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Biomedical subjects

S Isoyama

Publications and source records attributed to S Isoyama.

At least 73 records · Page 4Linked to original sources

Responses of left ventricle to changes in aortic input impedance.

In order to evaluate how pressure and flow at the outlet of a ventricle are determined by the interaction between the ventricle and an aortic input impedance, we examined the effects of independent changes in the peripheral resistance and in the aortic compliance using isolated canine left ventricle preparations. There was an inverse linear relationship of mean values between pressure and cardiac output under pure resistance changes when coronary flow was maintained constant. But, when the coronary perfusion pressure depended on mean aortic pressure, the relationship was no longer linear under a critical aortic pressure. When aortic compliance was increased, late systolic flow was enhanced and late systolic pressure decreased such that the stroke volume increased. The top part of the pressure-volume loop showed a configurational change from the right side down to the left side down. Changes in pressure and flow wave forms, and in the pressure-volume loop can be predicted by an electrical model in which time varying capacitance arranged in series with the internal resistance was used as a ventricular model.

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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.

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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.

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A high-pass phaseless filter for eliminating low-frequency ECG noise during exercise and its clinical application to automatic analysis of the heart rate and ST segment level.

We developed a new technique to eliminate low-frequency ECG noise by the use of a specially designed high-pass phaseless filter. The phaseless filter was tested by computer-simulated ECG signals and it proved to be highly effective in eliminating ECG noise without any significant deformation of the ST segment level. The maximum distortion of ST segment level at 0.8 Hz cut off frequency of this filter is equivalent to the distortion of the usual ECG Amp having 0.1 Hz cut off frequency (JIS). Furthermore, studies of the stabilized ECG recordings during exercise, which became possible by using the phaseless filter, enabled us to develop a method of automatic analysis of the heart rate-ST segment level relationship during and after exercise. The submaximal exercise ECG test was done on 78 ostensibly healthy men. The heart rate (X axis) and three points on the ST segment levels (Y axis) were plotted automatically on an X-Y recorder. Although a great variety of patterns were drawn, we could discern clearly different patterns for normal subject and those with typical ischemic heart disease. Further analysis of this relationship will undoubtedly contribute to the detection of ischemic heart disease.

Autoanalysis↗

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.

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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.

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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.

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A comparison of left ventricular volume-pressure relations of excised perfused canine hearts in isovolumic contraction, arrest and fibrillation.

The purpose of the present investigation was to study the effects of various conditions such as beating, arrest and fibrillation on left ventricular (LV) diastolic compliance. In coronary-arterially perfused canine isolated hearts, LV volume-pressure (v-p) relations for both inflation and deflation were obtained by infusing and withdrawing a saline. The v-p curves of inflation and deflation were both sigmoidal, but the resultant v-p relations for deflation produced a shift to the left inflation curves, showing hysteresis between inflation and deflation in three ventricular states. The effect of arrest or fibrillation, especially of fibrillation, on LV distensibility was discernible, and the resultant v-p relations produced a marked shift to the right, showing an apparent decrease in LV volume (LVv) at a given filling pressure. It was concluded that it is very questionable to identify the stiffness of the beating heart with the non-beating heart.

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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.

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The acoustic characteristics of the left ventricle.

A new method was developed to describe the instantaneous resonance curve (IRC) of the left ventricle (LV), which represents the acoustic characteristics and instantaneous viscoelastic properties of LV. This method was evaluated using coronary-perfused isolated canine LV preparations.

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Experimental study of afterload-reducing therapy: the effects of the reduction of systemic vascular resistance on cardiac output, aortic pressure and coronary circulation in isolated, ejecting canine hearts.

The relationship between cardiac output (CO) and peripheral resistance (Rp) was examined under the following conditions for coronary perfusion: constant coronary flow perfusion; perfusion with a pressure equal to mean aortic pressure (AoP perfusion); and perfusion with a pressure equal to the mean AoP - 30 mm Hg (AoP - 30 mm Hg perfusion). We also examined the coronary pressure-flow relationship. For these studies, we used paced, isolated, ejecting canine hearts, which were loaded by a hydraulic system that simulated the input impedance of a dog's systemic arterial tree. The CO in the constant coronary flow perfusion continued to increase with the reduction of Rp. The CO in the AoP perfusion became maximal at a slightly subphysiologic Rp, or at an average mean AoP of 65 mm Hg. This mean AoP was closely associated with the lower limit of the autoregulation of coronary blood flow. In the AoP - 30 mm Hg perfusion, the mean AoP at which CO became maximal was 72 mm Hg and the corresponding coronary perfusion pressure appeared to be lower than the lower limit of the perfusion pressure range for coronary flow autoregulation. The Rp value at that point was slightly higher than the physiologic range. We conclude that when coronary perfusion pressure changes with mean AoP, and when left ventricular end-diastolic pressure is fixed, there is a clear optimal Rp at which CO becomes maximal, and this optimal Rp is higher if coronary perfusion pressure is biased from mean AoP to a significant degree.

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Effects of changes in the aortic input impedance on systolic pressure-ejected volume relationships in the isolated supported canine left ventricle.

We examined the effects of aortic input impedance alteration on left ventricular pressure, aortic flow and ejected volume (integral value of aortic flow), in an isolated blood perfused ejecting canine heart, with special reference to end-systolic values. A hydraulic model which stimulates an aortic input impedance was attached to the aortic root of an excised heart. Left ventricular end-diastolic pressure was kept constant by electrical pacing. Three coronary arteries were perfused with arterial blood from support dogs. When the peripheral resistance in the hydraulic model was changed, there were inverse linear relationships between stroke volume and mean left ventricular systolic pressure and between ejected volume and pressure at end-systole. Time interval from the onset of contraction to end-systole did not change. Thus the relation between stroke volume and mean left ventricular pressure obtained by changes in peripheral resistance is governed by a source resistance, which can be considered as the contractile state of the ventricle. When the capacitance (arterial compliance) was changed, there was no inverse linear relation between stroke volume and mean systolic pressure. In many cases, there was an inverse linear relationship between ejected volume and pressure at end-systole. However, an increase in capacitance prolonged the time interval from the onset of contraction to end-systole. We conclude that the end-systolic pressure-ejected volume relationship in the ejecting heart is governed not only by contractility but also by arterial capacitance.

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The effect of graded coronary flow reduction in the left anterior descending and septal arteries on left ventricular function in the canine heart.

WE quantitatively analyzed the effect of graded left anterior descending and septal coronary flow (LAD + septal flow) reduction on left ventricular function with a left ventricular end-diastolic pressure (LVEDP) of 6 mm Hg and 12 mm Hg. We used an isolated, ejecting, canine heart preparation ( n = 8), the coronary flow of which could be controlled independently of the aortic pressure. We kept the other hemodynamic variables - heart rate, left circumflex coronary flow, right coronary flow and aortic input impendance - constant within their normal physiologic range. We considered this reduction in LAD + septal flow to be analogous to that of the most frequent lesion in ischemic heart disease. There was no plateau in the left ventricular work caused by this reduction of the regional coronary flow. Therefore, the plateau commonly reported in previous studies may be partially a result of the compensatory elevation of LVEDP, which is necessary to maintain the left ventricular work.

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Mechanical interaction between the ventricles.

We investigated ventricular interaction by the use of six excised, perfused, canine hearts. In this preparation, we could change the filling pressure of the right and left ventricles independently, thereby breaking the normal series-pump arrangement. We found that mechanical ventricular interaction exists in diastole and in systole. Namely, not only decreased diastolic ventricular compliance, but also the reduced performance in either ventricle was found, when the opposite ventricular pressure was increased. Thus, when the opposite ventricular filling pressure increases, we suspect that systolic ventricular function of either ventricle will be depressed significantly by these two factors; i.e., the Frank-Starling effect due to decreased ventricular diastolic volume following decreased diastolic ventricular compliance, and the depressed systolic ventricular function. Clinically, these findings may be important in considering the mechanism of the occurrence of simultaneous reduced performance of both ventricles in cases when only one side of the ventricle is affected hemodynamically and its filling pressure is greatly increased in various pathological states such as heart failure.

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The relationship between myocardial oxygen consumption and total work obtained by a new left ventricular model.

The relationship between myocardial oxygen consumption (MVO2) and left ventricular work was examined experimentally, assuming that the left ventricle is equivalent to an electrical current source generator consisting of parallel source resistance (Ri) and constant generator current (I0). The internal and external work can be calculated as (Ri X I1(2)) and (Rp X I2(2)) in this model, where I1 is current of source resistance, Rp is peripheral resistance and I2 is cardiac output. The experiments were performed with a blood-perfused isolated ejecting canine heart preparation in which the hydraulic model, simulated to an aortic input impedance, was attached to the aortic root. The peripheral resistance was changed in a stepwise fashion and left ventricular pressure, cardiac output and MVO2 were measured. The calculated total work showed a close linear correlation with the MVO2, which suggested that the left ventricle can be regarded as a current source generator and the total work as a main mechanical factor in determining the MVO2.

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