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M Sugimachi

Publications and source records attributed to M Sugimachi.

At least 73 records · Page 4Linked to original sources
PubMed1997

Inhibition of NO synthesis does not potentiate dynamic cardiovascular response to sympathetic nerve activity.

We examined whether the inhibition of nitric oxide (NO) synthesis potentiates the dynamic sympathetic regulation of the cardiovascular system through the baroreflex. In anesthetized rabbits, we imposed random pressure perturbations on the isolated carotid sinuses to evoke random changes in sympathetic nerve activity (SNA). We estimated the transfer functions from SNA to both aortic pressure (AoP) and heart rate (HR). The inhibition of NO synthesis by NG-monomethyl-L-arginine (L-NMMA, 40 mg/ kg) altered neither the transfer function from SNA to AoP nor that from SNA to HR. In contrast, sodium nitroprusside (3-6 micrograms.kg-1.min-1) significantly decreased the steady-state gain (40.3 +/- 11.7% of the control, P < 0.05) of the transfer function from SNA to AoP without affecting the HR responses. We conclude that the basal release of NO may have a role in the tonic blood pressure regulation, whereas it may not be involved in the dynamic sympathetic regulation of AoP or HR through the baroreflex.

Animals↗
PubMed1997

Closed-loop identification of carotid sinus baroreflex open-loop transfer characteristics in rabbits.

In the circulatory system, a change in blood pressure operates through the baroreflex to alter sympathetic efferent nerve activity, which in turn affects blood pressure. Existence of this closed feedback loop makes it difficult to identify the baroreflex open-loop transfer characteristics by means of conventional frequency domain approaches. Although several investigators have demonstrated the advantages of the time domain approach using parametric models such as the autoregressive moving average model, specification of the model structure critically affects their results. Thus we investigated the applicability of a nonparametric closed-loop identification technique to the carotid sinus baroreflex system by using an exogenous perturbation according to a binary white-noise sequence. To validate the identification method, we compared the transfer functions estimated by the closed-loop identification with those estimated by open-loop identification. The transfer functions determined by the two identification methods did not differ statistically in their fitted parameters. We conclude that exogenous perturbation to the baroreflex system enables us to estimate the open-loop baroreflex transfer characteristics under closed-loop conditions.

Animals↗
PubMed1997

Vagal stimulation decreases left ventricular contractility mainly through negative chronotropic effect.

Although an increase in vagal tone is known to slow heart rate (HR), whether it also depresses left ventricular contractility through mechanisms independent of the bradycardic effect remains unknown. The chief aim of this investigation, therefore, was the separation of the observed vagally mediated depression of ventricular contractility into direct and indirect vagal effects, the latter resulting via negative chronotropism. In 12 anesthetized, sympathectomized open-chest rabbits, we measured left ventricular contractility through determination of the end-systolic elastance (Ees). We found that tonic vagal stimulation administered at 0, 5, and 10 Hz decreased both HR (226.9 +/- 39.7, 201.9 +/- 25.7, and 171.3 +/- 18.5 beats/min, respectively; P = 0.0003) and Ees (109.5 +/- 25.7, 85.1 +/- 34.1, and 71.9 +/- 33.1 mmHg/ml, respectively; P = 5 x 10(-6)) in a frequency-dependent fashion. However, we observed that as long as HR was kept constant through fixed-rate atrial pacing, vagal stimulation resulted in little or no change in Ees. Thus we conclude that the negative inotropic effect of vagal stimulation is attributable primarily to its negative chronotropic effect when sympathetic tone is minimal.

Animals↗
PubMed1997

Interstitial norepinephrine level by cardiac microdialysis correlates with ventricular contractility.

Although a cardiac microdialysis technique has made it possible to estimate myocardial interstitial norepinephrine (NE) levels, whether such levels reflect the local NE concentration that would regulate ventricular contractility remains unknown. If such levels indicate locally regulating NE concentration, then ventricular contractility should be a unique function of the interstitial NE level regardless of how the latter is altered. To examine this hypothesis, we altered the interstitial NE level endogenously by stimulating the cardiac sympathetic nerves at 1 and 2 Hz while monitoring ventricular contractility. We also altered the interstitial NE level exogenously by means of intravenous NE infusions at 10 and 40 micrograms.kg-1.h-1. The basal NE levels did not differ between the stimulation and the infusion experiments (42.9 +/- 11.2 vs. 40.1 +/- 6.2 pg/ml, means +/- SE). The slopes of regression lines relating ventricular contractility and interstitial NE level were also not different between the two experiments [1.13 +/- 0.20 vs. 1.17 +/- 0.20%/(pg/ml), means +/- SE]. We conclude that the interstitial NE level estimated by cardiac microdialysis reflects the local NE concentration regulating ventricular contractility.

Animals↗
PubMed1997

Estimation of arterial mechanical properties from aortic and tonometric arterial pressure waveforms.

Although arterial mechanical properties have been evaluated using arterial input impedance, the relative difficulty in accurate flow measurement made the value of impedance somewhat limited. To develop an alternative method to evaluate arterial mechanical properties, we analyzed the aortic pressure (AoP)-radial arterial pressure (RAP) relationship because of relative ease in obtaining peripheral pressure waveform by tonometry. In 8 patients we simultaneously recorded aortic root and radial arterial pressure waveforms. We calculated the transfer function from AoP to RAP. We then fitted the transfer function to a model of a lossless uniform elastic tube terminated with a modified Windkessel model. The fact that the model transfer function predicted AoP from RAP waveform with considerable accuracy indicated that the model represented the arterial mechanical properties well. We conclude that we can estimate the arterial mechanical properties by the pressure-pressure transfer function analysis.

Adolescent↗
PubMed1996

Role of prostaglandins in intestinal epithelial restitution stimulated by growth factors.

Mucosal integrity is reestablished after superficial injuries by a rapid resealing process, termed epithelial restitution, that is regulated by several growth factors and cytokines. Growth factors are also known to stimulate the synthesis of endogenous prostaglandins that mediate important functions in intestinal epithelial cells. Therefore, we examined the effect of endogenous eicosanoid production modulators, piroxicam, dexamethasone, and nordihydroguaiaretic acid (NDGA) on intestinal epithelial restitution using two cultured cell wound-resealing models, IEC-6 and Caco-2 cells. Epidermal growth factor, transforming growth factor-beta, hepatocyte growth factor, and fetal calf serum (FCS) accelerated intestinal epithelial restitution, and piroxicam significantly suppressed these stimulatory effects. Dexamethasone mimicked the action of piroxicam. No additive effect of piroxicam and dexamethasone was observed. NDGA did not affect epithelial restitution. Piroxicam abolished the increase in 6-ketoprostaglandin F1 alpha (PGF1 alpha) release induced by FCS. Furthermore, addition of a stable PGI2 analogue, OP-41483 [5(E)-6,9-deoxa-6,9-methylene-15-cyclopentyl-16,17,18,19,20-pen tanor-PGI2], reversed the slowing of epithelial restitution induced by piroxicam. These results suggest that endogenous prostaglandins play an important role in regulating intestinal epithelial restitution.

6-Ketoprostaglandin F1 alpha↗
PubMed1996

Bidirectional augmentation of heart rate regulation by autonomic nervous system in rabbits.

Although the characteristics of the static interaction between the sympathetic and parasympathetic nervous systems in regulating heart rate (HR) have been well established, how the dynamic interaction modulates the HR response remains unknown. We therefore investigated dynamic interaction by estimating the transfer function from nerve stimulation to HR using a band-limited Gaussian white-noise technique. The transfer function relating dynamic sympathetic stimulation to HR had characteristics of a second-order low-pass filter. Simultaneous tonic vagal stimulation at 5 and 10 Hz increased gain of the transfer function by 55.0 +/- 40.1 and 80.7 +/- 50.5%, respectively (P < 0.05). The transfer function from dynamic vagal stimulation to HR had characteristics of a first-order low-pass filter. Simultaneous tonic sympathetic stimulation at 5 and 10 Hz increased the gain by 18.2 +/- 17.9 and 24.1 +/- 18.0%, respectively (P < 0.05). Thus interaction augmented dynamic gain bidirectionally, even though it affected mean HR antagonistically. By virtue of this interaction, the autonomic nervous system appears to extend its dynamic range of operation.

Animals↗
PubMed1996

Neural arc of baroreflex optimizes dynamic pressure regulation in achieving both stability and quickness.

The baroreflex loop consists of a fast neural arc and a slow mechanical arc. We hypothesized that the neural baroreflex arc compensates the slow mechanical response and thus improves the quality of blood pressure regulation. We estimated the open-loop transfer characteristics of the neural baroreflex arc (HP), i.e., from carotid sinus pressure to sympathetic nerve activity (SNA), and that of the effective peripheral baroreflex arc (Hp), i.e., from SNA to arterial pressure, in anesthetized rabbits. The gain of Hn was constant below 0.12 +/- 0.057 Hz and increased with a slope of 6.1 +/- 0.06 dB/octave above its frequency up to 1 Hz. In contrast, the gain of Hp was constant below 0.071 +/- 0.03 Hz and decreased with a slope of -11.0 +/- 1.48 dB/octave above the frequency. These data indicate that Hn accelerates slow peripheral responses in the frequency range of 0.1-1 Hz. Although too much acceleration in the high-frequency range could result in instability of the system, numerical analysis of the closed-loop baroreflex response indicated that the neural arc optimized arterial pressure regulation in achieving both stability and quickness.

Animals↗
PubMed1996

Role of microtubules in myocyte contractile dysfunction during cardiac hypertrophy in the rat.

We have shown that increased microtubules cause myocyte contractile dysfunction in feline right ventricular pressure-overload hypertrophy. To investigate the association between the progression of cardiac hypertrophy and microtubules and to delineate the role of microtubules in contractile defects in hypertrophied myocytes, we assessed the amounts of free and polymerized tubulin proteins, using Western blot analysis and immunofluorescence micrograph, and evaluated the sarcomere mechanics of myocytes isolated from rats with pressure-overload left ventricular (LV) hypertrophy. Total and polymerized tubulins were progressively and persistently increased in LV after the imposition of pressure overload. The increase in microtubules was associated with the development and progression of hypertrophy and not the immediate response to the stress loading to the myocardium. The contractile function of hypertrophied myocytes was depressed in parallel with the increase in microtubules. Depolymerization of microtubules normalized the initially depressed LV myocyte contractile function. Thus the progressive increase of microtubule density during LV hypertrophy due to persistent pressure overloading to the myocardium may cause the consequent myocyte contractile dysfunction.

Animals↗
PubMed1995

Percutaneous transvenous mitral commissurotomy immediately restores quick response of VO2 to mild exercise despite insignificant increases in peak VO2.

Percutaneous transvenous mitral commissurotomy (PTMC) increases peak oxygen uptake (VO2) chronically, but not acutely, despite early symptomatic improvements. Analysis of transient VO2 responses to submaximal exercise (an exercise regimen more comparable to the patients' daily activities than that provided by maximal exercise testing), may be sensitive in detecting the acute hemodynamic benefits of PTMC. Since no methods are available to accurately estimate the transient response of VO2, we developed a new technique, using random exercise. In 15 patients who underwent successful PTMC, we repeated the conventional maximal exercise test and the random exercise test before and within a few days after PTMC. For the random exercise test, we intermittently imposed upright bicycle exercise at 50 W, according to a random binary sequence, while measuring breath-by-breath VO2. After determining the transfer function relating workload to VO2, we computed the high resolution VO2 response to a hypothetical step increase in exercise. Despite improvements in resting hemodynamics and New York Heart Association (NYHA) Class, peak VO2 improved insignificantly (952 +/- 271 vs 1,029 +/- 342 ml/min, P = 0.063) shortly after successful PTMC. In contrast, the amplitude of the VO2 step response increased significantly in the early-to-mid portion (28-76s; P < 0.01-0.05). The remaining portion was unchanged. Consequently, the time constant shortened from 64 +/- 26 to 48 +/- 22s (P < 0.05). The maximal Borg scale value during random exercise decreased significantly (13.1 +/- 1.8 vs 11.4 +/- 1.1; P < 0.01). We conclude that the VO2 step response, using the random exercise test, is more sensitive than peak VO2 in detecting the functional improvement that is coupled with the hemodynamic improvement immediately after PTMC.

Adult↗
PubMed1995

Explorations into development of a neurally regulated cardiac pacemaker.

Although the artificial cardiac pacemaker has contributed to the management of patients with serious arrhythmias, its rate-responsive function is not sufficient to provide physiological regulation of heart rate (HR). To achieve truly physiological rate response in any given patient, we propose a framework to develop a pacemaker directly regulated by sympathetic nerve activity (SNA). In eight anesthetized rabbits, we quantified the dynamic transduction characteristics from SNA to HR as a transfer function. We then characterized the decoding rule as an impulse response, that is the transfer characteristics in the time domain. The transfer function was approximated by a first-order, low-pass filter with lag time (corner frequency: 0.024 +/- 0.013 Hz, lag time: 0.98 +/- 0.09 s). Predicted HR correlated well with measured HR (r = 0.80-0.98). The standard error of the prediction relative to mean HR was only 1.2 +/- 0.7%, indicating that the prediction was reasonably accurate. Direct decoding of SNA to predict instantaneous HR is possible through this analysis. This framework should enable development of a neurally regulated artificial pacemaker.

Animals↗
PubMed1995

Impaired endothelium-dependent vasodilation of large epicardial and resistance coronary arteries in patients with essential hypertension. Different responses to acetylcholine and substance P.

Hypertensive patients have impaired endothelium-dependent coronary vasodilation evoked with acetylcholine. The aim of this study was to examine whether the impaired endothelium-dependent dilation of coronary arteries is related to a specific abnormality of the muscarinic receptor that mediates the effects of acetylcholine. Responses of the large epicardial and resistance coronary arteries were assessed in seven hypertensive patients (mean arterial pressure, 106 +/- 14 mm Hg) and seven control subjects (83 +/- 6 mm Hg, P < .01) during cardiac catheterization. To assess coronary endothelial function, we infused acetylcholine and substance P (endothelium-dependent agents that act on different receptors) and papaverine and nitrate (direct vascular smooth muscle dilators) into the left anterior descending coronary artery and determined coronary artery diameter by arteriography and coronary blood flow with an intracoronary Doppler catheter technique. In control subjects, 3 micrograms/min acetylcholine increased (P < .05) and 30 micrograms/min acetylcholine decreased (P < .05) arterial diameter, and in hypertensive patients, 1, 3, 10, and 30 micrograms/min acetylcholine decreased arterial diameter in a dose-dependent manner. Substance P at 3, 10, and 30 ng/min caused comparable increases in diameter in both groups. Increases in coronary blood flow with both acetylcholine and substance P were significantly (P < .01) blunted in hypertensive patients compared with control subjects. No significant differences were noted between the groups in the responses of large epicardial coronary artery diameter and coronary blood flow to papaverine and nitrate.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1994

Right-to-left shunt across atrial septal defect related to tricuspid regurgitation: assessment by transesophageal Doppler echocardiography.

The purpose of this study was to assess the factors involved in the development of the right-to-left (R-L) shunt in patients with atrial septal defect (ASD), especially the role of tricuspid regurgitation (TR). Thirty-one consecutive patients with ASD underwent transesophageal Doppler echocardiography to determine the size of ASD, the shunt flow, and the TR flow, and they were compared with hemodynamics examined by cardiac catheterization. Sixteen patients with the R-L shunt were older (53 +/- 11 vs 34 +/- 9 years; p < 0.001) and had higher pulmonary arterial pressure (36 +/- 17 vs 25 +/- 5 mmHg; p < 0.05) and a greater Qp/Qs (3.6 +/- 1.2 vs 2.4 +/- 0.9 L/min; p < 0.01) as compared with 15 patients with the pure left-to-right shunt. In six of 21 patients with TR, the regurgitant flow oriented toward ASD and blew into the left atrium through the defect. Besides the deviation of TR flow, the prevalences of the maximum diameter of ASD > 2.5 cm and the maximal TR flow area > 4 cm2 were significantly higher in the six patients as compared with patients with TR not related to the R-L shunt (p < 0.05 and p < 0.05), despite the pulmonary arterial pressure being similar in the two groups. Reversal of pressure gradient between the left and right atrium was not observed during the cardiac cycle in all patients. In conclusion, TR is a determinant of the R-L shunt in patients with ASD even in the absence of the reversal of pressure gradient between the left and right atrium.

Adolescent↗
PubMed1994

Postganglionic sympathetic nerve discharges can contain both central and pulse-related oscillations simultaneously in rabbits.

We examined whether modulation of sympathetic nerve discharges (SND) by changes in carotid sinus pressure (CSP) is influenced by the pattern of the rhythm of central sympathetic neurons and whether the rhythm of the sympathetic nerve derived from central sympathetic neurons and that from the inputs from baroreceptors can coexist in postganglionic renal SND. In alpha-chloralose-anesthetized rabbits with aortic denervation and vagotomy, firing of central sympathetic neurons was at first left spontaneous and then driven artificially at 3 Hz by peroneal nerve stimulation. Under these conditions, renal SND were recorded and compared while CSP was altered at low frequencies. When central sympathetic neurons were firing spontaneously and low frequency oscillation was applied to CSP, two kinds of oscillation were noted in SND; first oscillation at the same frequency as that of central sympathetic neurons, and second oscillation of CSP changes. Power spectra of SND also showed two peaks at these two oscillations. When central sympathetic neurons regularly discharged at 3 Hz by electrical stimulation and CSP was kept constant, the power spectra of SND had a discrete single peak at 3 Hz. When a regular oscillation was applied to CSP at 1 Hz, the amplitude of central sympathetic outflow at 3 Hz was modulated at 1 Hz without disturbance of the frequency of the central 3 Hz rhythm. In other words, two apparently different rhythms coexisted in SND. In the power spectra, two discrete peaks were noted at the frequency of CSP changes and at the central sympathetic oscillation. When SND were averaged by CSP-triggered summation during spontaneous or artificial 3 Hz central firing, it was revealed that the shape of these two averaged SND were completely same in spite of obviously different central firing patterns. Nadir of SND occurred about 400 ms after the peak of CSP during changes in CSP at several frequencies in these two conditions. Thus, these results indicated two points; (1) CSP changes modulate the amplitude of SND in the same manner irrespective of the frequency or pattern of discharge of central sympathetic neurons; (2) both of frequency components of SND induced by oscillatory changes in central sympathetic neurons and oscillatory inhibitory input from baroreceptors can coexist even if their frequencies were different.

Action Potentials↗
PubMed1994

Effect of L-arginine on acetylcholine-induced endothelium-dependent vasodilation differs between the coronary and forearm vasculatures in humans.

OBJECTIVES: The goal of this study was to determine whether the effect of L-arginine on endothelium-dependent vasodilation evoked with acetylcholine differs between the coronary and forearm vasculatures in humans. BACKGROUND: Administration of L-arginine, a substrate in the production of endothelium-derived nitric oxide, may stimulate the release of nitric oxide. METHODS: Seven patients with normal coronary angiograms and seven with mild coronary artery disease and hypertension underwent coronary arteriography and an intracoronary Doppler catheter technique, and the diameter of the large epicardial coronary artery and coronary blood flow were measured. Forearm blood flow was measured by use of a strain gauge plethysmograph. RESULTS: Before L-arginine administration, acetylcholine (1 to 30 micrograms/min) increased coronary blood flow with modest vasoconstriction of a large coronary artery. Acetylcholine (4 to 24 micrograms/min) also increased forearm blood flow. The acetylcholine-induced increases in coronary and forearm blood flow were significantly less in patients with coronary artery disease than in control patients. Intracoronary infusion of L-arginine at 50 mg/min did not alter responses of the large coronary artery diameter or coronary blood flow to acetylcholine in either group. In contrast, L-arginine at 10 mg/min significantly (p < 0.01) augmented the forearm blood flow response to acetylcholine (4 to 24 micrograms/min) to a similar extent in the two groups. CONCLUSIONS: The effect of L-arginine on acetylcholine-induced vasodilation differs between the coronary and forearm vasculatures in humans. It is suggested that impaired acetylcholine-induced coronary and forearm vasodilation in patients with coronary artery disease and hypertension may not be related to a limited availability of L-arginine.

Acetylcholine↗
PubMed1994

Effects of intracoronary infusion of atrial natriuretic peptide on pacing-induced myocardial ischemia in patients with effort angina pectoris.

BACKGROUND: Atrial natriuretic peptide (ANP) has been shown to dilate the coronary artery. The aim of this study was to determine whether, in patients with effort angina pectoris, intracoronary infusion of ANP attenuates pacing-induced myocardial ischemia either by dilating the stenotic lesion in a large coronary artery or by dilating collateral vessels. METHODS: We studied six patients who had total or subtotal occlusion in one coronary artery and well-developed, angiographically visible collateral vessels (group A) and five patients who had a significant stenosis in a large coronary artery with no visible collateral vessels (group B). Their heart rate was increased by atrial pacing both before and after intracoronary infusion of ANP (0.03 microgram/kg/min for 15 min) into the donor artery of collateral vessels in group A or into the stenotic artery in group B. RESULTS: Before ANP infusion, all patients of both groups developed an ischemic ST-segment depression (> or = 0.1 mV) and angina-like chest pain from pacing tachycardia. After ANP infusion, significant ST-segment depression was induced by rapid pacing in only one out of six patients of group A, whereas it was noted in all patients of group B (P < 0.01). After ANP infusion, chest pain developed in one out of six patients in group A, whereas it appeared in four out of five patients in group B (P < 0.05). ANP significantly dilated the angiographically normal segment of the epicardial coronary artery, but it did not significantly change the severity of the stenotic lesion in either group. ANP did not change the basal arterial pressure or heart rate, nor did it change their response to pacing tachycardia. CONCLUSION: Infusing ANP into the donor artery of collateral vessels, but not into the artery with culprit stenotic lesion, attenuated pacing-induced myocardial ischemia. Therefore, the beneficial effects of ANP in reducing pacing-induced myocardial ischemia may result from the increase in myocardial perfusion to the ischemic area caused by dilating the collateral vessels.

Aged↗