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Biomedical subjects

H Shimamoto

Publications and source records attributed to H Shimamoto.

At least 37 records · Page 2Linked to original sources

Amplification of 5-hydroxytryptamine-induced contractile responses via 5-hydroxytryptamine receptors and alpha-adrenoceptors in dog mesenteric artery and vein.

The interactions between 5-hydroxytryptamine (5-HT) and both serotonergic and alpha adrenoceptors were investigated by using isolated dog mesenteric vascular rings mounted in tissue baths for the measurement of isometric contraction. In the mesenteric artery, 5-HT elicited concentration-dependent contractions, producing 46.5% of the KCl maximal response. At low concentrations, the 5-HT-induced contraction was effectively inhibited by 10(-6) M methysergide and by 10(-6) M ketanserin, but was prazosin-resistant. At high 5-HT concentrations, the contractile response was effectively antagonized by 10(-7) M prazosin. The presence in the medium of 20 mM KCl, which increased resting tension less than 10% of the KCl maximal response, markedly enhanced the responses to 5-HT primarily at concentrations lower than 10(-5) M. These amplified responses were methysergide-sensitive, but prazosin- and ketanserin-resistant. In the mesenteric vein, exposure to 5-HT caused an extremely small contraction, producing 5.2 +/- 4.3% of the KCl maximal response. In the presence of 20 mM KCl, which had small contractile effects, 5-HT produced a biphasic concentration-response curve. Methysergide (10(-6) M) and 10(-6) M ketanserin effectively inhibited the responses to low concentrations of 5-HT, and only 10(-7) M rauwolscine effectively blocked the responses to high concentrations of 5-HT. In the dog mesenteric artery, our data suggest that addition of threshold concentrations of KCl enhanced the contractile response to 5-HT through amplification of 5-HT1-like receptor-mediated responses. In the dog mesenteric vein, KCl enhanced 5-HT responses via amplification of both 5-HT2 receptor- and alpha-2 adrenoceptor-mediated responses.

Animals↗

Differential effects of putative protein kinase C inhibitors on contraction of rat aortic smooth muscle.

We investigated effects of three kinds of putative protein kinase C (PKC) inhibitors, calphostin C, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7), and stauro-sporine, on aortic muscle contractions induced by KCl, phenylephrine, 12-O-tetradecanoylphorbol-13-acetate (TPA), and phorbol 12, 13-dibutyrate (PDBu). Calphostin C noncompetitively inhibited TPA-induced contractions in a concentration-dependent manner. At 10(-6) M, calphostin C completely abolished responses to TPA and also effectively inhibited PDBu-induced contractions. Such a concentration of calphostin C had no effect on KCl-induced contractions but decreased the maximal tension of phenylephrine-induced response curve by 35.3 +/- 6.6% H-7 (10(-5) M had little effect on TPA-induced contraction but significantly inhibited contractile responses to phenylephrine and KCl. Staurosporine (10(-8) M, 3 x 10(-8) M) inhibited contractile responses to KCl, phenylephrine, and TPA. We suggest that staurosporine and H-7, which are known to act on the catalytic domain of PKC carrying high degree of sequence homology with other protein kinases, are relatively nonselective for PKC. On the other hand, calphostin C acting on the regulatory domain of PKC, which is distinct from other protein kinases, may serve as a relatively more selective PKC inhibitor.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

A case report of substernal goiter.

A case of substernal goiter is reported. A 78-year-old female was admitted to our hospital with no symptoms. Chest roentgenography on admission showed that a mass of 3 by 5 cm in size with calcification located in the substernal region. Computed tomography of the chest and aortography revealed that the mass was attached to the trachea, but the connection to the great vessels was not clear. Pathological findings of the incisional biopsy specimen showed thyroid tissue with no evidence of malignancy. Our clinical diagnosis was substernal goiter. Surgery was not carried out in this case, based on the literature. Surgery is indicated in case of malignancy or in cases with severe illness such as respiratory disorder and superior vena cava syndrome.

Aged↗

Rauwolscine induces contraction in the dog mesenteric artery precontracted with KCl and endothelin-1: mediation via 5-hydroxytryptamine1-like receptors.

Rauwolscine, a selective alpha-2 adrenoceptor antagonist, elicited a sustained contraction in the dog mesenteric artery precontracted with 20 mM KCl or 10(-9) M endothelin-1. Cumulative concentration-response curves to rauwolscine were not shifted by spiperone, propranolol, pindolol, mianserin, ketanserin, prazosin or phenoxybenzamine at the concentration of 10(-6) M. The pA2 values against rauwolscine were 8.34 +/- 0.32 for methysergide, 8.52 +/- 0.22 for methiothepin and 5.84 +/- 0.27 for phentolamine, which were in good agreement with the pA2 values for those antagonists against 5-hydroxytryptamine (5-HT) in the dog mesenteric artery precontracted with 20 mM KCl. Contractile responses to 5-HT after pretreatment with 20 mM KCl were antagonized in an apparently competitive manner by 10(-5) M rauwolscine. In the absence of precontraction, rauwolscine also shifted 5-HT-induced contractions in a parallel manner. These data suggest that rauwolscine is a partial agonist with a lower intrinsic activity than 5-HT and acts at the same 5-HT1-like receptors as 5-HT, most probably 5-HT1D receptors, in the dog mesenteric artery precontracted with KCl.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Pharmacological assessment of Ca2+ dependence of endothelin-1-induced response in rat aorta.

In rat aorta, endothelin-1 (ET-1) induced a slowly developing and sustained contraction in Ca(2+)-containing normal Krebs, nominally Ca(2+)-free Krebs, and Ca(2+)-free Krebs containing EGTA with a decreasing level of contraction. When ET-1-precontracted tissues were washed with Ca(2+)-free Krebs +50 microM EGTA, the tissues spontaneously and slowly relaxed. Readministration of Ca2+ during the early spontaneous relaxation phase caused a rapidly developing tonic contraction. When added during the late spontaneous relaxation phase, Ca2+ evoked slowly developing or, sometimes, biphasic contractions. In the presence of sarcoplasmic reticulum Ca(2+)-pump inhibitor, cyclopiazonic acid, the above biphasic contraction brought about by readministration of Ca2+ converted to a rapidly developing monophasic response. Thus, the first component of the biphasic contraction may be due to refilling of ET-1-sensitive Ca2+ store via the internal membrane Ca(2+)-pump. Furthermore, the ability of the phenylephrine-sensitive pool of internal Ca2+ to refill in the presence of 10(-8) M ET-1 suggests that the phenylephrine-sensitive pool differs from ET-1-sensitive pool and cannot be depleted by ET-1.

Animals↗

Does juxtamesenteric placement of intra-aortic balloon interrupt superior mesenteric flow?

To assess influences of intra-aortic balloon pumping (IABP) on superior mesenteric flow, 15 postoperative patients were examined, in whom distal aspects of balloons were distal to the superior mesenteric artery. Superior mesenteric flow velocity-time integral in systole (IntS), that in diastole (IntD), and the sum of IntS and IntD (IntS+IntD) were determined on and off IABP (IABP ON-OFF test). The same parameters were obtained with balloon inflating on every other beat (IABP 1:2 test). The cardiac cycle with balloon inflation during diastole was defined as "1:2 ON," and the cardiac cycle without balloon inflation during diastole was defined as "1:2 OFF." (1) IABP ON-OFF test. IABP increased IntS (p less than 0.01), IntD (p less than 0.01), IntS+IntD (p less than 0.01), and cardiac output (p less than 0.05). The increments in IntS, IntD and IntS+IntD on IABP are attributed largely to an increased in cardiac output. (2) IABP 1:2 test. IntS during 1:2 OFF was greater than IntS during 1:2 ON (p less than 0.01), whereas IntD during 1:2 OFF was smaller than IntD during 1:2 ON (p less than 0.01). There was no significant difference in IntS+IntD between 1:2 ON and 1:2 OFF. These data suggest that juxtamesenteric balloon placement did not interrupt the arterial inflow of a superior mesenteric artery.

Blood Flow Velocity↗

Doppler echocardiographic measurement of cardiac output in man using mitral annulus method.

The mitral inflow method of measuring cardiac output with pulsed Doppler two-dimensional echocardiography was developed and validated against the thermodilution technique in 42 patients. A mitral inflow method combined the velocity of left ventricular inflow at the mitral annulus (apical long-axis view) with the cross-sectional area of the annulus calculated from its diameter (parasternal long-axis view). A good correlation was observed between thermodilution and Doppler measurements of cardiac output (r = 0.93). The ratio of Doppler measurements to thermodilution measurements will be between 0.76 and 1.15 for about 95% of cases. There was a good correlation between percentage change in thermal cardiac output and those in Doppler cardiac output (r = 0.95); the limits of agreement were -11.5% to 10.5%, suggesting that this method can be most useful for assessing relative changes in cardiac output.

Blood Flow Velocity↗

Effects of intraaortic balloon pumping on mitral flow dynamics in patients with coronary artery bypass operations.

We evaluated the improvement in left ventricular function in 26 patients after coronary artery bypass grafting who were treated with intraaortic balloon pumping (IABP). Mitral flow velocity-time integral in the rapid filling phase (IntR) and that in the atrial contraction phase (IntA), the sum of IntR and IntA (IntR+IntA), and the ratio of IntA to IntR (IntA/IntR) were calculated with patients on and off balloon pumping (IABP ON-OFF test). IABP increased IntR and IntR+IntA, decreased IntA/IntR, and did not change IntA, suggesting that a decreased afterload or augmented coronary perfusion improves left ventricular relaxation. When the balloon inflated on every other beat (IABP 1:2 test), IntR and IntR+IntA increased without balloon assist, IntA/IntR decreased off IABP, and IntA did not change. The afterload reduction or augmented coronary perfusion on the previous beat with IABP might help ventricular filling on the next beat without balloon assist. A drastic decrease in IntR after IABP stopped indicated the need to continue IABP. Since the change in IntR during IABP ON-OFF test was significantly correlated with that in IntR during IABP 1:2 test, the change in IntR during IABP 1:2 test could help to predict the optimal time of weaning.

Aged↗

Participation of protein kinase C in endothelin-1-induced contraction in rat aorta: studies with a new tool, calphostin C.

1. Calphostin C at 10(-6) M was shown to be selective and highly effective in inhibiting contractile responses of rat aortae to 12-o-tetradecanoylphorbol-13-acetate, while it had no effect on contractile responses to elevated KCl. 2. In the rat aorta, endothelin-1 (ET-1) developed a sustained tonic contraction dose-dependently in both normal Ca(2+)-containing Krebs and Ca(2+)-free Krebs containing 1 mM EGTA. Calphostin C (10(-6) M), a selective protein kinase C inhibitor, antagonized the maximal tensions for cumulative addition of 10(-8) M ET-1 by 13.2% in Ca(2+)-containing medium and 25.8% in Ca(2+)-free Krebs containing 1 mM EGTA. 3. In both Ca(2+)-containing medium and Ca(2+)-free Krebs containing 1 mM EGTA, precontraction with 10(-8) M ET-1 had no effects on the contractile response to subsequently added 10(-6) M 12-o-tetradecanoylphorbol-13-acetate (TPA), an activator of protein kinase C. 4. In Ca(2+)-free Krebs containing 1 mM EGTA, precontraction with 10(-6) M TPA potentiated the contractile response to subsequently added 10(-8) M ET-1, whereas this potentiation was abolished by pretreatment with 10(-6) M calphostin C. The mechanism of the TPA-induced potentiating effect remains to be determined. 5. These results suggest that the participation of protein kinase C in the 10(-8) M ET-1-induced contraction may be 13.2% and 25.8% in the presence and absence of extracellular Ca2+, respectively, and that mechanisms other than protein kinase C may be predominantly responsible for ET-1-induced tonic contraction.

Animals↗

Transoesophageal Doppler echocardiographic measurement of cardiac output by the mitral annulus method.

OBJECTIVE: To compare cardiac output measured by the transoesophageal Doppler and thermodilution techniques. DESIGN: Prospective direct comparison of paired measurements by both techniques in each patient. SETTING: Intensive care unit in a cardiovascular centre. PATIENTS: 65 patients after open heart surgery (mean (SD) age 53 (12) years). INTERVENTIONS: Cardiac output was measured simultaneously by the transoesophageal Doppler and thermodilution techniques. Cardiac output was measured again after a mechanical intervention or volume loading. RESULTS: The limits of agreement were -2.53 to +0.83 1.min-1 for cardiac output measured by the Doppler and thermodilution techniques. This suggests that the Doppler method alone would not be suitable for clinical use. The second measurement of cardiac output by thermodilution was compared with cardiac output estimated from the first and second Doppler measurements and the first thermodilution measurement. The limits of agreement (-0.55 to +0.51 1.min-1) were good enough for clinical use. CONCLUSIONS: After cardiac output had been measured simultaneously by both the Doppler and thermodilution techniques, subsequent transoesophageal Doppler alone gave a clinically useful measurement of cardiac output.

Adult↗

Plasma norepinephrine is a major determinant of hemodynamic alterations with sodium loading.

OBJECTIVE: To assess hemodynamic responses to 3 weeks of sodium loading and to evaluate factors which contribute to hemodynamic alterations. DESIGN: Analysis of patients' central hemodynamic and laboratory variables before and after sodium loading. SETTING: A referral centre. PATIENTS: Thirty-one elderly hypertensives. INTERVENTIONS: Doppler flowmetry and laboratory examinations were performed during different sodium intake; 120 mmol/day for 8 weeks and 344 mmol/day for 3 weeks. RESULTS: Patients were divided into three groups; those in whom sodium loading increased total peripheral resistance (SST); those in whom salt repletion increased cardiac index (SCC); a non-salt-sensitive group (NSS). The overwhelming reaction to salt loading is that, with time, the NSS and SSC groups became part of the SST group. When the SSC patients became SST with sodium loading, serum sodium and plasma arginine vasopressin decreased and haematocrit increased, suggesting that the excretion of sodium and water accompanied with a decrease in circulating plasma volume may be responsible for the hemodynamic alteration from SSC to SST. In those who remained in the SSC group throughout the 3 weeks of salt repletion, plasma norepinephrine decreased on all of days 7, 14 and 21 of the high-sodium diet compared with the regular-sodium regimen, whilst in patients in the SST group on day 21 of the high-sodium diet plasma norepinephrine remained unchanged throughout the 3 weeks of salt loading. CONCLUSIONS: We confirmed a changing pattern of initially high cardiac index giving way to a persistently elevated total peripheral resistance with sodium loading. Plasma norepinephrine proved to be the best predictor of which subjects were or became SST.

Aged↗

[Surgical decisions for active infective endocarditis in patients with acute neurological complications].

The surgical management of 7 patients with active infective endocarditis and recent (within 16 days) neurological injury was presented. All patients had preoperative computed tomographic scans which revealed no evidence of intracranial hemorrhage and underwent successful corrective cardiac surgery. In the early postoperative period, 4 patients died of cerebral hemorrhage, subarachnoid hemorrhage, or progression of cerebral edema. Two of the 3 surviving patients showed no aggravation of cerebral infarcts postoperatively. In the remaining surviving patient, intracerebral mycotic aneurysms were resolved spontaneously after postoperative antibiotic therapy, although new cerebral hemorrhage, a complication of emboli, occurred after open heart surgery. The results of this study indicated that 1) cerebrovascular complications were the causes of the 4 deaths in this series, and 2) although heparinization during open heart surgery may result in intracerebral hemorrhage from mycotic aneurysm or infarction, early surgical intervention after recent cardiogenic embolic strokes may save patients with minor cerebral infarcts.

Adolescent↗

Amplification of alpha adrenergic vasoconstriction in canine isolated mesenteric artery and vein.

The interactions between UK-14304 and other vasoconstrictor agents were investigated using isolated canine mesenteric vascular rings mounted in tissue baths for the measurement of isometric contraction. In the mesenteric artery, exposure to UK-14304 caused a small contraction, producing 8% of the KCl maximal response. In the presence of either 20 mM KCl or 10(-9) M endothelin-1, which had small contractile effects, UK-14304 produced a biphasic concentration-response curve; 10(-7) M rauwolscine inhibited the responses to low concentrations of UK-14304 and 10(-7) M prazosin blocked the responses to high concentrations of UK-14304. In the presence of 10(-8) M Bay K 8644, UK-14304 elicited a monophasic concentration-dependent contraction that was antagonized by 10(-7) M prazosin, not by 10(-7) M rauwolscine. In the mesenteric vein, UK-14304 elicited concentration-dependent contractions, producing 63% of the KCl maximal response. The lower part of the biphasic concentration-response curve was inhibited by 10(-7) M rauwolscine and the upper part of the curve was antagonized by 10(-7) M prazosin. The presence in the medium of 20 mM KCl, 10(-11) M endothelin-1 or 10(-9) M Bay K 8644, which increased resting tension less than 10% of the KCl maximal response, markedly enhanced the responses to UK-14304 primarily at concentrations lower than 10(-6) M. The enhancement of responses were prazosin (10(-7) M)-resistant and rauwolscine (10(-7) M)-sensitive.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

Terminal aortic response to sodium intake is the major determinant of total peripheral resistance in elderly hypertensives.

Thirty-four elderly patients were studied using a Doppler flowmeter during different sodium intakes. Salt increased mean blood pressure and cardiac output (CO), while total peripheral resistance (TPR) remained unchanged. Neither carotid nor terminal aortic resistance changed, while coeliac, superior mesenteric or renal resistance increased. There was a significant and direct correlation (r = 0.82) between the change in TPR and that in terminal aortic resistance. Salt-sensitive patients were divided into two subgroups; the SST group in which sodium loading increased TPR more than CO, and the SSC group in which salt loading increased CO more than TPR. Terminal aortic resistance increased in the SST, decreased in the SSC, and remained unchanged in the non-salt-sensitive group with salt loading. The terminal aortic vascular bed received much of the increase of CO in the SSC patients. In the SST group, the contribution of the individual vascular area to increased TPR was assessed, which revealed that terminal aortic response to sodium loading was the major determinant of increased TPR. We concluded that the responses of terminal aortic vascular bed to sodium loading contributed to the changes in TPR.

Aged↗

[Validation of Doppler arterial flow in humans].

A method of measuring volumetric flow in human arteries with pulsed Doppler technique was developed. Doppler flowmetry was assessed in 11 adult patients whose admission-diagnoses included aneurysm of the aorta or dissections. During surgery, regional blood flows of the left common carotid artery, terminal aorta, common iliac artery, external iliac artery or common femoral artery were measured by Doppler method and electromagnetic flowmeter. Eighty four arterial flow determinations were obtained from the 11 patients studied. On comparison of simultaneous electromagnetic and Doppler measurements of blood flow, an excellent correlation (r = 0.93) was found between the two methods. The slope of the regression line was 0.587. Regional blood flow was measured with Doppler flowmetry in another 9 patients. The values of the left common carotid, celiac, superior mesenteric and terminal aortic flows were 251 +/- 62, 608 +/- 399, 687 +/- 381, 783 +/- 324 ml.min-1, respectively. This method provides an easy, reliable way of measuring regional blood flow.

Aged↗

Hemodynamic response to dietary sodium loading in essential hypertension studied with Doppler echocardiography.

The cardiac response to dietary salt loading was assessed by Doppler echocardiography during various sodium intakes (52-345 mEg per day) in 30 patients with essential hypertension. The Mitral flow velocity integral in the rapid filling phase (IntR) and the atrial contraction phase (IntA) was measured from the transmitral flow pattern, and the sum of IntR and IntA (IntR + IntA), the ratio of IntA to IntR (IntA/IntR), cardiac output (CO) and total peripheral resistance (TPR) were calculated. With salt loading, the mitral flow pattern remained almost unchanged in the nonsalt-sensitive (NSS) patients. Fourteen of the 19 salt-sensitive (SS) patients showed significant increases in IntR + IntA and CO with salt loading (IntR + IntA, from 13.9 +/- 2.8 to 17.9 +/- 3.6 cm, p less than 0.01; CO, from 6021 +/- 2130 to 8305 +/- 1699 ml/min, p less than 0.01), and were termed "salt-sensitive CO-dependent" (SS [COdep]), suggesting that the apparent pressor response to sodium loading was mediated by an increased CO. In the remaining five SS patients termed "salt-sensitive CO-independent" (SS [COindep]), IntA/IntR increased significantly with sodium repletion (from 0.66 +/- 0.23 to 0.90 +/- 0.31, p less than 0.01), without a significant change in IntR + IntA. Increments in IntA/IntR observed in the SS [COindep] patients were considered to be due to an elevation of total peripheral resistance (TPR), since changes in IntA/IntR were significantly correlated with those in TPR in all subjects (r = 0.617, p less than 0.01).

Adult↗

[Mitral flow responses to two-week salt loading in elderly hypertensive patients].

The effects of a two-week high sodium diet on mitral flow pattern were assessed in 29 patients with essential hypertension (81.9 +/- 6.9 years). Transmitral flow was recorded during different rates of salt intake; 7 g/day for 8 weeks and 20 g/day for 2 weeks. With sodium loading, 25 patients whose mean blood pressure (MBP) increased by 10 percent or more were termed salt-sensitive (SS) group, and 4 patients whose MBP did not change or increased by less than 10 percent were termed non-salt-sensitive (NSS) group with mitral flow velocity integral, cardiac output (CO) and total peripheral resistance (TPR) were calculated. Thirteen of the SS patients were defined as "SST" in which an increase in TPR was greater than that in CO with sodium repletion. In the remaining 12 SS patients termed "SSc", the increase in CO was greater than that in TPR with salt loading. CO increased significantly in the SSc patients, but did not change in the SST or NSS group with sodium loading. TPR increased significantly in the SST and NSS subjects, and decreased significantly in the SSc patients. Peak velocity of transmitral flow in the rapid filling phase (R) decreased significantly in the SST and NSS patients, and increased significantly in the SSc group. On the other hand peak velocity of transmitral flow in the atrial contraction phase (A) increased significantly in the SST and SSc groups, but remained unchanged in the NSS patients. There was a significant increase in A/R in the SSt group and a significant decrease in A/R in the SSc patients with sodium loading.

Aged↗

[Comparative systemic and regional hemodynamic effects of dopamine and dobutamine in the elderly].

Thirteen elderly subjects underwent a crossover study of dopamine and dobutamine at 5 micrograms/kg/min in order to compare the systemic and regional hemodynamic effects of the two drugs, using Doppler techniques. Although both drugs decreased mean arterial pressure significantly, cardiac index and total peripheral resistance remained unchanged. Both drugs increased heart rate significantly. Since neither drug altered the common carotid, celiac or superior mesenteric flow, there was no significant change in the resistances of these flows. Terminal aortic flow increased significantly and its resistance decreased significantly with both drugs. Both dopamine and dobutamine at 5 micrograms/kg/min act as a positive inotrope in general. Out data suggest, however, that both drugs may act mainly as a positive chronotrope in the aged and that both drugs may have direct effects on the terminal aortic vascular bed since terminal aortic flow increased significantly without augmentation in the cardiac index.

Aged↗