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Biomedical subjects

K Saegusa

Publications and source records attributed to K Saegusa.

At least 37 records · Page 2Linked to original sources
PubMed1989

[Comparison of SPECT images with four kinds of 99mTc collimators].

Performance of SPECT imaging systems which use a rotating gamma camera, are affected by characteristics of the detector-collimator assembly, the data acquisition method, and the filter used in image reconstruction. The purpose of this study is to examine image qualities of SPECT with different types of low energy collimators. The SPECT imaging system in this study is a rotating gamma camera ZLC-7500 (Siemens) and a data processing unit Scintipac-700 (Shimadzu). The four types of collimators compared are UHR (ultra high resolution), HR (high resolution), AP (general all purpose), and HS (high sensitivity), with 0.27, 0.66, 1.00, and 2.06 relative sensitivity, respectively. In the case of the same collimator, the spatial resolutions measured in the slice plane showed a slight difference in the FWHM values (mean values of UHR, HR, AP, and HS were 11.3 mm, 13.6 mm, 15.8 mm, and 20.4 mm, respectively.) between the center and the circumference of the field of view, in the radial direction, but a large difference in the tangential direction, with lower FWHM values (values of UHR, HR, AP, and HS were 8.4 mm, 8.7 mm, 9.3 mm, and 10.8 mm at 12 cm from the center, respectively.). In comparison of SPECT images with the four types of collimators, except for the HS collimator, image qualities of UHR, HR, and AP collimators showed only a slight difference. From the pont of view of sensitivity and spatial resolution of the collimator, it is expected that the AP collimator would be suitable for SPeCT imaging with 99mTc.

Models, Structural↗
PubMed1988

Cardiovascular effects of dibutyryl cyclic AMP in the intact dog heart and the isolated cross-perfused right atrium.

This study used an isolated right atrial preparation, cross-perfused with arterial blood from a support dog. We investigated the effects of dibutyryl cyclic AMP (DBcAMP) on heart rate and arterial blood pressure of the support dog and on the sinus rate and atrial contractile force of the isolated perfused atrium. DBcAMP was injected into the external jugular vein of the support dog or into the sinus node artery of the isolated atrium. DBcAMP to the support dog induced a small increase and/or decrease in arterial blood pressure at a dose of 3 or 10 mg/Kg i.v. It produced a decrease, with or without an increase in blood pressure, at a dose of 30 mg/Kg i.v., and a dose-dependent increase in heart rate in the support dog. In the isolated atrium, positive chronotropic and inotropic effects were observed. Direct injection of DBcAMP (3-30 mg) into the sinus node artery of the isolated atrium induced positive chronotropic and inotropic effects, after initial brief negative effects, in a dose-dependent manner. DBcAMP did not change norepinephrine-induced positive chronotropic and inotropic effects in the isolated atrium. These results demonstrate that DBcAMP induces a decrease in systemic arterial blood pressure with increases in sinus rate and atrial contractile force, and acts additively with the norepinephrine-induced positive cardiac effects in the dog heart.

Animals↗
PubMed1988

Chronotropic and inotropic effects of a new angiotensin converting enzyme inhibitor, MC-838 (altiopril calcium), on the dog heart.

The effects of calcium (-)-N-[(S)-3(N-cyclohexylcarbonyl-D-alanyl)-thio]-2-methylpropion] -L- prolinate (MC-838, altiopril calcium), an inhibitor of angiotensin converting enzyme, were investigated in 9 isolated atrial preparations and 7 intact anesthetized donor dogs. In 7 intact dogs, 1-10 mg/Kg of MC-838 caused a decrease in systemic blood pressure, but no significant influence on heart rate was observed. At the same time, in isolated atria perfused with donor's blood, significant increases in developed tension and slight increases in sinus rate were observed with 3 and 10 mg/Kg of MC-838. Intraarterial MC-838 at 10-300 micrograms did not induce significant cardiac effects and MC-838 at 1-3 mg caused an increase in developed tension and a slight increase in sinus rate. The positive inotropic and chronotropic effects were not blocked by adequate doses of propranolol, which significantly blocked norepinephrine-induced positive chronotropic and inotropic effects. It is concluded that a large amount of MC-838 has slight cardiotonic properties which are not mediated via a beta-adrenergic mechanism.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1988

Fade responses at neuroeffector junction to vagal stimulation in the isolated, blood-perfused dog atrium.

Effects of physostigmine and of beating rate on the negative chronotropic and inotropic responses to tonic intramural parasympathetic nerve stimulation at a frequency of 5 Hz for 2 min were investigated, using the isolated, blood-perfused dog atrium which was pretreated with propranolol. The responses to stimulation reached a maximum, and then "faded" back toward the control levels during stimulation. Before physostigmine, the fade of the inotropic response was consistently observed but the fade of the chronotropic response was minimal. Both the maximum effect and the fade of the chronotropic response were augmented dose-dependently by physostigmine in spontaneously beating atria. Physostigmine increased the maximum chronotropic response to infusion of acetylcholine (ACh) but did not potentiate the fade response. These results suggest that the potentiation of the fade of the chronotropic response to stimulation after physostigmine is due to decreases in the amount of ACh at the neuroeffector junction. The maximum negative inotropic responses were dose-dependently potentiated similarly by physostigmine in isolated spontaneously beating or paced atria. The fade of the inotropic response in spontaneously beating atria was decreased along with reduction of the rate by physostigmine, whereas the fades in paced atria at 2 and 3 Hz were not changed, showing that decreases in rate during stimulation influenced the reduction of the fade. Increases in contractile force induced by infusion of CaCl2 did not alter the maximum and fade responses to stimulation in 2 Hz paced atria. The blood flow into an isolated atrium was not changed detectably during stimulation. These results suggest that the fade of the inotropic response to parasympathetic nerve stimulation is related subsidiarily to acetylcholinesterase or washout of ACh at the neuroeffector junction in isolated perfused atria.

Acetylcholine↗
PubMed1987

Time dependent impairment of vagally mediated inhibition of noradrenaline release in the dog heart.

The effects of right vagal nerve stimulation on changes in heart rate, mean coronary sinus blood flow, and noradrenaline overflow rate induced by right cardiac sympathetic nerve stimulation were investigated in anaesthetised decentralised, open chest dogs, when autonomic nerve fibres were stimulated tonically at a frequency of 4 or 5 Hz for 2.5 min. Sympathetic nerve stimulation produced a mean(SEM) increase in each of the variables (50(7.0)% in heart rate, 48(6.3)% in coronary sinus blood flow, and 87.0(12.3) ng.min-1 in noradrenaline overflow rate into coronary sinus blood at 30 s), and the increments remained almost constant during continued stimulation. Vagal nerve stimulation induced a decrease of 34(3.4)% in heart rate and of 22(4.5)% in coronary sinus blood flow and a slight reduction (-9(3.2) ng.min-1) in noradrenaline overflow rate at 30 s. Only the decrease in heart rate faded slightly with time. Combined stimulation of the sympathetic and parasympathetic nerves induced a decrease of 19(5.0)% in heart rate and 4(7.5)% in coronary sinus blood flow and an increase of 34.3(12.0) ng.min-1 in noradrenaline overflow rate at 30 s. The decrease in heart rate and coronary sinus blood flow faded, and noradrenaline overflow rate increased significantly to 86.4(17.3) ng.min-1 at 120 s. The temporal changes in heart rate, coronary sinus blood flow, and noradrenaline overflow rate caused by combined nerve stimulation were readily inhibited by treatment with atropine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Cardiovascular responses to a newly developed cardiotonic agent, ZSY-39 [4-methyl-5-(4-pyridinyl)-thiazole-2-carboxyamide] in dog cross-circulated atrial and ventricular preparations.

The cardiovascular effects of ZSY-39 [4-methyl-5-(4-pyridinyl)-thiazole-2-carboxyamide] were investigated in isolated and blood-perfused atrial and ventricular muscles perfused with donor's arterial blood. When ZSY-39 was given i.v. to the intact donor dog, hypotension with a slight tachycardia was induced at a dose range of 30-1,000 micrograms/kg. At the same time, slight positive chronotropic and inotropic responses appeared in isolated, perfused atria at i.v. doses of 300 and 1,000 micrograms/kg ZSY-39, indicating a relatively dominant inotropic action. Direct injection of ZSY-39 into the cannulated sinus node artery of the isolated atrium produced positive chronotropic and inotropic responses in a dose-related manner (1 to 300 micrograms). ZSY-39 also induced a dose-dependent increase in developed tension in the isolated ventricle. The positive chronotropic and inotropic effects of ZSY-39 were not modified by an adequate dose of propranolol which completely blocked norepinephrine-induced positive chronotropic and inotropic responses. From these results, it is concluded that ZSY-39 has mild cardiotonic properties, showing relatively selective positive inotropic activity.

Animals↗
PubMed1987

Cardiovascular effects of a new phenoxyalkylamine derivative, 2-isopropyl-5-[3-(2-methoxyphenoxy)propylamino]-2-(3,4,5-trimethoxy phenyl) valeronitrile fumarate (HV-525), in cross-circulated dog atrial preparations.

A newly developed phenoxyalkylamine derivative, 2-isopropyl-5-[3-(2-methoxyphenoxy)propylamino]-2-(3,4, 5-trimethoxyphenyl)-valeronitrile fumarate (HV-525), was investigated in intact dogs and in isolated dog atria perfused with anesthetized donor dog's arterial blood. When 0.3 mg/kg of HV-525 was intravenously administered to the donor dog, a depressor effect without significant changes in heart rate was observed in donor dogs and a decrease in developed tension was observed in the isolated atrium. At 1 mg/kg, HV-525 caused a depressor response in donor dogs and decreases in developed tension and atrial rate in isolated atria. The decrease in systemic blood pressure seen following 1 mg/kg of HV-525 was between 15-40 mmHg. These effects continued for about 60 min. When HV-525 was administered into the cannulated sinus node artery of the isolated atrium, dose related negative inotropic and chronotropic actions were observed. Occasionally, HV-525 induced slight, brief positive chronotropic and inotropic effects followed by long-lasting negative effects. The threshold dose for inducing the negative chronotropic effect was approximately 3 micrograms while the negative inotropic one was approximately 1 microgram. A large dose of 100 micrograms of HV-525 caused a profound deceleration but not atrial arrest. The order of potencies for inducing a negative chronotropic effect in dog atria was verapamil greater than propranolol much greater than HV-525 greater than or equal to lidocaine greater than or equal to quinidine greater than phenytoin greater than disopyramide greater than procainamide, and that for inducing a negative inotropic effect was verapamil greater than or equal to propranolol greater than HV-525 greater than lidocaine greater than phenytoin greater than disopyramide greater than procainamide greater than or equal to quinidine. HV-525 did not induce a significant effect on sinoatrial conduction time. HV-525 at the doses studied, uniformly suppressed the frequency-force relationship, while verapamil, one of the phenoxyalkylamine derivatives, caused a marked depression of high frequency-induced contraction. Thus, it is concluded that HV-525 has mild depressant properties on the cardiovascular system and may have characteristics different from those of verapamil.

Animals↗
PubMed1987

Cardiac effects of piretanide and furosemide on intact anesthetized dogs and on isolated atria.

The effects of piretanide and furosemide on systemic arterial blood pressure and heart rate were examined in the anesthetized dog and the effects on atrial rate and contractile force were assessed in isolated atrial muscle perfused with heparinized arterial blood from a donor dog. When piretanide was administered intravenously to intact dogs, the depressor and bradycardic responses were produced dose-dependently. There were no significant simultaneous chronotropic or inotropic changes in the isolated atrium. On the other hand, furosemide (1-3 mg/kg) did not induce significant changes in either systemic blood pressure or heart rate in the intact dog. The atrial rate and developed tension were also not affected in the isolated atrium. A potent beta-adrenoceptor blocking agent, propranolol (1 mg/kg i.v.), consistently produced a significant depressor response and a profound negative chronotropic effect in the intact dogs; significant negative chronotropic and inotropic effects were also observed in the isolated atrium. When large doses of piretanide and furosemide were injected intraarterially into the sinus node artery of the isolated atrium, atropine-insensitive negative chronotropic and inotropic effects were induced dose-dependently. The potency of the negative chronotropic effect of piretanide was slightly greater than that of furosemide, but the negative inotropic effect of piretanide was slightly smaller than that of furosemide. These data indicate that piretanide has a depressor effect without significant cardiac influences. However, a high dose of piretanide has negative chronotropic and inotropic effects. These effects were not observed with the doses of furosemide (1-3 mg/kg) employed in this study.

Animals↗
PubMed1987

Effects of DJ-7141, a new alpha-2 agonist, 2-(2-chloro-6-fluorophenyl)-2,3,5,6-tetra-hydro-1H-imidazo[1,2-a] imidazole hydrochloride, on the isolated atrium, cross-perfused with blood from a support dog.

The effects of DJ-7141, a new alpha-2 agonist, on an isolated atrial preparation cross-perfused with arterial blood from a support dog were investigated. In the isolated atrium, a selective injection of DJ-7141 (1-100 micrograms) into the sinus node artery induced dose-dependent positive chronotropic and inotropic effects. The positive cardiac effects of DJ-7141 were not only inhibited by propranolol and by imipramine, but reversed to negative effects, whereas the positive cardiac effects of norepinephrine were blocked by propranolol and potentiated by imipramine. Tetrodotoxin (TTX) did not modify the cardiac responses to DJ-7141. After propranolol treatment, the negative chronotropic and inotropic responses to DJ-7141 were not influenced by atropine, which completely blocked acetylcholine-induced cardiac responses. When DJ-7141 was injected into the support dog at a dose of 10-300 micrograms/Kg i.v., it induced a brief increase in femoral arterial blood pressure and a long-lasting decrease in heart rate in the support dog and increases in atrial rate and contractile force in the isolated atrium. These results suggest that the new alpha-2 agonist, DJ-7141, induces indirect positive chronotropic and inotropic effects due to a tyramine-like action and direct negative cardiac effects in the isolated dog heart, and that the tyramine-like effect may be partially responsible for the increase in blood pressure seen with DJ-7141 in in situ dogs.

Adrenergic alpha-Agonists↗
PubMed1987

Pharmacologic basis of responses to midazolam in the isolated, cross-perfused, canine right atrium.

The effects of midazolam on atrial rate and contractile force in the isolated canine atrium perfused with donor blood were investigated. When midazolam in a dose range of 100-1000 micrograms was injected directly into the sinus node artery of the isolated atrium, biphasic (negative followed by positive) chronotropic and triphasic (positive, negative followed by positive) inotropic effects were induced. After propranolol or imipramine, the positive chronotropic and the secondary positive inotropic effects were significantly suppressed, but the initial positive inotropic effect was not affected. Tetrodotoxin, atropine, or R05-4864, a selective ligand for peripheral benzodiazepine binding sites, did not modify midazolam-induced effects. When midazolam in a dose of 0.1-1 mg/kg was administered intravenously to the donor dog, monophasic negative chronotropic and inotropic effects in the isolated atrium were observed but were not as prominent. We conclude that midazolam has direct cardiac inhibitory properties including catecholamine release due to a tyramine-like action.

Animals↗
PubMed1986

Effects of 4-aminopyridine on the fade response to vagal nerve stimulation in the isolated dog atrium.

Intramural parasympathetic nerve stimulation (5 Hz, 2 min) after propranolol treatment evoked negative chronotropic and inotropic responses in the isolated dog atrium. The cardiac responses were not maintained during stimulation; they reached maximum values and then faded back toward their control values ("fade" response). 4-Aminopyridine increased the maximum values of both responses, and it increased the fade of the chronotropic response but not that of the inotropic response. These results suggest that the fade response to parasympathetic nerve stimulation is modulated at the parasympathetic nerve terminals of the isolated dog atrium.

4-Aminopyridine↗
PubMed1986

Different effectiveness of glucagon on the pacemaker activity and contractility in intact dog hearts and in isolated perfused right atria.

In an isolated right atrial preparation, which was cross-perfused with heparinized arterial blood from a support dog, we investigated the effects of glucagon on heart rate and systemic arterial blood pressure of the support dog and on atrial rate and contractile force of the isolated perfused atrium when glucagon was injected into the external jugular vein of the support dog or into the sinus node artery of the isolated atrial preparation. Glucagon (0.3 to 3 micrograms/Kg i.v.) to the support dog dose-dependently induced a prominent increase in heart rate and a small increase in systemic arterial blood pressure. In the isolated, perfused atrium, marked positive chronotropic and slight, but significant, positive inotropic effects were evoked dose-dependently 1.5 min after intravenous injection of glucagon. These positive effects were not altered significantly by propranolol (1 mg/Kg i.v.). Direct injection of glucagon into the sinus node artery of isolated atria also induced marked positive chronotropic and small positive inotropic effects dose-dependently. CF/HR ratios, inotropic effect per chronotropic effect in isolated atria, of glucagon injected intravenously or intraarterially were less than 0.7 and they were much less than those of norepinephrine (more than 3.6). These results confirm that glucagon injected intravenously or regionally produces a prominent positive chronotropic effect and a small positive inotropic effect and suggest that glucagon may be less effective as a cardiotonic agent.

Animals↗
PubMed1986

Ouabain-induced negative frequency-force relationship in the isolated, blood-perfused dog atrium.

Effects of ouabain, CaCl2 and verapamil on the frequency-force relationship (FFR) were investigated in the isolated, blood-perfused dog atrial muscle preparation. When ouabain (3 and 10 micrograms) or CaCl2 (0.5, 1 and 2 mg/min) was given into the sinus node artery, the contractile force of the atrial muscle, driven at a constant pacing rate of 2 Hz, increased dose-dependently. Verapamil (1 and 3 micrograms) decreased the atrial contractile force dose-dependently. When the pacing rate was changed from 2 to 3.5 Hz, the atrial contractile force increased in parallel with the pacing rate (positive FFR). After treatment with ouabain and verapamil, the contractile force declined at higher frequencies (negative FFR). The verapamil-induced negative FFR was much steeper than the ouabain-induced relationship. An infusion of CaCl2 modified the FFR such that higher doses of CaCl2 elicited a negative FFR only at higher pacing rates. However, the CaCl2-induced FFR did not differ from the negative FFR induced by verapamil or ouabain. It was demonstrated that the cardiotonic agents ouabain and CaCl2, as well as verapamil induced negative FFR in the isolated dog heart.

Animals↗
PubMed1986

Inotropic and chronotropic activity of a new cardiotonic agent, DM 9278 (1,2,3,4,8,9,10,12-octahydro[2,1-b]pyrido[2,3-f]quinazolin-9-one ), on isolated dog atrial and ventricular muscles.

The cardiac effects of DM9278 were studied in isolated and blood-perfused atrial and ventricular preparations from mongrel dogs. In spontaneously beating isolated right atria, DM9278 caused positive chronotropic and inotropic responses in a dose-related manner (1-100 micrograms). DM9278 produced relatively larger positive inotropic than positive chronotropic effects as compared with effects of aminophylline or papaverine. DM9278 increased the developed tension in left ventricles electrically driven at 1.5-2.0 Hz. Positive inotropic and chronotropic responses to DM9278 in both atrial and ventricular preparations were suppressed slightly but not significantly by 1-3 micrograms of propranolol, which completely blocked the positive chronotropic and inotropic effects of norepinephrine (0.01-0.1 micrograms). From these results, it is concluded that DM9278 has direct cardiotonic properties in isolated dog heart tissues, showing relatively selective positive inotropic activity.

Animals↗
PubMed1986

Cardiovascular effects of budralazine in the dog.

Cardiovascular effects of budralazine were investigated in isolated and cross-circulated dog atrial preparations. When budralazine was injected into the jugular vein of the donor dog, a hypotension was produced with slight tachycardia in a dose-related manner. At the same time, slight positive chronotropic and biphasic inotropic effects were induced in the isolated atrium perfused with donor's arterial blood. When budralazine was injected into the cannulated sinus node artery of the isolated atrial preparation, it produced only slight negative chronotropic and inotropic responses, occasionally followed by positive responses. Vehicle injections induced monophasic negative chronotropic and inotropic effects. It is concluded that budralazine has a potent vasodilator action, a reflex-induced sympathomimetic action, but no direct cardiac stimulating properties. Moreover, a direct catecholamine releasing action of budralazine does not appear to be prominent.

Animals↗
PubMed1986

Cardiovascular effects of ZSY-27 [5-methyl-6-(4-pyridinyl)-2H-1,4-thiazine-3(4H)-one X hydrochloride] in the dog cross-circulated atrial preparation.

A new cardiotonic compound, 5-methyl-6-(4-pyridinyl)-2H-1,4-thiazine-3(4H)-one X hydrochloride (ZSY-27), was investigated in cross-circulated dog atrial muscle preparations. When ZSY-27 was intravenously administered to the donor dog, a dose-dependent depressor effect with slight sinus tachycardia was induced in the donor dog. At the same time, a significant dose-dependent increase in developed tension was usually observed in an isolated atrium perfused with donor's arterial blood, but there were no significant changes in sinus cycle length and sinoatrial conduction time. The ZSY-27-induced positive inotropic effect was not significantly influenced by treatment with propranolol in doses which completely inhibited norepinephrine-induced positive chronotropic and inotropic effects. When ZSY-27 was injected into the cannulated sinus node artery of the isolated atrium, dose dependent positive chronotropic and inotropic effects were induced. The dominant increases in developed tension by ZSY-27 were similar to effects of other phosphodiesterase inhibitors, such as papaverine and aminophylline. From these results, it is concluded that ZSY-27 has non-adrenergic, cardiotonic properties with a depressor effect.

Aminophylline↗
PubMed1986

[Performance of gamma camera collimators used for single photon emission computed tomography imaging with 123I-isopropyl iodoamphetamine].

123I Produced by 124Te(p, 2n)123I reaction is contaminated with 124I (less than 5%) and 126I (less than 0.3%). High energy photons from these mixed radioiodine compromise seriously image quality due to scattered photons and to septal penetration in the collimator. Four collimators of LEAP (for low energy all purpose), LEHR (for low energy high resolution), MESI (for medium energy made by Siemens) and MENU (for medium energy made by nuclear technology) mounted on a rotating gamma camera (Siemens, ZLC-7500), were examined in order to select a suitable collimator for 123I SPECT (single photon emission computed tomography) imaging. Sensitivities were measured with a plane source (5 X 5 X 0.5 cm) at the collimator face and distances from 2 to 30 cm in air. And, spatial resolutions in FWHM (full width at half maximum) and FWTM (full width at tenth maximum) were determined from line spread functions with planar and SPECT imaging. From the comparison of collimator performances with 99mTc and 123I, both collimators for low energy were not useful for 123I imaging. In other two collimators for medium energy, however, apparently the effect of septal penetration by the higher energy photons were also recognized, MENU with high geometrical resolution was more suitable for 123I SPECT imaging compared with MESI. And, it is important to perform the SPECT imaging with radius as short as possible.

Amphetamines↗