetic stimulation (4.3 +/- 1.4 vs. 0.7 +/- 0.6 beats . min-1 . Hz-1, P < 0.01). In contrast, the Ees responses without pacing were not significantly different between left and right sympathetic stimulation (0.72 +/- 0.34 vs. 0.76 +/- 0. 42 mmHg . ml-1 . Hz-1). Fixed-rate pacing significantly decreased the Ees response to right sympathetic stimulation (0.53 +/- 0.43 mmHg . ml-1 . Hz-1, P < 0.01), but not to left sympathetic stimulation (0.67 +/- 0.32 mmHg . ml-1 . Hz-1, not significant). Although the mechanism by which the sympathetic nervous system regulates cardiac contractility is different depending on whether the left or right sympathetic nerves are activated, this difference does not affect the apparent response of Ees to dynamic sympathetic stimulation.

Animals↗
PubMed1998

Accumulation of cAMP augments dynamic vagal control of heart rate.

Recent investigations in our laboratory using a Gaussian white noise perturbation technique have shown that simultaneous sympathetic stimulation augmented the gain of the transfer function from vagal stimulation frequency to heart rate response. However, the mechanism of that augmentation remains to be elucidated. In this study, we examined in anesthetized rabbits how three pharmacological interventions known to cause intracellular accumulation of cAMP affected the transfer function. Isoproterenol (0.3 microg . kg-1 . min-1 iv) increased the dynamic gain of transfer function from 7.12 +/- 0.67 to 12.4 +/- 1.21 beats . min-1 . Hz-1 (P < 0.05) without changing the corner frequency or the lag time. Similar augmentations were observed when forskolin (5 microg . kg-1 . min-1 iv) or theophylline (20 mg/kg iv) was administered under conditions of beta-adrenergic blockade. These results suggest that the accumulation of cAMP at postjunctional effector sites contributes, at least in part, to the sympathetic augmentation of the dynamic vagal control of heart rate.

Animals↗
PubMed1998

Cholinesterase affects dynamic transduction properties from vagal stimulation to heart rate.

Recent investigations in our laboratory using a Gaussian white noise technique showed that the transfer function representing the dynamic properties of transduction from vagus nerve activity to heart rate had characteristics of a first-order low-pass filter. However, the physiological determinants of those characteristics remain to be elucidated. In this study, we stimulated the vagus nerve according to a Gaussian white noise pattern to estimate the transfer function from vagal stimulation to the heart rate response in anesthetized rabbits and examined how changes in acetylcholine kinetics affected the transfer function. We found that although increases in the mean frequency of vagal stimulation from 5 to 10 Hz did not change the characteristics of the transfer function, administration of neostigmine (30 microg . kg-1 . h-1 iv), a cholinesterase inhibitor, increased the dynamic gain from 8.19 +/- 3.66 to 11.7 +/- 4.88 beats . min-1 . Hz-1 (P < 0.05), decreased the corner frequency from 0.12 +/- 0.05 to 0.04 +/- 0.01 Hz (P < 0.01), and increased the lag time from 0.17 +/- 0.12 to 0.27 +/- 0.08 s (P < 0.05). These results suggest that the rate of acetylcholine degradation at the neuroeffector junction, rather than the amount of available acetylcholine, plays a key role in determining the dynamic properties of transduction from vagus nerve activity to heart rate.

Acetylcholine↗
PubMed1997

Role of heparin-binding EGF-related peptides in proliferation and apoptosis of activated ras-stimulated intestinal epithelial cells.

The ras mutation is a common and critical step in carcinogenesis. Autocrine growth factors are also known to play an important role in cancer cell growth and transformation. However, the contribution of autocrine growth factors in regulation of proliferation and apoptosis of activated ras-stimulated intestinal epithelium is not fully understood. Therefore, we constructed activated ras-transfected intestinal epithelial cell clones (IEC-ras) to examine the role of epidermal growth factor (EGF)-related peptides in the behavior of IEC-ras. Overexpression of EGF family growth factors (transforming growth factor alpha, heparin-binding EGF-like growth factor, amphiregulin and betacellulin) and stronger phosphorylation of the EGF receptor was observed in IEC-ras compared with control cells. IEC-ras proliferated more rapidly than control cells, and a specific EGF receptor kinase inhibitor, AG 1478, abolished the increased proliferation of IEC-ras. Heparitinase and chlorate also prevented increased proliferation of IEC-ras. Additionally, IEC-ras expressed more bcl-2 and was more resistant to apoptosis induction by UV radiation and mitomycin C. AG 1478 suppressed bcl-2 expression and inhibited resistance to apoptosis of IEC-ras. Heparitinase and chlorate had effects similar to those of AG 1478. Our data indicate that heparin-binding EGF family growth factors play an important role in both increased proliferation and resistance to apoptosis of ras-stimulated intestinal epithelial cells.

Amphiregulin↗
PubMed1997

Negative inotropic effect of basic fibroblast growth factor on adult rat cardiac myocyte.

BACKGROUND: Basic fibroblast growth factor (bFGF) is highly expressed in the myocardium in some cardiac disorders, such as ischemia-reperfusion and cardiac allograft rejection. However, whether bFGF has any effects on myocardial contraction is unknown. METHODS AND RESULTS: We examined the effects of bFGF on myocardial contractility using isolated adult rat cardiac myocyte preparations. bFGF exerted a direct negative inotropic effect that was concentration and time dependent. The pretreatment of myocytes with a neutralizing anti-bFGF antibody (100 ng/mL) abolished the negative inotropic effects of bFGF (100 ng/mL). Platelet-derived growth factor (12.5 ng/mL) and transforming growth factor-beta (1 ng/mL) did not exert such effects, which indicated that bFGF-induced negative inotropism was considered to be specific for this growth factor. bFGF decreased the peak intracellular Ca2+ transient by 46% during systole. The enhanced production of nitric oxide was unlikely to be responsible for the bFGF-induced negative inotropic effect. CONCLUSIONS: bFGF, primarily a potent growth promoter, produced acute negative inotropic effects in the adult cardiac myocyte that could have resulted from alterations in intracellular Ca2+ homeostasis. The negative inotropic effect of bFGF may contribute to myocardial dysfunction associated with ischemia-reperfusion injury and heart transplant rejection.

Animals↗
PubMed1997

Aortic blood momentum--the more the better for the ejecting heart in vivo?

OBJECTIVES: The aim of the present study was to test two hypotheses: (1) the momentum of the blood flowing out of the left ventricle toward the aorta (inertia force) plays an important role in the initiation of decay and the maximum rate of decay (peak (-dP/dt)) of left ventricular pressure (P); (2) a normal heart itself generates the inertia force which enhances its function. METHODS: The contribution of the inertia force to (-dP/dt) was theoretically given as rho c alpha, where rho is the blood density, c the pulse wave velocity, and alpha the deceleration rate of aortic blood flow. The correlations of peak (-dP/dt) with rho c alpha and with the time constant (tau) of the pressure decay during isovolumic relaxation, which was considered to represent myocardial relaxation characteristics, were compared in seven dogs. We developed a method of grading the strength of the inertia force, using the phase loop of left ventricular pressure (dP/dt vs. P relation). The method was applied to the records of 25 patients with ischemic heart disease, from which high fidelity left ventricular pressure recordings were available. RESULTS: The correlation of peak (-dP/dt) with rho c alpha was much higher than with tau (0.75 vs. -0.46). 16 of the 25 patients showed evidence of the inertia force. However, other patients showed no inertia force. The strength of the inertia force showed a significant (P < 0.05) correlation with left ventricular end-diastolic pressure (r = -0.46), cardiac index (r = 0.62), stroke volume index (r = 0.69), ejection fraction (r = 0.46), and peak (-dP/dt) (r = 0.56). CONCLUSION: The inertia force of late systolic aortic flow contributed to ventricular relaxation in the normal heart.

Aged↗
PubMed1997

Characteristics of pulmonary artery pressure waveform for differential diagnosis of chronic pulmonary thromboembolism and primary pulmonary hypertension.

OBJECTIVES: The accurate diagnosis of chronic pulmonary thromboembolism (CPTE) is a prerequisite for life-saving surgical interventions. To help in the differential diagnosis of CPTE and primary pulmonary hypertension (PPH), we characterized the configuration of the pulmonary artery pressure waveform. BACKGROUND: Because CPTE predominantly involves the proximal arteries, whereas PPH involves the peripheral arteries, we hypothesized that patients with CPTE would have stiff or high resistance proximal arteries, whereas those affected by PPH would have high resistance peripheral arteries. These differences in the primary lesions would make arterial pulsatility relative to mean pressure larger in CPTE than in PPH. METHODS: In 34 patients with either CPTE (n = 22) or PPH (n = 12) whose pulmonary systolic pressure was > or = 50 mm Hg, we measured pulmonary artery pressure using a fluid-filled system that included a balloon-tipped flow-directed catheter. RESULTS: To quantify the magnitude of pulsatility relative to mean pressure, we normalized pulse pressure by mean pressure, hereinafter referred to as fractional pulse pressure (PPf). PPf was markedly higher in CPTE than in PPH (mean [+/-SD] 1.41 +/- 0.20 and 0.80 +/- 0.18, respectively, p < 0.001) and was diagnostic in separating the two groups without overlap. Similarly, the coefficient of variation of pulmonary artery pressure also separated the two groups without overlap (0.45 +/- 0.06 and 0.25 +/- 0.06, respectively, p < 0.001). Fractional time to half the area under the pressure curve separated the two groups reasonably well (0.35 +/- 0.02 and 0.43 +/- 0.03, respectively, p < 0.001). CONCLUSIONS: The analysis of pulsatility of pulmonary artery pressure is useful in the differential diagnosis of CPTE and PPH.

Adult↗
PubMed1997

Alterations in sarcoplasmic reticulum calcium-storing proteins in pressure-overload cardiac hypertrophy.

The alterations of intracellular calcium (Ca2+) homeostasis may be responsible for the contractile defects in pressure-overload cardiac hypertrophy. The Ca(2+)-adenosinetriphosphatase (ATPase) protein level of the sarcoplasmic reticulum (SR) is reduced in the hypertrophied or failing heart. However, it is not known whether Ca(2+)-storing proteins, including calsequestrin and calreticulin, are also altered during cardiac hypertrophy. We quantified SR Ca(2+)-regulatory proteins using Western blot analysis in left ventricular (LV) muscle isolated from sham-operated control rats (n = 6) and rats with pressure overload 4 wk after abdominal aortic constriction (n = 7). The contractile function of isolated LV myocytes, assessed by the sarcomere motion measured with laser diffraction, was depressed in aortic-constricted rats. The SR Ca(2+)-ATPase protein level was decreased to 56 +/- 9% (SE) of the control value in hypertrophied myocardium (P < 0.01). The calsequestrin protein level was not altered, whereas calreticulin was increased by 120 +/- 3% of the control value in aortic-constricted rats (P < 0.05). The alterations in SR Ca(2+)-regulatory proteins were equally observed in hypertrophied hearts even when the results were normalized using the amounts of myosin heavy chain proteins in each sample. Immunohistochemical staining of calsequestrin in the control heart showed cross striations at the Z lines, whereas calreticulin was hardly observed within myocytes but was intense within interstitial fibroblasts. In the hypertrophied heart, calreticulin was observed at the perinuclear region within the myocyte cytoplasm. These data indicate that pressure-overload cardiac hypertrophy causes the alterations in SR Ca(2+)-storing proteins as well as in Ca(2+)-ATPase, which may contribute to the contractile dysfunction of the hypertrophied myocytes.

Animals↗
PubMed1997

Dynamic vagosympathetic interaction augments heart rate response irrespective of stimulation patterns.

We previously demonstrated that tonic stimulation of either the sympathetic or the vagal nervous system augmented the dynamic heart rate response to the other of the two systems. We characterized the phenomenon as bidirectional augmentation of heart rate regulation. The question remained unanswered, however, as to whether such augmentation could occur under simultaneous dynamic stimulation of the two systems. The transfer characteristics from nerve stimulation to heart rate were well described by linear systems analysis, although no attention was paid to the aphasic nature of the stimuli in relation to each R-R interval. When we stimulated the two nerves with statistically independent Gaussian white noises, gain of the transfer function increased by 63.2 +/- 47.4% relative to individual stimulation (P < 0.05). When we stimulated the two nerves with mutually reciprocal Gaussian white noises, gain of the transfer function increased by 54.9 +/- 49.1% (P < 0.05). Thus simultaneous dynamic stimulation of the sympathetic and vagal systems bidirectionally augmented heart rate regulation irrespective of the pattern of the stimulation signals.

Animals↗
PubMed1997

Inhibition of NO synthesis minimally affects the dynamic baroreflex regulation of sympathetic nerve activity.

The purpose of this investigation was to examine the role of nitric oxide (NO) in the dynamic baroreflex regulation of cardiac sympathetic nerve activity. In anesthetized rabbits, we imposed random pressure perturbations on the isolated carotid sinuses before and after the intravenous administration of NG-monomethyl-L-arginine. We characterized the dynamic properties relating carotid sinus pressure input to sympathetic nerve activity by means of a transfer function analysis. NG-monomethyl-L-arginine decreased the corner frequency of the transfer function (0.100 +/- 0.054 vs. 0.074 +/- 0.035 Hz; P < 0.05), whereas other parameters such as the steady-state gain and transmission lag time remained unchanged. Although cursory examination of these findings would suggest a possible contribution of NO in the dynamic baroreflex regulation of sympathetic nerve activity, quantitative assessment of the transfer function reveals only a minimal effect on the baroreflex regulation of arterial pressure, particularly under closed-loop conditions. We conclude that NO noticeably affects the dynamic baroreflex regulation of sympathetic nerve activity. However, it may not significantly affect arterial pressure regulation through central modulation of the carotid sinus baroreflex.

Animals↗