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Biomedical subjects

K Ashikawa

Publications and source records attributed to K Ashikawa.

At least 37 records · Page 2Linked to original sources

ST segment changes under occlusion of the proximal portion of major coronary arteries in the isolated canine heart.

We studied the mechanisms of ST segment displacement in the ECG recorded from the epi- and subendocardium of ischemic ventricles in the isolated and perfused canine heart. ST segment changes were observed in association with a relatively large area of ischemia produced by occlusion of the left anterior descending and septal arteries (LAD + Sept.) or of the left circumflex artery (LCx). Contrary to previous reports, we found that the amount of subendocardial ST elevation was not always greater than that in the epicardial ECG recorded at the center of ischemia. Also, in the non-ischemic area, the degree of the ST depression in the subendocardial record was nearly the same as the epicardial record. On the other hand, the degree of the epicardial ST elevation on the border zone was always smaller than that at the ischemic center, which seemed to be due to the broadness of the border zone. The amplitude of the ST depression in the non-ischemic area was greater when the recording electrode was near the ischemic border, which supports the solid angle theory. The degrees of both ischemic ST elevation and reciprocal ST depression in the LCx perfused area were always greater than in the LAD + Sept. perfused area. These results strongly suggest that ST segment displacement depends on the relative position of the recording electrode to the electric double layer which exists at the border between the ischemic and non-ischemic area.

Animals↗

Effects of coronary artery stenosis on left ventricular end-ejection pressure-ejected volume relationships in isolated perfused canine hearts.

We investigated the behavior of the left ventricular end-ejection pressure-ejected volume relation with and without left circumflex coronary stenosis in isolated perfused canine hearts. To change ventricular afterload pressure, the peripheral resistance of the hydraulic model attached to the aortic root of the excised hearts was changed in a stepwise fashion to five different levels. The end-ejection pressure-ejected volume relationship was nearly linear in both pre-ischemic and ischemic states. The slope changes following left circumflex coronary stenosis differed among the hearts used in the present study, and there was no significant difference in average slope (n = 10) between the pre-ischemic and ischemic states (i.e., -7.4 +/- 1.0 and -8.4 +/- 1.2 mmHg/ml, respectively). Therefore, the, slope of the relation was not useful in judging the presence of depressed ventricular function induced by coronary stenosis. In contrast, the ejected volume axis intercept decreased significantly from 16.5 +/- 1.1 ml to 13.6 +/- 1.1 ml (p less than 0.05) with regional ischemia.

Animals↗

A new microscopic system for the continuous observation of the coronary microcirculation in the beating canine left ventricle.

A microscope system was designed using a new type of objective lens which makes possible the direct and continuous observation of the coronary microcirculation throughout the entire cardiac cycle in the beating canine heart. The microscope system consists of a standard microscope and a floating objective system which is composed of a pair of convex lenses and transmits a real image of the coronary microcirculatory bed to a standard microscope without any change in magnification. The convex lens facing the heart is supported by a weight-adjusting coil spring and low-resistance ball bearings which allow the lens to move perpendicularly in unison with cardiac motion. To reduce excessive cardiac movement, two 24-gauge needles connected to the animal table by a needle holder are horizontally inserted through the midmyocardium of the left ventricle beneath the area of interest. The epimyocardium of the left ventricle is transilluminated by means of a light pipe and a xenon-arc lamp. The distance between the floating lens and the cardiac surface is kept constant using a spacing device connected to the light pipe holder to prevent the compression of the tissue in the microscopic field of view. This improvement in the microscope system combined with high-speed cinematography greatly facilitates the continuous analysis of the coronary microcirculation in the beating left ventricle throughout the entire cardiac cycle, and may provide a useful approach to the understanding of the regulation mechanism of the coronary circulation.

Animals↗

The effect of heart rate and left ventricular end-diastolic pressure on the direction of ST segment displacement in acute ischemia.

The correlation between the ST segment displacement and coronary blood flow in various hemodynamic conditions was studied. Five isolated, isovolumic contracting canine hearts were used. The left main and the right and left circumflex (LCx) coronary arteries were cannulated and perfused with support dog's arterial blood. Four pairs of Ag-AgCl ECG electrodes were attached to the epicardium and subendocardium in the LCx perfused area. Heart rate and left ventricular end-diastolic pressure (LVEDP) were controlled by means of right atrial electrical pacing and infusion or withdrawal of arterial blood into the left ventricle, respectively. LCx flow was reduced by 75, 50, 25% of the control level under the condition of 200 beats/min of heart rate and 20 mmHg or 5 mmHg of LVEDP, and ECGs were recorded. The ST segment elevation was observed in epi- and subendocardial lead ECGs when LCx flow was reduced from 110 +/- 27.5 ml/min/100 g to 72 +/- 3 ml/min/100 g under the condition of normal LVEDP (5 mmHg) and a high heart rate (200 beats/min), whereas the same degree of reduction in LCx flow under the condition of high LVEDP (20 mmHg) and high heart rate (200 beats/min) resulted in an epicardial ST segment depression associated with marked subendocardial ST segment elevation. The results suggest that the coronary flow reduction with a higher LVEDP will induce subendocardial ischemia, whereas the same degree flow reduction with a normal LVEDP induce transmural ischemia.

Animals↗

Effects of afterload reduction on global left ventricular and regional myocardial functions in the isolated canine heart with stenosis of a coronary arterial branch.

We examined the effects of graded reduction of afterload on the global left ventricular and regional myocardial functions as well as coronary hemodynamics in hearts with regional ischemia. We used isolated, paced canine hearts that were loaded with a hydraulic system that simulated the aortic input impedance of the dog's arterial tree. The loading conditions could be quantitatively and sequentially changed by the reduction of the systemic vascular resistance of the hydraulic system, while the preload was kept constant using a variable-height reservoir connected to the left atrium. The heart was perfused with arterial blood from a support dog. Mean coronary perfusion pressure was maintained equal to mean aortic pressure (AoP) by a servo-controlled pump. Then, the left circumflex branch was constricted to an approximate 50% flow reduction of the preischemic control condition. The myocardial lengths at ischemic and nonischemic regions were measured with two pairs of ultrasonic crystals. In the hearts without ischemia, cardiac output continued to increase, from 535 +/- 14 to 1181 +/- 74 ml/min (p less than 0.01), as mean AoP decreased fom 111 +/- 4 to 52 +/- 3 mm Hg (p less than 0.01), although mean coronary blood flow decreased by approximately 50%. During regional ischemia, at control pressures, performance of the ischemic region diminished from 0.94 +/- 0.15 to 0.77 +/- 0.15 mm (p less than 0.05). With a small decrease in afterload, from 98 +/- 6 to 86 +/- 3 mm Hg, performance improved slightly as in the normal region. With a larger reduction in afterload, from 86 +/- 3 to 55 +/- 6 mm Hg, performance of the ischemic region decreased from 0.77 +/- 0.15 to 0.61 +/- 0.15 mm (p less than 0.05) while cardiac output increased. Thus, there appears to be a bimodal change in performance: a baseline performance, perfusion pressure-mediated decrease and a second, afterload-modulated change.

Animals↗

Mechanical interactions between four heart chambers with and without the pericardium in canine hearts.

By using excised postmortem hearts obtained from 15 mongrel dogs with the pericardium intact, we investigated mechanical interactions between the four heart chambers from the standpoint of ventricular pressure-volume relationships. The interactions investigated were those between (1) the atrium and the ventricle, (2) the right ventricle and left ventricles, (3) the atrium and one ventricle vs. the other ventricle, and finally (4) the left and right atrium and the right ventricle vs. the left ventricle. For these purposes, we inserted compliant balloons into the four heart chambers without injuring the pericardium, i.e., we incised the base of the atria which was not covered with the pericardium. We obtained the right and/or left ventricular pressure-volume relationships under a constant pressure in three other heart chambers by changing the height of the reservoir connected to each balloon. As a result, both ventricular pressure-volume relationships were hardly affected by an increase in the atrial pressure ranging from 5 to 30 cm H2O with the pericardium removed, although the ventricle became less compliant due to an increase of the same magnitude of the opposite ventricular pressure. On the other hand, the effect of an increase in atrial pressure was distinct with the pericardium intact. Also, all mechanical interactions were enhanced dramatically with the intact pericardium. Thus, the pericardium plays an important role in these mechanical interactions, especially when the filling pressures of all heart chambers increase simultaneously. Clinically, these findings may be important to understanding ventricular functions as related to various heart disease-especially acute heart failure.

Animals↗

A continuous and quantitative analysis of the uneven distribution of myocardial blood flow in dogs using a distribution function of the clearance time constant.

A continuous and quantitative analysis of the uneven distribution of coronary blood flow was accomplished in anesthetized open-chest dogs using the distribution function of the hydrogen (H2) clearance time constant. The distribution function was derived by analysing the H2 washout curves in the coronary sinus which were obtained by the H2 clearance method, using platinum electrodes placed in the coronary sinus. Twelve to seventeen platinum electrodes were employed to obtain simultaneous measurements of the regional myocardial flow before and after stenosis of the left anterior descending coronary artery. Theoretically, the H2 washout curves in the coronary sinus could be interpreted as a function with multi-exponential characteristics, represented by an equation similar to the Laplace transform of the distribution function of the H2 clearance time constant. Therefore, we assumed that such an equation would represent the uneven distribution of coronary blood. We obtained the distribution function by using an approximation method to solve the integral equation and we employed digital computation to increase the resolution. Before stenosis of the left anterior descending coronary artery, the log distribution function curves with respect to the H2 clearance time constant were roughly symmetrical in terms of the maximum peak in the time constant. After stenosis of the left anterior descending coronary artery, the log distribution function had two peaks and the range of distribution was much larger than that before coronary stenosis. Our findings may prove to be valuable as a technique to estimate continuously and quantitatively the heterogeneous distribution of myocardial blood flow.

Animals↗

[Distribution of cefotiam dihydrochloride to the intraabdominal exudate (author's transl)].

The concentration of serum and intraperitoneal exudate after dripping intravenous administration of CTM were measured. Four male cases of the emergent laparotomy, a Cushing's ulcer, a hemorrhagic gastric ulcer, an adhesive ileus and acute terminal ileitis were investigated on this study. Two grams of CTM dissolving into 100 ml of physiological saline solution were prepared and administered in a period of 1 hour by intravenous drip (i.v.d.) for all cases after operation. The measurement of CTM-concentration in serum and intraperitoneal exudate were made at 30 minutes, 60 minutes following administration by serum and intraperitoneal exudate were made at 30 minutes, 60 minutes following administration by i.v.d. and at 30 minutes, hourly intervals over a 6-hour period after total administration. The intraperitoneal exudate for this study were collected through a drain which provided at the operation. These samples were measured by Agar-well method at Takeda Central Research Laboratory. Takeda Co., Ltd. The mean value of serum CTM at 30 minutes after the beginning of i.v.d. administration was 65.7 micrograms/ml and the maximum value, 79 micrograms/ml was obtained at 60 minutes. The following mean values at 30 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 5 hours and 6 hours after total administration were 39.1, 26.4, 14.6, 8.9, 4.7 and 0.6 microgram/ml. On the other hand, the mean values of CTM intraperitineal exudate at the same time intervals were 4.9, 20.7, 32.0, 34.3, 22.4, 13.9, 11.2, 8.7 and 3.3 micrograms/ml. These results showed that there were much transfer of CTM between serum and intraperitoneal exudate corresponding to the amount of administration.

Adult↗

Effect of diltiazem, a calcium antagonist, on myocardial ischemia.

In line with studies on the metabolism of the ischemic myocardium, the effectiveness of diltiazem hydrochloride, a potent calcium antagonist, in reducing the effects of ischemia was evaluated. Nonischemic and ischemic tissue samples were examined in two groups of dogs--Group I, dogs receiving no drug and killed after 60 minutes of regional ischemia, and Group II, dogs given diltiazem after 10 minutes of ischemia and killed 50 minutes later. Administration of diltiazem proved beneficial in several ways: The decrease in adenosine-5'-triphosphate in the ischemic region was halved, inhibition of anaerobic glycolysis was reduced, tissue levels of lactic acid and free fatty acids were lowered and the contractility of glycerinated heart muscle fibers was improved. However, administration of the drug did not influence mitochondrial function. Mitochondrial oxygen consumption and respiratory control were reduced by equal amounts in both groups, as was mitochondrial calcium ion binding. These observations demonstrate that diltiazem is capable of minimizing the consequences of acute ischemic, although the beneficial effects do not extend to all aspects of myocardial metabolism.

Adenosine Diphosphate↗

The relationship of regional coronary blood flow to mitochondrial function during reperfusion of the ischemic myocardium.

The relationship of changes in regional coronary flow to the nature and degree of biochemical disturbances during occlusion of branches of the left anterior descending coronary artery and following reestablishment of flow was investigated in two groups of dogs: group I, moderate ischemia before reflow, and group II, severe ischemia prior to reflow. Regional coronary blood flow was determined before ligation, after 60 min of ischemia and after 15 min of reflow using labelled microspheres. Hearts made ischemic for 60 min but not reperfused served as controls. Groups I and II were distinguished by the following features. Group II showed a marked exacerbation of biochemical damage on reperfusion of the ischemic region (reduced levels of ATP, impairment of mitochondrial oxygen consumption and mitochondrial calcium binding). This was accompanied by significant subendocaridial hyperemia. Reperfusion in group I, on the otherhand, partially reversed these changes (increased level of ATP in the ischemic-reperfused region, improved mitochondrial oxygen consumption and calcium binding). Mitochondrial calcium uptake and oxidative phosphorylation (ADP/O ratio) were not affected in any group. These data illustrate that the degree of biochemical damage following reperfusion of the ischemic myocardium is determined by the degree of ischemia, and suggest that interference with ATP production by the mitochondria is not responsible for the damage.

Animals↗

Bile duct carcinoma associated with an anomaly in the bile duct.

This paper reports a case of bile duct carcinoma associated with an extra-hepatic bile duct anomaly. In the present case, the anomaly induced an uncorrect preoperative diagnosis and obliged to change the surgical procedures during operation. A correct preoperative diagnosis was difficult to make in the present case, when the anomaly in the biliary system was not kept in mind.

Bile Duct Neoplasms↗

Interaction in culture between mouse ascites mammary carcinoma (MM2) cells and lymphoid cells of isologous mice.

MM2 cells, ascitic tumor originated from spontaneous mammary carcinoma of C3H/He mouse, were mix-cultured with lymphoid cells of thymus or mesenteric lymph nodes from isologous animals of the same sex. The interaction in culture between these cells was examined by time-lapse cinemicrography. In single culture, thymocytes, mesenteric lymph node lymphocytes and MM2 cells were kept for 7 days with little change in cell population. Lymphocytes of both sources showed a marked decrease in cell number when cultured together with MM2 cells, being evidently phagocytosed by MM2 cells. Lymphocytes from MM2-bearing mice or mice sensitized with deoxycholate-extracted MM2 antigen were also all phagocytosed. MM2 cells exhibited no sign of damage or degeneration due to the phagocytosis. Thymocytes were not phagocytosed by histiocytes obtained from ascitic fluid 3 days after i.p. injection of 5% starch suspension. Phagocytosis of erythrocytes or lymphoid cells from spleen by MM2 cells was not detected.

Animals↗

Interaction in culture between mouse ascites hepatoma (MH-134) cells and lymphoid cells of isologous mice.

Thymocytes or lymphocytes of mesenteric lymph nodes were obtained from mice bearing subcutaneously mouse ascites hepatoma MH-134 for 5 to 40 days. These lymphoid cells were added into the cultures of MH-134 cells. Morphological changes of cells in the mixed cultures were observed by time-lapse cinemicrography for the period of 4 weeks. Lymphoid cells were phagocytosed by MH-134 cells, and, in most cases, the tumor cells did not undergo any damage due to the phagocytosis. The exceptional cases were as follows: When MH-134 cells were mixed with thymocytes from mice bearing MH-134 tumor for 5 days, MH-134 cells phagocytosed thymocytes but some of them died later. In the mixed cultures of MH-134 cells and thymocytes or mesenteric lymph node lymphocytes from mice bearing MH-134 for 14 or 15 days, MH-134 cells phagocytosed lymphoid cells but died later by the burst of cytoplasm. By the burst many lymphoid cells phagocytosed appeared from the broken cytoplasm of MH-134 cells and, in some cases, the lymphoid cells looked to be alive. These findings suggest the possibility that lymphoid cells attack tumor cells not only from the cell surface but also from the inside being phagocytosed by tumor cells.

Animals↗