Search PubMed⌕ Search

Biomedical subjects

D Saito

Publications and source records attributed to D Saito.

At least 163 records · Page 9Linked to original sources

Test of carcinogenicity of quercetin, a widely distributed mutagen in food.

The carcinogenicity of quercetin, a flavonol, was tested in six-week-old ddY mice of both sexes. Groups of 38 males and 35 females were given pellet diet containing 2% quercetin throughout their life span. As controls, 16 males and 15 females were given basal diet. Animals in both test and control groups developed leukemia and tumors of the lung, forestomach, mammary gland, adrenal, and soft part tissues. In addition, some animals in groups treated with quercetin developed tumors of the heart, liver, salivary gland, ovary, and uterus. The incidences of these tumors in test and control groups were not statistically different.

Animals↗

Purification and characterization of pepsinogens and a unique pepsin from rat stomach.

Four pepsinogens (1, 2, 3 and 4) (zymogens of pepsin A, EC 3.4.23.1, or pepsin C, EC 3.4.23.3) were purified from the fundic mucosa of rat stomach to homogeneous states as judged by sodium dodecyl sulfate/polyacrylamide gel electrophoresis and a unique pepsin was purified from pepsinogen 1. The molecular weights of pepsinogens 1, 2, 3 and 4 were 42 000, 40 000, 40 500 and 39 000, respectively, and those of the respective activated pepsins (1, 2, 3 and 4) were 35 500, 40 000, 35 500 and 37 000, respectively, as estimated by polyacrylamide gel electrophoresis. The amino acid compositions of these four zymogens differed, but resembled those of pepsinogen Cs from various animal species. Rabbit antiserum prepared against pepsinogen 1 reacted with pepsinogen 2, but not with pepsinogens 3 or 4. The precipitin line against pepsinogen 1 fused completely with that against pepsinogen 2. Purified pepsin 1 was a unique pepsin showing remarkable stability in alkali. It resembled pepsin A with respect to inhibition by pepstatin and pepsin C with respect to its amino acid composition, but had properties intermediate between those of pepsin A and C with respect to its optimal pH (2.1 to 3.1) with hemoglobin and activity on N-acetyl-L-phenylalanyl-L-diiodotyrosine.

Amino Acids↗

Limitations in predicting oxyhemoglobin saturation of dog blood from PO2.

This study compared oxyhemoglobin saturation (SO2) and O2 content (CO2) estimated from O2 tension (PO2) by the Rossing-Cain nomogram (J. Appl. Physiol. 21: 195-201, 1966) with SO2 and CO2 estimated by a galvanometric O2 analyzer in blood samples from eight dogs. The nomogram consistently and significantly overestimated SO2 over the range of 20-60%. The greatest absolute difference, which averaged 10% saturation, was between 40 and 59% saturation. Between 30 and 39% saturation, the difference averaged 30% of SO2 estimated galvanometrically. CO2, calculated as the product of SO2, hemoglobin concentration (cyanmethemoglobin method), and hemoglobin O2 capacity, was significantly overestimated by the nomogram by as much as 1.2 ml/dl between 2 and 9.9 ml/dl. Between 14 and 21.9 ml/dl, the nomogram underestimated CO2 by as much as 1.2 ml/dl. We conclude that because coronary venous SO2 and CO2 values normally lie in the range of greatest error, estimates of these values based on PO2 are particularly unsuited for studies of myocardial O2 usage.

Animals↗

Relationship of cardiac oxygen usage, adenosine content, and coronary resistance in dogs.

Analysis of the relationships between cardiac oxygen usage (MVO2), cardiac muscle adenosine levels([Ado]), and coronary vascular resistance (R) in open-chest, anesthetized dogs tested the hypothesis that adenosine is a physiological regulator of coronary flow. Experiments using each dog as its own control showed that [Ado] varied directly with MVO2 as the latter changed spontaneously or in response to atrial pacing, paired pacing, aortic constriction, of beta-adrenergic blockade. In turn, R varied inversely with changes in [Ado]. Stimulating MVO2 with isoproterenol significantly increased the slope of the regression of [Ado] on MVO2 as well as of R-1 on [Ado]. The effect of beta-adrenergic stimulation on [Ado] is unexplained, but its effect on R-1 seems to reflect the combined effects of adenosine and direct beta-adrenergic coronary relaxation. These results support the hypothesis that adenosine mediates the coronary flow responses to changes in MVO2.

Adenosine↗

Increase in the calculated resistance of anatomically fixed stenosis in vitro in association with decrease in distal resistance.

The effects of changes in distal resistance on stenotic resistance were studied in vitro. Physiological saline was passed through the left carotid artery obtained from the dog, flexible rubber tubing, or through solid polyethylene tubing with a constant perfusion pressure or with a constant flow rate. Various stenotic resistances were established using a screw type constrictor and the distal resistance was varied by allowing physiological saline to pass through either a 23 gauge hypodermic needle (high peripheral resistance) or 23 and 20 gauge needles (low peripheral resistance ). For arteries with anatomically fixed stenosis, the calculated resistance was increased in association with reduction of the distal resistance. The stenotic resistance in the flexible rubber tubing changed in the same manner as that of the carotid artery, while the solid polyethylene tubing showed no significant stenotic resistance changes due to altering the distal resistance. These findings suggest that the stenotic resistance change of the artery correlates with the elasticity of the vessel wall and also indicate that resistance values were of little usefulness for evaluating the effects of vasodilating stimuli on the vessel segment with a significant stenosis.

Animals↗

Inhibition of experimental blood-borne lung metastasis by protease inhibitors.

The inhibitory effects of protease inhibitors on blood-borne metastasis in male Donryu rat lung were studied. Injection i.v. of 10(6) Yoshida ascites hepatoma AH7974 cells induced about 118 +/- 92 (S.D.) metastatic foci in rat lung after 3 weeks. Leupeptin (50 mg/kg body weight twice a day), injected i.p. from 2 days before to 4 days after the inoculation of tumor cells, reduced the number of metastatic foci to about 49 +/- 45 (p less than 0.005). Leupeptin also suppressed the formation of metastatic foci of Yoshida ascites hepatoma AH100B cells (p less than 0.001). Elastatinal (100 mg/kg body weight twice a day) and chymostatin (100 mg/kg body weight once a day) did not inhibit formation of metastatic foci of AH7974 cells. Injection i.v. of 10(6) AH7974 cells induced pulmonary thrombi within 1 hr. Leupeptin (50 mg/kg body weight twice a day) reduced the number of thrombi from 1298 +/- 395 to 646 +/- 218, when injected i.p. for 2 days before the inoculation of the cells (p less than 0.005). Chymostatin and elastatinal did not significantly change the number of pulmonary thrombi. These results indicate that leupeptin inhibited metastasis formation and suggest that this effect may be due to the inhibition of thrombus formation after the arrest of circulating tumor cells.

Animals↗

Effect of graded coronary constriction on the flow reserve in regional myocardium in dog.

Effects of coronary constriction on the flow reserve of regional myocardium were studied in the anesthetized open-chest dogs. Regional myocardial blood flow (RMBF) was continuously measured using heated crossthermocouple method. Left circumflex coronary artery (LCX) was constricted gradually with a screw type constrictor. The coronary constriction decreased subendocardial myocardial blood flow, while subepicardial myocardial blood flow was not affected until reactive hyperemia in LCX nearly disappeared. Recovery and arrival to peak flow rate of RMBF following the release of 15-second's occlusion of LCX were progressively delayed with an increase in the constriction, especially in the subendocardial myocardium. Repayment of flow debt, however, was remained relatively well since the duration of reactive hyperemia in RMBF was prolonged by an increment of the constriction. From these findings, it might be concluded that in the heart with coronary stenosis recovery from ischemia was caused by prolonged duration of reactive hyperemia, and is suggested that the time required for recovery from ischemia or ischemic abnormalities after the cessation of stress might be an important marker for the severity of coronary insufficiency.

Animals↗

Vectorcardiogram of complete right bundle branch block with left axis deviation by the Frank and Kimura systems.

Vectorcardiogram (VCG) recorded by both the Frank and Kimura systems were examined in 45 patients with complete right bundle branch block (RBBB) and left axis deviation (LAD) to investigate the relationship seen on electrocardiogram (ECG) between RBBB with LAD and bilateral bundle. The sample included: 13 cases of type SI, SII, SIII, SaVF; 21 cases of type SI, SII, SIII, aVF; and 11 cases of types SI, SII, SIII. VCG recorded by the Frank system were classified into seven types according to the QRS loop pattern on the frontal plane and into three types according to the horizontal plane. The main findings were: (a) In the Frank system the QRS loop in the frontal plane showed a variety of patterns in RBBB with LAD. (b) On VCG of complete RBBB judged complicated by a left anterior hemiblock by the Frank system, the main portion of the QRS loop extended to the left superior or merely to the left in the frontal plane. The direction of rotation and position on the horizontal plane were not consistent. (c) The results of this study suggest the usefulness of the Kimura system as an auxiliary diagnostic technique.

Adult↗

Effect of atrial fibrillation on coronary circulation and blood flow distribution across the left ventricular wall in anesthetized open-chest dogs.

Effects of atrial fibrillation on coronary circulation and on blood flow distribution across the left ventricular wall were studied in anesthetized open-chest dogs. Atrial fibrillation was induced by pressing down mechanically the left atrial appendage or by stimulating electrically the left atrial appendage. Heated cross-thermocouples were used for measuring regional myocardial blood flow. The results showed a marked decrease in coronary blood flow with a significant increase in coronary vascular resistance; average values (SD) of flow and resistance during control simus rhythm were 71.6 +/- 7.36 ml/min . 100g heart muscle and 1.38 +/- 0.15 mmHg/ml/min . 100g heart muscle, respectively, and 54.0 +/- 13.60 ml/min . 100g and 1.54 +/- 0.18 mmHg/ml/min . 100gjust prior to cessation of atrial fibrillation. The termination of fibrillation caused a remarkable rise in coronary flow and a fall in coronary resistance. Pacing-induced tachycardia, similar to the average ventricular rate during atrial fibrillation, increased coronary blood flow and decreased coronary vascular resistance. These show that active coronary vasodilatation and an increase in extravascular support of coronary bed are produced by atrial fibrillation. Subendocardial myocardial blood flow during atrial fibrillation was reduced 22.0 +/- 14.8% from control levels followed by marked increase in flow after cessation of fibrillation, while subepicardial flow decreased only slightly. Thus, atrial fibrillation itself diminishes coronary flow reserve, especially in the subendocardial layer, partly due to the increase in myocardial component of coronary vascular resistance, and it is possible that irregular ventricular rhythm may play an important part in a rise in extravascular support.

Animals↗

Comparative vasodilator effects of nitroprusside, phentolamine, and nitroglycerin on hemodynamics, regional myocardial function and epicardial electrogram in dogs with acute myocardial ischemia.

The effects of nitroprusside (NP), phentolamine (PH), and nitroglycerin (NTG) were studied on systemic hemodynamics, regional contraction and epicardial ST segment in the border and non-ischemic zones of the left ventricle of anesthetized open chest dogs. The anterior descending coronary artery (LAD) was completely occluded. NP (5 microgram/Kg/min) or PH (100 microgram/Kg/min) was drip-infused, or a bolus injection of NTG (20 microgram/Kg) was administered intravenously. The 3 vasodilator agents produced somewhat similar reductions in systemic arterial pressure. However, NP caused a greater reduction in total peripheral resistance (TPR) than in left ventricular end-diastolic pressure (LVEDP), and caused a decline, in the ischemic marginal zone, in both ST segment eievation and paradoxical systolic lengthening. PH decreased TRP without reducing LVEDP and elevated the ST segment. NTG markedly reduced LVEDP and TPR slightly. NTG improved the elevated ST segment and paradoxical systolic expansion of the segmental myocardium in the border zone. Cardiac output rose with NP and PH, whereas injected NTG caused a reduction in cardiac output. These findings suggest that NP favourably affects the ischemic myocardium mainly by reducing the afterload and that the NTG-induced improvement of myocardial ischemia can be attributed mainly to preload reduction, while PH enhances cardiac function with slight or no improvement of myocardial ischemia in the border zone.

Acute Disease↗

Effect of myocardial ischemia and nitroglycerin on systolic time intervals in the segmental myocardium.

Effects of ischemia and nitroglycerin on systolic time intervals in the segmental myocardial length were studied in anesthetized open-chest dogs. Two strain-gauges were sutured on the surface of the left ventricular wall; one was in the central area perfused by the left circumflex coronary artery (LCX) and the other was in the area perfused by the left anterior descending coronary artery. LCX was partially occluded with a screw type constrictor to the degree at which reactive hyperemia after the transient total coronary occlusion almost disappeared. After the hemodynamics stabilized nitroglycerin (20 microgram/kg) was injected into the femoral vein. In the ischemic area, contraction time was shortened and precontraction time was prolonged in association with an elongation of end-systolic and early systolic segment-length, respectively. The systolic time intervals in the ischemic segment were improved as a result of the recovery in the segment-length toward the control. The results suggest the usefulness of analyzing the segmental myocardial systolic time intervals for verifying the asynchronous contraction of the ventricle and the favourable effects of nitroglycerin on segmental myocardial function in the ischemic area.

Animals↗

Correlation of systolic time interval with abnormal myocardial contraction by coronary occlusion in anesthetized open-chest dogs.

The correlation between the systolic time interval and abnormal contraction in ischemic myocardium was studied in anesthetized open-chest dogs. A strain-gauge was sutured on the surface of the left ventricular wall perfused by the left anterior descending coronary artery (LAD) for measuring segment-length. The left ventricular stroke volume decreased progressively after occlusion of LAD. The left ventricular ejection time (LVET) was progressively shortened in close correlation with the elongation of segment-length at the onset of isometric relaxation in 20 seconds after LAD occlusion when early systolic myocardial contraction and isometric contraction time (ICT) were not affected. ICT was gradually prolonged and closely related with the lengthening of the early systolic segment-length, while LVET recovered toward the control level in spite of further decrease in stroke volume. A close relationship was observed between ICT/LVET and stroke volume (gamma = 0.76, P less than 0.01). The results suggested the possibility that LVET was normalized even when the left ventricular function was impaired, and ICT/LVET ratio was the most sensitive index of LV dysfunction.

Animals↗

Effect of propranolol on regional myocardial function in anesthetized open-chest dogs with myocardial ischemia.

Effects of propranolol on ischemic segmental function were studied in anesthetized open-chest dogs. Two segment-length gauges were used for measuring the regional myocardial function: one was sutured on to the left ventricular surface perfused by the anterior descending coronary artery (ischemic zone) and the other was on to that perfused by the circumflex coronary artery (normal zone). A bolus of propranolol (0.5 mg/kg) was injected into the right femoral vein. Five min later, the left anterior descending coronary artery (LAD) was completely occluded for one mine and thereafter released. Then a second coronary occlusion for 20 min was performed; an interval of 20 min was allowed between two occlusions. Propranolol, in the ischemic segment, apparently decreased the extent of paradoxical lengthening in the late systole following one min LAD occlusion, and facilitated improvement of segmental function after release of the occlusion. Moreover, the extent of abnormal stretching induced by 20 min occlusion during early systole, was also reduced by propranolol pretreatment. In contrast, compensatory increase in shortening by the normal segment was disturbed by propranolol. These results suggest that propranolol might exert a favourable influence on the segmental myocardial function during either transient or maintained myocardial ischemia.

Animals↗

A patient with repeated syncopal attacks after using isosorbide dinitrate.

The case of a patient with repeated attacks of collapse induced by sublingual isosorbide dinitrate is reported. The patient was an 81 year-old female who was admitted to Yura Hospital because of attacks of precordial pain. Several minutes after the sublingual administration of isosorbide dinitrate (10 mg) for an anginal attack, she developed a sensation of general weakness, and thereafter because unconscious. Arterial blood pressure fell and became unmeasurable. Electrocardiograms recorded during the syncopal attack showed sinus tachycardia and significant elevation of ST-segment in right precordial leads. In response to a drip infusion of noradrenaline, arterial blood pressure returned to normal with recovery of consciousness. Two similar syncopal attacks induced by sublingual isosorbide dinitrate occurred in the next three days. These attacks were not due to augmentation of the vagal reflex. Decrease of venous return probably was the primary etiological factor.

Aged↗

Effect of diltiazem on coronary blood flow of the heart with experimental coronary sclerosis and on regional myocardial blood flow of the heart with acute myocardial ischemia.

Effects of 3-acetoxy-2,3-dihydro-5[2-(dimethyl-amino)ethyl]-2-(p-methoxyphenyl)-1,5-benzothiazepin-4 (5H)-one hydrochloride (diltiazem) on coronary circulation of the heart with experimental coronary sclerosis induced by i.v. allylamine (Group A), and on regional myocardial blood flow in acutely-induced ischemic myocardium (Group S) were studied in anesthetized open-chest dogs. Regional myocardial blood flow was continuously measured with heated cross thermocouple method and following results were obtained: 1. In Group A coronary blood flow and coronary flow resistance remained unchanged essentially after the injection of diltiazem, whereas coronary blood flow markedly rose and coronary flow resistance decreased in the normal heart. 2. Local blood flow in both of the inner and outer thirds of the ischemic myocardium was not affected by diltiazem in Group S. In the normal myocardium, however, it increased definitely. 3. From these findings it is concluded that the clinical effectiveness of diltiazem is independent of its vasodilator properties.

Acute Disease↗