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Biomedical subjects

A Kitabatake

Publications and source records attributed to A Kitabatake.

At least 19 recordsLinked to original sources

Predominant beta-adrenoceptor blocking effect of xamoterol averaged over the day in patients with mild to moderate heart failure: insight into the mechanism of its long-term clinical efficacy.

Xamoterol acts as a beta 1-adrenoceptor agonist at low sympathetic activity and as an antagonist at high activity. Although its long-term efficacy has been proven in patients with mild to moderate heart failure, it remains unclear which effect, agonism or antagonism, accounts for its long-term activity. To clarify the effect of xamoterol on cardiac sympathetic activity in daily life, 24-h R-R interval histograms were obtained during administration of xamoterol 100 mg b.d. for 1 week to 10 patients with mild to moderate heart failure. Eight normal subjects were also studied as controls. To examine the relation between the effect of xamoterol and sympathetic activity, plasma noradrenaline (NA) levels were measured under 5 graded conditions simulating daily living. Xamoterol administration significantly decreased the standard deviation of the R-R interval, both in patients with heart failure and in normal subjects. The mean R-R interval, however, was increased in patients with heart failure, relative to normal subjects. In both groups, the R-R interval histograms had two peaks, i.e. a short daytime peak and a long night-time peak. Xamoterol decreased the median of the night-time peak without changing the daytime peak in normal subjects. In contrast, it increased the median of the daytime peak without producing a significant change in the night-time peak in patients with heart failure. Levels of plasma NA were significantly higher in patients than in normal subjects under all conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists

Polyphosphoinositide metabolism in hypertrophic rat heart.

The accumulations of inositol-1,4,5-trisphosphate (IP3) and inositol-1,3,4,5-tetrakisphosphate (IP4) after hormonal stimulation may have a physiological role, possibly by alteration of Ca2+ levels in cardiac tissue. But the accumulation of inositol polyphosphate in a pathophysiological condition has not been studied. We investigated phosphatidylinositol-4,5-bisphosphate (PIP2) metabolism in hypertrophic cardiac myocytes, and clarified that the accumulations of IP3, IP4 and diacylglyceride after stimulation with norepinephrine were significantly enhanced in isolated myocytes from spontaneously hypertensive rat heart. Phospholipase C activity increased with age in SHRSP heart cells. These data suggest that PI turnover pathways, which can be mediated by both phosphatidylinositol-4,5-bisphosphate and diacylglyceride, may play an important role in development of hypertrophy in the hearts of rats with spontaneous hypertension.

Animals

Role of atrial contraction and synchrony of ventricular contraction in the optimisation of ventriculoarterial coupling in humans.

OBJECTIVE: To examine the effects of pacing modes on the interaction between the left ventricle and arterial system in humans. DESIGN: The slope of the end systolic pressure-volume relation (end systolic elastance), effective arterial elastance, the ratio of effective arterial elastance to end systolic elastance, and mechanical energy efficiency were compared under different pacing modes (atrial, atrioventricular, and ventricular). PATIENTS: Nine male patients with sick sinus syndrome who had cardiac catheterisation for diagnosis and to see whether they needed a pacemaker. INTERVENTIONS: A conductance catheter with tip-manometer was inserted into the left ventricle to obtain pressure-volume loops, and two pacing catheters were inserted into the right atrium and into the right ventricle respectively. RESULTS: End systolic elastance was lower in atrioventricular pacing than in atrial pacing, but effective arterial elastance was not significantly different. End systolic elastance was lower in ventricular pacing than in atrioventricular pacing, and effective arterial elastance was higher in ventricular pacing than in atrioventricular pacing. Consequently the ratio of effective arterial elastance to end systolic elastance was lowest in atrial pacing and highest in ventricular pacing, and mechanical energy efficiency was highest in atrial pacing and lowest in ventricular pacing. CONCLUSIONS: Atrial contraction and synchronous ventricular contraction independently optimise ventriculoarterial coupling in terms of a transfer of energy. Thus atrial pacing gives the best ventriculo-arterial coupling among these pacing modes.

Adult

Endogenous adenosine blunts beta-adrenoceptor-mediated inotropic response in hypoperfused canine myocardium.

BACKGROUND: Adenosine attenuates beta-adrenoceptor-mediated inotropic responses through GTP-binding protein in vitro. The goal of the present study was to test the hypothesis that endogenous adenosine released from the ischemic myocardium blunts the inotropic response to beta-adrenergic stimulation. METHODS AND RESULTS: In 45 open-chest dogs, the left anterior descending coronary artery was perfused through an extracorporeal bypass tube from the carotid artery. Coronary perfusion pressure was reduced so that coronary blood flow was decreased to 60% of the basal level by partial occlusion of the bypass tube, and the reduced coronary perfusion pressure was kept constant thereafter. Inotropic responses to isoproterenol were assessed by fractional shortening of the myocardium in the perfused area. After the onset of hypoperfusion, lactate extraction ratio (18.8 +/- 1.2%) and fractional shortening (20.7 +/- 1.1%) were significantly decreased to -8.4 +/- 8.0% and 5.9 +/- 1.5%, respectively, and coronary arteriovenous differences of adenosine were increased from 4.6 +/- 3.6 to 89.4 +/- 10.5 pmol/ml. In the untreated condition, an intravenous infusion of isoproterenol (150 ng/kg/min) augmented fractional shortening from 5.9 +/- 1.5% to 13.6 +/- 0.8%. When adenosine release was attenuated by administration of prazosin (4 micrograms/kg/min i.c.) during hypoperfusion, the response of fractional shortening to isoproterenol (from 5.3 +/- 1.2% to 20.5 +/- 1.4%) was much greater (p less than 0.05) than that in the untreated control condition. Exogenous administration of adenosine significantly attenuated the inotropic response to isoproterenol in the prazosin-treated hearts. In contrast, an adenosine receptor antagonist, 8-phenyltheophylline, also enhanced the inotropic response to isoproterenol. The attenuation of beta-adrenoceptor-mediated inotropic response by adenosine could not be attributed to the inhibition of norepinephrine release from the sympathetic nerve endings, because identical results were observed in the chemically denervated hearts. CONCLUSIONS: Endogenous adenosine released from the ischemic myocardium attenuates beta-adrenoceptor-mediated inotropic response in the ischemic heart.

Adenosine

Assessment of valvular regurgitation using cine magnetic resonance imaging coupled with phase compensation technique: comparison with Doppler color flow mapping.

To elucidate whether or not a newly developed technique in cinematic-displayed (cine) magnetic resonance imaging (MRI) can improve the semiquantitative evaluation of valvular regurgitant flow, 20 patients with valvular lesions were studied. Three pulse sequences of cine MRI, ie, standard, short echo time (TE), and rephasing scans, were compared with reference obtained by Doppler color flow mapping. Short TE technique and rephasing scan technique improved image quality remarkably as compared with standard technique. Each of the three cine MRI techniques showed good correlation with the Doppler method (p < 0.001). However, short TE and rephasing scan techniques gave a faithful estimation of the extent as compared with the Doppler method, whereas standard technique overestimated the regurgitation. Thus, cine magnetic resonance imaging with phase compensation technique can be utilized for the semiquantitative assessment of valvular regurgitation in a manner similar to that of Doppler color flow mapping.

Aged

Doppler assessment of left ventricular diastolic filling pattern during the convalescent stage of acute myocardial infarction. Effects of infarct size and coronary thrombolysis.

Pulsed Doppler echocardiography was used to study left ventricular diastolic filling pattern (LVDFP) over the convalescent stage of acute myocardial infarction (AMI) in 25 patients. Twelve normal subjects served as a control group. The patients were divided on the basis of enzymatically estimated infarct size into 2 groups: 7 as the large AMI group, and the other 18 as the small AMI group. Peak early diastolic filling velocity (E) and the ratio of E to peak filling velocity at atrial contraction (E/A ratio) were determined from the Doppler transmitral flow velocity recordings at 1 and 4 weeks after the onset of AMI. At 1 week E and E/A ratio were significantly lower in the small AMI group compared to the control and the large AMI groups, however, there was no significant difference in E and E/A ratio between the control and the large AMI groups. E/A increased with cumulative CK release among the patients (r = 0.54, p < 0.01). In the following 3 weeks E and E/A ratio decreased only in the large AMI group, and E and E/A ratio at 4 weeks weakly correlated with pulmonary capillary wedge pressure (r = 0.63, p < 0.01 and r = 0.65, p < 0.01) and ejection fraction (r = 0.50, p < 0.05 and r = 0.62, p < 0.01) among the patients. There was no significant difference in E or E/A ratio between patients with and without coronary thrombolysis. Thus, LVDFP in the early convalescent stage of AMI was characterized by low E and E/A ratio in patients with small AMI, however, a "pseudonormalized" pattern was observed in patients with large AMI. The effect of the infarct size on LVDFP diminished in the late convalescent stage of AMI. LVDFP in patients with AMI appears to be influenced by the infarct size and by the time of study. The effect of coronary thrombolysis on LVDFP was not evident throughout the convalescent stage of AMI in this study.

Convalescence

The role of calcium activated neutral protease on myocardial cell injury in hypoxia.

The aim of this study was to investigate the correlation between hypoxic myocardial cell injury and intracellular protease activity. Cardiac myocytes were isolated from neonatal rat hearts and cultured in Eagle's modified minimum essential medium. Myocytes were incubated in hypoxic conditions for 6 hours. The cell death rate during hypoxia rose to 80% after 6 hours. Extracellular protease activity was elevated to 4 units during hypoxia, much higher than the 0.7 units in aerobic states at 6 hours. This extracellular protease activity in hypoxic conditions was markedly inhibited by leupeptin and EDTA, and weakly inhibited by the cysteine protease inhibitor, NCO-700, but phenylmethyl sulfonyl fluoride did not inhibit the protease activity. To identify the protease activated during hypoxia, calpain-specific inhibitors were added to the incubation mixture. Calpain inhibitor 1 and calpastatin, an endogenous selective calpain inhibitor, markedly inhibited extracellular protease activity during hypoxia. NCO-700 also inhibited intracellular protease activity. NCO-700 reduced hypoxic cell death to 30% after 6 hours of hypoxygenation. These observations indicate that calpain is activated during hypoxia and leads to irreversible cell membrane degradation after 6 hours of hypoxygenation.

Animals

A central nervous system action of nitric oxide in blood pressure regulation.

We had reported that the systemic administration of N omega-methyl-L-arginine (L-NMA), a specific inhibitor of nitric oxide (NO) synthesis from L-arginine (ARG), raises arterial blood pressure (BP) while paradoxically enhancing central sympathetic outflow. Cervical spinal cord transection abolishes the increase in sympathetic outflow and attenuates the pressor effect of L-NMA. Thus, in addition to lowering BP by direct vasorelaxation, NO may also act in the central nervous system to reduce vascular sympathetic tone. To test this hypothesis we have injected L-NMA directly into the central nervous system in anesthetized rats. Intracisternally (i.c.), L-NMA elicited a small pressor response accompanied by a marked increase in sympathetic renal nerve activity (RNA). In contrast, the inactive stereoisomer N omega-methyl-D-arginine had neither pressor nor neural effects. The increases in RNA and BP elicited by i.c. L-NMA were abolished by spinal cord transection at C1 to C2 and by the i.v. administration of ARG. When administered i.c., ARG also abolished the increase in RNA elicited by i.v. L-NMA and significantly attenuated the pressor response. Thus, our findings indicate that L-NMA acts centrally by an ARG-reversible mechanism in the anesthetized rat to stimulate sympathetic nerve activity. Inasmuch as centrally synthesized NO has been postulated to play a second messenger and/or neurotransmitter role, our findings suggest that one such function would be the central regulation of sympathetic outflow and hence, BP.

Animals

[Evaluation of left ventricular relaxation by mitral regurgitant curve].

To examine whether left ventricular (LV) isovolumic relaxation can be assessed noninvasively using a continuous-wave Doppler technique, we compared Doppler-determined parameters derived from mitral regurgitation (MR) velocity curve with micromanometer-derived indices of LV relaxation, peak negative dP/dt and tau, in 9 patients with MR (5 with dilated cardiomyopathy, 2 with old myocardial infarction and 2 with rheumatic MR). The rate of LV pressure decay (delta P/delta t) at aortic valve closure was calculated from the recordings of MR jet velocities based on the simplified Bernoulli equation. The time constant of LV pressure decay (tD) was determined as the time from the aortic valve closure to the point where the velocity declined by (1/e)1/2. Doppler-determined delta P/delta t correlated well with hemodynamic peak negative dP/dt (r = 0.97, p < 0.001), and tD with hemodynamic tau (r = 0.89, p < 0.005). Thus, we concluded that left ventricular isovolumic relaxation can be noninvasively assessed with a continuous-wave Doppler technique in the presence of mitral regurgitation.

Blood Flow Velocity

A new modulation method with range resolution for ultrasonic Doppler flow sensing.

This paper proposes a new pair of sequences whose cross-correlation values are zero except for the peak value and presents a new modulation method for an ultrasonic Doppler flowmeter with high sensitivity utilizing these sequences. In this method, transmitted and received waves are modulated and demodulated, respectively, by the specified new sequences. Since ulfavourable reflected waves can be almost completely eliminated by this proposed modulation method, a high signal-to-noise ratio is easily achieved. Elementary experimental results are also given.

Doppler Effect

Diastolic stress-strain relation of nonexcised blood-perfused canine papillary muscle.

We studied diastolic stiffness of 10 coronary-perfused twitching papillary muscles of the canine right ventricle. The muscle beat at a regular sinus rhythm of 122 +/- 20 (SD) beats/min at 37 degrees C. They were stretched slowly at a constant rate. Diastolic force increased exponentially with the stretch. Calculating Lagrangian stress (sigma) and strain (epsilon) from diastolic force and length, we found a linear relationship between ln sigma and epsilon within the physiological range of strain (0.025 less than epsilon less than 0.4). This indicates that the diastolic stress-strain relationship of the canine papillary muscle can be approximated by a single exponential curve: sigma = a.exp(b.epsilon). The mean +/- SD of the stiffness constant b was 18.0 +/- 3.2 (dimensionless). Our b values are comparable to those of dogs and human subjects, either indirectly assessed from the ventricular pressure-volume relationship or directly obtained in excised quiescent muscle specimens. Different coronary perfusion pressures (75-125 mmHg) in 10 muscles showed a statistically significant positive correlation to b values.

Animals